\r\n\tAn update on clinical manifestations, their assessment, monitoring, and imagiology, including peripheral arthritis, enthesopathy, and extra-articular findings, and, the differential diagnosis with other diseases which evolves with axial and peripheral calcifications will be provided.
\r\n
\r\n\t \r\n\tAn important component of this book must be dedicated to the more recent treatments namely with biologic therapies but focusing also on new small molecule inhibitors and experimental therapies.
",isbn:"978-1-80356-243-8",printIsbn:"978-1-80356-242-1",pdfIsbn:"978-1-80356-244-5",doi:null,price:0,priceEur:0,priceUsd:0,slug:null,numberOfPages:0,isOpenForSubmission:!0,isSalesforceBook:!1,hash:"e07e8cf78550507643fbcf71a6a9d48b",bookSignature:"Dr. Jacome Bruges Armas",publishedDate:null,coverURL:"https://cdn.intechopen.com/books/images_new/11273.jpg",keywords:"Diagnostic Criteria, Occurrence, Peripheral Involvement, Extra-Articular Manifestations, Axial Imaging, MRI, Disease Activity, Physical Function, Potential Pathways, MHC, Drug Treatment, New Small Molecules",numberOfDownloads:null,numberOfWosCitations:0,numberOfCrossrefCitations:null,numberOfDimensionsCitations:null,numberOfTotalCitations:null,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"February 9th 2022",dateEndSecondStepPublish:"May 6th 2022",dateEndThirdStepPublish:"July 5th 2022",dateEndFourthStepPublish:"September 23rd 2022",dateEndFifthStepPublish:"November 22nd 2022",remainingDaysToSecondStep:"17 days",secondStepPassed:!0,currentStepOfPublishingProcess:3,editedByType:null,kuFlag:!1,biosketch:"Senior Specialist in Internal Medicine and Specialist in Oncology. Dr. Bruges Armas is a member of the Comprehensive Health Research Center (CHRC), Nova Medical School, University of Lisbon, and Director of the Oncology Service and Director of the Epidemiology and Molecular Biology Service (SEEBMO) at the Hospital de Santo Espirito de Angra do Heroísmo, Terceira Island, Azores, Portugal.",coeditorOneBiosketch:null,coeditorTwoBiosketch:null,coeditorThreeBiosketch:null,coeditorFourBiosketch:null,coeditorFiveBiosketch:null,editors:[{id:"70522",title:"Dr.",name:"Jacome",middleName:null,surname:"Bruges Armas",slug:"jacome-bruges-armas",fullName:"Jacome Bruges Armas",profilePictureURL:"https://mts.intechopen.com/storage/users/70522/images/system/70522.jpg",biography:"Senior Specialist in Internal Medicine and Specialist in Oncology. Member of the Comprehensive Health Research Center (CHRC), Nova medical School, University of Lisbon, and Director of the Oncology Service and Director of the Epidemiology and Molecular Biology Service (SEEBMO) at the Hospital de Santo Espirito de Angra do Heroísmo, Terceira Island, Azores, Portugal. Main research interests are the epidemiology and molecular genetics of Spondyloarthritis (SpA), Diffuse Idiopathic Skeletal Hyperostosis (DISH), and Chondrocalcinosis (CC). 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1. Introduction
Multiple myeloma is a plasma cell malignancy characterized with clonal expansion of malignant plasma cells within the bone marrow and followed by osteolytic bone disease. It accounts for approximately 1% of all malignant diseases and represents about 10% of hematologic malignancies. Data from cloning and gene-sequencing studies strongly imply that the malignant clone in MM arises from a late cell in B-cell development. Investigation of a patient with suspected myeloma should include the screening tests. Electrophoresis of serum and concentrated urine should be performed, followed by immunofixation to confirm and type any M-protein present.
The common clinical presentations are fatigue and bone pain with or without associated fractures or infection. Mechanical impacts like intraosseous tumor pressure, microfractures, periost irritation, muscle spasm, nerve entrapment and compression of nerves by the collapsed vertebrae are reasons of severe myeloma pain.
Radiographic skeletal survey and bone marrow aspiration and biopsy are performed for diagnosis. Angtuaco EJ et al reported a radiologic review and explained that MR imaging bone marrow surveys in patients with MM demonstrate the broad spectrum of involvement, the results of treatment, the areas of potential complications, and the sites of focal disease for safe bone biopsies [1].
Pain characteristics clinically can be summarised as, pain is worse in supine position, especially at night or awakens from sleep, band like distribution around body, not relieved with rest and nonsteroidal anti-inflammatory drugs (NSAIDS), associated symptoms like fever, weight loss and progressive neurologic deficite in lower extremities. Somatic, visceral and neuropathic components can be easily involved in myeloma pain [2].
Chronic pain is extremely prevalent among patients with cancer. According to studies cancer pain can be relieved in more than 70% of patients using a simple opioid- based regimen. Whether there is a relatively lesser degree of opioid responsiveness in chronic cancer pain, then adjuvant analgesics are neccessary. Adjuvant analgesics describe the drug with a primary indication other than pain, but with analgesic properties in some painful conditions, they are usually coadministered with analgesics (acetaminophen, NSAIDS, opioids) when treating cancer pain. Common causes of chronic pain in cancer patients as multiple myeloma patients are releated to peripheral neuropathy due to chemotheraphy, radiotheraphy and tumor invasion, chronic postsurgical incisional pain, phantom pain, musculoskeletal pain, visceral pain from viscera or tumor.
The pain is one of the most common symptoms at diagnosis experienced by myeloma patients and it may also be an indicator of a subsequent relapse. Up to 67% of patients report pain at diagnosis, although this may have been present for several months before [3]. At diagnosis, pain may be due to the disease process itself (predominantly from destructive bone disease, but occasionally from plasmacytomas directly affecting neural tissues), or it may signify a co-morbidity (e.g. degenerative arthritis or osteoporosis).
Later in the course of the disease, pain often arises as a sideeffect of therapies, e.g. thalidomide or bortezomib neuropathy. Particularly in older patients, it is important to always consider co-morbidities, such as arthritis or osteoporosis, mimicking bony malignant pain; diabetes or carpal tunnel syndrome mimicking peripheral neuropathy (PN); and postherpetic neuralgia as a common cause of persistent pain.
Assessment of pain, should start with taking a history but may involve imaging by X ray, bone scan, CT or MRI. Myeloma patients should be evaluated for the presence and severity of pain regularly. Pain severity can be assessed by visual analogue scales (VAS), numerical rated scales (NRS) or verbal rated scales (VRS) [4]. To diagnose the presence of neuropathic pain, the Leeds assessment of neuropathic symptoms and signs scale (LANSS) can be used [5].
The pain is usually in constant and dull at first but, as the disease progresses, it becomes more severe until it is agonizing and constant. Severity of pain may be particularly devastating and can negatively affect the quality of patient life and their functional status. This should be managed using a multi-modal, mechanism-based approach including evidence-based pharmacological therapies alongside non-drug methods such as radiotherapy, bisphosphonates, and where appropriate, interventional and psychological techniques.
The critical importance of pain management as part of routine cancer care has been forcefully advanced by WHO, international and national professional organisations, and governmental agencies.
American Pain Society Quality of Care Task Force reviewed recommendations for faciliating improvements in the quality of cancer pain management.
Recognize and treat pain promptly (emphasis on comprehensive assessment and importance of preventive and prompt treatment based on evidence for neuroplasticity)
Involve patients and families in pain management plan (emphasis on customization of care and participation of patient in treatment plan)
Improve treatment patterns (eliminate inappropriate practices, provide multimodal therapy)
Reassess and adjust pain management plan as needed (respond not only to pain intensity but to functional status and side effects)
Monitor processes and outcomes of pain management (new standardized indicators and comments about forthcoming national performance indicators)
According to the European Society of Medical Oncology (ESMO) clinical practice guidelines with WHO ladder, general approach to management of cancer pain is,
STEP I: Mild pain (NRS: 1–4) is treated with non-opioid analgesics such as acetaminophen/paracetamol or a NSAID
Paracetamol is a useful analgesic in cancer-related pain and other chronic pains and should be prescribed at a dose of up to 1 gram qid (p.o. or i.v. in patients who cannot take oral medication, e.g. because of vomiting or mucositis).
NSAIDS should be avoided apart from very short term use (eg 3-5 days) with acute severe pain, eg bone fracture. They should not be used in the presence of renal impairment, and used with extreme caution in myeloma patients in view of the risk of precipitating renal compromise
For patients with mild pain (<5/10), normal release tramadol is a reasonable choice of analgesic agent. Tramadol has 1/5th the potency of oral morphine and the starting dose is 50mg 6 hourly prn or qid. Codeine can also be used but it is a pro-drug of morphine, and 10-15% of the population is unable to convert it into active morphine, leaving them with unacceptable toxicity [6].
STEP II: Traditionally, patients with moderate pain (NRS: 5–7) have been treated with a combination product containing acetaminophen plus a weak immediate-release opioid
For patients with mild to moderate pain or whose pain is not adequately controlled by paracetamol or a NSAID given regularly by mouth, the addition of a step II opioid (eg, codeine or tramadol; table 1) given orally might achieve good pain relief without troublesome adverse effects. Alternatively, low doses of a step III opioid (eg, morphine or oxycodone; table 1) may be used instead of codeine or tramadol.
\n\t\t
\n\t\t
\n\t\t
\n\t\t\t
Oral opioid
\n\t\t\t
Characteristics and comments
\n\t\t
\n\t\t
\n\t\t\t
Codeine
\n\t\t\t
Step II drug only: use alone or in combination with paracetamol; daily doses ≥360 mg not recommended
\n\t\t
\n\t\t
\n\t\t\t
Tramadol
\n\t\t\t
Step II drug only: use alone or in combination with paracetamol; daily doses ≥400 mg not recommended
\n\t\t
\n\t\t
\n\t\t\t
Hydrocodone
\n\t\t\t
Step II drug only: used as a substitute for codeine in some countries
\n\t\t
\n\t\t
\n\t\t\t
Oxycodone
\n\t\t\t
Step II opioid when used at low doses (eg, ≤20 mg per day) alone or in combination with paracetamol
\n\t\t
\n\t\t
\n\t\t\t
Morphine
\n\t\t\t
Step II opioid when used at low doses (eg, ≤30 mg per day)
\n\t\t
\n\t\t
\n\t\t\t
Hydromorphone
\n\t\t\t
Step II opioid when used at low doses (eg, ≤4 mg per day)
\n\t\t
\n\t
Table 1.
Step II opioids
STEP III: In severe pain (NRS: 8–10), morphine, oxycodone, and hydromorphone can use and the data show no important differences between morphine, oxycodone, and hydromorphone given by the oral route. Morphine is most commonly used. Oral administration is the preferred route. If given parenterally, the equivalent dose is one-third of the oral medication. The buccal, sublingual and nebulized routes of administration of morphine are not recommended because at the present time there is no evidence of clinical advantage over the conventional routes.
Patients with chronic moderate (5-7/10) or severe pain (>7/10) can be started on tramadol as above, but will usually need to go onto more potent opioids rapidly if they do not respond. Hydromorphone or oxycodone, in both immediate-release and modified-release formulations for oral administration are effective alternatives to oral morphine. Oxycodone is twice the potency of morphine and is associated with less drowsiness and hallucinations. For rapid onset, the normal release preparation can be used 4-6 hourly or qid, but most patients eventually prefer the convenience of the bd sustained release forms [7].
Methadone is a valid alternative but may be more complicated to use because of marked inter-individual differences in its plasma half-life and duration of action. Methadone use should be initiated by physicians with experience and expertise in its use. Strong opioids may be combined with ongoing use of a nonopioid analgesic (step I). Patients presenting with severe pain that needs urgent relief should be treated with parenteral opioids, usually administered by the subcutaneous (s.c.) or intravenous (i.v.) route. Intramuscular injections are painful and have no pharmacokinetic advantage.
Patches can be used to deliver either fentanyl or buprenorphine, both of which are very potent opioids. Fentanyl causes significantly less nausea, sedation and constipation compared to morphine [8]. When given the choice of fentanyl patches or oral morphine for chronic pain, patients prefer the patches [9]. They are usually the treatment of choice for patients who are unable to swallow, patients with poor tolerance to morphine and patients with poor compliance. Earlier worries regarding an inferior equipotency ratio of buprenorphine to oral morphine or of a ceiling effect and partial antagonistic effects of buprenorphine as compared with fentanyl have not been substantiated by newer publications [10]. Buprenorphine often initially causes nausea but this can be covered by the use of an anti-emetic such as metoclopramide and is otherwise well tolerated.
Immediate-release and slow-release oral formulations of morphine, oxycodone, and hydromorphone can be used for dose titration. The titration schedules for both types of formulation should be supplemented with oral immediate-release opioids given as needed. When using normal release oral medication, the dose can be titrated up daily by 30-50% until pain is controlled or unacceptable side effects occur. With sustained release oral medication it is advisable to wait 2-3 days between dose increments. With patches, doses should not normally be increased at less than 3 days intervals.
With all sustained release analgesics, it is essential to offer the patient a normal release ‘rescue medication’ for breakthrough pain. This is particularly important when breakthrough pain occurs quickly and predictably. It is important to distinguish this kind of ‘incident pain’ from pain arising from end of dose failure with sustained release medications, or spontaneous pains associated with neuropathy or opioid-induced hyperalgesia [11]. The ‘breakthrough dose’ is usually equivalent to +10% - 15% of the total daily dose. If more than four ‘breakthrough doses’ per day are necessary, the baseline opioid treatment with a slow-release formulation has to be adapted. Normal release oxycodone or morphine can be used, at 1/6th of the current 24 hour total opioid dose. However, often the absorption of these oral drugs can be too slow for breakthrough pain.. Opioids with a rapid onset and short duration are preferred for breakthrough doses. Fentanyl has a high bioavailability via the transmucosal route, which has led to the development of fast-acting (but short-lived) fentanyl formulations. These include fentanyl lozenges (Actiq ®); buccal tablets (Effentora®); or sublingual tablets [12]. Nasal sprays will also soon be available. Normally, a patient should not need to use more 2–3 of these relatively expensive fentanyl formulations per day for breakthrough pain; if more are being taken, either the background medication needs to be increased or the patient should be referred to a specialist. There is no place for pethidine in the treatment of pain in myeloma.
In addition, there is also worth noting that the recommendations for opioids for breakthrough of the EAPC. The pain exacerbations resulting from uncontrolled background pain should be treated with additional doses of immediate-release oral opioids, and that an appropriate titration of around-the-clock opioid therapy should always precede the recourse to potent rescue opioid analgesics. Breakthrough pain (eg, incident pain) can be effectively managed with oral, immediate-release opioids or with buccal or intranasal fentanyl preparations. In some cases the buccal or intranasal fentanyl preparations are preferable to immediate-release oral opioids because of more-rapid onset of action and shorter duration of effect. Additionally, immediate-release formulations of opioids with short half-lives should be used to treat pre-emptively predictable episodes of breakthrough pain in the 20–30 min preceding the provoking manoeuvre.
With all opioids, it is important to offer the patient a laxative and to keep checking for the development of constipation. Transdermal fentanyl and buprenorphine are associated with reduced incidence of constipation [13]. It is not necessary to routinely prescribe an anti-emetic with opioids, except for the first week when starting buprenorphine.
Respiratory depression is uncommon in patients treated chronically with opioids as long as dose increments are made carefully as outlined above. With the initiation of opioids, it is common to see a reduction in respiratory rate; however, this is usually balanced by changes in tidal volume so that minute ventilation initially remains steady. Care needs to be taken in patients with COPD or obstructive sleep apnoea, in whom the respiratory depression can occur even with low doses of opioids. True respiratory depression caused by opioids is diagnosed by a reduction in oxygen saturation (SaO2 < 90%) or by arterial blood gases. If this occurs, naloxone can be given but care must be taken not to provoke a serious increase in pain. Advice on future opioid dosing should be sought from a specialist in pain or palliative medicine.
Recently a condition known as opioid-induced hyperalgesia has been consistently identified in animal studies and has also been demonstrated to occur in human studies. This condition is characterised by increasing reporting of pain in the presence of increasing opioid dosage. The pain can be localised to the original lesion but is often generalised to adjacent dermatomes. The skin in the affected area may show hyperalgesia (increased pain response on normal painful stimulus) or allodynia (pain felt even on light touch). The treatment involves reduction in the opioid dosage along with the introduction of an NMDA channel blocker such as ketamine or methadone [14].
Most opioids cause dose-related sedation; however, fentanyl and oxycodone are associated with reduced sedation compared to morphine [15]. Patients who experience intolerable sedation due to opioids (or other drugs, e.g. thalidomide) may be considered for a trial of a psychostimulant such as methylphenidate or modafanil; this should only be prescribed by a specialist in palliative medicine. In patients with opioid-related neurotoxic effects (delirium, hallucination, and myoclonus), dose reduction or opioid switching should be considered.
Patients receiving step III opioids who have side-effects and do not achieve adequate analgesia that are severe, unmanageable, or both, might benefit from switching to an alternative opioid.
When switching from one opioid drug to another, dose conversion ratios can be recommended with different levels of confidence (table 2). These conversion ratios are specific for patients in whom analgesia from the first opioid is satisfactory. Therefore, when the opioid is switched because of unsatisfactory analgesia, excessive side-effects, or both, clinical experience suggests that the starting dose should be lower than that calculated from published equianalgesic ratios. In all cases the dose needs to be titrated in accordance with clinical response.
\n\t\t
\n\t\t
\n\t\t
\n\t\t
\n\t\t\t
RELATIVE ANALGESIC RATIO
\n\t\t\t
STRENGTH OF THE RECOMMENDATION FOR USE
\n\t\t\t
\n\t\t
\n\t\t
\n\t\t\t
Oral morphine to oral oxycodone
\n\t\t\t
1.5 : 1
\n\t\t\t
Strong
\n\t\t
\n\t\t
\n\t\t\t
Oral oxycodone to oral hydromorphone
\n\t\t\t
4 : 1
\n\t\t\t
Strong
\n\t\t
\n\t\t
\n\t\t\t
Oral morphine to oral hydromorphone
\n\t\t\t
5 : 1
\n\t\t\t
Weak
\n\t\t
\n\t\t
\n\t\t\t
Oral morphine to TD buprenorphine (*)
\n\t\t\t
75 : 1
\n\t\t\t
Weak
\n\t\t
\n\t\t
\n\t\t\t
Oral morphine to TD fentanyl (**)
\n\t\t\t
100 : 1
\n\t\t\t
Strong
\n\t\t
\n\t
Table 2.
Relative analgesic dose ratios
(*) Example: 60 mg oral morphine to 35 μg/h TD buprenorphine (equivalent to 0.8 mg per 24 h).
(**) Example: 60 mg oral morphine to 25 μg/h TD fentanyl (equivalent to 0.6 mg per 24 h).
TD=transdermal.
For patients with continuing severe (>6/10) pain or those who are unable to tolerate analgesics because of adverse effects, help should be sought from a specialist service such as the palliative care team or chronic pain team.
Haematology teams should readily seek to share care of pain and other symptoms with local palliative and supportive care teams. Patients at home can be seen by community or hospicebased palliative care teams. Hospital chronic pain teams should be consulted for severe pain if palliative and supportive care teams are not available. Acute pain teams may be helpful if the patient has an acute severe pain, e.g. bone fracture causing immobilization, which may respond to interventional procedures, e.g. local nerve blockade or spinal delivery of opioids and local anaesthetic. Orthopaedic surgeons or interventional radiologists are able to perform cement vertebroplasty or kyphoplasty for uncontrolled pain arising from vertebral collapse. Psychologists can help with patients who have severe anxiety overlying pain and with other issues.
In many of multiple myeloma patients, musculoskeletal complications with enhanced bone destruction lead to pain with pathologic fractures, spinal cord compression and radiculopathy. Bone lesions result not only from the direct deposits of myeloma cells within the bone, but also from the release of soluble factors by both the tumor and the microenvironment, resulting in the stimulation of osteoclast activity and bone resorption. The inhibition of bone resorption and hypercalcaemia can be reduced by the use of bisphosphonates. This class of drugs potentiate the effects of analgesics in improving myeloma bone pain with reducing bone releated events, but not mortality.
Management of spinal pain is often conservative, in the absence of instability/neurological compromise, orthopaedic, neurosurgical or interventional radiological advice should be sought in cases of persistent/refractory pain. Vertebroplasty and kyphoplasty are alternative options for controlling pain associated with vertebral collapse. Vertebroplasty and kyphoplasty are both vertebral body augmentation techniques of percutaneous injection of bone cement to the vertebral bodies. They are best performed soon after the vertebra collapses and may be ineffective if many months have elapsed. Both techniques carry the small risk of cement leakage leading to pulmonary embolism and neural compromise. It is therefore important that there is access to a spinal surgery service when these procedures are performed.
Vertebroplasty involves the percutaneous injection, under general anaesthetic and i.v. sedation and using radiological imaging, of polymethacrylate bone cement or equivalent biomaterial into the vertebral body. Several vertebrae can be treated simultaneously. The injection allows local pain relief and bone strengthening but will not restore vertebral height. No randomized studies on the use of vertebroplasty in myeloma have been published. However, a recent review of 67 cases demonstrated improvements in pain (89%), mobility (70%) and use of opioid analgesia (65%) [16].
Kyphoplasty involves the percutaneous insertion of a small, inflatable balloon into the vertebral body; when inflated it produces a potential space. The balloon is then removed and bone cement is injected to fill the cavity. Although more time consuming than vertebroplasty the complication rates appear lower with similar potential benefits of both pain relief and improved function to vertebroplasty but with reduced risk of cement leak. There is also the potential to restore vertebral height but this only occurs in a minority of patients. At the present time, the documented use of kyphoplasty in myeloma is limited to case reports and small case series although outcomes in myeloma do appear comparable to those in osteoporosis [17, 18].
Many patients with myeloma have subclinical or even clinical peripheral neuropathy (PN) at diagnosis, often due to co-morbidities. These patients are at risk of worsening PN when exposed to potentially neurotoxic drug treatments, such as thalidomide and bortezomib. The cause of PN in myeloma patients is multifactorial and when patients are assessed, it is important to grade the degree of neuropathy using a recognized scale, such as the National Cancer Institute (NCI), Common Toxicity Criteria [19], LANSS [20] or the Total Neuropathy Score [21].
PN in myeloma patients can be subdivided as follows:
Disease- or M protein-associated peripheral neuropathy
Peripheral neuropathy related to co-morbidities
Chemotherapy-induced peripheral neuropathy
Disease- or M protein-associated peripheral neuropathy: Spinal cord or nerve root compression is a common neurological complication of myeloma due to compression by plasmacytoma, lytic or extramedullary disease and requires appropriate imaging and specific treatment including a specialist opinion as to the need for surgical intervention or radiotherapy.
The reported prevalence of sensory PN may depend on the study cohort, the methods of detection and the criteria used, with a recent study reporting rates of pretreatment sensory PN in up to 20% of patients, and neuropathic abnormalities in as many as 54%. [22].
The cause of the neuropathy in many cases of myeloma is not clear and may be multifactorial, and studies have also varied in relation to rates of small or large fibre or mixed PN. In those cases where amyloidosis and toxicity due to chemotherapy are not the cause, the M protein itself or other consequences of the underlying disease may play a part. Clinically, a symmetrical, distal sensory/motor neuropathy inducing paraesthesiae and numbness in the hands and feet is seen.
POEMS (Polyneuropathy, Organomegaly, Endocrinopathy, M-protein and Skin abnormalities) syndrome and AL amyloidosis are more specialized situations, PN is a significant clinical feature in 85–100% of patients affected by POEMS syndrome [23]. It is a consequence of axonal degeneration and demyelination, typically distal, symmetrical and initially sensory, but as the condition progresses, a disabling symmetrical weakness may develop.
PN affects 17% of patients with AL amyloidosis at diagnosis. The PN is typically axonal and characteristically painful, distal and symmetrical and often associated with an autonomic neuropathy. Cryoglobulinaemia is another recognized source of PN.
Peripheral neuropathy related to co-morbidities: Conditions such as diabetes mellitus, carpal tunnel and other nerve compression syndromes, including chronic inflammatory demyelinating polyradiculoneuropathy, chronic renal failure and vitamin B12 deficiency, should be actively sought and appropriately managed, with specialist input as needed.
Chemotherapy-induced peripheral neuropathy: Chemotherapy-induced peripheral neuropathy (CIPN), also known as treatment-emergent peripheral neuropathy, is a major aspect of myeloma management. CIPN has been a long recognized complication of vinca alkaloid and platinum-based treatments and may be significantly dose limiting, but these drugs are no longer in regular use in myeloma. There is emerging evidence for the incidence and natural history of PN due to novel therapies, including thalidomide-induced PN (TiPN) and bortezomib-induced PN (BiPN), which may be considered as distinct clinical entities.
TiPN may arise after prolonged administration of thalidomide, is mostly mild to moderate in severity and appears to be a cumulative effect [24]. Initial symptoms include sensory changes, such as paraesthesia and hyperaesthesia, motor symptoms and autonomic dysfunction. Later effects include loss of vibration and joint position sense, which may lead to ataxia and progressive gait disturbance. Nerve conduction studies do not reliably predict the onset of significant TiPN and do not necessarily correlate with the clinical findings. Reduction or temporary discontinuation of the drug usually leads to a clinical improvement in the symptoms whereas continuation of dose intense treatment in the face of neuropathy may cause permanent neurological damage. Mileshkin et al and other investigators have recommended that thalidomide therapy should not exceed 6 months as the risk of TiPN is unacceptably high [25].
BiPN is characterized by neuropathic pain and a lengthdependent distal sensory neuropathy with suppression of reflexes. Motor neuropathy may follow and infrequently results in mild to severe distal weakness in the lower limbs. There may also be a significant autonomic component, which manifests as dizziness, hypotension, diarrhoea or constipation and/or extreme fatigue. It is thought to occur at a certain threshold (within five cycles but rarely beyond) of treatment and may be more likely to occur within the setting of renal impairment, in keeping with other therapy related toxicities in this setting. Electrophysiological testing reveals a mainly distal sensorimotor axonal loss, with secondary demyelination. The symptoms of BiPN improve or completely resolve in the majority of patients after a median of 3 months following discontinuation of the drug, but in a proportion of cases, symptoms have taken up to 2 years to improve [26]. Apart from a graded dose reduction or withdrawal [27], the only treatment for BiPN is symptomatic relief. No effective prophylactic treatment is available and any use of nutritional supplements should be restricted to low doses to avoid harm from excessive doses of pyridoxine. In particular, caution should be exercized with supplements containing ascorbic acid, which may inhibit the anti-myeloma effect of bortezomib [28].
An accurate neurological history should be taken from all patients prior to commencement of neurotoxic agents and regularly during the course of therapy. Patients should be reviewed in person at the start of each cycle to ensure that emergent symptoms are detected and acted upon. Dose-reductions may be needed within a treatment cycle if symptoms are progressive, so as to avoid the irreversible neurological damage that may result from waiting until the next cycle to make a change.
Initial investigations should be tailored according to the history and examination. Vitamin B12 deficiency should be screened for periodically. Metabolic and autoimmune causes should also be considered. If there are prominent features of small fibre neuropathy, then AL amyloidosis should be excluded by tissue biopsy or serum amyloid P scan; any further investigations, such as electrophysiological studies or cerebrospinal fluid protein estimation, should be directed by a neurologist.
The management of PN should include symptom control along with treatment of any potentially reversible causes. Identification and correction of Vitamin B12 deficiency is important and optimal management of co-morbid causes, such as diabetes mellitus or alcohol excess, may also improve tolerance of neurotoxic drugs. An awareness of the spectrum of symptoms that herald CIPN is crucial. Such symptoms need to be carefully sought at each meeting with the patient.
Careful monitoring of patients receiving bortezomib and prompt dose and schedule modifications are essential. Temporary interruptions in therapy may also be beneficial, before resuming on a new schedule/dose. Recent data from front line protocols incorporating bortezomib suggest that a weekly regimen is as effective and associated with less neuropathy than twice-weekly regimens [29]. Although, the twice weekly regimens of subcutaneous bortezomib offers non-inferior efficacy to standard intravenous administration, with an improved safety profile for peripheral neuropathy in patients with relapsed multiple myeloma [30]. Continuation of dose intense treatment in the face of neuropathy may cause permanent neurological damage. Measurement of lying and standing blood pressures weekly in patients receiving bortezomib may detect autonomic neuropathy before it becomes a debilitating problem for the patient. The administration of intravenous normal saline prior to each dose of bortezomib may improve tolerance of the drug.
Neuropathic pain is often poorly responsive to standard analgesic regimes. There has been very little research specifically in the management of painful CIPN, and that has mostly been in solid tumours [31]. Opioids can be effective but if used alone in high dose are associated withsignificant adverse effects [32]. A multimodal approach using opioids together with other pain modulating drugs is now recommended [33]. Thus a calcium channel blocker should be added early (e.g. gabapentin or pregabalin); it may be necessary to add a sodium channel blocking agent, e.g. oxcarbazepine (carbamazepine should be avoided because of drug interactions); or an SNRI, e.g. amitryptiline or duloxetine.
Several studies have shown that adding gabapentin to an opioid in patients with cancer-related neuropathic pain can give improved analgesia with reduced adverse effects compared to using either agent alone [34]. The response to gabapentin correlated with the severity of the underlying neurotoxicity. Approximately 25% of patients receiving gabapentin experienced mild somnolence, but none discontinued it. Note that gabapentin may be associated with myelosuppression and so should be avoided around the time of stem cell transplant.
The haematologist who is not familiar with these agents should seek advice from the local chronic pain or palliative care service. For patients with continuing severe pain in spite of initiating these drugs or those who are unable to tolerate analgesics because of adverse effects, specialist help is essential. They will advise on dose modifications and can also initiate specialist options, such as ketamine, methadone or spinal analgesia.
In addition, topical treatments may be of benefit. Capsaicin cream 0.075% acts on peripheral nerve TRPV1 heat and pain receptors; menthol acts on TRPM8 receptors for cold and may both be helpful in patients with „cold‟ or „hot‟ dysaesthesia respectively [35]. Emollients, such as cocoa butter, may help some patients but the physiological mechanism is unclear. In other forms of superficial neuropathic pains (e.g. post-herpetic neuralgia or scar pain), the sodium channel blocker lidocaine can be used topically as a 5% plaster, applied to the affected area for 12 hours and then left off for 12 hours. Some patients obtain relief within a few days but the peak effect is reached with 2-4 weeks [36].
Complementary therapy can be defined as therapies that are used alongside, or integrated with, conventional health care. These differ from alternative therapies, which are designed to be used in place of conventional therapy. However, a clear definition of what constitutes complementary and alternative medicine has not yet been elucidated, and therefore discretion must be exercised when interpreting guidance pertaining to these therapies.
Complementary therapy has a role in the management of multiple myeloma when used as adjunct to conventional medicine. It improves patients’ perceived quality of life and ability to cope with the effects of the disease. The development of an evidence-base to support complementary therapy use in myeloma is in the early stages of development.
Patients with myeloma may express preference for complementary therapy and place value in the role they have to play within the context of their cancer care plan – for the management of both the psycho-social and physiological effects associated with myeloma. Patients may value complementary therapy and the sense of control gained when they are used as part of their cancer treatment plan. Consequently, patient choice should be informed and respected by healthcare professionals in order to ensure the best overall treatment and care plan for myeloma is delivered.
There is a dearth of scientific evidence to support the effectiveness of complementary therapy in the management of myeloma; however, some studies have shown that complementary therapy can help patients with myeloma to: manage their symptoms, live with altered body image, promote relaxation, alleviate anxiety, reduce chemotherapy side-effects, improve sleep pattern, reduce stress and tension, reduce psychological distress/provide emotional support and improve well-being. Importantly, cancer patients using complementary therapy also perceive an improved quality of life.
Some complementary therapies, such as acupuncture, have been submitted to more rigorous evaluation and are acknowledged for their effective use in cancer treatment for the management of chemotherapy-associated nausea and vomiting. However, no convincing scientific-evidence has emerged to date that shows complementary therapy slows cancer progression [37].
The types of complementary therapies and frequency with which they are used by myeloma patients vary considerably. Among the most common therapies are homoeopathy, touch therapies such as aromatherapy, massage and reflexology, healing and energy therapies such as reiki, spiritual healing and therapeutic touch, hypnosis and hypnotherapy, acupuncture, herbal medicines and dietary interventions [38].
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(2010) Cancer Pain: Part 2: Physical, Interventional and Complimentary Therapies; Management in the Community; Acute, Treatment-Related and Complex Cancer Pain: A Perspective from the British Pain Society Endorsed by the UK Association of Palliative Medicine and the Royal College of General Practitioners. Pain Medicine, 11, 872–896.'},{id:"B34",body:'Ho, T.W., Backonja, M., Ma, J., Leibensperger, H., Froman, S. & Polydefkis, M. (2009) Efficient assessment of neuropathic pain drugs in patients with small fiber sensory neuropathies. Pain, 141, 19–24.'},{id:"B35",body:'Vriens J, Nilius B, Vennekens R (2008) Herbal compounds and toxins modulating TRP channels. Curr Neuropharmacol. 6:79-96.'},{id:"B36",body:'Binder A, Bruxelle J, Rogers P, Hans G, Bösl I, Baron R (2009). Topical 5% lidocaine (lignocaine) medicated plaster treatment for post-herpetic neuralgia: results of a double-blind, placebo-controlled, multinational efficacy and safety trial. Clin Drug Investig. 29:393-408.'},{id:"B37",body:'Leukemia and Lymphoma Society. (2006) Integrative medicine and complementary and alternative therapies as part of blood cancer care. HYPERLINK "http://www.leukemia-lymphoma.org/attachments/" http://www.leukemia-lymphoma.org/attachments/ National/br_1150734030.pdf.'},{id:"B38",body:'Molassiotis, A., Margulies, A., Fernandez-Ortega, P., Pud, D., Panteli, V., Bruyns, I., Scott, J.A., Gudmundsdottir, G., Browall, M., Madsen, E., Ozden, G., Magri, M., Selvekerova, S., Platin, N., Kearney, N. & Patiraki, E. (2005) Complementary and alternative medicine use in patients with haematological malignancies in Europe. Complementary Therapies in Clinical Practice. 11, 105–110.'}],footnotes:[],contributors:[{corresp:null,contributorFullName:"Emine Ozyuvaci",address:null,affiliation:'
Istanbul Education and Research Hospital, Department of Anaesthesiology and Pain Management Center, Istanbul, Turkey
Istanbul Education and Research Hospital, Department of Anaesthesiology and Pain Management Center, Istanbul, Turkey
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1. Introduction
Milk protein is most important for baby’s growth, development and protects the baby from different illness. Whey proteins and Casein proteins are two types of proteins in breast milk; whey proteins contain antibodies, lactoferrin and lysozyme, which protect baby from infection and are easy to digest. Casein proteins are harder to digest with more complex molecules. Colostrum is produced during early days immediately after child birth, which contains important nutrients and antibodies [1]. During early stages, lactating mothers may produce small quantity of colostrum; later milk production will be increased to the maximum, which makes the breast fuller and firmer causing increased blood flow and lymph fluids [2] to the breast tissue. If baby is not fed properly or any problem in lactating, the breast milk is stored, and some mothers may face problems related to over production of milk; all these components make the breast heavy and later turns to very hard as rock, this uncomfortable condition is known as breast engorgement. Breast engorgement problem [3] should be addressed because if it is left untreated, that may lead to serious issues [4], and in future it may result in painful blebs, and plugged milk ducts may also lead to mastitis. Without the knowledge of identification, many lactating mothers are suffering with breast engorgement [5]. Severe engorgement may also rise body temperature around 99–100 degree F, and this rise in body temperature is termed as “Milk fever.” According to Academy of Breastfeeding Medicine Protocol Committee, breast engorgement is defined as “the swelling and distension of the breasts” [6]. Sometime engorgement results due to interrupted or infrequent or delayed milk from breast [7, 8]; this kind of problems may place the mother at high risk of engorgement [9], causing unhealthy growth and development of the infant. The infant may not get the required milk protein if the mother is facing problems of engorgement. This problem should definitely bring to the notice, which is troubling to both mother and infant where its incidence in the world is 1:8000 and in India is 1:6500. According to NFHS [10], painful breast problems are the most common reason for giving up breastfeeding. Treatment for breast engorgement can prevent future breast-related complication and also helps the baby to get proper milk proteins, which helps in proper growth and development of the baby. It is a major issue in early postpartum period as the breast under the influence of hormonal shift increased milk production rapidly. Interventions such as ultrasound therapy [11, 12, 13, 14] application of hot moist [15], gentle massage [16] before feeding are beneficial. Through, Kinesio taping at the engorgement area, it decreases the inflammation, pain and improves circulation and lymphatic drainage. Hence, this study was to determine whether taping offers any advantage over ultrasound.
2. Methods
An experimental study was conducted on 30 subjects using convenient sampling technique based on inclusion and exclusion criteria. Lactating mothers with breast engorgement and pain for at least 2–3 days in postpartum period between 20 and 35 years of age were included in the study. Non-lactating women, pregnant women, lactating mothers with soft breast, lactating mothers receiving lactating suppressants, and lactating mothers with breast abscess, breast infection, mastitis, broken skin of the breast, bleeding or cracked nipple were excluded from the study. After receiving informed consent from the subjects, detailed explanation of the study is provided to them. All the information related to outcome measures, i.e., Six-Point Self-rated Engorgement Scale (SPES) [17] and Visual Analogue Scale (VAS), is given in Figures 1 and 2.
Figure 1.
Six-point self-rated engorgement scale.
Figure 2.
Visual analogue scale.
In this study, 30 subjects were divided into two groups, group-A and group-B. Fifteen subjects were allotted in each group. Pain parameter was measured with visual analogue scale in both groups before and after the treatment. Functional evaluation of both the groups was done with six-point self-rated engorgement scale before and after the treatment. Both the parameters were measured first day and after 1 week of treatment procedure. All the subjects received their treatment at the outpatient department of Saveetha College of Physiotherapy, Saveetha Institute of Medical and Technical Sciences, Chennai. Every subject followed the treatment for required period of 1 week.
Group-A: Fifteen subjects were treated with ultrasound for 1 week. The subjects were made to lie in supine with the arm of the treated side placed behind the head. A continuous mode of therapeutic ultrasound was given using ultrasound transmission gel as the coupling agent, with the intensity of 1 W/cm2 and frequency of 1MHZ passing the head of the ultrasound firmly over the breast from the periphery toward the areola, lightly back to the chest, and firmly down again to the areola, gradually working around the breast for 8 minutes.
Group-B: To the next 15 patients, continuous mode of therapeutic ultrasound was given using ultrasound transmission gel as the coupling agent, with the intensity of 1 W cm2 and frequency of 1MHZ passing the head of the ultrasound firmly over the breast from the periphery toward the areola, lightly back to the chest, and firmly down again to the areola, gradually working around the breast for 8 min, then subjects are treated with the taping techniques by using Kinesio tape (KT). Breast was exposed to clean with wet cotton dipped in water and breast is allowed to dry for few seconds and after drying, two pieces of tape which was about 7–9 inches, were taken. Seven to nine inches of tape was further cut into five strips equally. Taping was done with minimal stretch of 10–5% without extra tension by avoiding axilla with an anchoring base and rounded corners. Patients were instructed to wear the tape for 42–72 hours and also instructed to remove the tape prior to the prescribed time only if any skin irritation occurs. At the day 3 follow-up, the skin was inspected and assessed their primary outcome measures and then taped with the same technique used previously for 1 week. After the end of 1 week post Visual Analogue Scale and Six-Point self-rated Engorgement Scale were taken, and results are analyzed.
3. Results
Database was statistically analyzed using descriptive and inferential statistics; mean and standard deviation were estimated using paired and independent t test. Paired t test was used to compare data sets within the groups, and independent t test was used to compare the data sets between the groups (Tables 1–4).
Groups
Mean Age(Yrs) + SD
Group-A
25.05 (± 2.04)
Group-B
25.25 (±1.82)
Table 1.
Mean age distribution.
GROUP-A
MEAN
STANDARD DEVIATION
t VALUE
P VALUE
SIX-POINT SELF-RATED ENGORGEMENT SCALE(SPES)
PRE TEST
4.53
1.06
11.3436
<0.0001
POST TEST
1.20
0.41
VAS SCORE (VAS)
PRE TEST
7.00
1.25
13.6871
<0.0001
POST TEST
1.80
0.77
Table 2.
Comparison of pre-test and post-test values of SPES and VAS in group-A.
(GROUP-B)
MEAN
STANDARD DEVIATION
t VALUE
P VALUE
SIX-POINT SELF-RATED ENGORGEMENT SCALE
PRE TEST
4.73
1.16
12.4335
<0.0001
POST TEST
1.00
0.00
VAS SCORE
PRE TEST
7.00
1.13
17.4611
<0.0001
POST TEST
1.40
0.51
Table 3.
Comparison of pre-test and post-test values of SPES and VAS in Group-B.
POST TEST
MEAN
STANDARD DEVIATION
t VALUE
P VALUE
SIX-POINT SELF-RATED ENGORGEMENT SCALE
Group A
1.20
0.41
1.8708
<0.0001
Group B
1.00
1.16
VAS SCORE
Group A
1.80
0.77
1.8708
<0.0001
Group B
1.40
0.51
Table 4.
Comparison of post-test values of SPES and VAS in groups A and B.
Age distribution:
The average age of the subjects in group-A was 25.05 ± 2.04 years and in group-B was 25.25 ±.
1.82 years. There was no significant difference between the mean ages of the subjects in both the groups
Pre-test and post-test values of SPES and VAS of subjects in group A. The pre-test mean value of SPES was 4.53, and post-test mean value was 1.20. This shows that the SPES was gradually decreasing significantly at p < 0.0001. The pre-test mean value of VAS was 7.0, and post-test mean value was 1.80.This shows that the VAS scores were gradually decreasing significantly at p < 0.0001.
Pre-test and post-test values of SPES and VAS of subjects in group-B. The pre-test mean value of SPES was 4.73, and post-test mean value was 1.00.This shows that the SPES scores were gradually decreasing significantly at p < 0.0001.The pre-test mean value of VAS was 7.00, and post-test mean value was 1.40.This shows that the VAS scores were gradually decreasing significantly at p < 0.0001.
Post-test values of SPES and VAS of subjects in group-A and group-B. The post-test mean value of SPES in group-A was 1.20, and post-test mean value of SPES in group-B was 1.00.This shows group-B has greater improvement in reduction of engorgement than group A with the p value (0.0001). The post-test mean value of VAS in group-A was 1.80, and post-test mean value of VAS of group-B was 1.40.This shows group-B has greater improvement in reduction of pain than group-A with the p value (0.0001).
Quantitative data analysis revealed that there is a significant difference between group A and B and within the groups. SPES post-test mean value in group-A was 1.20, and in group-B was 1.00. SPES Scores in group-B were comparatively lesser than those of group-A, p < 0.0001. The post-test mean value of VAS in group-A was 1.80, and post-test mean value of VAS in group-B was 1.40. This shows VAS scores in group-B were comparatively lesser than those in group-A, p < 0.0001.Statistical analysis of post-test for pain and engorgement revealed that subjects who received ultrasound and taping in group-B showed marked improvement compared with patients who received only ultrasound in group-A.
4. Discussion
Milk proteins are very essential for the baby in the early age of life; breast engorgement is a condition that troubles the baby as well as the mother by creating difficulties in breastfeeding, which is considered as second most problem affecting the lactation. To provide milk proteins and nutrients to the child, breast engorgement has to be treated in lactating mothers. So this study was designed to compare the effect of ultrasound and taping in lactating mothers with breast engorgement, with the help of ultrasound and taping technique, which reduces pain, engorgement and also prevents further complications. Reduction of engorgement helps the mother to feed her child and to provide proper milk proteins to the child. Breast milk is most important for the babies to get benefits of milk proteins. Breastfeeding plays an important role in reproductive age of women and beneficial for mother and child as well [18]. Breastfeeding is a physiological process, and it has to be encouraged; numerous studies demonstrate the importance of breastfeeding in providing protection against various diseases and decreasing the incidence of infant morbidity and mortality [19]. “All health professional groups support breastfeeding as the ideal way to nourish an infant, but numerous surveys have shown that, in general, even perinatal health professionals are not prepared to provide lactation management as part of routine care” [12]. Ultrasound helps the tissue to heal more effectively as it gives: 1) essential micromassage for individual cells, 2) increases cellular activity, and 3) responsible for the effect of therapeutic benefits. Ultrasound frequency was selected based on the depth of the tissue to be treated. The depth of ultrasound penetration was usually described in terms of half-value depth for the specific ultrasound frequency. Through, Kinesio taping at the engorgement area, it decreases the inflammation, pain and improves circulation and lymphatic drainage. In recent years, the use of Kinesio Tape (KT) has become increasingly popular. KT has same thickness as the epidermis in the skin when stretched to 30–40% of its resting length longitudinally, which is suitable to human skin, and was designed to mimic the qualities of human skin. It has roughly the same thickness as the epidermis and stretched between 30% and 40% of its resting length longitudinally. Kenzo Kase [20] proposed many benefits of Kinesio taping, which depends on the stretch applied during taping. It provides positional stimulus, creates sensory stimulation to limit motion, and removes edema. It is latex-free,heat-activated, and 100% cotton fiber helps to dry quickly. The purpose of our study was to investigate whether KT has an effect on breast engorgement in breastfeeding mothers during the postpartum period and also to help lactating mothers in providing proper milk proteins to the infant. We hypothesized that breastfeeding mothers would experience a decrease in breast engorgement by using the KT method, which helps in lactation and also provides milk proteins to the baby. Hence, the present study was undertaken with an intention to compare the effect of ultrasound therapy with Kinesio taping in lactating mothers. The result of the study showed that there was a significant difference between the pre- and post-test intervention.
5. Conclusion
In this study by comparing the effects of ultrasound versus taping in lactating mothers with breast engorgement, the result of the study showed that there was a significant difference between the pre- and post-test intervention. Both the groups resulted in positive outcomes, but group-B with ultrasound and Kinesio taping showed a higher level of positive outcome in terms of decreasing pain and engorgement, when compared with group-A with ultrasound among lactating mothers. The study concluded that ultrasound and Kinesio taping help in reducing pain and engorgement, which helps the mother to provide proper lactation, which in turn helps the baby to get proper milk proteins without delaying the feeding.
\n',keywords:"milk protein, Lactating mothers, engorgement, VAS, SPES, ultrasound, taping, breastfeeding",chapterPDFUrl:"https://cdn.intechopen.com/pdfs/80610.pdf",chapterXML:"https://mts.intechopen.com/source/xml/80610.xml",downloadPdfUrl:"/chapter/pdf-download/80610",previewPdfUrl:"/chapter/pdf-preview/80610",totalDownloads:16,totalViews:0,totalCrossrefCites:0,dateSubmitted:"September 20th 2021",dateReviewed:"December 22nd 2021",datePrePublished:"April 15th 2022",datePublished:null,dateFinished:"February 25th 2022",readingETA:"0",abstract:"Human milk has hundreds of milk proteins, which provides many benefits on breastfeeding. Breastfeeding is a mother’s gift to herself, her baby, and the earth, there is no substitute for mother’s milk. Milk protein is most important for baby’s growth, development and protects the baby from different illness. Colostrum is produced during early days immediately after child birth, which contains important nutrients and antibodies. Breast engorgement is a problem that is commonly encountered in breastfeeding mothers, which is to be addressed and treated to provide good milk proteins to baby, by relieving discomforts of lactating mothers. A randomized controlled trial was conducted with 30 subjects based on inclusion and exclusion criteria where the subjects are divided into two groups, which contain 15 lactating mothers in each group. The control group that is group-A was treated with ultrasound, and the experimental group that is group-B was treated with ultrasound and Taping Technique. The result of the study showed that there was a significant difference between the pre- and posttest intervention, and we conclude that the ultrasound therapy and Kinesio taping was effective in treating lactating mothers with breast engorgement.",reviewType:"peer-reviewed",bibtexUrl:"/chapter/bibtex/80610",risUrl:"/chapter/ris/80610",signatures:"Dasarapu Indrani, Jagatheesan Alagesan, Prathap Suganthirababu, M.V. Sowmya and Dubba NagaRaju",book:{id:"11360",type:"book",title:"Milk Protein - New Research Approaches",subtitle:null,fullTitle:"Milk Protein - New Research Approaches",slug:null,publishedDate:null,bookSignature:"Prof. Narongsak Chaiyabutr",coverURL:"https://cdn.intechopen.com/books/images_new/11360.jpg",licenceType:"CC BY 3.0",editedByType:null,isbn:"978-1-80355-202-6",printIsbn:"978-1-80355-201-9",pdfIsbn:"978-1-80355-203-3",isAvailableForWebshopOrdering:!0,editors:[{id:"76047",title:"Prof.",name:"Narongsak",middleName:null,surname:"Chaiyabutr",slug:"narongsak-chaiyabutr",fullName:"Narongsak Chaiyabutr"}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"}},authors:null,sections:[{id:"sec_1",title:"1. Introduction",level:"1"},{id:"sec_2",title:"2. Methods",level:"1"},{id:"sec_3",title:"3. Results",level:"1"},{id:"sec_4",title:"4. Discussion",level:"1"},{id:"sec_5",title:"5. Conclusion",level:"1"}],chapterReferences:[{id:"B1",body:'Godhia M. Colostrums – its composition. Benefits as a Nutracentical-A Review. Current Research in Nutrition and Food Science. 2013;1(1):37-47'},{id:"B2",body:'Newton M, Newton NR. Postpartum engorgement of the breast. American Journal of Obstetrics and Gynecology. 1951;61(3):664-667'},{id:"B3",body:'Hill PD, Humenick SS. The occurrence of breast engorgement. Journal of Human Lactation. 1994;10(2):79-86'},{id:"B4",body:'Hewat RJ, Ellis DJ. A comparison of the effectiveness of two methods of nipple care. Birth. 1987;14(1):41-45'},{id:"B5",body:'Humenick SS, Hill PD, Anderson MA. Breast engorgement: Patterns and selected outcomes. Journal of Human Lactation. 1994;10(2):87-93'},{id:"B6",body:'Academy of Breastfeeding Medicine Protocol Committee, Eglash A. ABM clinical protocol#8:human milk storage information for home use for full-term infants (original protocol March 2004; revision#1 March 2010). Breastfeeding Medicine. 2010;5(3):127-130'},{id:"B7",body:'Lee WT, Lui SS, Chan V, Wong E, Lau J. A population-based survey on infant feeding practice (0-2 years) in Hong Kong: Breastfeeding rate and patterns among 3,161 infants below 6 months old. Asia Pacific Journal of Clinical Nutrition. 2006;15(3):377-387'},{id:"B8",body:'Priyanka P et al. Comparative effect of ultrasound therapy with conventional therapy on breast engorgement in immediate post-partum mothers. Integrative Molecular Medicine. 2016;3(2):553-558'},{id:"B9",body:'Arora S, Vatsa M, Dadhwal V. A comparison of cabbage leaves vs. hot and cold compresses in the treatment of breast engorgement. Indian Journal of Community Medicine. 2008;33(3):160'},{id:"B10",body:'Sagar K. Engorgement of breast-potential problem in lactation. Nightingale Nursing Times. 2004;1(5):17-21'},{id:"B11",body:'Mclachlan Z et al. Ultrasound threatment for breast engorgement: A randomized double blind trial. The Australian Journal of Physiotherapy. 1991;37(1):23-28'},{id:"B12",body:'Manna M, Devis PL. Effectiveness of hot fomentation versus cold compression on breast engorgement among postnatal mothers. International Journal of Nursing Research and Practice. 2016;33(3):160-123'},{id:"B13",body:'Mangesi L, Dowswell T. Treatments for breast engorgement during lactation (Review). The Cochrane Library. 2010;9:CD006946'},{id:"B14",body:'Newton M, Newton N. Postpartum engorgement of the breast. American Journal of Obstetrics & Gynecology. 1951;61:664-666'},{id:"B15",body:'Snowden HM et al. Treatment for breast engorgement during lactating. Cochrane Database Systematic Review. 2007;2:CD000046'},{id:"B16",body:'Öztürk G, Külcü DG, Mesci N, Şilte AD, Aydog E. Efficacy of kinesio tape application on pain and muscle strength in patients with myofascial pain syndrome: A placebo-controlled trial. Journal of Physical Therapy Science. 2016;28(4):1074-1079'},{id:"B17",body:'Del Ciampo LA, Del Ciampo IR. Breastfeeding and the Benefits of Lactation for Women\'s Health. Revista Brasileira de Ginecologia e Obstetrícia/RBGO Gynecology and Obstetrics. 2018;40(06):354-359'},{id:"B18",body:'Kacew S. Current issues in lactation: advantages, environment, silicone. Biomedical and environmental sciences: BES. 1994;7(4):307-319'},{id:"B19",body:'Naylor AJ, Creer AE, Woodward-Lopez G, Dixon S. Lactation management education for physicians. In Seminars in Perinatology. 1994;18(6):525-531'},{id:"B20",body:'Tantawy SA, Kamel DM. The effect of kinesio taping with exercise compared with exercise alone on pain, range of motion, and disability of the shoulder in postmastectomy females: A randomized control trial. Journal of Physical Therapy Science. 2016;28(12):3300-3305'}],footnotes:[],contributors:[{corresp:"yes",contributorFullName:"Dasarapu Indrani",address:"indranidasarapu@gmail.com",affiliation:'
Urology and Obstetrics, Saveetha College of Physiotherapy, Saveetha Institute of Medical and Technical Sciences, India
'}],corrections:null},book:{id:"11360",type:"book",title:"Milk Protein - New Research Approaches",subtitle:null,fullTitle:"Milk Protein - New Research Approaches",slug:null,publishedDate:null,bookSignature:"Prof. Narongsak Chaiyabutr",coverURL:"https://cdn.intechopen.com/books/images_new/11360.jpg",licenceType:"CC BY 3.0",editedByType:null,isbn:"978-1-80355-202-6",printIsbn:"978-1-80355-201-9",pdfIsbn:"978-1-80355-203-3",isAvailableForWebshopOrdering:!0,editors:[{id:"76047",title:"Prof.",name:"Narongsak",middleName:null,surname:"Chaiyabutr",slug:"narongsak-chaiyabutr",fullName:"Narongsak Chaiyabutr"}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"}}},profile:{item:{id:"192036",title:"Ph.D.",name:"Yu-Shin",middleName:null,surname:"Nai",email:"ysnai@niu.edu.tw",fullName:"Yu-Shin Nai",slug:"yu-shin-nai",position:null,biography:null,institutionString:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",totalCites:0,totalChapterViews:"0",outsideEditionCount:0,totalAuthoredChapters:"1",totalEditedBooks:"0",personalWebsiteURL:null,twitterURL:null,linkedinURL:null,institution:{name:"National Ilan University",institutionURL:null,country:{name:"Taiwan"}}},booksEdited:[],chaptersAuthored:[{id:"53655",title:"Determination of Nucleopolyhedrovirus’ Taxonomic Position",slug:"determination-of-nucleopolyhedrovirus-taxonomic-position",abstract:"To date\n, over 78 genomes of nucleopolyhedroviruses (NPVs) have been sequenced and deposited in NCBI. How to define a new virus from the infected larvae in the field is usually the first question. Two NPV strains, which were isolated from casuarina moth (L. xylina) and golden birdwing larvae (Troides aeacus), respectively, displayed the same question. Due to the identity of polyhedrin (polh) sequences of these two isolates to that of Lymantria dispar MNPV and Bombyx mori NPV, they are named LdMNPV-like virus and TraeNPV, provisionally. To further clarify the relationships of LdMNPV-like virus and TraeNPV to closely related NPVs, Kimura 2-parameter (K-2-P) analysis was performed. Apparently, the results of K-2-P analysis that showed LdMNPV-like virus is an LdMNPV isolate, while TraeNPV had an ambiguous relationship to BmNPV. Otherwise, MaviNPV, which is a mini-AcMNPV, also exhibited a different story by K-2-P analysis. Since K-2-P analysis could not cover all species determination issues, therefore, TraeNPV needs to be sequenced for defining its taxonomic position. For this purpose, different genomic sequencing technologies and bioinformatic analysis approaches will be discussed. We anticipated that these applications will help to exam nucleotide information of unknown species and give an insight and facilitate to this issue.",signatures:"Yu-Shin Nai, Yu-Feng Huang, Tzu-Han Chen, Kuo-Ping Chiu and\nChung-Hsiung Wang",authors:[{id:"192036",title:"Ph.D.",name:"Yu-Shin",surname:"Nai",fullName:"Yu-Shin Nai",slug:"yu-shin-nai",email:"ysnai@niu.edu.tw"},{id:"195612",title:"Dr.",name:"Yu-Feng",surname:"Huang",fullName:"Yu-Feng Huang",slug:"yu-feng-huang",email:"yfh1202@sinica.edu.tw"},{id:"195613",title:"Mr.",name:"Tzu-Han",surname:"Chen",fullName:"Tzu-Han Chen",slug:"tzu-han-chen",email:"tzuhanchen@msn.com"},{id:"195614",title:"Prof.",name:"Kuo-Ping",surname:"Chiu",fullName:"Kuo-Ping Chiu",slug:"kuo-ping-chiu",email:"chiukp@gate.sinica.edu.tw"},{id:"195615",title:"Prof.",name:"Chung-Hsiung",surname:"Wang",fullName:"Chung-Hsiung Wang",slug:"chung-hsiung-wang",email:"wangch@ntu.edu.tw"}],book:{id:"5526",title:"Biological Control of Pest and Vector Insects",slug:"biological-control-of-pest-and-vector-insects",productType:{id:"1",title:"Edited Volume"}}}],collaborators:[{id:"82718",title:"Dr.",name:"Nabil",surname:"El-Wakeil",slug:"nabil-el-wakeil",fullName:"Nabil El-Wakeil",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Martin Luther University Halle-Wittenberg",institutionURL:null,country:{name:"Germany"}}},{id:"191853",title:"Dr.",name:"Nawal",surname:"Gaafar",slug:"nawal-gaafar",fullName:"Nawal Gaafar",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"191854",title:"Prof.",name:"Mahmoud",surname:"Saleh",slug:"mahmoud-saleh",fullName:"Mahmoud Saleh",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"191856",title:"Prof.",name:"László",surname:"Nowinszky",slug:"laszlo-nowinszky",fullName:"László Nowinszky",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Sopron",institutionURL:null,country:{name:"Hungary"}}},{id:"192128",title:"Prof.",name:"Grzegorz",surname:"Wegrzyn",slug:"grzegorz-wegrzyn",fullName:"Grzegorz Wegrzyn",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Gdańsk",institutionURL:null,country:{name:"Poland"}}},{id:"192142",title:"Dr.",name:"Hamadttu",surname:"El-Shafie",slug:"hamadttu-el-shafie",fullName:"Hamadttu El-Shafie",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/192142/images/system/192142.jpg",biography:"Hamadttu Abdel Farag El-Shafie is an associate professor of entomology and senior research entomologist at the Date Palm Research Center of Excellence, King Faisal University, Saudi Arabia. He is the head of IPM research program in date palm. El-Shafie obtained his B.Sc. and M.Sc. degrees from the University of Khartoum, Sudan in 1988 and 1993, respectively. He received his Ph.D. degree from University of Giessen, Germany in 2001. He was appointed head of Crop Protection Department at University of Khartoum in 2008, and then deputy dean for academic affairs at Faculty of Agriculture, University of Khartoum. He supervised 25 M.Sc. students and 5 Ph.D. students at University of Khartoum. His research interest focuses on management of field crop pests using neem biopesticides, and biology and ecology of date palm pests including mites. He also has interest in control of red palm weevil using semiochemicals. He published more than 60 research papers in international peer-reviewed journals and 10 book chapters with international publishers such as Springer, John Wiley and IntechOpen, in addition to more than 30 international conferences in the field of entomology. During the last ten years, he has been reviewing manuscripts for 30 renowned international journals.",institutionString:"King Faisal University",institution:{name:"King Faisal University",institutionURL:null,country:{name:"Saudi Arabia"}}},{id:"194787",title:"Dr.",name:"János",surname:"Puskás",slug:"janos-puskas",fullName:"János Puskás",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"194792",title:"Mrs.",name:"Kinga",surname:"Lukasiewicz",slug:"kinga-lukasiewicz",fullName:"Kinga Lukasiewicz",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"194793",title:"Prof.",name:"Marek",surname:"Sanak",slug:"marek-sanak",fullName:"Marek Sanak",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"197643",title:"Dr.",name:"Huda",surname:"Elbehery",slug:"huda-elbehery",fullName:"Huda Elbehery",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null}]},generic:{page:{slug:"compacts",title:"IntechOpen Compacts",intro:"
IntechOpen Compacts provide a mid-length publishing format which bridges the gap between journal articles, book chapters and monographs, and cover content across all scientific disciplines. Compacts are the preferred publishing option for brief research reports on new topics, in-depth case studies, dissertations, or essays exploring new ideas, issues or broader topics on the research subject.
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Without sacrificing the quality of carefully edited and produced peer-reviewed content, Compacts are published as part of IntechOpen’s book collection but on a faster schedule, typically 4-6 weeks after acceptance. With an average of 132,000 visitors per week, publishing in Compacts not only guarantees high visibility but also facilitates international content sharing. As a fully Open Access publisher, the utilization of a CC BY NC 4.0 license means that other researchers will never have to pay permission fees and can adapt, use, and further build upon the material published in Compacts, eliminating any barriers to the further development of scientific research.
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Without sacrificing the quality of carefully edited and produced peer-reviewed content, Compacts are published as part of IntechOpen’s book collection but on a faster schedule, typically 4-6 weeks after acceptance. With an average of 132,000 visitors per week, publishing in Compacts not only guarantees high visibility but also facilitates international content sharing. As a fully Open Access publisher, the utilization of a CC BY NC 4.0 license means that other researchers will never have to pay permission fees and can adapt, use, and further build upon the material published in Compacts, eliminating any barriers to the further development of scientific research.
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COMPACTS-SHORT FORM MONOGRAPH
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50 - 130 pages
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Peer-reviewed
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Self-contained works on a particular subject compiled by one or more authors
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A unique hybrid between a book chapter and monograph
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Online only, and print options available
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The final price will depend on the volume of the publication and includes project management, editorial and peer-review services, technical editing, language copyediting, cover design, book layout, book promotion and ISBN assignment.
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*The price does not include Value-Added Tax (VAT). Residents of European Union countries need to add VAT based on the specific rate applicable in their country of residence. Institutions and companies registered as VAT taxable entities in their own EU member state will not pay VAT by providing us with their VAT registration number. This is made possible by the EU reverse charge method.
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IntechOpen Authors that wish to use this service will receive a 20% discount on all translation work. For more information or a quote, please visit: https://www.enago.com/intech.
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+560,000 visitors per month guarantees high visibility and opportunities for international content sharing
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He has both an MS and Ph.D. in Biomedical Engineering. He was previously a research scientist at the University of California Los Angeles (UCLA) and visiting professor and researcher at the University of North Dakota. He is currently working in artificial intelligence and its applications in medical signal processing. In addition, he is using digital signal processing in medical imaging and speech processing. Dr. Asadpour has developed brain-computer interfacing algorithms and has published books, book chapters, and several journal and conference papers in this field and other areas of intelligent signal processing. He has also designed medical devices, including a laser Doppler monitoring system.",institutionString:"Kaiser Permanente Southern California",institution:null},{id:"169608",title:"Prof.",name:"Marian",middleName:null,surname:"Găiceanu",slug:"marian-gaiceanu",fullName:"Marian Găiceanu",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/169608/images/system/169608.png",biography:"Prof. Dr. Marian Gaiceanu graduated from the Naval and Electrical Engineering Faculty, Dunarea de Jos University of Galati, Romania, in 1997. He received a Ph.D. (Magna Cum Laude) in Electrical Engineering in 2002. Since 2017, Dr. Gaiceanu has been a Ph.D. supervisor for students in Electrical Engineering. He has been employed at Dunarea de Jos University of Galati since 1996, where he is currently a professor. Dr. Gaiceanu is a member of the National Council for Attesting Titles, Diplomas and Certificates, an expert of the Executive Agency for Higher Education, Research Funding, and a member of the Senate of the Dunarea de Jos University of Galati. He has been the head of the Integrated Energy Conversion Systems and Advanced Control of Complex Processes Research Center, Romania, since 2016. He has conducted several projects in power converter systems for electrical drives, power quality, PEM and SOFC fuel cell power converters for utilities, electric vehicles, and marine applications with the Department of Regulation and Control, SIEI S.pA. (2002–2004) and the Polytechnic University of Turin, Italy (2002–2004, 2006–2007). He is a member of the Institute of Electrical and Electronics Engineers (IEEE) and cofounder-member of the IEEE Power Electronics Romanian Chapter. He is a guest editor at Energies and an academic book editor for IntechOpen. He is also a member of the editorial boards of the Journal of Electrical Engineering, Electronics, Control and Computer Science and Sustainability. Dr. Gaiceanu has been General Chairman of the IEEE International Symposium on Electrical and Electronics Engineering in the last six editions.",institutionString:'"Dunarea de Jos" University of Galati',institution:{name:'"Dunarea de Jos" University of Galati',country:{name:"Romania"}}},{id:"4519",title:"Prof.",name:"Jaydip",middleName:null,surname:"Sen",slug:"jaydip-sen",fullName:"Jaydip Sen",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/4519/images/system/4519.jpeg",biography:"Jaydip Sen is associated with Praxis Business School, Kolkata, India, as a professor in the Department of Data Science. His research areas include security and privacy issues in computing and communication, intrusion detection systems, machine learning, deep learning, and artificial intelligence in the financial domain. He has more than 200 publications in reputed international journals, refereed conference proceedings, and 20 book chapters in books published by internationally renowned publishing houses, such as Springer, CRC press, IGI Global, etc. Currently, he is serving on the editorial board of the prestigious journal Frontiers in Communications and Networks and in the technical program committees of a number of high-ranked international conferences organized by the IEEE, USA, and the ACM, USA. He has been listed among the top 2% of scientists in the world for the last three consecutive years, 2019 to 2021 as per studies conducted by the Stanford University, USA.",institutionString:"Praxis Business School",institution:null},{id:"320071",title:"Dr.",name:"Sidra",middleName:null,surname:"Mehtab",slug:"sidra-mehtab",fullName:"Sidra Mehtab",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y00002v6KHoQAM/Profile_Picture_1584512086360",biography:"Sidra Mehtab has completed her BS with honors in Physics from Calcutta University, India in 2018. She has done MS in Data Science and Analytics from Maulana Abul Kalam Azad University of Technology (MAKAUT), Kolkata, India in 2020. Her research areas include Econometrics, Time Series Analysis, Machine Learning, Deep Learning, Artificial Intelligence, and Computer and Network Security with a particular focus on Cyber Security Analytics. Ms. Mehtab has published seven papers in international conferences and one of her papers has been accepted for publication in a reputable international journal. She has won the best paper awards in two prestigious international conferences – BAICONF 2019, and ICADCML 2021, organized in the Indian Institute of Management, Bangalore, India in December 2019, and SOA University, Bhubaneswar, India in January 2021. Besides, Ms. Mehtab has also published two book chapters in two books. Seven of her book chapters will be published in a volume shortly in 2021 by Cambridge Scholars’ Press, UK. Currently, she is working as the joint editor of two edited volumes on Time Series Analysis and Forecasting to be published in the first half of 2021 by an international house. Currently, she is working as a Data Scientist with an MNC in Delhi, India.",institutionString:"NSHM College of Management and Technology",institution:null},{id:"226240",title:"Dr.",name:"Andri Irfan",middleName:null,surname:"Rifai",slug:"andri-irfan-rifai",fullName:"Andri Irfan Rifai",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/226240/images/7412_n.jpg",biography:"Andri IRFAN is a Senior Lecturer of Civil Engineering and Planning. He completed the PhD at the Universitas Indonesia & Universidade do Minho with Sandwich Program Scholarship from the Directorate General of Higher Education and LPDP scholarship. He has been teaching for more than 19 years and much active to applied his knowledge in the project construction in Indonesia. His research interest ranges from pavement management system to advanced data mining techniques for transportation engineering. He has published more than 50 papers in journals and 2 books.",institutionString:null,institution:{name:"Universitas Internasional Batam",country:{name:"Indonesia"}}},{id:"314576",title:"Dr.",name:"Ibai",middleName:null,surname:"Laña",slug:"ibai-lana",fullName:"Ibai Laña",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/314576/images/system/314576.jpg",biography:"Dr. Ibai Laña works at TECNALIA as a data analyst. He received his Ph.D. in Artificial Intelligence from the University of the Basque Country (UPV/EHU), Spain, in 2018. He is currently a senior researcher at TECNALIA. His research interests fall within the intersection of intelligent transportation systems, machine learning, traffic data analysis, and data science. He has dealt with urban traffic forecasting problems, applying machine learning models and evolutionary algorithms. He has experience in origin-destination matrix estimation or point of interest and trajectory detection. Working with large volumes of data has given him a good command of big data processing tools and NoSQL databases. He has also been a visiting scholar at the Knowledge Engineering and Discovery Research Institute, Auckland University of Technology.",institutionString:"TECNALIA Research & Innovation",institution:{name:"Tecnalia",country:{name:"Spain"}}},{id:"314575",title:"Dr.",name:"Jesus",middleName:null,surname:"L. Lobo",slug:"jesus-l.-lobo",fullName:"Jesus L. Lobo",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/314575/images/system/314575.png",biography:"Dr. Jesús López is currently based in Bilbao (Spain) working at TECNALIA as Artificial Intelligence Research Scientist. In most cases, a project idea or a new research line needs to be investigated to see if it is good enough to take into production or to focus on it. That is exactly what he does, diving into Machine Learning algorithms and technologies to help TECNALIA to decide whether something is great in theory or will actually impact on the product or processes of its projects. So, he is expert at framing experiments, developing hypotheses, and proving whether they’re true or not, in order to investigate fundamental problems with a longer time horizon. He is also able to design and develop PoCs and system prototypes in simulation. He has participated in several national and internacional R&D projects.\n\nAs another relevant part of his everyday research work, he usually publishes his findings in reputed scientific refereed journals and international conferences, occasionally acting as reviewer and Programme Commitee member. Concretely, since 2018 he has published 9 JCR (8 Q1) journal papers, 9 conference papers (e.g. ECML PKDD 2021), and he has co-edited a book. He is also active in popular science writing data science stories for reputed blogs (KDNuggets, TowardsDataScience, Naukas). Besides, he has recently embarked on mentoring programmes as mentor, and has also worked as data science trainer.",institutionString:"TECNALIA Research & Innovation",institution:{name:"Tecnalia",country:{name:"Spain"}}},{id:"103779",title:"Prof.",name:"Yalcin",middleName:null,surname:"Isler",slug:"yalcin-isler",fullName:"Yalcin Isler",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRyQ8QAK/Profile_Picture_1628834958734",biography:"Yalcin Isler (1971 - Burdur / Turkey) received the B.Sc. degree in the Department of Electrical and Electronics Engineering from Anadolu University, Eskisehir, Turkey, in 1993, the M.Sc. degree from the Department of Electronics and Communication Engineering, Suleyman Demirel University, Isparta, Turkey, in 1996, the Ph.D. degree from the Department of Electrical and Electronics Engineering, Dokuz Eylul University, Izmir, Turkey, in 2009, and the Competence of Associate Professorship from the Turkish Interuniversity Council in 2019.\n\nHe was Lecturer at Burdur Vocational School in Suleyman Demirel University (1993-2000, Burdur / Turkey), Software Engineer (2000-2002, Izmir / Turkey), Research Assistant in Bulent Ecevit University (2002-2003, Zonguldak / Turkey), Research Assistant in Dokuz Eylul University (2003-2010, Izmir / Turkey), Assistant Professor at the Department of Electrical and Electronics Engineering in Bulent Ecevit University (2010-2012, Zonguldak / Turkey), Assistant Professor at the Department of Biomedical Engineering in Izmir Katip Celebi University (2012-2019, Izmir / Turkey). He is an Associate Professor at the Department of Biomedical Engineering at Izmir Katip Celebi University, Izmir / Turkey, since 2019. In addition to academics, he has also founded Islerya Medical and Information Technologies Company, Izmir / Turkey, since 2017.\n\nHis main research interests cover biomedical signal processing, pattern recognition, medical device design, programming, and embedded systems. He has many scientific papers and participated in several projects in these study fields. He was an IEEE Student Member (2009-2011) and IEEE Member (2011-2014) and has been IEEE Senior Member since 2014.",institutionString:null,institution:{name:"Izmir Kâtip Çelebi University",country:{name:"Turkey"}}},{id:"339677",title:"Dr.",name:"Mrinmoy",middleName:null,surname:"Roy",slug:"mrinmoy-roy",fullName:"Mrinmoy Roy",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/339677/images/16768_n.jpg",biography:"An accomplished Sales & Marketing professional with 12 years of cross-functional experience in well-known organisations such as CIPLA, LUPIN, GLENMARK, ASTRAZENECA across different segment of Sales & Marketing, International Business, Institutional Business, Product Management, Strategic Marketing of HIV, Oncology, Derma, Respiratory, Anti-Diabetic, Nutraceutical & Stomatological Product Portfolio and Generic as well as Chronic Critical Care Portfolio. A First Class MBA in International Business & Strategic Marketing, B.Pharm, D.Pharm, Google Certified Digital Marketing Professional. Qualified PhD Candidate in Operations and Management with special focus on Artificial Intelligence and Machine Learning adoption, analysis and use in Healthcare, Hospital & Pharma Domain. Seasoned with diverse therapy area of Pharmaceutical Sales & Marketing ranging from generating revenue through generating prescriptions, launching new products, and making them big brands with continuous strategy execution at the Physician and Patients level. Moved from Sales to Marketing and Business Development for 3.5 years in South East Asian Market operating from Manila, Philippines. Came back to India and handled and developed Brands such as Gluconorm, Lupisulin, Supracal, Absolut Woman, Hemozink, Fabiflu (For COVID 19), and many more. In my previous assignment I used to develop and execute strategies on Sales & Marketing, Commercialization & Business Development for Institution and Corporate Hospital Business portfolio of Oncology Therapy Area for AstraZeneca Pharma India Ltd. Being a Research Scholar and Student of ‘Operations Research & Management: Artificial Intelligence’ I published several pioneer research papers and book chapters on the same in Internationally reputed journals and Books indexed in Scopus, Springer and Ei Compendex, Google Scholar etc. Currently, I am launching PGDM Pharmaceutical Management Program in IIHMR Bangalore and spearheading the course curriculum and structure of the same. I am interested in Collaboration for Healthcare Innovation, Pharma AI Innovation, Future trend in Marketing and Management with incubation on Healthcare, Healthcare IT startups, AI-ML Modelling and Healthcare Algorithm based training module development. I am also an affiliated member of the Institute of Management Consultant of India, looking forward to Healthcare, Healthcare IT and Innovation, Pharma and Hospital Management Consulting works.",institutionString:null,institution:{name:"Lovely Professional University",country:{name:"India"}}},{id:"1063",title:"Prof.",name:"Constantin",middleName:null,surname:"Volosencu",slug:"constantin-volosencu",fullName:"Constantin Volosencu",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/1063/images/system/1063.png",biography:"Prof. Dr. Constantin Voloşencu graduated as an engineer from\nPolitehnica University of Timișoara, Romania, where he also\nobtained a doctorate degree. He is currently a full professor in\nthe Department of Automation and Applied Informatics at the\nsame university. Dr. Voloşencu is the author of ten books, seven\nbook chapters, and more than 160 papers published in journals\nand conference proceedings. He has also edited twelve books and\nhas twenty-seven patents to his name. He is a manager of research grants, editor in\nchief and member of international journal editorial boards, a former plenary speaker, a member of scientific committees, and chair at international conferences. His\nresearch is in the fields of control systems, control of electric drives, fuzzy control\nsystems, neural network applications, fault detection and diagnosis, sensor network\napplications, monitoring of distributed parameter systems, and power ultrasound\napplications. He has developed automation equipment for machine tools, spooling\nmachines, high-power ultrasound processes, and more.",institutionString:"Polytechnic University of Timişoara",institution:{name:"Polytechnic University of Timişoara",country:{name:"Romania"}}},{id:"221364",title:"Dr.",name:"Eneko",middleName:null,surname:"Osaba",slug:"eneko-osaba",fullName:"Eneko Osaba",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/221364/images/system/221364.jpg",biography:"Dr. Eneko Osaba works at TECNALIA as a senior researcher. He obtained his Ph.D. in Artificial Intelligence in 2015. He has participated in more than twenty-five local and European research projects, and in the publication of more than 130 papers. He has performed several stays at universities in the United Kingdom, Italy, and Malta. Dr. Osaba has served as a program committee member in more than forty international conferences and participated in organizing activities in more than ten international conferences. He is a member of the editorial board of the International Journal of Artificial Intelligence, Data in Brief, and Journal of Advanced Transportation. He is also a guest editor for the Journal of Computational Science, Neurocomputing, Swarm, and Evolutionary Computation and IEEE ITS Magazine.",institutionString:"TECNALIA Research & Innovation",institution:{name:"Tecnalia",country:{name:"Spain"}}},{id:"275829",title:"Dr.",name:"Esther",middleName:null,surname:"Villar-Rodriguez",slug:"esther-villar-rodriguez",fullName:"Esther Villar-Rodriguez",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/275829/images/system/275829.jpg",biography:"Dr. Esther Villar obtained a Ph.D. in Information and Communication Technologies from the University of Alcalá, Spain, in 2015. She obtained a degree in Computer Science from the University of Deusto, Spain, in 2010, and an MSc in Computer Languages and Systems from the National University of Distance Education, Spain, in 2012. Her areas of interest and knowledge include natural language processing (NLP), detection of impersonation in social networks, semantic web, and machine learning. Dr. Esther Villar made several contributions at conferences and publishing in various journals in those fields. Currently, she is working within the OPTIMA (Optimization Modeling & Analytics) business of TECNALIA’s ICT Division as a data scientist in projects related to the prediction and optimization of management and industrial processes (resource planning, energy efficiency, etc).",institutionString:"TECNALIA Research & Innovation",institution:{name:"Tecnalia",country:{name:"Spain"}}},{id:"49813",title:"Dr.",name:"Javier",middleName:null,surname:"Del Ser",slug:"javier-del-ser",fullName:"Javier Del Ser",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/49813/images/system/49813.png",biography:"Prof. Dr. Javier Del Ser received his first PhD in Telecommunication Engineering (Cum Laude) from the University of Navarra, Spain, in 2006, and a second PhD in Computational Intelligence (Summa Cum Laude) from the University of Alcala, Spain, in 2013. He is currently a principal researcher in data analytics and optimisation at TECNALIA (Spain), a visiting fellow at the Basque Center for Applied Mathematics (BCAM) and a part-time lecturer at the University of the Basque Country (UPV/EHU). His research interests gravitate on the use of descriptive, prescriptive and predictive algorithms for data mining and optimization in a diverse range of application fields such as Energy, Transport, Telecommunications, Health and Industry, among others. In these fields he has published more than 240 articles, co-supervised 8 Ph.D. theses, edited 6 books, coauthored 7 patents and participated/led more than 40 research projects. He is a Senior Member of the IEEE, and a recipient of the Biscay Talent prize for his academic career.",institutionString:"Tecnalia Research & Innovation",institution:null},{id:"278948",title:"Dr.",name:"Carlos Pedro",middleName:null,surname:"Gonçalves",slug:"carlos-pedro-goncalves",fullName:"Carlos Pedro Gonçalves",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRcmyQAC/Profile_Picture_1564224512145",biography:'Carlos Pedro Gonçalves (PhD) is an Associate Professor at Lusophone University of Humanities and Technologies and a researcher on Complexity Sciences, Quantum Technologies, Artificial Intelligence, Strategic Studies, Studies in Intelligence and Security, FinTech and Financial Risk Modeling. He is also a progammer with programming experience in:\n\nA) Quantum Computing using Qiskit Python module and IBM Quantum Experience Platform, with software developed on the simulation of Quantum Artificial Neural Networks and Quantum Cybersecurity;\n\nB) Artificial Intelligence and Machine learning programming in Python;\n\nC) Artificial Intelligence, Multiagent Systems Modeling and System Dynamics Modeling in Netlogo, with models developed in the areas of Chaos Theory, Econophysics, Artificial Intelligence, Classical and Quantum Complex Systems Science, with the Econophysics models having been cited worldwide and incorporated in PhD programs by different Universities.\n\nReceived an Arctic Code Vault Contributor status by GitHub, due to having developed open source software preserved in the \\"Arctic Code Vault\\" for future generations (https://archiveprogram.github.com/arctic-vault/), with the Strategy Analyzer A.I. module for decision making support (based on his PhD thesis, used in his Classes on Decision Making and in Strategic Intelligence Consulting Activities) and QNeural Python Quantum Neural Network simulator also preserved in the \\"Arctic Code Vault\\", for access to these software modules see: https://github.com/cpgoncalves. He is also a peer reviewer with outsanding review status from Elsevier journals, including Physica A, Neurocomputing and Engineering Applications of Artificial Intelligence. Science CV available at: https://www.cienciavitae.pt//pt/8E1C-A8B3-78C5 and ORCID: https://orcid.org/0000-0002-0298-3974',institutionString:"University of Lisbon",institution:{name:"Universidade Lusófona",country:{name:"Portugal"}}},{id:"241400",title:"Prof.",name:"Mohammed",middleName:null,surname:"Bsiss",slug:"mohammed-bsiss",fullName:"Mohammed Bsiss",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/241400/images/8062_n.jpg",biography:null,institutionString:null,institution:null},{id:"276128",title:"Dr.",name:"Hira",middleName:null,surname:"Fatima",slug:"hira-fatima",fullName:"Hira Fatima",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/276128/images/14420_n.jpg",biography:"Dr. Hira Fatima\nAssistant Professor\nDepartment of Mathematics\nInstitute of Applied Science\nMangalayatan University, Aligarh\nMobile: no : 8532041179\nhirafatima2014@gmal.com\n\nDr. Hira Fatima has received his Ph.D. degree in pure Mathematics from Aligarh Muslim University, Aligarh India. Currently working as an Assistant Professor in the Department of Mathematics, Institute of Applied Science, Mangalayatan University, Aligarh. She taught so many courses of Mathematics of UG and PG level. Her research Area of Expertise is Functional Analysis & Sequence Spaces. She has been working on Ideal Convergence of double sequence. She has published 17 research papers in National and International Journals including Cogent Mathematics, Filomat, Journal of Intelligent and Fuzzy Systems, Advances in Difference Equations, Journal of Mathematical Analysis, Journal of Mathematical & Computer Science etc. She has also reviewed few research papers for the and international journals. She is a member of Indian Mathematical Society.",institutionString:null,institution:null},{id:"414880",title:"Dr.",name:"Maryam",middleName:null,surname:"Vatankhah",slug:"maryam-vatankhah",fullName:"Maryam Vatankhah",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Borough of Manhattan Community College",country:{name:"United States of America"}}},{id:"414879",title:"Prof.",name:"Mohammad-Reza",middleName:null,surname:"Akbarzadeh-Totonchi",slug:"mohammad-reza-akbarzadeh-totonchi",fullName:"Mohammad-Reza Akbarzadeh-Totonchi",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Ferdowsi University of Mashhad",country:{name:"Iran"}}},{id:"414878",title:"Prof.",name:"Reza",middleName:null,surname:"Fazel-Rezai",slug:"reza-fazel-rezai",fullName:"Reza Fazel-Rezai",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"American Public University System",country:{name:"United States of America"}}},{id:"302698",title:"Dr.",name:"Yao",middleName:null,surname:"Shan",slug:"yao-shan",fullName:"Yao Shan",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Dalian University of Technology",country:{name:"China"}}},{id:"125911",title:"Prof.",name:"Jia-Ching",middleName:null,surname:"Wang",slug:"jia-ching-wang",fullName:"Jia-Ching Wang",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"National Central University",country:{name:"Taiwan"}}},{id:"357085",title:"Mr.",name:"P. 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\r\n\tThe Business and Management series topic focuses on the most pressing issues confronting organizations today and in the future. Businesses are trying to figure out how to lead in a time of global uncertainty. In emerging markets, issues such as ill-defined or unstable policies, as well as corrupt practices, can be hugely problematic. Changes in governments can result in new policy, regulations, and interest rates, all of which can be detrimental to foreign businesses and investments. A growing trend towards economic nationalism also makes the current global political landscape potentially hostile towards international businesses.
\r\n
\r\n\tThe demographic shifts are creating interesting challenges. People are living longer, resulting to an aging demographic. We have a large population of older workers and retirees who are living longer lives, combined with a declining birthrate in most parts of the world. Businesses of all types are looking at how technology is affecting their operations. Several questions arise, such as: How is technology changing what we do? How is it transforming us internally, how is it influencing our clients and our business strategy? It is about leveraging technology to improve efficiency, connect with customers more effectively, and drive innovation. The majority of innovative companies are technology-driven businesses. Realizing digital transformation is today’s top issue and will remain so for the next five years. Improving organizational agility, expanding portfolios of products and services, creating, and maintaining a culture of innovation, and developing next -generation leaders were also identified as top challenges in terms of both current and future issues.
\r\n
\r\n\tThe most sustained profitable growth occurs when a company expands its core business into an adjacent space. This has significant implications for management because innovation in business ecosystems differs from traditional, vertically integrated firms. Every organization in the ecosystem must be aware of the bigger picture. Innovation in ecosystems necessitates collaborative action to invent and appraise, efficient, cross-organizational knowledge flows, modular architectures, and good stewardship of legacy systems. It is built on multiple, interconnected platforms. Environmental factors have already had a significant impact in the West and will continue to have an impact globally. Businesses must take into account the environmental impact of their daily operations. The advantage of this market is that it is expected to grow more rapidly than the overall economy. Another significant challenge is preparing the next generation of leaders to elevate this to the number one priority within the next five years. There can be no culture of innovation unless there is diverse leadership or development of the next generation of leaders; and these diverse, next-generation leaders are the ones who will truly understand the digital strategies that will drive digital transformation.
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