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By H. Ballock. North Carolina Wesleyan College.

Non-pharmacological Management Exercise Education Non- pharmacological Energy Conservation Management Cognitive Behavourial Therapy Stress Management Figure 9 purchase oxybutynin line. Three showed no effect or failed to achieve statistical significance (Schmitz et al order oxybutynin 2.5mg otc, 2010) buy generic oxybutynin 5 mg on-line. Patients should also be educated if they experience fatigue, it may be a side-effect of the treatment and not automatically a sign that the treatment in not successful or that the disease is evolving. It encompasses a common sense approach that helps patients to prioritize and pace activities, and to delegate less essential activities if they are experiencing moderate-to-severe fatigue. A useful plan is to maintain a daily and weekly diary that allows the patient to ascertain peak energy periods. Goedendorp et al Psychosocial interventions (education, 7 of 27 studies reviewed (2009) self-care, coping techniques, and showed a significant (Cochrane Review) learned activity management) reduction in fatigue Kangas et al (2009) Psychosocial interventions: restorative 119 studies. Identifying for each individual what has been helpful in managing stress prior to their diagnosis may help 64 the patient recognise what option to explore first in dealing with his or her emotions regarding the malignancy. Time spent fatigue both during one component bias) low-unclear risk (2012) of cancer- -Participants may specific exercise training and exercising and after treatment of a of bias Cochrane related have been actively programme flexibility 3. The management -Blinding of outcome Review fatigue in receiving prescribed) or an exercises. Quality of life on fatigue were fatigue that may bias) high risk of bias -56 studies term follow-up treatment 5. Anxiety and observed include a -Selective reporting included (28 or palliative care. Depression specifically for range of other (reporting bias) low risk breast cancer 6. Effects of exercise on fatigue in cancer patients 66 5) Pain Chronic pain after cancer surgery may occur in up to 50% of patients. Risk factors include: 1) Young age 2) Chemotherapy 3) Radiotherapy 4) Poor post-operative pain control 5) Certain surgical factors. The neurophysiology of cancer pain is complex: it involves inflammatory, neuropathic, ischemic and compression mechanisms at multiple sites. Knowledge of these mechanisms and the ability to decide whether a pain is nocioceptive, neuropathic, and visceral or a combination of all three will lead to best practice in pain management. Acute pain; brief, intense, and arises suddenly, limits activities almost immediately. Medication is prescribed as needed for a short period of time until the episodes of pain subside. It can be an uncomfortable ache that is always there, or a much more intense feeling of physical distress or suffering that makes it impossible to focus on anything else. Pain Relief For Breast Cancer Pain  Non-narcotic Analgesics (non- opoids)  Nerve Blocking Strategies  Narcotic Analgesics (opoids)  Nerve Stimulation  Coanalgesics  Physiotherapy  Topical Analgesics Role of Physiotherapy  Strategies for preventing and treating lymphoedema (see lymphoedema section)  Manual stretching and soft tissue massage  Information about exercise programs designed to build strength and range of motion. Consequences of neuropathy can be severe for patients with cancer and may result in reduced quality of life, disability, and potentially shorter survival. Small sensory fibres are affected early and most frequently by chemotherapeutic agents. Motor nerves are generally less frequently or seriously affected by neurotoxic chemotherapy. Motor nerves that have survived a chemotherapeutic insult have the capacity for distal sprouting and reinnervation of muscle fibres that have lost their innervation (Stubblefield et al, 2009). Chemotherapeutic drugs and anticancer biologics frequently reported as associated with symptomatic neuropathy. Drug Clinical Manifestation Recovery Cisplatin Symmetrical painful parenthesis or Partial, symptoms may Carboplatin numbness in a stocking-glove progress for months Oxaliplatin distribution, sensory ataxia with gait Oxaliplatin: Resolution in 3 dysfunction months, may persist longer Oxaliplatin Cold-induced painful dysesthesia Resolution within a week Vincristine, Symmetrical tingling parenthesis, Resolution usually within vinblastine, loss of ankle stretch reflexes, 3 months, may persist for vinorelbine, vindesine constipation, occasional weakness, vincristine gait dysfunction Paclitaxel Symmetrical painful parenthesis or Docetaxel numbness in stocking-glove Abraxane distribution, decreased vibration or proprioception, occasionally weakness, sensory ataxia, and gait dysfunction Bortezomib Painful parenthesis, burning Resolution usually within 3 sensation, occasional w weakness, months, may persist sensory ataxia, and gait dysfunction. Rare autonomic dysfunction including orthostatic hypotension Xabepilone Painful parenthesis, burning Resolution in 4–6 weeks sensation Thalidomide Symmetrical tingling or numbness, May persist for over 1 year pain. The assessment methods available include clinical evaluation (grading systems), objective testing, and patient questionnaires. Physical examination should describe clinical features of the neuropathy, such as sensory abnormalities, deep tendon reflex dysfunction, motor weakness, pain characteristics, autonomic symptoms, and most importantly, functional impairment. Sensory Symptom Management: As with pain medications, most evidence supporting neurostimulation came from studies on diabetic or other types of neuropathy. However, it is an invasive technique that includes the risks and costs of surgery. Evidence for acupuncture Article Intervention Outcome Donald et al (2011) six weekly acupuncture 82% of patients reported an improvement in sessions symptoms. Clinical trial Some patients also reported a reduction in analgesic use and improved sleeping patterns. Balance Rehabilitation: Gait training and lower limb resistance training help significantly improve balance in diabetic patients compared with a control exercise regimen (Richardson et al, 2001). Assistive Devices: Assistive devices including canes, walkers, wheelchairs, and ankle-foot orthoses may also be provided if required. Compression caused by:  Obstruction  Invasion  Thrombosis  Or fibrosis of the vessel Lung cancer accounts for 85% of all incidences, malignant lymphomas of non-Hodgkin’s origin are the second main cause, other primary mediastinal tumours like thymoma or germ cell tumours make up <2% of occurrences. Signs & Symptoms  Neck and Facial Swelling  Hoarseness (especially around the eyes)  Headaches  Dyspnoea  Nasal congestion  Cough  Epistaxis  Head Fullness and Pressure  Hemoptysis Sensation  Dizziness  Proptosis  Dysphagia  Stridor  Arm Oedema  Venous Distension in neck and  Syncope thorax *Symptoms often get worse leaning forward or lying down. Also can be used to show location of obstruction and help as a guide for fine needle aspiration biopsy. Causes  Obstruction of lymphatic drainage  Excess fluid secretion from tumour nodules on pericardial surfaces Differential Diagnosis of Pericardial Effusion  Non-malignant e. Treatment Options  Pericardiocentesis plus sclerosing agents like bleomycin or tetracycline  The creation of a pericardial window  Complete pericardial stripping  Systematic chemotherapy 3) Malignant Spinal Cord Compression Compression is caused by extradural metastases from tumours involving the spine. Bone metastases of thoracic (70%), lumbar (20%) or cervical (10%) regions may cause a cord injury. It presents in 5-10% of all cancer patients throughout the course of their disease. Only 10% unable to walk pre diagnosis will recover the ability to mobilise post treatment Signs & Symptoms  Localised back pain o May increase overnight o Does not improve with common analgesics o Worsens with recumberance or with manoeuvres o Worsens with increased pressure e. Severe hypercalcaemia (>13 mg/dl) is linked to a short survival time of several weeks to a few months. Causes  Bone metastases due to increased release of calcium from bone as a result of osteoclastic activity  Increased parathyroid hormone-related protein production  Calcitrol secretion Signs & Symptoms (Serum calcium levels >2. The tumour mass plus surrounding oedema may produce hydrocephalus and as the mass increases, various herniation syndromes may start. However, less than 22% of cancer survivors are physically active and breast cancer survivors have the lowest rate of physical activity of all cancer survivors (Courneya et al 2008). Precautions and contraindications for exercise in breast cancer patients Precautions Contraindications Pts with severe anaemia- delay exercise until improved.

Following birth purchase oxybutynin 5mg mastercard, most hemopoiesis occurs in the red marrow buy cheap oxybutynin line, a connective tissue within the spaces of spongy (cancellous) bone tissue order 5 mg oxybutynin overnight delivery. In children, hemopoiesis can occur in the medullary cavity of long bones; in adults, the process is largely restricted to the cranial and pelvic bones, the vertebrae, the sternum, and the proximal epiphyses of the femur and humerus. This process is referred to as extramedullary hemopoiesis (meaning hemopoiesis outside the medullary cavity of adult bones). When a disease such as bone cancer destroys the bone marrow, causing hemopoiesis to fail, extramedullary hemopoiesis may be initiated. Differentiation of Formed Elements from Stem Cells All formed elements arise from stem cells of the red bone marrow. Recall that stem cells undergo mitosis plus cytokinesis (cellular division) to give rise to new daughter cells: One of these remains a stem cell and the other differentiates into one of any number of diverse cell types. Stem cells may be viewed as occupying a hierarchal system, with some loss of the This OpenStax book is available for free at http://cnx. The next level is the pluripotent stem cell, which gives rise to multiple types of cells of the body and some of the supporting fetal membranes. Beneath this level, the mesenchymal cell is a stem cell that develops only into types of connective tissue, including fibrous connective tissue, bone, cartilage, and blood, but not epithelium, muscle, and nervous tissue. Hemopoiesis begins when the hemopoietic stem cell is exposed to appropriate chemical stimuli collectively called hemopoietic growth factors, which prompt it to divide and differentiate. However, hemopoiesis of lymphocytes progresses somewhat differently from the process for the other formed elements. In brief, lymphoid stem cells quickly migrate from the bone marrow to lymphatic tissues, including the lymph nodes, spleen, and thymus, where their production and differentiation continues. Lymphoid and myeloid stem cells do not immediately divide and differentiate into mature formed elements. For instance, megakaryoblasts are the precursors of megakaryocytes, and proerythroblasts become reticulocytes, which eject their nucleus and most other organelles before maturing into erythrocytes. They act locally as autocrine or paracrine factors, stimulating the proliferation of progenitor cells and helping to stimulate both nonspecific and specific resistance to disease. Some trigger the differentiation of myeloblasts into granular leukocytes, namely, neutrophils, eosinophils, and basophils. They were initially thought to be secreted uniquely by leukocytes and to communicate only with other leukocytes, and were named accordingly, but are now known to be produced by a variety of cells including bone marrow and endothelium. Researchers now suspect that interleukins may play other roles in body functioning, including differentiation and maturation of cells, producing immunity and inflammation. The source of the cells was either2 from the recipient (autologous) or from a donor with compatible blood (homologous). These practices are considered illegal in virtually all sports and run the risk of infection, significantly increasing the viscosity of the blood and the potential for transmission of blood-borne pathogens if the blood was collected from another individual. This increased viscosity raises the resistance of the blood and forces the heart to pump more powerfully; in extreme cases, it has resulted in death. Lance Armstrong, winner of seven Tour de France and many other cycling titles, was stripped of his victories and admitted to blood doping in 2013. Bone Marrow Sampling and Transplants Sometimes, a healthcare provider will order a bone marrow biopsy, a diagnostic test of a sample of red bone marrow, or a bone marrow transplant, a treatment in which a donor’s healthy bone marrow—and its stem cells—replaces the faulty bone marrow of a patient. These tests and procedures are often used to assist in the diagnosis and treatment of various severe forms of anemia, such as thalassemia major and sickle cell anemia, as well as some types of cancer, specifically leukemia. In the past, when a bone marrow sample or transplant was necessary, the procedure would have required inserting a large- bore needle into the region near the iliac crest of the pelvic bones (os coxae). This location was preferred, since its location close to the body surface makes it more accessible, and it is relatively isolated from most vital organs. The isolated stem cells are then grown in culture using the appropriate hemopoietic growth factors, and analyzed or sometimes frozen for later use. For an individual requiring a transplant, a matching donor is essential to prevent the immune system from destroying the donor cells—a phenomenon known as tissue rejection. To treat patients with bone marrow transplants, it is first necessary to destroy the patient’s own diseased marrow through radiation and/or chemotherapy. As you can imagine, they are quite small cells, with a mean diameter of only about 7–8 micrometers (µm) (Figure 18. The primary functions of erythrocytes are to pick up inhaled oxygen from the lungs and transport it to the body’s tissues, and to pick up some (about 24 percent) carbon dioxide waste at the tissues and transport it to the lungs for exhalation. Although leukocytes typically leave the blood vessels to perform their defensive functions, movement of erythrocytes from the blood vessels is abnormal. During the first day or two that it is in the circulation, an immature erythrocyte, known as a reticulocyte, will still typically contain remnants of organelles. These remnants, primarily of networks (reticulum) of ribosomes, are quickly shed, however, and mature, circulating erythrocytes have few internal cellular structural components. This means that they do not utilize any of the oxygen they are transporting, so they can deliver it all to the tissues. Erythrocytes do, however, contain some structural proteins that help the blood cells maintain their unique structure and enable them to change their shape to squeeze through capillaries. Erythrocytes are biconcave disks; that is, they are plump at their periphery and very thin in the center (Figure 18. Since they lack most organelles, there is more interior space for the presence of the hemoglobin molecules that, as you will see shortly, transport gases. The biconcave shape also provides a greater surface area across which gas exchange can occur, relative to its volume; a sphere of a similar diameter would have a lower surface area-to-volume ratio. In the capillaries, the oxygen carried by the erythrocytes can diffuse into the plasma and then through the capillary walls to reach the cells, whereas some of the carbon dioxide produced by the cells as a waste product diffuses into the capillaries to be picked up by the erythrocytes. Capillary beds are extremely narrow, slowing the passage of the erythrocytes and providing an extended opportunity for gas exchange to occur. However, the space within capillaries can be so minute that, despite their own small size, erythrocytes may have to fold in on themselves if they are to make their way through. Fortunately, their structural proteins like spectrin are flexible, allowing them to bend over themselves to a surprising degree, then spring back again when they enter a wider vessel. In wider vessels, erythrocytes may stack up much like a roll of coins, forming a rouleaux, from the French word for “roll. It consists of four folded chains of a protein called globin, designated alpha 1 and 2, and beta 1 and 2 (Figure 18. Each of these globin molecules is bound to a red pigment 794 Chapter 18 | The Cardiovascular System: Blood 2+ molecule called heme, which contains an ion of iron (Fe ) (Figure 18. Each iron ion in the heme can bind to one oxygen molecule; therefore, each hemoglobin molecule can transport four oxygen molecules. An individual erythrocyte may contain about 300 million hemoglobin molecules, and therefore can bind to and transport up to 1. The bright red, oxygenated hemoglobin travels to the body tissues, where it releases some of the oxygen molecules, becoming darker red deoxyhemoglobin, sometimes referred to as reduced hemoglobin. Oxygen release depends on the need for oxygen in the surrounding tissues, so hemoglobin rarely if ever leaves all of its oxygen behind. About 23–24 percent of it binds to the amino acids in hemoglobin, forming a molecule known as carbaminohemoglobin.

It articulates superiorly with the hip bone at the hip joint effective oxybutynin 5mg, and inferiorly with the tibia at the knee joint 2.5mg oxybutynin mastercard. Multiple muscles that act across the hip joint attach to the greater trochanter discount oxybutynin 5 mg mastercard, which, because of its projection from the femur, gives additional leverage to these muscles. The lesser trochanter is a small, bony prominence that lies on the medial aspect of the femur, just below the neck. Running between the greater and lesser trochanters on the anterior side of the femur is the roughened intertrochanteric line. The trochanters are also connected on the posterior side of the femur by the larger intertrochanteric crest. At its proximal end, the posterior shaft has the gluteal tuberosity, a roughened area extending inferiorly from the greater trochanter. Multiple muscles of the hip and thigh regions make long, thin attachments to the femur along the linea aspera. On the lateral side, the smooth portion that covers the distal and posterior aspects of the lateral expansion is the lateral condyle of the femur. Similarly, the smooth region of the distal and posterior medial femur is the medial condyle of the femur, and the irregular outer, medial side of this is the medial epicondyle of the femur. Posteriorly, the medial and lateral condyles are separated by a deep depression called the intercondylar fossa. Anteriorly, the smooth surfaces of the condyles join together to form a wide groove called the patellar surface, which provides for articulation with the patella bone. The combination of the medial and lateral condyles with the patellar surface gives the distal end of the femur a horseshoe (U) shape. A sesamoid bone is a bone that is incorporated into the tendon of a muscle where that tendon crosses a joint. The sesamoid bone articulates with the underlying bones to prevent damage to the muscle tendon due to rubbing against the bones during movements of the joint. The patella is found in the tendon of the quadriceps femoris muscle, the large muscle of the anterior thigh that passes across the anterior knee to attach to the tibia. The patella articulates with the patellar surface of the femur and thus prevents rubbing of the muscle tendon against the distal femur. The patella also lifts the tendon away from the knee joint, which increases the leverage power of the quadriceps femoris muscle as it acts across the knee. It often results from excessive running, particularly downhill, but may also occur in athletes who do a lot of knee bending, such as jumpers, skiers, cyclists, weight lifters, and soccer players. The pain may be felt when walking or running, going up or down stairs, kneeling or squatting, or after sitting with the knee bent for an extended period. Patellofemoral syndrome may be initiated by a variety of causes, including individual variations in the shape and movement of the patella, a direct blow to the patella, or flat feet or improper shoes that cause excessive turning in or out of the feet or leg. These factors may cause in an imbalance in the muscle pull that acts on the patella, resulting in an abnormal tracking of the patella that allows it to deviate too far toward the lateral side of the patellar surface on the distal femur. Because the hips are wider than the knee region, the femur has a diagonal orientation within the thigh, in contrast to the vertically oriented tibia of the leg (Figure 8. The Q-angle is normally 10–15 degrees, with females typically having a larger Q-angle due to their wider pelvis. During extension of the knee, the quadriceps femoris muscle pulls the patella both superiorly and laterally, with the lateral pull greater in women due to their large Q-angle. Normally, the large lip on the lateral side of the patellar surface of the femur compensates for the lateral pull on the patella, and thus helps to maintain its proper tracking. However, if the pull produced by the medial and lateral sides of the quadriceps femoris muscle is not properly balanced, abnormal tracking of the patella toward the lateral side may occur. With continued use, this produces pain and could result in damage to the articulating surfaces of the patella and femur, and the possible future development of arthritis. Treatment generally involves stopping the activity that produces knee pain for a period of time, followed by a gradual resumption of activity. Proper strengthening of the quadriceps femoris muscle to correct for imbalances is also important to help prevent reoccurrence. Tibia The tibia (shin bone) is the medial bone of the leg and is larger than the fibula, with which it is paired (Figure 8. The tibia is the main weight-bearing bone of the lower leg and the second longest bone of the body, after the femur. The medial side of the tibia is located immediately under the skin, allowing it to be easily palpated down the entire length of the medial leg. The two sides of this expansion form the medial condyle of the tibia and the lateral condyle of the tibia. Between the articulating surfaces of the tibial condyles is the intercondylar eminence, an irregular, elevated area that serves as the inferior attachment point for two supporting ligaments of the knee. Both the anterior border and the medial side of the triangular shaft are located immediately under the skin and can be easily palpated along the entire length of the tibia. A small ridge running down the lateral side of the tibial shaft is the interosseous border of the tibia. This is for the attachment of the interosseous membrane of the leg, the sheet of dense connective tissue that unites the tibia and fibula bones. Located on the posterior side of the tibia is the soleal line, a diagonally running, roughened ridge that begins below the base of the lateral condyle, and runs down and medially across the proximal third of the posterior tibia. The large expansion found on the medial side of the distal tibia is the medial malleolus (“little hammer”). Both the smooth surface on the inside of the medial malleolus and the smooth area at the distal end of the tibia articulate with the talus bone of the foot as part of the ankle joint. It articulates with the inferior aspect of the lateral tibial condyle, forming the proximal tibiofibular joint. The thin shaft of the fibula has the interosseous border of the fibula, a narrow ridge running down its medial side for the attachment of the interosseous membrane that spans the fibula and tibia. The distal end of the fibula forms the lateral malleolus, which forms the easily palpated bony bump on the lateral side of the ankle. The deep (medial) side of the lateral malleolus articulates with the talus bone of the foot as part of the ankle joint. This has a relatively square-shaped, upper surface that articulates with the tibia and fibula to form the ankle joint. Three areas of articulation form the ankle joint: The superomedial surface of the talus bone articulates with the medial malleolus of the tibia, the top of the talus articulates with the distal end of the tibia, and the lateral side of the talus articulates with the lateral malleolus of the fibula. Inferiorly, the talus articulates with the calcaneus (heel bone), the largest bone of the foot, which forms the heel. The medial calcaneus has a prominent bony extension called the sustentaculum tali (“support for the talus”) that supports the medial side of the talus bone. The cuboid has a deep groove running across its inferior surface, which provides passage for a muscle tendon.

Although there may be differences among drugs within the same class cheap oxybutynin 2.5 mg amex, 5 buy oxybutynin online pills,20 effective 5 mg oxybutynin,29,32-38 previous comparative effectiveness reviews in allergic rhinitis have found insufficient evidence to support superior effectiveness of any single drug within a drug class. A direct consequence of the decision to conduct across-class comparisons is the inability to compare individual drugs across studies. Additionally, limited conclusions can be drawn about drug classes that are poorly represented by the drugs studied. To our knowledge, methodological approaches for meta-analysis of class comparisons based on studies of single within-class treatment comparisons have not been published. How do effectiveness and adverse effects vary with long-term (months) or short-term (weeks) use? How do effectiveness and adverse effects vary with intermittent or continuous use? How do effectiveness and adverse effects vary with long-term (months) or short-term (weeks) use? How do effectiveness and adverse effects vary with intermittent or continuous use? Analytic Framework The analytic framework for this report is presented in Figure A. Adverse events may occur at any point after treatment is received and may impact quality of life directly. Key Informants were patients, providers (allergists, a pediatric pulmonologist, pharmacists, otorhinolaryngologists, and family physicians), and payers. Their input was sought to identify important clinical and methodological issues pertinent to the review. Articles were limited to those published in the English language, based on technical expert advice that the majority of the literature on this topic is published in English. Scientific information packets provided by product manufacturers were evaluated to identify unpublished trials that met inclusion criteria. We sought expert guidance to identify the drug class comparisons most relevant for treatment decisionmaking. A total of 60 treatment comparisons were identified for all three patient populations. Two reviewers screened abstracts and full-text reports, with conflicts resolved by consensus or a third reviewer. Selective and nonselective antihistamine (based on specificity for peripheral H1 receptors) and different routes of administration (oral or nasal) were considered different classes for this purpose. Data Abstraction and Quality Assessment Comparative effectiveness and harms data from included studies were abstracted into an electronic database by two team members. Extracted information included general trial characteristics, baseline characteristics of trial participants, eligibility criteria, interventions, outcome measures and their method of ascertainment, and results of each predefined outcome. Particular care was taken to ascertain whether patients were properly blinded to treatment because all outcomes of interest were patient reported. Open-label trials and trials in which patient blinding was deemed inadequate received a quality rating of poor. In particular, the process of harms ascertainment was noted and characterized as either an active process if structured questionnaires were used, a passive process if only spontaneous patient reports were collected, or intermediate if active surveillance for at least one adverse event was reported. Trials using only passive harms ascertainment were considered to have a high risk of bias—specifically, underreporting or inconsistent reporting of harms. Data Synthesis and Analysis Evidence on the comparative effectiveness and harms for each class comparison was summarized in narrative text. Quantitative pooling of results (meta-analysis) was considered if three or more clinically and methodologically similar studies reported on a given outcome. Only studies that reported variance estimates for group-level treatment effects could be pooled. The pooling method involved inverse variance weighting and a random-effects model. Meta-analysis was performed for adverse events that investigators reported as severe or that led to discontinuation of treatment. Mean differences were calculated for continuous outcomes (effectiveness outcomes), and risk differences were calculated for dichotomous outcomes (harms). For studies that could not be quantitatively pooled, results were qualitatively combined when it was reasonable to do so (e. In this review, we formed conclusions about treatment classes based on meta-analyses of studies that compared single treatments. In allergen-specific immunotherapy trials, a minimum 30-percent greater improvement than placebo in composite 50 symptom/rescue medication use scores is considered clinically meaningful. This threshold was based on an evaluation of 68 placebo-controlled double-blind trials. The concordance of these values increased our confidence that 30 percent of maximum score is a useful threshold for purposes of our analysis and could be applied across symptom scales. Technical Expert Panel input 2-4 0–12 interval aA 30% greater improvement compared with placebo in composite symptom/rescue medication use scores was proposed as minimally clinically meaningful. We initially assessed the evidence to determine whether one treatment was therapeutically superior to another and found that, for many comparisons, the evidence suggested equivalence of the treatments compared. Equivalence: Treatments demonstrated comparable effectiveness, either for symptom improvement or harm avoidance. Two reviewers independently evaluated the strength of evidence, and agreement was reached through discussion and consensus when necessary. Four main domains were assessed: risk of bias, consistency, directness, and precision. Further research is very unlikely to change our confidence in the estimate of effect. Further research may change our confidence in the estimate of effect and may change the estimate. Further research is likely to change the confidence in the estimate of effect and is likely to change the estimate. Results Overview Of the 4,513 records identified through the literature search, 4,458 were excluded during screening. Four records were identified through gray literature and hand searching of bibliographies. However, this trial was not included because quality assessment was not possible without the published report. No observational studies, systematic reviews, or meta-analyses that met our inclusion criteria were identified. For most outcomes, evidence was insufficient to form any comparative effectiveness conclusion. In five comparisons, we found evidence for comparable effectiveness (equivalence) of treatments for at least one outcome (rows 5, 6, 8, 11, and 12 in Table B). We found evidence for superior effectiveness of one treatment over another for one outcome in each of two comparisons (row 5 and row 9 in Table B). For seven comparisons, trials included only a small proportion of the drugs in each class (rows 1, 6, 8, 9, 10, 11, and 12 in Table B).

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