Osteoarthritis year in review 2018: rehabilitation and outcomes.

OBJECTIVE: Conduct a systematic review of systematic reviews and randomised controlled trials (RCTs) from the past year evaluating rehabilitation for people with osteoarthritis, and provide narrative synthesis of findings focused on core recommended treatments for osteoarthritis (exercise, education, biomechanical interventions, weight loss). DESIGN: A comprehensive search strategy was used to search PubMed, EMBASE and Cochrane databases (16th May 2017 to 22nd March 2018). Search terms included 'osteoarthritis', 'rehabilitation', 'systematic review', and 'randomised controlled trial'. Inclusion criteria were: (1) RCT, or systematic review of randomised clinical trials (RCTs); (2) human participants with osteoarthritis (any joint); (3) evaluation of rehabilitation intervention; and (4) at least one patient-reported measure. Methodological quality was evaluated using the Assessment of Multiple Systematic Reviews (AMSTAR) tool (systematic reviews) and PEDro rating scale (RCTs). Narrative synthesis mapped findings to core recommendations from existing osteoarthritis clinical guidelines. RESULTS: From 1994 records, 13 systematic reviews and 36 RCTs were included. 73% of these evaluated knee osteoarthritis (36 studies). The remaining studies evaluated hand osteoarthritis (6 studies), hip, hip/knee and general osteoarthritis (each 2 studies), and neck osteoarthritis (1 study). Exercise was the most common intervention evaluated (31%). Updated recommendations for exercise prescription and preliminary guidance for psychological interventions are provided. CONCLUSION: Level 1 and 2 osteoarthritis rehabilitation literature continues to be dominated by knee osteoarthritis studies. Consistent with current clinical guidelines, exercise should be a core treatment for osteoarthritis, but future studies should ensure that exercise programs follow published dose guidelines. There is a clear need for research on rehabilitation for hip, hand, foot/ankle, shoulder and spine osteoarthritis.

Imaging biomarkers of adiposity and sarcopenia as potential predictors for overall survival among patients with endometrial cancer treated with bevacizumab.

OBJECTIVE: To examine associations of body mass index (BMI), subcutaneous fat area (SFA) and density (SFD), visceral fat area (VFA) and density (VFD) and total psoas area (TPA) to outcomes among patients receiving chemotherapy with or without bevacizumab for advanced or recurrent endometrial cancer (EC). METHODS: This was a multi-institutional, retrospective study of patients with EC treated with and without bevacizumab as part of front-line, platinum based chemotherapy. Demographics and clinical characteristics were collected. SFA, VFA, SFD, VFD, and TPA were determined from pre-treatment CT scans using a deep learning algorithm. Data was compared with overall survival (OS) and progression free survival (PFS). RESULTS: Seventy-eight patients were analyzed. The majority were Caucasian (87.2%) with a mean BMI of 34.7 kg/m2. PFS and OS did not differ between patients with BMI, SFA, VFA, SFD, VFD, or TPA ≥ the 50th percentile compared to <50th percentile (p = 0.91, 0.45, 0.71, 0.74, 0.60, and 0.74 respectively) and (p = 0.99, 0.59, 0.14, 0.77, and 0.85 respectively). When adjusting for prognostic factors, elevated VFA trended towards shorter OS (25.1 vs 59.5 months, HR = 1.68 [0.92-3.05]).Patients receiving bevacizumab had similar OS compared to those who did not (37.6 vs 44.5 months, p = 0.409). When stratified by adiposity markers, no subset demonstrated benefit from bevacizumab. CONCLUSION: Obesity has been associated with increased levels of vascular endothelial growth factor (VEGF), the main target for bevacizumab therapy. Imaging measurements of VFA may provide prognostic information for patients with EC but no adiposity marker was predictive of improved response to bevacizumab.

ICOS protects against mortality from acute lung injury through activation of IL-5+ ILC2s.

Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease causing irreversible lung scarring and loss of pulmonary function. IPF Patients suffer from a high rate of pulmonary infections and acute exacerbations of disease that further contribute to pulmonary decline. Low expression of the inducible T-cell costimulatory molecule (ICOS) in peripheral blood mononuclear cells predicts decreased survival of IPF patients, but the mechanisms by which ICOS protects are unclear. Using a model of bleomycin-induced lung injury and fibrosis, we now demonstrate that ICOS expression enhances survival from lung injury rather than regulating fibrogenesis. Of ICOS-expressing cells, type 2 innate lymphocytes (ILC2s) are the first to respond to bleomycin-induced injury, and this expansion is ICOS dependent. Interestingly, a similar decrease in ICOS+ ILCs was found in lung tissue from IPF patients. Interleukin (IL)-5, produced primarily by ILC2s, was significantly reduced after lung injury in ICOS-/- mice, and strikingly, treatment with IL-5 protected both ICOS-/- and wild-type mice from mortality. These results imply that low ICOS expression and decreased lung ILC2s in IPF patients may contribute to poor recovery from infections and acute exacerbation and that IL-5 treatment may be a novel therapeutic strategy to overcome these defects and protect against lung injury.

Development and validation of a procedure for the determination of minoxidil in hair-regrowth formulations using two variants of capillary zone electrophoresis.

A high performance capillary electrophoresis method was developed and validated for purity assessment of minoxidil bulk drug and for determination of minoxidil in Rogaine. The principal use of the method was in analyzing illicit minoxidil-containing hair-regrowth samples. Although validated for Rogaine, the procedure proved equally viable on illicit minoxidil-containing preparations. The developed method fulfilled the goal of providing an orthogonal technique to HPLC for confirmation of the presence of minoxidil in these imitations. The method was validated on two instruments, one utilizing EK injection, the other gravity injection. It is selective for minoxidil, which is separated from known process impurities and the single degradation impurity. Validation figures of merit for linearity/recovery (accuracy) and precision were in accordance with current expectations for method validation.

Prenatal diagnosis of Smith-Lemli-Opitz syndrome.

An abnormality in cholesterol synthesis was described recently in the Smith-Lemli-Opitz (SLO) syndrome. Here we describe how the application of this finding has enabled an accurate prenatal diagnosis. We also discuss the possible use of this test in detecting heterozygotes.

Orbital lymphoma associated with acquired immune deficiency syndrome (AIDS).

A new case of AIDS-associated, small noncleaved cell (Burkitt's) lymphoma that presented as an orbital mass is described. Extraocular muscle involvement was documented by computed tomography and confirmed by orbital biopsy. Extensive abdominal involvement was subsequently diagnosed and this caused the patient's death only 15 days after the initial consultation and orbital biopsy. A literature review discloses only eight previous case reports of AIDS-associated non-Hodgkin's lymphoma (NHL) involving the orbit: two cases of Burkitt's type and six cases of large cell immunoblastic type. Three additional cases of orbital NHL can be found among larger series of AIDS cases. Affected patients are uniformly young adult males with a history of homosexuality and/or IV drug abuse. Variations in clinical presentation are discussed. Although the morphology of the histopathologic specimen in our case was consistent with a high-grade, small noncleaved cell NHL, flow cytometry revealed an atypical immunophenotype for Burkitt's lymphoma in that CD20 and immunoglobulin light chain antigens were not expressed. Morphologic classification and immunophenotypic characteristics of AIDS-associated NHLs are discussed.

Mechanisms of free radical oxidation of unsaturated lipids.

The primary products formed from the autoxidation of lipids can be understood based upon a mechanism that involves five different reaction types. These reactions are: reaction of a carbon radical and molecular oxygen, atom transfer of a hydrogen from substrate to the chain carrying peroxyl, fragmentation of the chain carrying peroxyl to give oxygen and a carbon radical, rearrangement of the peroxyl, and cyclization of the peroxyl. The mechanism of these primary reaction steps has been the focus of extensive research over the past fifty years, and the current level of understanding of these transformations is the subject of this review.

Capsular tissue: a new local flap.

Capsular tissue, the interface that forms between an implanted device and the body's own soft tissues, has recently been shown to develop its own unique blood supply. This capsular tissue with its extensive vascular plexus has not been described previously as an isolated flap. The purpose of our study was to determine whether an isolated flap of capsular tissue would survive as a local pedicle flap and provide enough inherent vascularity to support a skin graft. Isolated expanded and nonexpanded capsular flaps were compared by using 20 expanders (10 expanded and 10 nonexpanded) in two mixed-breed female pigs. Expanded and nonexpanded capsular flaps were elevated 8 weeks following expander placement. These flaps were raised on their capsular bases alone, and skin grafts were placed onto the capsular surfaces. All the expanded capsular flaps and their skin grafts had 100 percent survival. Skin grafts on the nonexpanded flaps survived an average of 28 percent, with graft survival corresponding to flap survival. This study confirms that flaps of isolated expanded capsular tissue survive and provide enough inherent vascularity to support a split-thickness skin graft.

General practitioner workload with 2,000 patients.

This study was designed to investigate the relationship between general practice workload, the number of partners in the practice, and the use of health centre premises. Thirty general practitioners in twelve randomly selected practices (each with a list size of 2,000 patients per doctor) agreed to record a week's work on pre-printed forms. Information was gathered on content of care in the surgery, number of non-surgery and indirect contacts and time spent on work activities. Content of care was influenced by whether or not the doctors were based in a health centre, rather on how many partners they had. Conversely the numbers of non-surgery and indirect contacts and the time spent on all work activities were more affected by the number of partners. Two factors - consultation rate and the rate at which doctors initiate consultations - were found to be independent of either of the two variables considered.

Diabetes care by general practitioners in Northern Ireland: present state and future trends.

A questionnaire returned by 250 (71.4%) of the 350 general practices in Northern Ireland indicated that although only 34 practices had special arrangements for seeing their diabetic patients, 178 practices stated that they would like to be more involved in the care of their non-insulin-dependent diabetes mellitus (NIDDM) patients. One hundred and eight practices felt the same way about their insulin-dependent diabetes mellitus (IDDM) patients. One hundred practices stated that the partners felt competent to manage their diabetic patients. The main area where general practitioners felt they needed to improve their knowledge was ophthalmology (56 practices). When asked which type of care scheme would appeal most to their practice, 135 practices stated that regular attendance with the general practitioner and annual hospital review would be the preferred arrangement. Overall there was a positive attitude towards increased general practitioner involvement in diabetes care.

Alterations in acetylcholine, PGE2 and IL6 release from urothelial cells following treatment with pyocyanin and lipopolysaccharide.

The effects of pseudomonal virulence factor pyocyanin, and LPS from Pseudomonas aeruginosa and Escherichia coli on urothelial mediator release and cytokine production were examined. RT4 urothelial cells were treated with pyocyanin (1-100 µM) or LPS (1-100 ng/mL) for 24-h. Effects were measured in terms of changes in cell viability, basal and stretch-induced acetylcholine (Ach) and PGE2 release, and inflammatory cytokines (IL-6 and IL-12) production. Twenty-four hour pyocyanin (100 µM) treatment significantly decreased urothelial cell viability, while stretch-induced Ach release response was inhibited. E. coli LPS (100 ng/mL) produced a similar response with an additional significant increase in basal Ach release. All three virulence factors significantly increased urothelial PGE2 release; under basal release for pyocyanin (100 µM), stretch-induced release for pseudomonal LPS (≥ 10 ng/mL) and both basal and stimulated release for E. coli LPS (≥ 10 ng/mL). IL-6 and IL-12 were not detected in control samples, however 24h treatment with pyocyanin (100 µM) or LPS (100 ng/mL) resulted in IL-6 release from urothelial cells. The changes in urothelial Ach and PGE2, and release of inflammatory cytokine IL-6 induced by exposure to the bacterial virulence factors may play a role in the symptoms of pain and urinary urgency experienced with urinary tract infections.

Computer based learning in general practice--options and implementation.

A survey of the 30 departments of general practice in the UK revealed that only three are currently making use of any form of computer based learning materials for teaching their undergraduate students. One of the reasons for the low level of usage is likely to be the relatively poor availability of suitable courseware and lack of guidance as to how to utilise what is available. This short paper describes the types of courseware that are available and the advantages and disadvantages of using acquired courseware as opposed to writing your own. It also considers alternative strategies for making computer based learning (CBL) courseware available to students.

Parathyroid cyst: case report of a rare surgical lesion of the neck.

A thirty-two year old female presented with a neck mass of probable thyroid origin. Repeated fine needle aspirations failed to provide diagnostic tissue or long-term resolution of the cystic mass. The clinical and pathologic findings in this case of a parathyroid cyst are presented. Parathyroid cyst is a rare cause of neck mass. Recurrence of a cyst is also unusual following aspiration. The aspiration of clear watery fluid from a neck mass offers presumptive evidence of a parathyroid cyst. The demonstration of parathyroid hormone in the cyst fluid is considered diagnostic.

Pleural effusion with rheumatoid arthritis.

Pleural effusions complicating rheumatoid arthritis occur most commonly in middle-aged men. The majority of these individuals will be symptomatic with pleuritic chest pain and/or dyspnea. Rheumatoid pleural effusions have distinct chemical characteristics including elevated LDH, low glucose and low pH. The finding of a rheumatoid nodule on pleural biopsy, is pathognomonic of a rheumatoid associated pleural effusion. Treatment of this spectrum of the disease is aimed at preventing progressive pleural fibrosis.

The molecular genetics of human facioscapulohumeral muscular dystrophy and the myodystrophy mouse model.

Facioscapulohumeral dystrophy is an autosomal dominant muscular dystrophy, the gene for which is localized to 4q35. It appears to be caused by deletion of tandem repeats that do not contain an expressed sequence. One current hypothesis is that the deletion affects expression of a centromeric gene (not yet identified) through a position effect. The mouse mutant, myodystrophy (myd), is a candidate model for facioscapulohumeral dystrophy. Myd has a progressive muscular dystrophy and maps to a segment of mouse chromosome 8 that is syntenic with human 4q31-4q35.

Laboratory and radiological investigations in general practice. I-Type requested and rate of use.

The use that 30 general practitioners in four group practices made of open access laboratory and radiological facilities was studied for one year. We were particularly interested in whether general practitioners hoped to exclude rather than confirm abnormality when requesting investigations. All but two of the general practitioners studied used investigations to exclude abnormality to a greater extent than to confirm it. The rate at which the practices investigated patients and the number of investigations requested were appreciably different and were different for individual general practitioners, part time general practitioners requesting more investigations than trainees and full time general practitioners. Haematological investigations accounted for over 30% of requests for investigations in all but one practice, biochemical investigations being requested as often as bacteriological investigations in two of the four practices. The ratio of expected to unexpected results varied among general practitioners; no general practitioner had more unexpected results and the range of ratios was similar for full time and part time general practitioners and for trainees. The proportion of patients with abnormalities uncovered by each practice increased disproportionately as the use of investigations increased, supporting a higher rather than lower rate of investigation among general practitioners. Compared with the results of other studies the use of the radiological facilities available was low. X ray examinations of the skeleton were requested more than chest and contrast media examinations by three of the four practices. Most x ray examinations were used to exclude rather than confirm abnormality by all the practices, with over 85% of results confirming the general practitioner's initial diagnosis.

A computerized audit of non-steroidal anti-inflammatory drug prescribing in general practice.

The two group practices based in a city health centre decided to prescribe non-steroidal anti-inflammatory drugs in generic form from an agreed date. The practices' computer was used to identify the number of repeat prescriptions being issued for this group of drugs and to monitor the effectiveness of the changeover. Although both practices showed a marked increase in the level of generic prescribing there was considerable interpractice variation. Generic prescribing for one practice increased from 4% to 64% and for the other from 1% to 38% of repeat prescriptions issued for non-steroidal anti-inflammatory drugs over the study period. The reasons for this variation, the advantages of computerized audit and the problems associated with this self-imposed audit are discussed.

General practitioner records on computer--handle with care.

This 1 year prospective study involved nine general practitioners in an urban health centre who routinely record all patient contacts on computer. The study determines by comparison with a manual record how accurately doctors record laboratory investigations on computer and compares the effectiveness of three interventions in improving the completeness of computerized recording of presenting symptoms, problems/diagnoses and laboratory investigations. Recording was analysed for 1 month prior to and for two 1 month periods following each intervention. A control group was used. A total of 7983 patient contacts were analysed. Intervention led to an improvement in the recording of presenting symptoms and problems/diagnoses. Recording of investigations on the computer showed no improvement, remaining at one-third of the total in the treatment room book for both study and control doctors. The effectiveness of the different forms of intervention depended on both the aspect of the consultation considered and the familiarity of individual doctors with the method of data collection. Aspects considered less important required greater intervention to bring about a marked improvement, as did doctors relatively new to the practice. It may not be possible to get all aspects of the consultation recorded with the same degree of accuracy. This has implications for the accuracy of retrospective studies dependent on existing computerized data.

Effect on prescribing of the limited list in a computerised group practice.

The prescribing of drugs in the therapeutic classes that are affected by the government's limited list was investigated in a computerised group practice of just over 3,000 patients. Prescribable drugs in categories that are affected by the list were identified for two consecutive six month periods before and one six month period after the introduction of the list. A significant decrease in the prescribing of cough and cold remedies, vitamins, and antacids occurred after the list was introduced, whereas no change occurred in the prescribing of laxatives, benzodiazepines, or analgesics. The prescribing of iron and penicillin increased significantly after the list was introduced, whereas the use of H2 antagonists and non-steroidal anti-inflammatory drugs showed no significant change.

Patients on H2-receptor antagonists--are we investigating them?

A survey was made of patients receiving H2-receptor antagonists in a group practice serving 8600 patients. Two hundred and twelve patients (2%) who had received at least one prescription for H2 antagonists in a 12 month period were identified. When compared with the practice population, men and patients over 50 years old were more likely to be taking these drugs (P less than 0.01 and P less than 0.001, respectively). One hundred and fifty-seven patients (74%) were investigated before commencing therapy; 114 (73%) of these patients were investigated via the hospital outpatient department, despite the general practitioners having full open access to barium meals. Only 23 (15%) of the patients investigated were found to have no active pathology. Twenty-nine (14%) of the 212 study patients had received one or more gastrointestinal investigations in the 18 months subsequent to starting H2-antagonist therapy. Twenty-five of these patients had also received an investigation before starting therapy. One hundred and eleven patients (52%) had had their H2 antagonist therapy initiated by their general practitioner.