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1.  No association between vitamin D deficiency and parathyroid hormone, bone density and bone turnover in a large cohort of HIV-infected men on tenofovir 
Journal of the International AIDS Society  2014;17(4Suppl 3):19568.
Combination antiretroviral therapy (cART) may affect vitamin D [25(OH)D], parathyroid hormone (PTH), bone mineral density (BMD) and bone turnover (BT). Reduced BMD and secondary hyperparathyroidism have been reported with tenofovir (TDF). We investigated the associations between TDF and bone markers, especially in 25(OH)D-deficient patients.
Materials and Methods
In a single-centre longitudinal study investigating BMD in HIV-positive men, serum 25(OH)D, calcium, phosphate, PTH and alkaline phosphatase (ALP) were measured. Lumbar spine, non-dominant total hip and non-dominant femoral neck BMD (g/cm2) were measured using dual-energy X-ray absorptiometry. BT was assessed by serum type 1 procollagen (P1NP) and carboxy-terminal collagen cross-links (CTX). Mann–Whitney U tests compared serum markers and BT, and t-tests compared BMD according to TDF in all and 25(OH)D-deficient patients.
A total of 422 men were recruited: mean age 47 (SD 9.8) years, 94% white ethnicity, 93% MSM, diagnosed HIV positive for median 9.6 (IQR 5.0,15.5) years, median CD4 547 (IQR 411,696) cells/µL, HIV RNA <40 copies/mL in 87% (96% of those on cART). 25(OH)D (nmol/L) was normal (>75), insufficient (50–75), deficient (25–50) and severely deficient (<25) in 14%, 29%, 50% and 7%, respectively. Of 381 men on cART, 77% were currently on TDF. TDF was not associated with median calcium (p=0.69) or phosphate (p=0.52), but patients had higher (but normal) median ALP [81 (IQR 69,103) vs. 73 (IQR 60,89) IU/L, p=0.005) compared to non-TDF cART. There was no difference in the association between vitamin D and PTH according to whether someone currently was (r=0.11, p=0.06, Figure 1) or was not using TDF (r=0.12, p=0.29, Figure 1). TDF was also not associated with PTH, BMD or BT in either all patients on cART (Table 1a) or in patients with 25(OH)D deficiency (Table 1b).
In this largely TDF-experienced cohort of HIV-positive men, there was no association between TDF and 25(OH)D deficiency, hyperparathyroidism, reduced BMD or increased BT, although patients on TDF had higher but normal ALP. We found no evidence to support additional monitoring of bone markers in patients on TDF regardless of 25(OH)D status.
PMCID: PMC4224824  PMID: 25394075
2.  Maintained physical activity and physiotherapy in the management of distal upper limb pain – a protocol for a randomised controlled trial (the arm pain trial) 
Distal upper limb pain (pain affecting the elbow, forearm, wrist, or hand) can be non-specific, or can arise from specific musculoskeletal disorders. It is clinically important and costly, the best approach to clinical management is unclear. Physiotherapy is the standard treatment and, while awaiting treatment, advice is often given to rest and avoid strenuous activities, but there is no evidence base to support these strategies. This paper describes the protocol of a randomised controlled trial to determine, among patients awaiting physiotherapy for distal arm pain, (a) whether advice to remain active and maintain usual activities results in a long-term reduction in arm pain and disability, compared with advice to rest; and (b) whether immediate physiotherapy results in a long-term reduction in arm pain and disability, compared with physiotherapy delivered after a seven week waiting list period.
Between January 2012 and January 2014, new referrals to 14 out-patient physiotherapy departments were screened for potential eligibility. Eligible and consenting patients were randomly allocated to one of the following three groups in equal numbers: 1) advice to remain active, 2) advice to rest, 3) immediate physiotherapy. Patients were and followed up at 6, 13, and 26 weeks post-randomisation by self-complete postal questionnaire and, at six weeks, patients who had not received physiotherapy were offered it at this time. The primary outcome is the proportion of patients free of disability at 26 weeks, as determined by the modified DASH (Disabilities of the Arm, Shoulder and Hand) questionnaire.
We hypothesise (a) that advice to maintain usual activities while awaiting physiotherapy will be superior than advice to rest the arm; and (b) that fast-track physiotherapy will be superior to normal (waiting list) physiotherapy. These hypotheses will be examined using an intention-to-treat analysis.
Results from this trial will contribute to the evidence base underpinning the clinical management of patients with distal upper limb pain, and in particular, will provide guidance on whether they should be advised to rest the arm or remain active within the limits imposed by their symptoms.
Trial registration
Registered on (reference number: ISRCTN79085082).
PMCID: PMC3975277  PMID: 24612447
Randomised controlled trial; Arm pain; Physiotherapy; Advice; Rest; Active; Pain management
Rheumatology (Oxford, England)  2011;51(2):305-310.
To explore the relationship between occupational exposures and lateral and medial epicondylitis and the effect of epicondylitis on sickness absence in a population sample of working aged adults.
This was a cross-sectional study of 9696 randomly selected adults aged 25-64 years involving a screening questionnaire and standardised physical examination. Age- and sex-specific prevalence rates of epicondylitis were estimated and associations with occupational risk factors explored.
Among 6038 respondents, 636 (11%) reported elbow pain in the last week. 0.7% of those surveyed were diagnosed with lateral epicondylitis and 0.6% with medial epicondylitis. Lateral epicondylitis was associated with manual work (OR 4.0, 95% CI 1.9-8.4). In multivariate analyses, repetitive bending/straightening elbow > 1 hour day was independently associated with lateral (OR 2.5, 95% CI 1.2-5.5) and medial epicondylitis (OR 5.1, 95% CI 1.8-14.3). 5% of adults with epicondylitis took sickness absence because of their elbow symptoms in the past 12 months (median 29 days).
Repetitive exposure to bending/straightening the elbow was a significant risk factor for medial and lateral epicondylitis. Epicondylitis is associated with prolonged sickness absence in 5% of affected working-aged adults.
PMCID: PMC3427015  PMID: 22019808
lateral epicondylitis; medial epicondylitis; epidemiology; occupation; sickness absence
4.  A young man with oligoarthritis: what is his cardiovascular risk? 
Gout is the commonest cause of inflammatory arthritis among young men. A case of acute gout in a 39-year-old man is described. As part of his assessment, his cardiovascular risk factors were evaluated. He was found to have elevated body mass index, central obesity, hypertension, a family history of cardiovascular disease, and hypercholesterolemia. This case highlights the association between gout, hyperuricaemia and elevated cardiovascular risk. In young male patients, acute presentation with gout in primary care may provide the first opportunity for assessment of cardiovascular risk factors and primary prevention of ischaemic heart disease.
PMCID: PMC2991745  PMID: 21144202
general practice; gout; hyperuricaemia; risk factors, cardiovascular
5.  Clinical and Microbiological Determinants of Outcome in Staphylococcus aureus Bacteraemia 
Staphylococcus aureus bacteraemia (SAB) is commonly complicated by metastatic infection or relapse after treatment. Objectives. The study aim was to determine the role of bacterial, host, and management factors in development of complicated SAB. Methods. A prospectively-conducted observational study gathered data on predisposition, management and outcome of 100 consecutive SAB cases. Antibiotic susceptibilities and genetic lineage of bacterial isolates were determined. Further clinical and microbiological data were gathered on two retrospective series from 1999–2000 (n = 57) and 2004 (n = 116). Results. In the prospective cases, 27% met our definition of complicated disease. Expressed as RR and 95% CI, complicated disease was associated with diabetes (1.58, 1.00–2.48), injecting-drug use (5.48, 0.88–33.49), community-onset of symptoms (1.4, 1.02–1.92), and symptom duration ≥48 hours prior to starting effective antibiotic therapy (2.10, 1.22–3.61). Uncomplicated disease was associated with the presence of a central line (0.69, 0.55–0.88) and prompt removal of a primary focus (0.71, 0.57–0.90). Neither methicillin resistance nor genetic lineage was associated with complicated disease, but methicillin resistance was associated with higher mortality. Conclusions. This study demonstrates that clinical rather than microbial factors are the major determinants of SAB outcome and underscores the importance of early treatment.
PMCID: PMC2840372  PMID: 20300477
6.  Rheumatoid arthritis 
BMJ Clinical Evidence  2007;2007:1124.
Rheumatoid arthritis usually starts as a symmetrical polyarthritis, and its course is marked by flares and remissions. The aims of treatment are to relieve pain and swelling, and to improve function. In addition, disease-modifying antirheumatic drugs (DMARDs) may reduce disease progression.
Methods and outcomes
We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of drug treatments in people with rheumatoid arthritis who have not previously received any disease-modifying antirheumatic drug treatment? How do different drug treatments compare in people with rheumatoid arthritis who have either not responded to or are intolerant of first-line disease-modifying antirheumatic drugs? We searched: Medline, Embase, The Cochrane Library and other important databases up to June 2005 (BMJ Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
We found 62 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
In this systematic review we present information relating to the effectiveness and safety of the following interventions: adalimumab, anakinra, antimalarial drugs, azathioprine, ciclosporin, corticosteroids, cyclophosphamide, etanercept, infliximab plus methotrexate, leflunomide, methotrexate (alone; or plus sulfasalazine plus hydroxychloroquine), oral gold, parenteral gold, penicillamine, sulfasalazine.
Key Points
Rheumatoid arthritis is a chronic inflammatory disorder that mainly affects the peripheral joints and surrounding tissue. It usually starts as a symmetrical polyarthritis, and its course is marked by flares and remissions.The aims of treatment are to relieve pain and swelling, and to improve function. In addition, disease-modifying antirheumatic drugs (DMARDs) may reduce disease progression.
The DMARD methotrexate is widely used as first-line treatment in people with rheumatoid arthritis because of consensus about its effectiveness in practice. Sulfasalazine and combined treatment with methotrexate and sulfasalazine are as effective as methotrexate in improving pain, joint swelling, and function in people with early rheumatoid arthritis who have not previously received DMARDs. Antimalarials may improve symptoms and function in DMARD-naïve people, and are reasonably well tolerated, but radiological evidence of erosion is more marked with antimalarials than with sulfasalazine.
There is a variety of DMARDs available for second-line treatment of rheumatoid arthritis, and we found no clear evidence that one is superior. Methotrexate, sulfasalazine, penicillamine , and leflunomide cause similar improvements in symptoms and function when given to people as second-line DMARD treatment, although methotrexate causes fewer adverse effects.The combination of methotrexate plus sulfasalazine plus hydroxychloroquine is more effective in reducing measures of disease activity in people receiving second-line treatment than any of the drugs used alone. Adding the cytokine inhibitors infliximab or etanercept to methotrexate is more effective than using methotrexate alone.Although antimalarials and oral gold seem to improve clinical disease activity when given as second-line treatment, they are not as effective as methotrexate or sulfasalazine. Although parenteral gold is more effective than oral gold, it leads to higher levels of toxicity than most of the other commonly used DMARDs. Ciclosporin offers short-term control of rheumatoid arthritis when used as second-line treatment, but is associated with nephrotoxicity.We don′t know whether cyclophosphamide is as effective as other DMARDs for second-line treatment.Cytokine inhibitors may offer an alternative to traditional DMARDs for second line treatment of rheumatoid arthritis, but more research is needed. Etanercept may be as effective as methotrexate in improving symptoms, function, and radiological evidence of progression, but more evidence for its effect is needed Azathioprine is less effective and is less well tolerated than methotrexate.We don't know whether anakinra or adalimumab are as effective as other DMARDs for second-line treatment.Although widely used for the initial short-term relief of clinical disease activity in rheumatoid arthritis, we don't know how corticosteroids compare with other drugs for first or second-line treatment.
PMCID: PMC2943775  PMID: 19454108

Results 1-8 (8)