https://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736(05)71142-9.pdf

Acquired mutation of the tyrosine kinase JAK2 in human myeloproliferative disorders.

Staphylococcus aureus is a major human pathogen that causes a wide range of clinical infections. It is a leading cause of bacteremia and infective endocarditis as well as osteoarticular, skin and soft tissue, pleuropulmonary, and device-related infections. This review comprehensively covers the epidemiology, pathophysiology, clinical manifestations, and management of each of these clinical entities. The past 2 decades have witnessed two clear shifts in the epidemiology of S. aureus infections: first, a growing number of health care-associated infections, particularly seen in infective endocarditis and prosthetic device infections, and second, an epidemic of community-associated skin and soft tissue infections driven by strains with certain virulence factors and resistance to β-lactam antibiotics. In reviewing the literature to support management strategies for these clinical manifestations, we also highlight the paucity of high-quality evidence for many key clinical questions.

Staphylococcus aureus Infections: Epidemiology, Pathophysiology, Clinical Manifestations, and Management

https://www.just.edu.jo/DIC/ClinicGuidlines/Management%20of%20hip%20and%20knee%20Osteoarthritis.pdf

OARSI recommendations for the management of hip and knee osteoarthritis, Part II: OARSI evidence-based, expert consensus guidelines

Analysis of cytokine mRNA and protein in rheumatoid arthritis tissue revealed that many proinflammatory cytokines such as TNF alpha, IL-1, IL-6, GM-CSF, and chemokines such as IL-8 are abundant in all patients regardless of therapy. This is compensated to some degree by the increased production of anti-inflammatory cytokines such as IL-10 and TGF beta and cytokine inhibitors such as IL-1ra and soluble TNF-R. However, this upregulation in homeostatic regulatory mechanisms is not sufficient as these are unable to neutralize all the TNF alpha and IL-1 produced. In rheumatoid joint cell cultures that spontaneously produce IL-1, TNF alpha was the major dominant regulator of IL-1. Subsequently, other proinflammatory cytokines were also inhibited if TNF alpha was neutralized, leading to the new concept that the proinflammatory cytokines were linked in a network with TNF alpha at its apex. This led to the hypothesis that TNF alpha was of major importance in rheumatoid arthritis and was a therapeutic target. This hypothesis has been successfully tested in animal models, of, for example, collagen-induced arthritis, and these studies have provided the rationale for clinical trials of anti-TNF alpha therapy in patients with long-standing rheumatoid arthritis. Several clinical trials using a chimeric anti-TNF alpha antibody have shown marked clinical benefit, verifying the hypothesis that TNF alpha is of major importance in rheumatoid arthritis. Retreatment studies have also shown benefit in repeated relapses, indicating that the disease remains TNF alpha dependent. Overall these studies demonstrate that analysis of cytokine expression and regulation may yield effective therapeutic targets in inflammatory disease.

Role of cytokines in rheumatoid arthritis

Recommendation 1: Clinicians should conduct a focused history and physical examination to help place patients with low back pain into 1 of 3 broad categories: nonspecific low back pain, back pain potentially associated with radiculopathy or spinal stenosis, or back pain potentially associated with another specific spinal cause. The history should include assessment of psychosocial risk factors, which predict risk for chronic disabling back pain (strong recommendation, moderate-quality evidence). Recommendation 2: Clinicians should not routinely obtain imaging or other diagnostic tests in patients with nonspecific low back pain (strong recommendation, moderate-quality evidence). Recommendation 3: Clinicians should perform diagnostic imaging and testing for patients with low back pain when severe or progressive neurologic deficits are present or when serious underlying conditions are suspected on the basis of history and physical examination (strong recommendation, moderate-quality evidence). Recommendation 4: Clinicians should evaluate patients with persistent low back pain and signs or symptoms of radiculopathy or spinal stenosis with magnetic resonance imaging (preferred) or computed tomography only if they are potential candidates for surgery or epidural steroid injection (for suspected radiculopathy) (strong recommendation, moderate-quality evidence). Recommendation 5: Clinicians should provide patients with evidence-based information on low back pain with regard to their expected course, advise patients to remain active, and provide information about effective self-care options (strong recommendation, moderate-quality evidence). Recommendation 6: For patients with low back pain, clinicians should consider the use of medications with proven benefits in conjunction with back care information and self-care. Clinicians should assess severity of baseline pain and functional deficits, potential benefits, risks, and relative lack of long-term efficacy and safety data before initiating therapy (strong recommendation, moderate-quality evidence). For most patients, first-line medication options are acetaminophen or nonsteroidal anti-inflammatory drugs. Recommendation 7: For patients who do not improve with selfcare options, clinicians should consider the addition of nonpharmacologic therapy with proven benefits—for acute low back pain, spinal manipulation; for chronic or subacute low back pain, intensive interdisciplinary rehabilitation, exercise therapy, acupuncture, massage therapy, spinal manipulation, yoga, cognitive-behavioral therapy, or progressive relaxation (weak recommendation, moderate-quality evidence).

/pdf/diagnosis-and-treatment-of-low-back-pain-a-joint-clinical-wx8jag77hu.pdf

Diagnosis and Treatment of Low Back Pain: A Joint Clinical Practice Guideline from the American College of Physicians and the American Pain Society

Objective: To examine the placebo effect and its potential determinants in the treatment of osteoarthritis (OA) via a systematic literature search of Medline, EMBASE, Scientific Citation Index, Cumulative Index to Nursing and Allied Health Literature (CINAHL) and Cochrane Library Methods: Randomised placebo controlled trials in OA were included The placebo effect was defined as the overall change from baseline in the placebo group It was estimated as the effect size (ES; the standard mean difference between baseline and endpoint) and this was compared with the ES obtained from untreated control ES for pain was the primary outcome Statistical pooling was undertaken as appropriate and 95% CIs were used for comparison Quality of trials was assessed and potential determinants of placebo effect were examined using multiple regression analysis The partial regression coefficient (β) was used to present the adjusted size of the association Results: We identified 198 trials with 193 placebo groups (16 364 patients) and 14 untreated control groups (1167 patients) that met our inclusion criteria These included a range of therapies (non-pharmacological, pharmacological and surgical treatments) Placebo was effective at relieving pain (ES 051, 95% CI 046 to 055 for the placebo group and 003, 95% CI –013 to 018 for untreated control) Placebo was also effective at improving function and stiffness The pain-relieving effect increased when the active treatment effect (β = 038, p Conclusion: Placebo is effective in the treatment of OA, especially for pain, stiffness and self-reported function The size of this effect is influenced by the strength of the active treatment, the baseline disease severity, the route of delivery and the sample size of the study

https://ard.bmj.com/content/annrheumdis/early/2008/06/09/ard.2008.092015.full.pdf

The placebo effect and its determinants in osteoarthritis – meta-analysis of randomised controlled trials

OBJECTIVES (1) To determine the importance of quadriceps strength, structural change, and psychological status in terms of knee pain in the community. (2) To determine the relative importance of quadriceps function, structural change, and psychological status with respect to disability in subjects with knee pain.

METHODS 300 men and women with pain and 300 controls without pain (aged 40–79) were seen. Isometric quadriceps strength (MVC) was measured and muscle activation was assessed by twitch superimposition. Disability (Western Ontario McMaster Osteoarthritis Index (WOMAC)) and anxiety and depression were assessed (Hospital Anxiety and Depression Index (HAD)). Radiographs were obtained of the tibiofemoral and patellofemoral joints and total score for osteophyte, narrowing, and sclerosis calculated for each knee.

RESULTS Subjects with knee pain had lower voluntary quadriceps strength than those without pain (p<0.005). Quadriceps activation was also lower (p<0.005), but did not fully explain the reduction in strength. When analysed by multiple logistic regression: quadriceps strength (odds ratio 18.8, CI 4.8, 74.1 for MVC ⩽10 kgF); depression (odds ratio 2.4, CI 1.0, 5.5 for HAD score⩾8); and radiographic change (odds ratio 4.1, CI 1.9, 8.6 for radiographic score ⩾4) were independently associated with pain. In those with knee pain, disability was independently associated with quadriceps strength (odds ratio 8.2, CI 1.5, 44.4 for MVC ⩽10 kgF) and depression (odds ratio 6.2, CI 2.1, 18.0 for HAD score⩾8); but not with radiographic score.

CONCLUSIONS Quadriceps strength is strongly associated with knee pain and disability in the community, even when activation and psychological factors are taken into account. This has important therapeutic implications.

https://ard.bmj.com/content/annrheumdis/57/10/588.full.pdf

Quadriceps weakness in knee osteoarthritis: the effect on pain and disability

https://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736(09)61595-6.pdf

Bacterial septic arthritis in adults.

Objectives To determine whether a home based
exercise programme can improve outcomes in
patients with knee pain.
Design Pragmatic, factorial randomised controlled
trial of two years' duration.
Setting Two general practices in Nottingham.
Participants 786 men and women aged >45 years
with self reported knee pain.
Interventions Participants were randomised to four
groups to receive exercise therapy, monthly telephone
contact, exercise therapy plus telephone contact, or no
intervention. Patients in the no intervention and
combined exercise and telephone groups were
randomised to receive or not receive a placebo health
food tablet.
Main outcome measures Primary outcome was self
reported score for knee pain on the Western Ontario
and McMaster universities (WOMAC) osteoarthritis
index at two years. Secondary outcomes included
knee specific physical function and stiffness (scored on
WOMAC index), general physical function (scored on
SF­36 questionnaire), psychological outlook (scored
on hospital anxiety and depression scale), and
isometric muscle strength.
Results 600 (76.3%) participants completed the study.
At 24 months, highly significant reductions in knee
pain were apparent for the pooled exercise groups
compared with the non­exercise groups (mean
difference –0.82, 95% confidence interval –1.3 to
–0.3). Similar improvements were observed at 6, 12,
and 18 months. Regular telephone contact alone did
not reduce pain. The reduction in pain was greater
the closer patients adhered to the exercise plan.
Conclusions A simple home based exercise
programme can significantly reduce knee pain. The
lack of improvement in patients who received only
telephone contact suggests that improvements are not
just due to psychosocial effects because of contact
with the therapist.

https://www.bmj.com/content/bmj/325/7367/752.full.pdf

Home based exercise programme for knee pain and knee osteoarthritis: randomised controlled trial.

AIMS To determine the clinical features of a large number of unselected UK hospital patients with confirmed septic arthritis and to determine those features associated with a poor outcome. STUDY DESIGN Retrospective, case-note survey. SETTING A single English Health District. PATIENTS All patients admitted to hospital in Nottingham during the period 1 January 1982 to 31 December 1991 with confirmed septic arthritis were included. OUTCOME MEASURES Death, osteomyelitis and recorded functional impairment. RESULTS The spectrum of causative organisms remains similar to that seen in previous studies with the Gram positive organisms Staphylococcus aureus and Streptococci responsible for 74% of cases, gonococcal infections though were less common. Culture of joint aspirates and or blood were positive in 82% of cases, with the Gram stain demonstrating the causative organism in 50% of cases. Pre-existing joint disease was evident in 35% of cases. The mortality remains high at 11.5% with a significant additional morbidity of 31.6%. Multivariate analysis suggests that important predictors of death are: confusion at presentation, age ⩾65 years, multiple joint sepsis or involvement of the elbow joint, and of morbidity are: age ⩾ 65 years, diabetes mellitus, open surgical drainage, and Gram positive infections other than S aureus. CONCLUSIONS Septic arthritis continues to be associated with a considerable degree of morbidity and mortality. These results confirm the importance of obtaining synovial fluid and blood for culture before starting antimicrobial treatment. The apparent poorer outcome found with surgical intervention is in line with some previous suggestions but should be interpreted with caution in light of the retrospective nature of this study.

https://ard.bmj.com/content/annrheumdis/58/4/214.full.pdf

Adrian Jones

Papers

The placebo effect and its determinants in osteoarthritis – meta-analysis of randomised controlled trials

Quadriceps weakness in knee osteoarthritis: the effect on pain and disability

Bacterial septic arthritis in adults.

Home based exercise programme for knee pain and knee osteoarthritis: randomised controlled trial.

Clinical features and outcome of septic arthritis in a single UK Health District 1982-1991