Does arthroscopic or open washout in native knee septic arthritis result in superior post-operative function? A systematic review and meta-analysis of randomised controlled trials and observational studies.

AIMS: Septic arthritis (SA) of the native knee joint is associated with significant morbidity. This review compared post-operative functional outcomes (patient-reported outcome measures (PROMs) and range of movement (ROM)) following arthroscopic washout (AW) and open washout (OW) amongst adult patients with SA of the native knee. The need for further operative intervention was also considered. METHODS: Electronic databases of PubMed, MEDLINE, Embase, Cochrane, Web of Science and Scopus were searched between 16 February 2023 and 18 March 2023. Randomised controlled trials (RCTs) and comparative observational analytic studies comparing function (reflected in PROMs or ROM) at latest follow-up following AW and OW were included. A narrative summary was provided concerning post-operative PROMs. Pooled estimates for mean ROM and re-operation rates were conducted using the random-effects model. The risk of bias was assessed using the Cochrane risk-of-bias assessment tool-2 for RCTs and the Risk of Bias in Non-Randomized Studies of Interventions tool for observational analytic studies. RESULTS: Of 2580 retrieved citations, 7 articles (1 RCT and 6 cohort studies) met the inclusion criteria. Of these, five had some concerns/moderate risk of bias, and two had serious risk. There was a slight tendency for superior mean PROMs following AW compared with OW, but due to small effect sizes, this was unlikely clinically relevant. Additionally, the use of four different PROMs scales made direct comparisons impossible. AW was associated with superior ROM (mean difference 20.18° (95% CI 14.35, 26.02; p < 0.00001)), whilst there was a tendency for lower re-operation requirements following AW (OR 0.64, 95% CI 0.26, 1.57, p = 0.44). CONCLUSIONS: AW was associated with equivalent to superior post-operative function and lower requirement for further intervention compared with OW. Results need to be interpreted cautiously, taking into consideration the methodological and clinical heterogeneity of the included studies. SYSTEMATIC REVIEW REGISTRATION: PROSPERO 2022, CRD42022364062.

Comparing pinning in situ and capital realignment procedures for severe, stable slipped capital femoral epiphysis: a systematic review.

In severe, stable slipped capital femoral epiphysis, it is unclear whether pinning in situ (PIS) or capital realignment procedures (CRPs) are superior. Our primary aim was to compare patient-reported outcome measures (PROMs) following each strategy. Secondary aims were to compare rates of femoral head avascular necrosis (AVN) and complications. MEDLINE, Embase and Cochrane databases were searched according to an agreed strategy. Narrative review articles, case reports, letters to the editor and articles not written in English were excluded. The risk of bias was assessed using the Newcastle-Ottawa Scale. Of the 132 citations identified, 127 were excluded following de-duplication and application of the exclusion criteria. Three observational studies comparing PIS with CRP and two case series considering CRP alone were identified. One article was considered fair quality, and four articles were considered poor. In total, 198 hips from five studies were included (66 PIS, 132 CRP). PIS was associated with moderate-good functional outcomes, and CRP with good-high outcomes. Two comparative studies reported significantly better PROMs following CRP. AVN was reported in 1.5% following PIS and 10.6% following CRP. Regarding other complications, chondrolysis occurred in 3.0% following PIS and 2.4% following CRP. Femoroacetabular impingement rates were markedly higher following PIS (60.6% versus 2.3%). Reoperation rates were also greater following PIS (34.5% versus 13.3%). PIS tends to be associated with favourable AVN rates, but CRP with favourable PROMs and complication rates. However, comparisons were drawn from heterogeneous studies lacking long-term follow-up. Further high-quality research is required.

Improving Identification of Cognitive Impairment in Fragility Fracture Patients: Impact of Educational Guidelines on Current Practice.

INTRODUCTION: Cognitive impairment can hinder a fracture patient's capacity to consent to surgery and negatively impact their postoperative recovery and rehabilitation. National guidelines recommend screening for cognitive impairment upon admission, and the Abbreviated Mental Test Score (AMTS) is a commonly used tool for this. This project aimed to assess current practice regarding documentation of AMTS among frail fracture patients upon admission and to improve AMTS documentation following a simple intervention. METHODS: Baseline data were obtained by inpatient chart review throughout November to December 2018 in a district general hospital with emergency fracture services. All patients admitted with a fragility hip fracture and patients over 65 years with any fracture were included. National guidelines and baseline results were then distributed among junior doctors. Following an intervention, further data were collected throughout January to February 2019. RESULTS: Preintervention, 40 suitable patients (mean age: 82 years) were identified; 9 (22.0%) of whom had an AMTS recorded upon admission. Among the hip fracture subgroup (n = 25), 7 (26.9%) had an AMTS recorded. Postintervention, 39 patients (mean age: 80 years) were identified; 15 (38.5%) of whom had an AMTS recorded. Among the hip fracture subgroup (n = 30), 11 (36.7%) had an AMTS recorded. Statistical analysis demonstrated a significant improvement in AMTS documentation both among the overall cohort (P = .001) and hip fracture patients (P = .019). No significant association was found between AMTS documentation and patient age (P = .566), grade of admitting doctor (P = .058), or prior cognitive/mental health disorder (P = .256). DISCUSSION: A small yet significant improvement in AMTS documentation among elderly/hip fracture patients was observed following distribution of educational material. Further work should explore the effect of cognitive impairment on outcomes related to orthopedic injuries beyond hip fractures.

Nutritional status, the development and persistence of malnutrition and dietary intake in oesophago-gastric cancer: a longitudinal cohort study.

BACKGROUND: Patients with oesophago-gastric (OG) cancer may be at risk of malnutrition, troublesome gastrointestinal symptoms (GI) and reduced dietary intake in view of the tumour location and multimodality curative treatment approach. Longitudinal research is lacking. The present study aimed to assess (i) nutritional status and how it evolved over the first year; (ii) the association between nutritional status scores and GI symptom scores; and (iii) the nutrient and food group intake pattern. METHODS: This was a prospective, observational study of patients with an OG lesion planned for radical treatment, with assessment at diagnosis, 3 months and 12 months after the start of treatment. Nutritional assessment was performed using the Patient-Generated Subjective Global Assessment, GI symptoms measured using the modified Gastrointestinal Symptom Rating Scale and dietary intake assessed using a semi-quantitative food frequency approach. RESULTS: Eighty patients (61 males, 19 females; aged 46-89 years) were recruited. At baseline, 3 (n = 68) and 12 months (n = 57), 61%, 62% and 60%, respectively, were moderately/severely malnourished. Higher symptom burden was associated with poorer nutritional status at baseline (r = 0.55, P < 0.001), 3 months (r = 0.51, P < 0.001) and 12 months (r = 0.42, P = 0.001). At each respective time point, 37%, 38% and 42% were meeting their estimated average requirement for energy. No change in mean (SD) intake of energy, fibre, nutrient and food groups was observed over time. CONCLUSIONS: Patients with OG cancer have progressive weight loss, with malnutrition present over the majority of the 12-month study period. Optimising nutritional status and symptom management throughout the treatment pathway should be a clinical priority.

Feedback-amplified electrochemical dual-plate boron-doped diamond microtrench detector for flow injection analysis.

An electrochemical flow cell with a boron-doped diamond dual-plate microtrench electrode has been developed and demonstrated for hydroquinone flow injection electroanalysis in phosphate buffer pH 7. Using the electrochemical generator-collector feedback detector improves the sensitivity by one order of magnitude (when compared to a single working electrode detector). The diffusion process is switched from an analyte consuming "external" process to an analyte regenerating "internal" process with benefits in selectivity and sensitivity.

Cavity transport effects in generator-collector electrochemical analysis of nitrobenzene.

Two types of generator-collector electrode systems, (i) a gold-gold interdigitated microband array and (ii) a gold-gold dual-plate microtrench, are compared for nitrobenzene electroanalysis in aerated aqueous 0.1 M NaOH. The complexity of the nitrobenzene reduction in conjunction with the presence of ambient levels of oxygen in the analysis solution provide a challenging problem in which feedback-amplified generator-collector steady state currents provide the analytical signal. In contrast to the more openly accessible geometry of the interdigitated array electrode, where the voltammetric response for nitrobenzene is less well-defined and signals drift, the voltammetric response for the cavity-like microtrench electrode is stable and readily detectable at 1 µM level. Both types of electrode show oxygen-enhanced low concentration collector current responses due to additional feedback via reaction intermediates. The observations are rationalised in terms of a "cavity transport coefficient" which is beneficial in the dual-plate microtrench, where oxygen interference effects are suppressed and the analytical signal is amplified and stabilised.

Generator-collector double electrode systems: a review.

A variety of generator-collector systems are reviewed, from the original rotating ring-disc electrodes developed in the 1950s, to very recent developments using new geometries and microelectrodes. An overview of both theoretical and experimental aspects are given, and the power of these double electrode systems in analytical electrochemistry is illustrated with a range of applications.

Relationship between neuronal loss and 'inflammatory plaques' in early onset Alzheimer's disease.

We have previously described a novel 'inflammatory plaque' in the cortex of early onset Alzheimer's disease (EOAD) cases with presenilin 1 mutations (PS1). These plaques are associated with a significant inflammatory infiltrate consisting of reactive microglia and astrocytes. We speculated that these inflammatory plaques might be responsible for the more severe disease process seen in EOAD. In the present study using the superior frontal cortex, 63 EOAD cases with mutations in PS1, presenilin 2 (PS2) and amyloid precursor protein (APP) were categorized as either having inflammatory plaques (13 cases, two APP and 11 PS1) or not. To determine the impact on cell loss, seven EOAD cases with inflammatory plaques (EOIP) and seven EOAD cases without (EONIP) were selected and neuronal cell counts performed. These were compared with neuronal counts taken from the same cortical region of seven control and six sporadic AD cases. Cases with EOAD had significantly less neurones per field compared with sporadic AD and control cases (EOAD = 19.5 +/- 0.8 neurones/field, spAD = 23.7 +/- 1.2 neurones/field, controls = 30.37 +/- 1.2 neurones/field). However, no significant difference in the number of neurones per field was seen in EOAD cases with or without inflammatory plaque pathology (EOIP = 19.2 +/- 1.4, EONIP = 19.7 +/- 0.8). These data demonstrate that EOAD cases exhibit greater neuronal cell loss in the superior frontal cortex than sporadic AD and that this effect is independent of the presence or absence of inflammatory plaque pathology.

Evaluating health-related quality of life outcomes in clinical trials of antiepileptic drug therapy.

PURPOSE: To provide an overview of condition-specific health-related quality of life (HRQL) assessment in clinical trials of antiepileptic drug (AED) therapy in adults. We describe the key measurement issues in HRQL evaluation, identify the instruments that have been used in this population, summarize the psychometric characteristics of these instruments, propose areas of HRQL most likely to change with treatment, and offer recommendations for further research. METHODS: We conducted a comprehensive review of the literature using repeated searches of the MEDLINE database together with a review of reference lists from published papers. Psychometric information on the instruments was gathered from published literature. RESULTS: Three epilepsy-specific HRQL measures were identified: the Epilepsy-Surgery Inventory (ESI-55), the Liverpool Assessment Battery, and the Quality of Life in Epilepsy Inventory (QOLIE, the 89-, 31-, and 10-item versions). One new measure, the Epilepsy Foundation of America (EFA) Concerns Index was also found. The psychometric characteristics of these instruments are discussed in relationship to performance or expected performance in a clinical trial setting. A review of descriptive studies and trials to date suggests that subscales reflecting the psychological and social domains of HRQL may be most sensitive to treatment designed to increase seizure-free periods, reduce seizure severity, and minimize undesirable side effects. CONCLUSIONS: Although evaluation of HRQL outcomes in clinical trials of epilepsy is still in its infancy, several reliable and valid condition-specific measures are available for understanding the impact of disease and treatment on HRQL. Further research is needed to determine minimal clinically important change scores and to assess the psychometric stability of measures across cultures and mode of administration (self, interview, telephone). Studies of patient preferences for health outcomes in the form of utilities will provide needed data for evaluating the cost-effectiveness of new treatments.

The pharmacokinetics of flurbiprofen in younger and elderly patients with rheumatoid arthritis.

The pharmacokinetics of flurbiprofen (Ansaid Tablets, Upjohn Company of Canada, Don Mills, Ontario) were evaluated in both younger (40 to 60 years) and elderly (65 to 83 years) rheumatoid arthritic patients after both a 100-mg single-dose administration and at steady state during a 100-mg twice-a-day dosage regimen. Both flurbiprofen plasma concentration-time profiles and the urinary excretion of flurbiprofen and its major metabolites were evaluated. The results indicate that the pharmacokinetics of flurbiprofen are linear in both age groups based on only minor changes between single-dose and steady-state parameter determinations and the agreement between calculated and predicted accumulation values in plasma concentrations. Only minor differences in the pharmacokinetic parameters were observed between the younger and elderly patients. Only free flurbiprofen clearance was found to have a significant but variable correlation to patient age. The effect of flurbiprofen on the urinary excretion of two prostaglandins were also evaluated throughout this study. In both age groups, the maximum decrease in urinary excretion was observed after the first dose, and this effect was maintained throughout the remainder of the study. Percent decreases from baseline in urinary excretion during drug administration were similar for both age groups. Similar side-effect profiles were observed between age groups.

50-foot walking time: a critical assessment of an outcome measure in clinical therapeutic trials of antirheumatic drugs.

Fifty-foot walking time was used in 51 of 187 clinical therapeutic trials of antirheumatic drugs and in only 21 instances was statistical significance reached. Measurement of the 50-foot walking time showed no better performance in long-term trials of SAARDs than in short-term trials of NSAIDs. It is concluded that the 50-foot walking time is a poor outcome measure in rheumatic disease trials, despite a high intra- and interobserver reproducibility.

Effects of aspirin, naloxone and placebo.

This study was designed to examine the effects of aspirin, naloxone and placebo treatment on serum beta-endorphin concentration and joint pain in patients with rheumatoid arthritis (RA). Ten patients with definite or classical RA were studied. All treatments were administered in a randomized sequence. On each study day, the following measurements were carried out at specified time intervals: serum beta-endorphin concentration, serum salicylate concentration and joint pain score on a visual analogue horizontal scale. We conclude that in patients with rheumatoid arthritis suffering from chronic joint pain, serum beta-endorphin does not appear to play a role in pain relief.

The pharmacokinetics of isoxicam in elderly patients with rheumatoid arthritis.

Nineteen patients, aged 60 years and over, with rheumatoid arthritis participated in a clinical trial to investigate the pharmacokinetics of isoxicam (a new non-steroidal anti-inflammatory drug) in this age group. The purpose of the study was to determine if the pharmacokinetics are different compared to a younger healthy population. The half-lives were independent of dosage, indicating linearity of pharmacokinetics. Furthermore, the half-lives after repeated dosing were not different from those found after single doses of 400 mg. This shows that there is neither undue accumulation of the drug nor induction of its own metabolism. These results are similar to the results obtained in other centres when isoxicam was administered to healthy subjects between 18 and 32 years.

Lowering of plasma isoxicam concentrations with acetylsalicylic acid.

The pharmacokinetics of isoxicam 200 mg administered orally in 10 healthy male volunteers was studied before and during administration of acetylsalicylic acid 3.9 g daily by mouth starting 5 days after isoxicam. There was a statistically significant decrease in plasma isoxicam concentrations, but no significant change in time to reach maximum plasma concentration or disappearance time. The mechanisms of this interaction is probably competitive displacement of isoxicam from albumin by acetylsalicylic acid or salicylate. These results are consistent with the known effect of ASA in producing competitive displacement of other protein bound antiinflammatory drugs.

Trimipramine in rheumatoid arthritis: a randomized double-blind trial in relieving pain and joint tenderness.

The effect of low-dose trimipramine (25 to 75 mg/day) on joint pain and tenderness in 36 patients with rheumatoid arthritis was studied in a randomized double-blind trial carried out over a period of 12 weeks. The patients were pre-selected to include only patients who were depressed on a 'self-rating depression scale' but had no evidence of fibrositic 'trigger-points'. The results showed that joint pain and tenderness were significantly reduced with trimipramine, but depression scores remained unchanged.

Pharmacokinetics of isoxicam in the elderly.

Several studies are under way to determine the pharmacokinetics of isoxicam in the elderly; this report presents preliminary results of these studies. Data have been collected from: eight healthy subjects older than 65 years old receiving single oral doses of 200 mg; eight patients with rheumatoid arthritis, 61 to 69 years old, receiving oral doses of 400 mg per day; and the same eight patients with arthritis receiving 100 mg per day (four patients), 200 mg per day (one patient), or 300 mg per day (three patients). The plasma levels of isoxicam were determined in the subjects for 96 hours following administration. The results indicate that the mean half-life of isoxicam is approximately 24 hours and is independent of dosage. The results were compared with those in 30 healthy subjects aged 18 to 32 years. The comparison showed that the half-life of isoxicam appears to be independent of dosage, duration of treatment, and age of subject. On the basis of these preliminary results, it appears that elderly patients are not at risk of excessive accumulation of isoxicam during treatment with therapeutic dosages.

Statistical reappraisal of the clinical significance of nail beading in rheumatoid arthritis.

Nail beading has previously been reported as an accompaniment of rheumatoid arthritis. In order to assess the clinical significance of this form of nychodystrophy the fingernails and toenails of 119 patients with rheumatoid arthritis and an equal number of control subjects were studied. Analysis of data based on 4642 nails indicates that the presence of a global pattern of beading (i.e. greater than or equal to 50% involvement of the nail area) on the surface of at least six fingernails or four toenails is highly suggestive of underlying rheumatoid disease. The positive predictive value of these configurations is in the order of 95%. Nail beading, however, is infrequent in early disease and therefore its diagnostic value is limited. Although there is a strong association between nail beading and rheumatoid arthritis, the aetiology and prognostic implications of this clinical sign remain obscure.