Assessing the quality of water quality assessments: An analytical quality control protocol for benthic diatoms

In this paper, the background to the development of an analytical quality control procedure for the Trophic Diatom Index (TDI) is explained, highlighting some of the statistical and taxonomic problems encountered, and going on to demonstrate how the system works in practice. Most diatom-based pollution indices, including the TDI, use changes in the relative proportions of different taxa to indicate changing environmental conditions. The techniques involved are therefore much simpler than those involved in many studies of phytoplankton, for example, where absolute numbers are required

Matching the outcomes to treatment targets of exercise for low back pain: does it make a difference? Results of secondary analyses from individual patient data of randomised controlled trials and pooling of results across trials in comparative meta-analyses.

OBJECTIVE: To explore whether using a single matched or composite outcome might impact the results of previous randomised controlled trials (RCTs) testing exercise for non-specific low back pain (NSLBP). The first objective was to explore whether a single matched outcome generated a greater standardised mean differences (SMD) when compared to the original unmatched primary outcome SMD. The second objective was to explore whether a composite measure, comprised of matched outcomes, generated a greater SMD when compared to the original primary outcome SMD. DESIGN: We conducted exploratory secondary analyses of data. SETTING: Seven RCTs were included, of which two were based in the USA (University research clinic, Veterans Affairs medical centre) and the UK (primary care clinics, nonmedical centres). One each were based in Norway (clinics), Brazil (primary care), and Japan (outpatient clinics). PARTICIPANTS: The first analysis comprised 1) five RCTs (n=1,033) that used an unmatched primary outcome but included (some) matched outcomes as secondary outcomes, and the second analysis comprised 2) four RCTs (n=864) that included multiple matched outcomes by developing composite outcomes. INTERVENTION: Exercise compared to no exercise. MAIN OUTCOME MEASURES: The composite consisted of standardised averaged matched outcomes. All analyses replicated the RCTs' primary outcome analyses. RESULTS: Of five RCTs, three had greater SMDs with matched outcomes (pooled effect SMD 0.30 (95% CI 0.04, 0.56), p=0.02) compared to an unmatched primary outcome (pooled effect SMD 0.19 (95% CI -0.03, 0.40) p=0.09). Of four composite outcome analyses, three RCTs had greater SMDs in the composite outcome (pooled effect SMD 0.28 (95%CI 0.05, 0.51) p=0.02) compared to the primary outcome (pooled effect SMD 0.24 (95%CI -0.04, 0.53) p=0.10). CONCLUSIONS: These exploratory analyses suggest that using an outcome matched to exercise treatment targets in NSLBP RCTs may produce greater SMDs than an unmatched primary outcome. Composite outcomes could offer a meaningful way of investigating superiority of exercise than single domain outcomes

Models used for case-mix adjustment of patient reported outcome measures (PROMs) in musculoskeletal healthcare: A systematic review of the literature.

BACKGROUND: Case-mix adjustment is an established method to take account of variations across cohorts in baseline patient factors, when comparing health outcomes. Although commonplace, there is a lack of evidence as to the most appropriate case-mix adjustment model to use to enable fair comparisons of PROM data in musculoskeletal services. OBJECTIVES: To conduct a systematic review summarising evidence of the development, validation, and performance of musculoskeletal case-mix adjustment models, and to make recommendations for future methods. DATA SOURCES: Searches included; AMED, CINAHL, EMBASE, HMIC, MEDLINE, and grey literature. ELIGIBILITY CRITERIA: Studies; from January 1992-May 2017, English language, musculoskeletal adult population, developing or validating a case-mix adjustment model, using a relevant PROM, and using patient factors feasible for clinical collection. DATA SYNTHESIS: Two reviewers evaluated selected papers. The CASP Cohort Tool was used to assess quality. RESULTS: Fourteen studies were included; eight US studies on the Focus on Therapeutic Outcomes model (pooled n=546,726 patients (with pre/post treatment data)) and six UK studies related to the UK National PROMs Programme model (pooled n=282,424 patients (with pre/post treatment data)). The majority used retrospective data, restricted to complete datasets. Both US and UK models showed good predictive ability (R2 18-42%). Common model variables were; baseline PROM score, age, sex, comorbidities, symptom duration, and surgical history. Reduced quality scores were mainly due to acceptability of patient recruitment, and completeness and length of patient follow up. CONCLUSION: Significant methodological crossover was found. Further studies are however needed to externally validate and develop models across musculoskeletal settings

Origin of the thiopyrone CTP-431 “unexpectedly” isolated from the marine sponge Cacospongia mycofijiensis

An intriguing hypothesis that latrunculin A, a well-known natural product, might have undergone transformation into the unprecedented thiopyrone CTP-431 upon long-term storage in methanol is advanced. Thus opening of the hemiacetal of latrunculin A, followed by E1CB elimination, and dehydration would give a polyene that could undergo intramolecular Diels-Alder reaction, followed by methanolysis of the thiazolidinone ring and ring closure by intramolecular thiol addition to an enone. Experimental evidence that the novel thiazolidinone to thiopyrone rearrangement can occur is presented.The marine sponge Cacospongia mycofijiensis, found in the ocean surrounding Fiji, is a source of several polyketide natural products with interesting biological properties,1 including the tubulin binding macrolide fijianolide B (also known as laulimalide),2,3 the HIF1 signal inhibitor mycothiazole,4,5 and the macrolide latrunculins (Figure 1).6 The thiazolidinone-containing latruculins are of mixed polyketide synthesis (PKS) and non-ribosomal peptide synthesis (NRPS) origin, and latrunculin A 1 disrupts microfilament assembly to such an extent that it is the most widely used chemical tool to study actin binding

Assessing the quality of water quality assessments: an analytical quality control protocol for benthic diatoms

Analytical Quality Control (AQC) is becoming increasingly recognised as anessential guarantee of the quality of environmental data. Techniques forassessing the quality of chemical data and some biological data (such aschlorophyll concentration) are well developed and, conceptually, quitestraightforward. Depending upon the system, either a proportion of thesamples are subjected to independent analysis, or samples with knownconcentrations of a determinand are inserted into routine analytical runs.Matching the "observed" and "expected" values is then a relativelystraightforward statistical exercise

Arthroplasties for hip fracture in adults: Review

Background Hip fractures are a major healthcare problem, presenting a huge challenge and burden to individuals and healthcare systems. The number of hip fractures globally is rising rapidly. The majority of hip fractures are treated surgically. This review evaluates evidence for types of arthroplasty: hemiarthroplasties (HAs), which replace part of the hip joint; and total hip arthroplasties (THAs), which replace all of it. Objectives To determine the effects of different designs, articulations, and fixation techniques of arthroplasties for treating hip fractures in adults. Search methods We searched CENTRAL, MEDLINE, Embase, seven other databases and one trials register in July 2020. Selection criteria We included randomised controlled trials (RCTs) and quasi‐RCTs comparing different arthroplasties for treating fragility intracapsular hip fractures in older adults. We included THAs and HAs inserted with or without cement, and comparisons between different articulations, sizes, and types of prostheses. We excluded studies of people with specific pathologies other than osteoporosis and with hip fractures resulting from high‐energy trauma. Data collection and analysis We used standard methodological procedures expected by Cochrane. We collected data for seven outcomes: activities of daily living, functional status, health‐related quality of life, mobility (all early: within four months of surgery), early mortality and at 12 months after surgery, delirium, and unplanned return to theatre at the end of follow‐up. Main results We included 58 studies (50 RCTs, 8 quasi‐RCTs) with 10,654 participants with 10,662 fractures. All studies reported intracapsular fractures, except one study of extracapsular fractures. The mean age of participants in the studies ranged from 63 years to 87 years, and 71% were women. We report here the findings of three comparisons that represent the most substantial body of evidence in the review. Other comparisons were also reported, but with many fewer participants. All studies had unclear risks of bias in at least one domain and were at high risk of detection bias. We downgraded the certainty of many outcomes for imprecision, and for risks of bias where sensitivity analysis indicated that bias sometimes influenced the size or direction of the effect estimate. HA: cemented versus uncemented (17 studies, 3644 participants) There was moderate‐certainty evidence of a benefit with cemented HA consistent with clinically small to large differences in health‐related quality of life (HRQoL) (standardised mean difference (SMD) 0.20, 95% CI 0.07 to 0.34; 3 studies, 1122 participants), and reduction in the risk of mortality at 12 months (RR 0.86, 95% CI 0.78 to 0.96; 15 studies, 3727 participants). We found moderate‐certainty evidence of little or no difference in performance of activities of daily living (ADL) (SMD ‐0.03, 95% CI ‐0.21 to 0.16; 4 studies, 1275 participants), and independent mobility (RR 1.04, 95% CI 0.95 to 1.14; 3 studies, 980 participants). We found low‐certainty evidence of little or no difference in delirium (RR 1.06, 95% CI 0.55 to 2.06; 2 studies, 800 participants), early mortality (RR 0.95, 95% CI 0.80 to 1.13; 12 studies, 3136 participants) or unplanned return to theatre (RR 0.70, 95% CI 0.45 to 1.10; 6 studies, 2336 participants). For functional status, there was very low‐certainty evidence showing no clinically important differences. The risks of most adverse events were similar. However, cemented HAs led to less periprosthetic fractures intraoperatively (RR 0.20, 95% CI 0.08 to 0.46; 7 studies, 1669 participants) and postoperatively (RR 0.29, 95% CI 0.14 to 0.57; 6 studies, 2819 participants), but had a higher risk of pulmonary embolus (RR 3.56, 95% CI 1.26 to 10.11, 6 studies, 2499 participants). Bipolar HA versus unipolar HA (13 studies, 1499 participants) We found low‐certainty evidence of little or no difference between bipolar and unipolar HAs in early mortality (RR 0.94, 95% CI 0.54 to 1.64; 4 studies, 573 participants) and 12‐month mortality (RR 1.17, 95% CI 0.89 to 1.53; 8 studies, 839 participants). We are unsure of the effect for delirium, HRQoL, and unplanned return to theatre, which all indicated little or no difference between articulation, because the certainty of the evidence was very low. No studies reported on early ADL, functional status and mobility. The overall risk of adverse events was similar. The absolute risk of dislocation was low (approximately 1.6%) and there was no evidence of any difference between treatments. THA versus HA (17 studies, 3232 participants) The difference in the risk of mortality at 12 months was consistent with clinically relevant benefits and harms (RR 1.00, 95% CI 0.83 to 1.22; 11 studies, 2667 participants; moderate‐certainty evidence). There was no evidence of a difference in unplanned return to theatre, but this effect estimate includes clinically relevant benefits of THA (RR 0.63, 95% CI 0.37 to 1.07, favours THA; 10 studies, 2594 participants; low‐certainty evidence). We found low‐certainty evidence of little or no difference between THA and HA in delirium (RR 1.41, 95% CI 0.60 to 3.33; 2 studies, 357 participants), and mobility (MD ‐0.40, 95% CI ‐0.96 to 0.16, favours THA; 1 study, 83 participants). We are unsure of the effect for early functional status, ADL, HRQoL, and mortality, which indicated little or no difference between interventions, because the certainty of the evidence was very low. The overall risks of adverse events were similar. There was an increased risk of dislocation with THA (RR 1.96, 95% CI 1.17 to 3.27; 12 studies, 2719 participants) and no evidence of a difference in deep infection. Authors' conclusions For people undergoing HA for intracapsular hip fracture, it is likely that a cemented prosthesis will yield an improved global outcome, particularly in terms of HRQoL and mortality. There is no evidence to suggest a bipolar HA is superior to a unipolar prosthesis. Any benefit of THA compared with hemiarthroplasty is likely to be small and not clinically appreciable. We encourage researchers to focus on alternative implants in current clinical practice, such as dual‐mobility bearings, for which there is limited available evidence

Variance components linkage analysis for adjusted systolic blood pressure in the Framingham Heart Study

We performed variance components linkage analysis in nuclear families from the Framingham Heart Study on nine phenotypes derived from systolic blood pressure (SBP). The phenotypes were the maximum and mean SBP, and SBP at age 40, each analyzed either uncorrected, or corrected using two subsets of epidemiological/clinical factors. Evidence for linkage to chromosome 8p was detected with all phenotypes except the uncorrected maximum SBP, suggesting this region harbors a gene contributing to variation in SBP

A randomised, controlled study of outcome and cost effectiveness for RA patients attending nurse-led rheumatology clinics: Study protocol of an ongoing nationwide multi-centre study

Background: The rise in the number of patients with arthritis coupled with understaffing of medical services has seen the deployment of Clinical Nurse Specialists in running nurse-led clinics alongside the rheumatologist clinics. There are no systematic reviews of nurse-led care effectiveness in rheumatoid arthritis. Few published RCTs exist and they have shown positive results for nurse-led care but they have several limitations and there has been no economic assessment of rheumatology nurse-led care in the UK. Objective: This paper outlines the study protocol and methodology currently being used to evaluate the outcomes and cost effectiveness for patients attending rheumatology nurse-led clinics. Design and methods: A multi-centred, pragmatic randomised controlled trial with a non-inferiority design; the null hypothesis being that of 'inferiority' of nurse-led clinics compared to physician-led clinics. The primary outcome is rheumatoid arthritis disease activity (measured by DAS28 score) and secondary outcomes are quality of life, self-efficacy, disability, psychological well-being, satisfaction, pain, fatigue and stiffness. Cost effectiveness will be measured using the EQ-5D, DAS28 and cost profile for each centre. Power calculations: In this trial, a DAS28 change of 0.6 is considered to be the threshold for clinical distinction of 'inferiority'. A sample size of 180 participants (90 per treatment arm) is needed to reject the null hypothesis of 'inferiority', given 90% power. Primary analysis will focus on 2-sided 95% confidence interval evaluation of between-group differences in DAS28 change scores averaged over 4 equidistant follow up time points (13, 26, 39 and 52 weeks). Cost effectiveness will be evaluated assessing the joint parameterisation of costs and effects. Results: The study started in July 2007 and the results are expected after July 2011. Trial registration: The International Standard Randomised Controlled Trial Number ISRCTN29803766. © 2011 Elsevier Ltd