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SummaryThe trial compared three physiotherapy approaches: manual or exercise therapy compared with a single session of physiotherapy education (SSPT) for people with osteoporotic vertebral fracture(s). At 1 year, there were no statistically significant differences between the groups meaning there is inadequate evidence to support manual or exercise therapy.IntroductionTo evaluate the clinical and cost-effectiveness of different physiotherapy approaches for people with osteoporotic vertebral fracture(s) (OVF).Methods>Prospective, multicentre, adaptive, three-arm randomised controlled trial. Six hundred fifteen adults with back pain, osteoporosis, and at least 1 OVF participated. Interventions: 7 individual physiotherapy sessions over 12 weeks focused on either manual therapy or home exercise compared with a single session of physiotherapy education (SSPT). The co-primary outcomes were quality of life and back muscle endurance measured by the QUALEFFO-41 and timed loaded standing (TLS) test at 12 months.ResultsAt 12 months, there were no statistically significant differences between groups. Mean QUALEFFO-41: − 1.3 (exercise), − 0.15 (manual), and − 1.2 (SSPT), a mean difference of − 0.2 (95% CI, − 3.2 to 1.6) for exercise and 1.3 (95% CI, − 1.8 to 2.9) for manual therapy. Mean TLS: 9.8 s (exercise), 13.6 s (manual), and 4.2 s (SSPT), a mean increase of 5.8 s (95% CI, − 4.8 to 20.5) for exercise and 9.7 s (95% CI, 0.1 to 24.9) for manual therapy. Exercise provided more quality-adjusted life years than SSPT but was more expensive. At 4 months, significant changes above SSPT occurred in endurance and balance in manual therapy, and in endurance for those ≤ 70 years, in balance, mobility, and walking in exercise.ConclusionsAdherence was problematic. Benefits at 4 months did not persist and at 12 months, we found no significant differences between treatments. There is inadequate evidence a short physiotherapy intervention of either manual therapy or home exercise provides long-term benefits, but arguably short-term benefits are valuable.Trial registrationISRCTN 49117867.

Background Stage I non-small cell lung cancer (NSCLC) is potentially curable, and surgery is considered to be the standard of care for patients with good performance status and minimal co-morbidity. However, a significant proportion of patients with stage I NSCLC have a poorer performance status and significant medical co-morbidity that make them at higher risk of morbidity and mortality from surgery. Stereotactic ablative radiotherapy (SABR), which uses modern radiotherapeutic techniques to deliver large doses of radiation, has shown superiority over conventional radiotherapy in terms of local control and toxicity and is a standard of care for patients with stage I NSCLC who are at too high risk for surgery. However, it is not known whether surgery or SABR is the most effective in patients with stage I NSCLC who are suitable for surgery but are less fit and at higher risk surgical complications. Previous randomised studies have failed to recruit in this setting, and therefore, a feasibility study is required to see whether a full randomised control trial would be possible. Methods/design SABRTooth is a UK-based, multi-centre, open-label, two-group individually (1:1) randomised controlled feasibility study in patients with peripheral stage I NSCLC considered to be at higher risk from surgical resection. The study will assess the feasibility of conducting a definitive large-scale phase III trial. The primary objective is to assess recruitment rates to provide evidence that, when scaled up, recruitment to a large phase III trial would be possible; the target recruitment being 54 patients in total, over a 21-month period. There are multiple secondary and exploratory objectives designed to explore the optimum recruitment and data collection strategies to help optimise the design of a future phase III trial. Discussion To know whether SABR is a better, equivalent or inferior alternative to surgery for higher risk patients is a key question in lung cancer. Other studies comparing SABR to surgery have closed early due to poor recruitment, and therefore, the SABRTooth feasibility study has been designed around the UK National Health Service (NHS) cancer pathway incorporating many design features in order to maximise recruitment for a future definitive phase III trial. Trial registration controlled-trials.com ISRCTN13029788

After publication of the original article [1], it came to the authors' attention that a source of funding had been inadvertently omitted from the Acknowledgements section; support from Yorkshire Cancer Research should have mentioned originally.

Seasonal variations in anaerobic respiration pathways were investigated at three saltmarsh sites using chemical data, sulfate reduction rate measurements, enumerations of culturable populations of anaerobic iron-reducing bacteria (FeRB), and quantification of in situ 16S rRNA hybridization signals targeted for sulfate-reducing bacteria (SRB). Bacterial sulfate reduction in the sediments followed seasonal changes in temperature and primary production of the saltmarsh, with activity levels lowest in winter and highest in summer. In contrast, a dramatic decrease in the FeRB population size was observed during summer at all sites. The collapse of FeRB populations during summer was ascribed to high rates of sulfide production by SRB, resulting in abiotic reduction of bioavailable Fe(III) (hydr)oxides. To test this hypothesis, sediment slurry incubations at 10, 20 and 30 °C were carried out. Increases in temperature and labile organic carbon availability (acetate or lactate additions) increased rates of sulfate reduction while decreasing the abundance of culturable anaerobic FeRB. These trends were not reversed by the addition of amorphous Fe(III) (hydr)oxides to the slurries. However, when sulfate reduction was inhibited by molybdate, no decline in FeRB growth was observed with increasing temperature. Addition of dissolved sulfide adversely impacted propagation of FeRB whether molybdate was added or not. Both field and laboratory data therefore support a sulfide-mediated limitation of microbial iron respiration by SRB. When total sediment respiration rates reach their highest levels during summer, SRB force a decline in the FeRB populations. As sulfate reduction activity slows down after the summer, the FeRB are able to recover.

Recommendations for the management of low back pain in primary care emphasise the importance of recognising and addressing psychosocial factors at an early stage. We compared the effectiveness of a brief pain-management programme with physiotherapy incorporating manual therapy for the reduction of disability at 12 months in patients consulting primary care with subacute low back pain. For this pragmatic, multicentre, randomised clinical trial, eligible participants consulted primary care with non-specific low back pain of less than 12 weeks' duration. They were randomly assigned either a programme of pain management (n=201) or manual therapy (n=201). The primary outcome was change in the score on the Roland and Morris disability questionnaire at 12 months. Analysis was by intention to treat. Of 544 patients assessed for eligibility, 402 were recruited (mean age 40·6 years) and 329 (82%) reached 12-month follow-up. Mean disability scores were 13·8 (SD 4·8) for the pain-management group and 13·3 (4·9) for the manual-therapy group. The mean decreases in disability scores were 8·8 (6·4) and 8·8 (6·1) at 12 months (difference 0 [95% CI −1·3 to 1·4], p=0·99), and median numbers of physiotherapy visits per patient were three (IQR one to five) and four (two to five), respectively (p=0·001). One adverse reaction (an exacerbation of pain after the initial assessment) was recorded. Brief pain management techniques delivered by appropriately trained clinicians offer an alternative to physiotherapy incorporating manual therapy and could provide a more efficient first-line approach for management of non-specific subacute low back pain in primary care.

Background: The 1997 BTS/RCP national audit of acute chronic obstructive pulmonary disease (COPD) in terms of process of care has previously been reported. This paper describes from the same cases the outcomes of death, readmission rates within 3 months of initial admission, and length of stay. Identification of the main pre-admission predictors of outcome may be used to control for confounding factors in population characteristics when comparing performance between units. Methods: Data on 74 variables were collected retrospectively using an audit proforma from patients admitted to UK hospitals with acute COPD. Important prognostic variables for the three outcome measures were identified by relative risk and logistic regression was used to place these in order of predictive value. Results: 1400 admissions from 38 acute hospitals were collated. 14% of cases died within 3 months of admission with variation between hospitals of 0–50%. Poor performance status, acidosis, and the presence of leg oedema were the best significant independent predictors of death. Age above 65, poor performance status, and lowest forced expiratory volume in 1 second (FEV1) tertile were the best predictors of length of stay (median 8 days). 34% of patients were readmitted (range 5–65%); lowest FEV1 tertile, previous admission, and readmission with five or more medications were the best predictors for readmission. Conclusions: Important predictors of outcome have been identified and formal recording of these may assist in accounting for confounding patient characteristics when making comparisons between hospitals. There is still wide variation in outcome between hospitals that remains unexplained by these factors. While some of this variance may be explained by incomplete recording of data or patient factors as yet unidentified, it seems likely that deficiencies in the process of care previously identified are responsible for poor outcomes in some units.

Poor design of elements in a healthcare system produce the latent conditions which result in patient safety incidents. A better understanding of these elements and specific healthcare design challenges will result in improved patient safety.

Patients who received 3 doses of pembrolizumab before surgery and 15 doses after surgery had significantly longer event-free survival than those who received adjuvant-only therapy with 18 doses after surgery.

Background Metastatic uveal melanoma (mUM) has a poor prognosis, with liver metastases typically presenting a therapeutic challenge. Melphalan/Hepatic Delivery System (Melphalan/HDS) is a drug/medical device combination used for liver-directed treatment of unresectable mUM patients. This study assessed efficacy and safety of Melphalan/HDS versus best alternative care (BAC). Methods Eligible patients with unresectable mUM were randomized (1:1) to receive Melphalan/HDS (3 mg/kg ideal body weight) once every 6 to 8 weeks for a maximum of 6 cycles or BAC. Due to slow enrollment and patient reluctance to receive BAC treatment, the study design was amended to a single-arm Melphalan/HDS study, and all efficacy analyses of the randomized study were treated as exploratory. Results The study enrolled 85 patients. Eligible patients were randomized to receive Melphalan/HDS ( n = 43) or BAC ( n = 42), and 72 patients received study treatment (Melphalan/HDS [ n = 40]; BAC [ n = 32]). Exploratory analyses of efficacy endpoints showed numerical differences consistently favoring the Melphalan/HDS arm versus BAC (median overall survival: 18.5 vs. 14.5 months; median progression-free survival: 9.1 vs. 3.3 months; objective response rate: 27.5% vs. 9.4%; and disease control rate: 80.0% vs. 46.9%). Serious adverse events (SAEs) occurred in 51.2% of Melphalan/HDS and in 21.9% of BAC patients. The most common (>5%) SAEs included thrombocytopenia (19.5%), neutropenia (9.8%), leukopenia (9.8%) and febrile neutropenia (7.3%) in Melphalan/HDS patients and cholecystitis, nausea and vomiting (6.3% each) in BAC patients. No treatment-related deaths were observed. Conclusion Treatment with Melphalan/HDS shows clinically meaningful efficacy and demonstrates a favorable benefit-risk profile in patients with unresectable mUM as compared to BAC.