Association between femur size and a focal defect of the superior femoral neck.

Within each sex, there is an association between hip fracture risk and the size of the proximal femur, with larger femurs apparently more susceptible to fracture. Here, we investigate whether the thickness and density of the femoral cortex play a role in this association: might larger femurs harbour focal, cortical defects? To answer this question, we used cortical bone mapping to measure the distribution of cortical mass surface density (CMSD, mg/cm(2)) in cohorts of 308 males and 125 females. Principal component analysis of the various femoral surfaces led to a measure of size that is linearly independent from shape. After mapping the data onto a canonical femur surface, we used statistical parametric mapping to identify any regions where CMSD depends on size, allowing for other confounding covariates including shape. Our principal finding was a focal patch on the superior femoral neck, where CMSD is reduced by around 1% for each 1% increase in proximal-distal size (p<0.000005 in the males, p<0.001 in the females). This finding appears to be consistent with models of functional adaptation, and may help with the design of interventional strategies for reducing fracture risk.KESP acknowledges the support of the NIHR Biomedical Research Centre, Cambridge, and funding from Arthritis Research UK (reference 20109). The MrOS study is supported by National Institutes of Health (NIH) funding. The following institutes provide support: the National Institute on Aging, the National Institute of Arthritis and Musculoskeletal and Skin Diseases, the National Center for Advancing Translational Sciences and the NIH Roadmap for Medical Research, under the following grant numbers: U01 AG027810, U01 AG042124, U01 AG042139, U01 AG042140, U01 AG042143, U01 AG042145, U01 AG042168, U01 AR066160 and UL1 TR000128.This is the final version of the article. It first appeared from Elsevier via http://dx.doi.org/10.1016/j.bone.2015.06.024

The feasibility of monitoring exercise intensity in mechanically ventilated patients recovering from critical illness in Intensive Care

Critical illness survivorship is frequently characterised by profound long-term physical and psychological disabilities. These arise as a result of the complex interaction between the patho-physiological e ects of critical illness, clinical interventions and the impact of prolonged bed rest on physical and psychological health. Early rehabilitation in the ICU is an important intervention that can overcome some of the devastating impacts of critical illness on patients and their carers. However, with little or no scienti c basis for its prescription and no validated means of assessing individual patient workload during rehabilitation, a \one-size- ts-all" approach is generally adopted. In contrast, the eld of sports science has an extensive literature base describing the optimisation of individual training programs. This thesis explores the potential translation of key precepts of exercise physiology into the ICU setting in order to quantify the workload during rehabilitation in mechanically ventilated (MV) patients recovering from critical illness. Breath-by-breath-gas-exchange-analysis (BBGEA) is the gold standard for measuring exercise capacity and intensity in non-ventilated individuals. However, validated devices in MV patients are lacking. In this thesis the MedGraphics Ultima, a BBGEA device, was validated in the critical care setting, within the limits of two reference techniques; Douglas bag collection and Deltatrac II. The feasibility of using BBGEA in patients rehabilitating in the ICU and the oxygen cost of this rehabilitation were then investigated. I established that, while this device is an invaluable research tool, it is impractical for day-to-day clinical practice. I further identi ed that the oxygen cost of rehabilitation activities in the ICU is not directly activity-dependent. I then developed two models to generate proxy values of oxygen consumption, during rehabilitation interventions, evaluating their performance with a small validation sample. The huge variations in the exercise load of rehabilitation interventions between and within patients highlights the need to establish personalised exercise regimens

Effectiveness of management strategies for uninvestigated dyspepsia: systematic review and network meta-analysis

Objective To determine the effectiveness of management strategies for uninvestigated dyspepsia. Design Systematic review and network meta-analysis. Data sources Medline, Embase, Embase Classic, the Cochrane Central Register of Controlled Trials, and clinicaltrials.gov from inception to September 2019, with no language restrictions. Conference proceedings between 2001 and 2019. Eligibility criteria for selecting studies Randomised controlled trials that assessed the effectiveness of management strategies for uninvestigated dyspepsia in adult participants (age ≥18 years). Strategies of interest were prompt endoscopy; test for Helicobacter pylori and perform endoscopy in participants who test positive; test for H pylori and eradication treatment in those who test positive (“test and treat”); empirical acid suppression; or symptom based management. Trials reported dichotomous assessment of symptom status at final follow-up (≥12 months). Results The review identified 15 eligible randomised controlled trials that comprised 6162 adult participants. Data were pooled using a random effects model. Strategies were ranked according to P score, which is the mean extent of certainty that one management strategy is better than another, averaged over all competing strategies. “Test and treat” ranked first (relative risk of remaining symptomatic 0.89, 95% confidence interval 0.78 to 1.02, P score 0.79) and prompt endoscopy ranked second, but performed similarly (0.90, 0.80 to 1.02, P score 0.71). However, no strategy was significantly less effective than “test and treat.” Participants assigned to “test and treat” were significantly less likely to receive endoscopy (relative risk v prompt endoscopy 0.23, 95% confidence interval 0.17 to 0.31, P score 0.98) than all other strategies, except symptom based management (relative risk v symptom based management 0.60, 0.30 to 1.18). Dissatisfaction with management was significantly lower with prompt endoscopy (P score 0.95) than with “test and treat” (relative risk v “test and treat” 0.67, 0.46 to 0.98), and empirical acid suppression (relative risk v empirical acid suppression 0.58, 0.37 to 0.91). Upper gastrointestinal cancer rates were low in all trials. Results remained stable in sensitivity analyses, with minimal inconsistencies between direct and indirect results. Risk of bias of individual trials was high; blinding was not possible because of the pragmatic trial design. Conclusions “Test and treat” was ranked first, although it performed similarly to prompt endoscopy and was not superior to any of the other strategies. “Test and treat” led to fewer endoscopies than all other approaches, except symptom based management. However, participants showed a preference for prompt endoscopy as a management strategy for their symptoms. Systematic review registration PROSPERO registration number CRD42019132528

Latent class analysis does not support the existence of Rome IV functional bowel disorders as discrete entities

Background Previously, we used latent class analysis (LCA) to identify novel subgroups in people with irritable bowel syndrome (IBS). There are four other functional bowel disorders that, although characterized as discrete disorders, overlap considerably with, and fluctuate to, IBS. These might instead be conceptualized as a milder form of IBS. We explored this hypothesis using LCA in a cohort of people with non-IBS functional bowel disorders. Methods We collected demographic, symptom, and psychological health data from 1375 adults in the community who self-identified as having IBS and identified individuals meeting Rome IV criteria for any non-IBS functional bowel disorder. We performed LCA to identify specific subgroups (clusters). We followed participants up at 12 months to reassess gastrointestinal and psychological heath and also gather data about healthcare utilization and impact of symptoms. Key results 811 people met Rome IV criteria for IBS and 558 Rome IV criteria for another functional bowel disorder (76 (5.5%) functional constipation; 198 (14.5%) functional diarrhea; 129 (9.5%) functional abdominal bloating or distension; and 155 (11.4%) unspecified functional bowel disorder). LCA in these 558 people identified five clusters defined by a combination of gastrointestinal symptoms and the extent of psychological co-morbidity. However, correlation between these clusters and the Rome IV functional bowel disorder diagnoses was poor and 75% of people were classified as having mild IBS using our previous IBS-derived model. By 12 months, one-third of people had fluctuated and met criteria for IBS. Clusters with high psychological burden had a poorer prognosis, with higher rates of medical consultation, medication use, and greater impact of symptoms on daily life. Conclusions and inferences The functional bowel disorders may be better characterized as a spectrum of IBS rather than separate disorders. Adopting this pragmatic stance may help to simply diagnosis, treatment, and recruitment of patients to research trials

Systematic review with network meta-analysis: Risk of Herpes zoster with biological therapies and small molecules in inflammatory bowel disease.

Background Biologics and small molecules for inflammatory bowel disease (IBD) may increase infection risk. Herpes zoster causes acute and long-term symptoms, but vaccination is not recommended in patients with IBD, unless >50 years of age. Aims To examine risk of Herpes zoster infection with all licensed biologics and small molecules for IBD using network meta-analysis. Methods We searched the literature to 4th October 2022, for randomised controlled trials of these drugs in luminal Crohn's disease or ulcerative colitis reporting data on occurrence of Herpes zoster infection during follow-up. We used a frequentist approach and a random effects model, pooling data as relative risks (RRs) with 95% confidence intervals (CIs). Results We identified 25 trials (9935 patients). Only tofacitinib 10 mg b.d. (RR = 6.90; 95% CI 1.56–30.63, number needed to harm (NNH) = 97; 95% CI 19–1022) and upadacitinib 45 mg o.d. (RR = 7.89; 95% CI 1.04–59.59, NNH = 83; 95% CI 10–14,305) were significantly more likely to increase risk of Herpes zoster infection. Janus kinase inhibitors were the most likely drug class to increase risk of infection, and risk increased with higher doses (RR with lowest dose = 3.16; 95% CI 1.02–9.84, NNH = 265; 95% CI 65–28,610, RR with higher dose = 5.91; 95% CI 2.21–15.82, NNH = 117; 95% CI 39–473). Conclusions In a network meta-analysis, the janus kinase inhibitor tofacitinib, and all janus kinase inhibitors considered as a class, were most likely to increase risk of Herpes zoster infection. Risk increased with higher doses

Direct healthcare costs of Rome IV or Rome III-defined irritable bowel syndrome in the United Kingdom

Background Previous studies have demonstrated a substantial economic impact of irritable bowel syndrome (IBS). Aims To provide contemporaneous estimates of direct healthcare costs of IBS in the United Kingdom. Methods We collected demographic, gastrointestinal and psychological symptoms, quality of life and healthcare usage data from adults with Rome IV or Rome III IBS in the United Kingdom. We calculated the mean annual direct healthcare costs of IBS per person and used contemporaneous IBS prevalence data, together with census data, to estimate annual direct costs of IBS. We also examined predictors of higher costs. Results The mean annual direct cost of IBS per person among 752 individuals with Rome IV IBS was £556.65 (SD £1023.92) and £474.16 (SD £897.86) for 995 individuals with Rome III IBS. We estimate the annual direct healthcare cost of IBS in the United Kingdom is £1.27 billion if the Rome IV criteria are used to define IBS, and £2.07 billion using Rome III. Among individuals with Rome IV IBS, mean annual costs were higher in those with opiate use (£907.90 vs £470.58, p 5 years £501.60, p = 0.002), lower quality of life (p < 0.001 for trend), and higher depression, somatisation and gastrointestinal symptom-specific anxiety scores (P < 0.001 for trend for all). Conclusion We estimate annual direct healthcare costs of IBS of between £1.3 and £2 billion in the United Kingdom

Willingness to accept risk with medication in return for cure of symptoms among patients with Rome IV irritable bowel syndrome

Background Some drugs for irritable bowel syndrome (IBS) have serious side effects. Aims To examine the willingness of individuals with IBS to accept risks with medication in return for symptom cure. Methods We collected demographic, gastrointestinal symptoms, psychological health, quality of life and impact on work and daily activities data from 752 adults with Rome IV-defined IBS. We examined median willingness to accept death in return for cure with a hypothetical medication using a standard gamble, according to these variables. Results Participants would accept a median 2.0% (IQR 0.0%-9.0%) risk of death in return for a 98.0% (IQR 91.0%-100.0%) chance of permanent symptom cure. The median accepted risk of death was higher in men (5.0% vs 2.0%, P < 0.001), those with continuous abdominal pain (4.0% vs 1.0%, P < 0.001), more severe symptoms (P = 0.005 for trend), abnormal depression scores (P < 0.001 for trend), higher gastrointestinal symptom-specific anxiety (P < 0.001 for trend), and lower IBS-related quality of life (P < 0.001 for trend). Those willing to accept above median risk of death were more likely to be male (17.1% vs 9.1%, P < 0.001), take higher levels of risks in their daily life (P = 0.008 for trend), and report continuous abdominal pain (53.1% vs 39.4%, P < 0.001), and had higher depression (P = 0.004 for trend) and lower quality of life (P < 0.001 for trend) scores. Conclusion Patients are willing to accept significant risks in return for cure of their IBS symptoms