Is the SMART risk prediction model ready for real-world implementation? A validation study in a routine care setting of approximately 380 000 individuals

AIMS: Reliably quantifying event rates in secondary prevention could aid clinical decision-making, including quantifying potential risk reductions of novel, and sometimes expensive, add-on therapies. We aimed to assess whether the SMART risk prediction model performs well in a real-world setting. METHODS AND RESULTS: We conducted a historical open cohort study using UK primary care data from the Clinical Practice Research Datalink (2000-2017) diagnosed with coronary, cerebrovascular, peripheral, and/or aortic atherosclerotic cardiovascular disease (ASCVD). Analyses were undertaken separately for cohorts with established (≥6 months) vs. newly diagnosed ASCVD. The outcome was first post-cohort entry occurrence of myocardial infarction, stroke, or cardiovascular death. Among the cohort with established ASCVD [n = 244 578, 62.1% male, median age 67.3 years, interquartile range (IQR) 59.2-74.0], the calibration and discrimination achieved by the SMART model was not dissimilar to performance at internal validation [Harrell's c-statistic = 0.639, 95% confidence interval (CI) 0.636-0.642, compared with 0.675, 0.642-0.708]. Decision curve analysis indicated that the model outperformed treat all and treat none strategies in the clinically relevant 20-60% predicted risk range. Consistent findings were observed in sensitivity analyses, including complete case analysis (n = 182 482; c = 0.624, 95% CI 0.620-0.627). Among the cohort with newly diagnosed ASCVD (n = 136 445; 61.0% male; median age 66.0 years, IQR 57.7-73.2), model performance was weaker with more exaggerated risk under-prediction and a c-statistic of 0.559, 95% CI 0.556-0.562. CONCLUSIONS: The performance of the SMART model in this validation cohort demonstrates its potential utility in routine healthcare settings in guiding both population and individual-level decision-making for secondary prevention patients

GPs' decision-making when prescribing medicines for breastfeeding women: Content analysis of a survey

<p>Abstract</p> <p>Background</p> <p>Many breastfeeding women seek medical care from general practitioners (GPs) for various health problems and GPs may consider prescribing medicines in these consultations. Prescribing medicines to a breastfeeding mother may lead to untimely cessation of breastfeeding or a breastfeeding mother may be denied medicines due to the possible risk to her infant, both of which may lead to unwanted consequences. Information on factors governing GPs' decision-making and their views in such situations is limited.</p> <p>Methods</p> <p>GPs providing shared maternity care at the Royal Women's Hospital, Melbourne were surveyed using an anonymous postal survey to determine their knowledge, attitudes and practices on medicines and breastfeeding, in 2007/2008 (n = 640). Content analysis of their response to a question concerning decision-making about the use of medicine for a breastfeeding woman was conducted. A thematic network was constructed with basic, organising and global themes.</p> <p>Results</p> <p>335 (52%) GPs responded to the survey, and 253 (76%) provided information on the last time they had to decide about the use of medicine for a breastfeeding woman. Conditions reported were mastitis (24%), other infections (24%) and depressive disorders (21%). The global theme that emerged was "<it>complexity of managing risk in prescribing for breastfeeding women"</it>. The organising themes were: <it>certainty around decision-making; uncertainty around decision-making; need for drug information to be available, consistent and reliable; joint decision-making; the vulnerable "third party" </it>and <it>infant feeding decision</it>. Decision-making is a spectrum from a straight forward decision, such as treatment of mastitis, to a complicated one requiring multiple inputs and consideration. GPs use more information seeking and collaboration in decision-making when they perceive the problem to be more complex, for example, in postnatal depression.</p> <p>Conclusion</p> <p>GPs feel that prescribing medicines for breastfeeding women is a contentious issue. They manage the risk of prescribing by gathering information and assessing the possible effects on the breastfed infant. Without evidence-based information, they sometimes recommend cessation of breastfeeding unnecessarily.</p

Associations between attainment of incentivised primary care indicators and incident diabetic retinopathy in England: a population-based historical cohort study

Background The associations between England’s incentivised primary care-based diabetes prevention activities and hard clinical endpoints remain unclear. We aimed to examine the associations between attainment of primary care indicators and incident diabetic retinopathy (DR) among people with type 2 diabetes. Methods A historical cohort (n = 60,094) of people aged ≥ 18 years with type 2 diabetes and no DR at baseline was obtained from the UK Clinical Practice Research Datalink (CPRD). Exposures included attainment of the Quality and Outcomes Framework (QOF) HbA1c (≤ 7.5% or 59 mmol/mol), blood pressure (≤ 140/80 mmHg), and cholesterol (≤ 5 mmol/L) indicators, and number of National Diabetes Audit (NDA) care processes completed (categorised as 0–3, 4–6, or 7–9), in 2010–2011. Outcomes were time to development of DR and sight-threatening diabetic retinopathy (STDR). Nearest neighbour propensity score matching was undertaken and Cox proportional hazards models then fitted using the matched samples. Concordance statistics were calculated for each model. Results 8263 DR and 832 STDR diagnoses were observed over mean follow-up periods of 3.5 (SD 2.1) and 3.8 (SD 2.0) years, respectively. HbA1c and blood pressure (BP) indicator attainment were associated with lower rates of DR (adjusted hazard ratios (aHRs) 0.94 (95% CI 0.89–0.99) and 0.87 (0.83–0.92), respectively), whereas cholesterol indicator attainment was not (aHR 1.03 (0.97–1.10)). All QOF indicators were associated with lower rates of STDR (aHRs 0.74 (0.62–0.87) for HbA1c, 0.78 (0.67–0.91) for BP, and 0.82 (0.67–0.99) for cholesterol). Completion of 7–9 vs. 0–3 NDA processes was associated with fewer STDR diagnoses (aHR 0.72 (0.55–0.94)). Conclusions Attainment of key primary care indicators is associated with lower incidence of DR and STDR among patients with type 2 diabetes in England

A failed RCT to determine if antibiotics prevent mastitis: Cracked nipples colonized with Staphylococcus aureus: A randomized treatment trial [ISRCTN65289389]

BACKGROUND: A small, non-blinded, RCT (randomised controlled trial) had reported that oral antibiotics reduced the incidence of mastitis in lactating women with Staphylococcus aureus (S. aureus)- colonized cracked nipples. We aimed to replicate the study with a more rigorous design and adequate sample size. METHODS: Our intention was to conduct a double-blind placebo-controlled trial to determine if an antibiotic (flucloxacillin) could prevent mastitis in lactating women with S. aureus-colonized cracked nipples. We planned to recruit two groups of 133 women with S. aureus-colonized cracked nipples. RESULTS: We spent over twelve months submitting applications to five hospital ethics committees and seven funding bodies, before commencing the trial. Recruitment to the trial was very slow and only ten women were randomized to the trial after twelve months, and therefore the trial was stopped early. CONCLUSIONS: In retrospect we should have conducted a feasibility study, which would have revealed the low number of women in these Melbourne hospitals (maternity wards and breastfeeding clinics) with damaged nipples. The appropriate use of antibiotics for breastfeeding women with cracked nipples still needs to be tested

I’m not joking! The strategic use of humour in stories of racism

This study examines the use of humour by Black football coaches in England as a rhetorical device against racism. The paper draws on humour studies and critical race theory to illustrate signs of humour as defence. Research on humour has popularly explored the ambiguities and qualities of humour and, in particular, joke telling through its use as a foil to stem racial ills is less well understood. Where previous work has focused on explicit joke telling/banter in sport, this paper examines how techniques of humour are used in everyday racialised experiences. The use of techniques of humour enables feelings of subordination, and humiliation to be transposed into forms of resistance, while its physiological and psychological benefits can lead to inter-racial relief and catharsis. The paper concludes that techniques of humour remain underexplored as important tools of resistance to everyday racism

The Escherichia coli SOS Gene dinF Protects against Oxidative Stress and Bile Salts

DNA is constantly damaged by physical and chemical factors, including reactive oxygen species (ROS), such as superoxide radical (O2−), hydrogen peroxide (H2O2) and hydroxyl radical (•OH). Specific mechanisms to protect and repair DNA lesions produced by ROS have been developed in living beings. In Escherichia coli the SOS system, an inducible response activated to rescue cells from severe DNA damage, is a network that regulates the expression of more than 40 genes in response to this damage, many of them playing important roles in DNA damage tolerance mechanisms. Although the function of most of these genes has been elucidated, the activity of some others, such as dinF, remains unknown. The DinF deduced polypeptide sequence shows a high homology with membrane proteins of the multidrug and toxic compound extrusion (MATE) family. We describe here that expression of dinF protects against bile salts, probably by decreasing the effects of ROS, which is consistent with the observed decrease in H2O2-killing and protein carbonylation. These results, together with its ability to decrease the level of intracellular ROS, suggests that DinF can detoxify, either direct or indirectly, oxidizing molecules that can damage DNA and proteins from both the bacterial metabolism and the environment. Although the exact mechanism of DinF activity remains to be identified, we describe for the first time a role for dinF

Association between Helicobacter pylori genotypes and severity of chronic gastritis, peptic ulcer disease and gastric mucosal interleukin-8 levels: evidence from a study in the Middle East

Background: The varied clinical presentations of Helicobacter pylori (H. pylori) infection are most likely due to differences in the virulence of individual strains, which determines its ability to induce production of interleukin-8 (IL-8) in the gastric mucosa. The aim of this study was to examine association between cagA, vacA-s1 and vacA-s2 genotypes of H. pylori and severity of chronic gastritis and presence of peptic ulcer disease (PUD), and to correlate these with IL-8 levels in the gastric mucosa. Methods: Gastric mucosal biopsies were obtained from patients during esophagogastroduodenoscopy. The severity of chronic gastritis was documented using the updated Sydney system. H. pylori cagA and vacA genotypes were detected by PCR. The IL-8 levels in the gastric mucosa were measured by ELISA. Results: H. pylori cagA and/or vacA genotypes were detected in 99 patients (mean age 38.4±12.9; 72 males), of whom 52.5% were positive for cagA, 44.4% for vacA-s1 and 39.4% for vacA-s2; and 70.7% patients had PUD. The severity of inflammation in gastric mucosa was increased with vacA-s1 (p=0.017) and decreased with vacA-s2 (p=0.025), while cagA had no association. The degree of neutrophil activity was not associated with either cagA or vacA-s1, while vacA-s2 was significantly associated with decreased neutrophil activity (p=0.027). PUD was significantly increased in patients with cagA (p=0.002) and vacA-s1 (p=0.031), and decreased in those with vacA-s2 (p=0.011). The level of IL-8 was significantly increased in patients with cagA (p=0.011) and vacA-s1 (p=0.024), and lower with vacA-s2 (p=0.004). Higher levels of IL-8 were also found in patients with a more severe chronic inflammation (p=0.001), neutrophil activity (p=0.007) and those with PUD (p=0.001). Conclusions: Presence of vacA-s1 genotype of H. pylori is associated with more severe chronic inflammation and higher levels of IL-8 in the gastric mucosa, as well as higher frequency of PUD. Patients with vacA-s2 have less severe gastritis, lower levels of IL-8, and lower rates of PUD. The presence of cagA genotype is not associated with the severity of gastritis or IL-8 induction in the gastric mucosa. The association of cagA with PUD may be a reflection of its presence with vacA-s1 genotype

Dry Needling for Spine Related Disorders: a Scoping Review

Introduction/Background: The depth and breadth of research on dry needling (DN) has not been evaluated specifically for symptomatic spine related disorders (SRD) from myofascial trigger points (TrP), disc, nerve and articular structures not due to serious pathologies. Current literature appears to support DN for treatment of TrP. Goals of this review include identifying research published on DN treatment for SRD, sites of treatment and outcomes studied. Methods: A scoping review was conducted following Levac et al.’s five part methodological framework to determine the current state of the literature regarding DN for patients with SRD. Results: Initial and secondary search strategies yielded 55 studies in the cervical (C) region (71.43%) and 22 in the thoracolumbar-pelvic (TLP) region (28.57%). Most were randomized controlled trials (60% in C, 45.45% in TLP) and clinical trials (18.18% in C, 22.78% in TLP). The most commonly treated condition was TrP for both the C and TLP regions. In the C region, DN was provided to 23 different muscles, with the trapezius as treatment site in 41.88% of studies. DN was applied to 31 different structures in the TLP region. In the C region, there was one treatment session in 23 studies (41.82%) and 2–6 treatments in 25 (45.45%%). For the TLP region, one DN treatment was provided in 8 of the 22 total studies (36.36%) and 2–6 in 9 (40.9%). The majority of experimental designs had DN as the sole intervention. For both C and TLP regions, visual analogue scale, pressure pain threshold and range of motion were the most common outcomes. Conclusion: For SRD, DN was primarily applied to myofascial structures for pain or TrP diagnoses. Many outcomes were improved regardless of diagnosis or treatment parameters. Most studies applied just one treatment which may not reflect common clinical practice. Further research is warranted to determine optimal treatment duration and frequency. Most studies looked at DN as the sole intervention. It is unclear whether DN alone or in addition to other treatment procedures would provide superior outcomes. Functional outcome tools best suited to tracking the outcomes of DN for SRD should be explored.https://doi.org/10.1186/s12998-020-00310-

HIV-induced immune activation - pathogenesis and clinical relevance. Summary of a workshop organised by the German AIDs Society (DAIG e.v.) and the ICH Hamburg, Hamburg, Germany, November 22, 2008

This manuscript is communicated by the German AIDS Society (DAIG) http://www.daignet.de. It summarizes a series of presentations and discussions during a workshop on immune activation due to HIV infection. The workshop was held on November 22nd 2008 in Hamburg, Germany. It was organized by the ICH Hamburg under the auspices of the German AIDS Society (DAIG e.V.)