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Introduction The contributing factors of aspiration pneumonia have been well documented. However, there are gaps in the literature regarding identifying the weight associated with each factor and the relationship between factors. Method In this study, 20 potential predictors of aspiration pneumonia (with four additional variables) have been applied to historic Speech and Language Therapy records to greater understand the significance of each contributor of aspiration pneumonia. 152 cases with an oropharyngeal dysphagia, and a Speech and Language Therapy recommendation of eating and drinking with known aspiration and the associated potential risk of developing an aspiration pneumonia, were included in the data. These were inpatients and outpatients, and had various diagnoses but all had had a videofluoroscopy. Results Logistic regression analysis found seven factors that were individually significant in predicting the development of aspiration pneumonia with 84.93% sensitivity and 91.03% specificity Discussion Logistic regression and random forest analyses led to the proposal of a new matrix of predictors of aspiration pneumonia with respective scoring weights for individual and cumulative contributors (a direction for future research).

Type 2 diabetes shows evidence of underlying heterogeneity. No studies have assessed whether different causes for diabetes change the response to oral hypoglycaemic therapy. In a few cases, patients with diabetes caused by mutations in the hepatocyte nuclear factor 1α (HNF-1α) gene have been described as sensitive to the hypoglycaemic effects of sulphonylureas. We aimed to see whether the glycaemic response to the sulphonylurea gliclazide and the biguanide metformin differed in HNF-1α diabetes and type 2 diabetes, and to investigate the mechanism for differences in sulphonylurea sensitivity. We did a randomised crossover trial of glicazide and metformin in 36 patients, either with diabetes caused by HNF-1α mutations or type 2 diabetes, who were matched for body-mass index and fasting plasma glucose. The primary outcome was reduction in fasting plasma glucose. Analysis was by intention to treat. We assessed possible mechanisms for sulphonylurea sensitivity through insulin sensitivity, insulin secretory response to glucose and tolbutamide, and tolbutamide clearance. Patients with HNF-1α diabetes had a 5.2-fold greater response to gliclazide than to metformin (fasting plasma glucose reduction 4·7 vs 0·9 mmol/L, p=0·0007) and 3.9-fold greater response to gliclazide than those with type 2 diabetes (p=0·002). Patients with HNF-1α diabetes had a strong insulin secretory response to intravenous tolbutamide despite a small response to intravenous glucose, and were more insulin sensitive than those with type 2 diabetes. Sulphonylurea metabolism was similar in both patient groups. The cause of hyperglycaemia changes the response to hypoglycaemic drugs; HNF-1α diabetes has marked sulphonylurea sensitivity. This pharmacogenetic effect is consistent with models of HNF-1α deficiency, which show that the β-cell defect is upstream of the sulphonylurea receptor. Definition of the genetic basis of hyperglycaemia has implications for patient management.

ObjectiveClinicians predominantly use clinical features to differentiate type 1 from type 2 diabetes yet there are no evidence-based clinical criteria to aid classification of patients. Misclassification of diabetes is widespread (7–15% of cases), resulting in patients receiving inappropriate treatment. We sought to identify which clinical criteria could be used to discriminate type 1 and type 2 diabetes.DesignSystematic review of all diagnostic accuracy studies published since 1979 using clinical criteria to predict insulin deficiency (measured by C-peptide).Data sources14 databases including: MEDLINE, MEDLINE in Process and EMBASE. The search strategy took the form of: (terms for diabetes) AND (terms for C-Peptide).Eligibility criteriaDiagnostic accuracy studies of any routinely available clinical predictors against a reference standard of insulin deficiency defined by cut-offs of C-peptide concentrations. No restrictions on race, age, language or country of origin.Results10 917 abstracts were screened, and 231 full texts reviewed. 11 studies met inclusion criteria, but varied by age, race, year and proportion of participants who were C-peptide negative. Age at diagnosis was the most discriminatory feature in 7/9 studies where it was assessed, with optimal cut-offs (>70% mean sensitivity and specificity) across studies being <30 years or <40 years. Use of/time to insulin treatment and body mass index (BMI) were also discriminatory. When combining features, BMI added little over age at diagnosis and/or time to insulin (<1% improvement in classification).ConclusionsDespite finding only 11 studies, and considerable heterogeneity between studies, age at diagnosis and time to insulin were consistently the most discriminatory criteria. BMI, despite being widely used in clinical practice, adds little to these two criteria. The criteria identified are similar to the Royal College of General Practitioners National Health Service (RCGP/NHS) Diabetes classification guidelines, which use age at diagnosis <35 years and time to insulin <6 m. Until further studies are carried out, these guidelines represent a suitable classification scheme.Systematic review registrationPROSPERO reference CRD42012001736.

Background Total knee replacement surgery is common, with over 107,000 operations performed in the UK in 2019. After surgery, about 1% of patients develop a deep infection, known as a prosthetic joint infection. Two types of operations, one- or two-stage revision surgery, are routinely performed to treat the infection. Re-infection rates are similar, but there is uncertainty regarding longer-term outcomes for patients. The aim of this study was to establish the feasibility of conducting a future randomised controlled trial that will compare clinical and cost-effectiveness of one-stage versus two-stage revision knee surgery for prosthetic joint infection. Methods Following eligibility screening, consenting patients took part in an audio-recorded consultation with their surgeon and were then randomised on a 1:1 allocation to one-stage or two-stage revision surgery. Patient-reported outcome measures were administered at baseline and 3 and 6 months postoperatively. Embedded qualitative work with patient participants and nonparticipants and with surgeons to understand the acceptability of trial processes and involvement was undertaken. Patient and public involvement and engagement activities were conducted throughout the study. Results Of 136 patients screened, only 3 were randomised and had surgery as part of the study. Qualitative data were collected from the three participants, as well as from two eligible patients who declined participation and two who withdrew from participation after the initial patient-surgeon consultation. Five surgeons took part in qualitative interviews prior to study end. Conclusion This study indicated that a larger randomised controlled trial evaluating one-stage versus two-stage revision knee surgery for prosthetic joint infection is not feasible with the current straightforward randomised controlled trial design. Future research needs to consider the most appropriate study design and methodology to address this important research question. Trial registration No.: NCT04458961.

Background The HemiSPAIRE trial is being conducted to determine whether a modified muscle sparing technique (SPAIRE-“Save Piriformis and Internus, Repairing Externus”) in hip hemiarthroplasty brings clinical benefits compared to the standard lateral technique in adults aged 60 years or older, with a displaced intracapsular hip fracture. This article describes the detailed statistical analysis plan for the trial.  Methods and design HemiSPAIRE is a definitive, pragmatic, superiority, multicentre, randomised controlled trial (with internal pilot) with two parallel groups. Participants, ward staff and all research staff involved in post-operative assessments are blinded to allocation. This article describes in detail (1) the primary and secondary outcomes; (2) the statistical analysis principles, including a survivor average causal effect (SACE) method chosen specifically to address the issue of potential bias from differential survival between trial arms, which was seen from data review by the Trial Steering Committee, the participants that will be included in each analysis, the covariates that will be included in each analysis, and how the results will be presented; (3) planned main analysis of the primary outcome; (4) planned analyses of the secondary outcomes; and (5) planned additional analyses of the primary and secondary outcomes. Trial registration ClinicalTrials.gov NCT04095611. Registered on 19 September 2019.

IntroductionCurrently National Institute for Health and Care Excellence clinical guidelines in the UK suggest that surgeons performing partial hip replacements (hemiarthroplasty) should consider using the lateral approach. Alternatively, a newer, modified posterior approach using a muscle sparing technique named ‘Save Piriformis and Internus, Repairing Externus’ (SPAIRE) can be used leaving the major muscles intact. This randomised controlled trial (RCT) aims to compare the SPAIRE approach to the standard lateral approach, to determine if it allows patients to mobilise better and experience improved function after surgery.Methods and analysisHemiSPAIRE is a two-arm, assessor-blinded, definitive pragmatic RCT with nested pilot and qualitative studies. Two hundred and twenty-eight participants with displaced intracapsular fractures requiring hip hemiarthroplasty will be individually randomised 1:1 to either the SPAIRE, or control (standard lateral approach) surgical procedure. Outcomes will be assessed at postoperative day 3 (POD3) and 120 (POD120). The primary outcome measure will be level of function and mobility using the Oxford Hip Score at POD120. Secondary outcomes include: De Morton Mobility Index (DEMMI), Cumulated Ambulatory Score and Numeric Pain Rating Scale (NPRS) at POD3; DEMMI, NPRS and EQ-5D-5L at POD120, complications, acute and total length of hospital stay, and mortality. Primary analysis will be on an intention-to-treat basis. Participant experiences of the impact of surgery and recovery period will be examined via up to 20 semi-structured telephone interviews.Ethics and disseminationThe protocol has been approved by Yorkshire and the Humber—Bradford Leeds Research Ethics Committee. Recruitment commenced in November 2019. Findings will be disseminated via research articles in peer-reviewed journals, presentations at conferences, public involvement events, patient groups and media releases. A summary of the trial findings will be shared with participants at the end of the study.Trial registration numberNCT04095611.

ObjectivesAssess the effect of a modified muscle sparing posterior approach; SPAIRE (Save Piriformis and Internus, Repairing Externus), in hip hemiarthroplasty for displaced intracapsular fractures on postoperative mobility and function compared with a standard lateral approach.DesignPragmatic, superiority, multicenter, parallel-group, randomized controlled trial (with internal pilot). Participants, ward staff, and research staff conducting postoperative assessments were blinded to allocation. A CTU allocated treatments centrally using computer-generated lists.SettingSix hospitals in Southwest England, recruiting November 25, 2019–April 25, 2022.Participants244 adults (≥60 years) requiring hip hemiarthroplasty (122 allocated to each approach). 90 and 85 participants allocated to SPAIRE and lateral, respectively, had primary outcome data within the prespecified data collection window.InterventionsSurgery using SPAIRE or standard lateral approach. Follow-up 3 days and 120 days postoperation.Main outcome measureOxford Hip Score (OHS), via telephone at 120 days. Secondary outcomes: function and mobility (3 days), pain (3 days, 120 days), discharge destination, length of hospital stay, complications and mortality (within 120 days), quality of life and place of residence (120 days).ResultsParticipants’ mean age was 84.6 years (SD 7.2); 168 (69%) were women. Primary outcome: little evidence of a difference in OHS at 120 days; adjusted mean difference (SPAIRE—lateral) −1.23 (95% CI −3.96 to 1.49, p=0.37). Secondary outcomes: indication of lower participant-reported pain at 3 days in SPAIRE arm; no differences between arms for remaining outcomes.ConclusionsParticipants’ mobility and function are similar in the short term (3 days) and longer term (120 days), whether receiving the SPAIRE or lateral approach. Neither approach confers benefit over the other in terms of length of hospital stay, return to prefracture residence, survival within 120 days, or quality of life at 120 days. Participants receiving SPAIRE approach may experience less pain in the early postoperative period. Modifying the posterior approach in hip hemiarthroplasty to the SPAIRE approach gives equivalent patient outcomes to the lateral approach within 120 days.Trial registration number NCT04095611.

OBJECTIVE:-- We aimed to examine sex differences in insulin and insulin propeptide concentrations at birth using validated cord blood collection. RESEARCH DESIGN AND METHODS-- We tested the impact on insulin and insulin propeptides of taking 13 cord blood samples in heparin and EDTA and then centrifuging and separating plasma after 1, 2, 24, or 48 h at room temperature (heparin) or 4°C (EDTA). Cord plasma insulin and insulin propeptides concentrations were measured in 440 babies and correlated with offspring anthropometry measured at birth. RESULTS:-- Cord insulin concentrations significantly decreased (74% those at baseline by 24 h; P = 0.01) in the samples taken in heparin and stored at room temperature, but those taken on EDTA and refrigerated remained stable for up to 48 h. Insulin propeptides were stable in both. Cord plasma insulin and insulin propeptides measured in EDTA were related to all measures of birth size and maternal glycemia and BMI (r > 0.11; P < 0.03 for all) and were higher in those delivered via caesarean section. Girls were lighter (3,497 vs. 3,608 g; P = 0.01) but had higher cord insulin (46.7 vs. 41.2 pmol/l; P = 0.031), total proinsulin (34.1 vs. 25.8 pmol/l; P < 0.001), and intact proinsulin (9.5 vs. 8.3 pmol/l; P = 0.004) concentrations than boys; this was further confirmed when cord insulin concentrations of boys and girls were compared after pair matching for birth weight (insulin 49.7 vs. 42.1 pmol/l; P = 0.004). CONCLUSIONS:-- When using appropriate sample collection methods, female newborns have higher insulin concentrations than male newborns, despite being smaller, suggesting intrinsic insulin resistance in girls.

Background Inherited abnormalities of complement are found in ∼60% of patients with atypical haemolytic uraemic syndrome (aHUS). Such abnormalities are not fully penetrant. In this study, we have estimated the penetrance of the disease in three families with a CFH mutation (c.3643C>G; p. Arg1215Gly) in whom a common lineage is probable. 25 individuals have been affected with aHUS with three peaks of incidence—early childhood (n=6), early adulthood (n=11) and late adulthood (n=8). Eighteen individuals who have not developed aHUS carry the mutation. Methods We estimated penetrance at the ages of 4, 27, 60 and 70 years as both a binary and a survival trait using MLINK and Mendel. We genotyped susceptibility factors in CFH, CD46 and CFHR1 in affected and unaffected carriers. Results and Conclusions We found that the estimates of penetrance at the age of 4 years ranged from <0.01 to 0.10, at the age of 27 years from 0.16 to 0.29, at the age of 60 years from 0.39 to 0.51 and at the age of 70 years from 0.44 to 0.64. We found that the CFH haplotype on the allele not carrying the CFH mutation had a significant effect on disease penetrance. In this family, we did not find that the CD46 haplotypes had a significant effect on penetrance.

OBJECTIVE:--Offspring of mothers with diabetes have increased birth weight and higher rates of obesity in early childhood. The relative role of maternal glycemia and maternal obesity is uncertain. We therefore studied the impact of maternal glycemia and maternal obesity on offspring birth measures and early postnatal growth in nondiabetic pregnancies. RESEARCH DESIGN AND METHODS--We studied 547 full-term singleton babies of nondiabetic parents. Data available included parental height and weight; maternal prepregnant weight; maternal fasting plasma glucose (FPG) at 28 weeks of gestation; and offspring weight and length at birth, 12 weeks of age, and 1 and 2 years of age. Relationships between parental and offspring measures were estimated using Pearson correlations. RESULTS:--Maternal FPG was correlated with offspring birth weight (r = 0.25, P < 0.001), length (r = 0.17, P < 0.001), and BMI (r = 0.2, P < 0.001) but was not correlated with offspring growth at 12 weeks. Maternal prepregnancy BMI was significantly correlated with offspring weight (r = 0.26, P < 0.001), length (r = 0.12, P = 0.01), and BMI at birth (r = 0.26, P < 0.001) and remained correlated with offspring weight (r = 0.13-0.14, P = 0.007-0.002) and BMI (r = 0.14-0.19, P = 0.002 to <0.001) during the first 2 years. Paternal BMI was correlated with offspring weight from 12 weeks onwards (r = 0.11-0.22, P = 0.017 to <0.001), length (r = 0.10-0.12, P = 0.01-0.05), and BMI from 1 year onwards (r = 0.16-0.25, P = <0.001). CONCLUSIONS:--In a nondiabetic cohort, the effect of maternal glycemia on birth weight is transitory, while the impact on growth of maternal BMI continues into early childhood. The independent association of paternal BMI with offspring postnatal growth suggests that the impact of parental BMI could be explained by genetic factors, shared environment, or both.