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Individuals with rare kidney diseases account for 5–10% of people with chronic kidney disease, but constitute more than 25% of patients receiving kidney replacement therapy. The National Registry of Rare Kidney Diseases (RaDaR) gathers longitudinal data from patients with these conditions, which we used to study disease progression and outcomes of death and kidney failure.

Aims:The authors share their early experiences of developing and implementing a telehealth service for patients with chronic obstructive pulmonary disease (COPD), through a collaborative approach. The article will explore the process of implementing telehealth service in a local care community team, identifying opportunities for improving care delivery and person-centred care. Discussion:The initial feedback and thoughts of both patients and healthcare professionals were obtained. Such feedback included patient’s health insights, which helped improve risk assessment and personalised parameter settings. Conclusions:To-date, there has been a lack of robust evidence for the clinical benefits of telehealth. However, the feedback from staff and patients using telehealth was positive in several areas. Person-centred care plans also helped provide greater insight into patient’s health goals, thereby streamlining care.

Anti-TNF drugs, such as infliximab, are associated with attenuated antibody responses after SARS-CoV-2 vaccination. We aimed to determine how the anti-TNF drug infliximab and the anti-integrin drug vedolizumab affect vaccine-induced neutralising antibodies against highly transmissible omicron (B.1.1.529) BA.1, and BA.4 and BA.5 (hereafter BA.4/5) SARS-CoV-2 variants, which possess the ability to evade host immunity and, together with emerging sublineages, are now the dominating variants causing current waves of infection.

Background: Childhood steroid-sensitive nephrotic syndrome is a frequently relapsing disease with significant short- and long-term complications, leading to high healthcare costs and reduced quality of life for patients. The majority of relapses are triggered by upper respiratory tract infections (URTIs) and evidence shows that daily low-dose prednisolone at the time of infection may reduce the risk of relapse. Objective: The aim of this study was to assess the cost effectiveness of a 6-day course of low-dose prednisolone at the start of a URTI when compared with placebo. Methods: A state-transition Markov model was developed to conduct a cost-utility analysis with the outcome measured in quality-adjusted life-years (QALYs). Resource use and outcome data were derived from the PREDNOS2 trial. The analysis was performed from a UK National Health Service perspective and the results were extrapolated to adulthood. Model parameter and structural uncertainty were assessed using sensitivity analyses. Results: The base-case results showed that administering low-dose prednisolone at the time of a URTI generated more QALYs and a lower mean cost at 1 year compared with placebo. In the long-term, low-dose prednisolone was associated with a cost saving (£176) and increased effectiveness (0.01 QALYs) compared with placebo and thus remained the dominant treatment option. These findings were robust to all sensitivity analyses. Conclusion: A 6-day course of low-dose prednisolone at the time of a URTI in children with steroid-sensitive nephrotic syndrome has the potential to reduce healthcare costs and improve quality of life compared with placebo.

IMPORTANCE: In children with corticosteroid-sensitive nephrotic syndrome, many relapses are triggered by upper respiratory tract infections. Four small studies found that administration of daily low-dose prednisolone for 5 to 7 days at the time of an upper respiratory tract infection reduced the risk of relapse, but the generalizability of their findings is limited by location of the studies and selection of study population. OBJECTIVE: To investigate the use of daily low-dose prednisolone for the treatment of upper respiratory tract infection–related relapses. DESIGN, SETTING, AND PARTICIPANTS: This double-blind, placebo-controlled randomized clinical trial (Prednisolone in Nephrotic Syndrome [PREDNOS] 2) evaluated 365 children with relapsing steroid-sensitive nephrotic syndrome with and without background immunosuppressive treatment at 122 pediatric departments in the UK from February 1, 2013, to January 31, 2020. Data from the modified intention-to-treat population were analyzed from July 1, 2020, to December 31, 2020. INTERVENTIONS: At the start of an upper respiratory tract infection, children received 6 days of prednisolone, 15 mg/m2 daily, or matching placebo preparation. Those already taking alternate-day prednisolone rounded their daily dose using trial medication to the equivalent of 15 mg/m2 daily or their alternate-day dose, whichever was greater. MAIN OUTCOMES AND MEASURES: The primary outcome was the incidence of first upper respiratory tract infection–related relapse. Secondary outcomes included overall rate of relapse, changes in background immunosuppressive treatment, cumulative dose of prednisolone, rates of serious adverse events, incidence of corticosteroid adverse effects, and quality of life. RESULTS: The modified intention-to-treat analysis population comprised 271 children (mean [SD] age, 7.6 [3.5] years; 174 [64.2%] male), with 134 in the prednisolone arm and 137 in the placebo arm. The number of patients experiencing an upper respiratory tract infection–related relapse was 56 of 131 (42.7%) in the prednisolone arm and 58 of 131 (44.3%) in the placebo arm (adjusted risk difference, −0.02; 95% CI, −0.14 to 0.10; P = .70). No evidence was found that the treatment effect differed according to background immunosuppressive treatment. No significant differences were found in secondary outcomes between the treatment arms. A post hoc subgroup analysis assessing the primary outcome in 54 children of South Asian ethnicity (risk ratio, 0.66; 95% CI, 0.40-1.10) vs 208 children of other ethnicity (risk ratio, 1.11; 95% CI, 0.81-1.54) found no difference in efficacy of intervention in those of South Asian ethnicity (test for interaction P = .09). CONCLUSIONS AND RELEVANCE: The results of PREDNOS 2 suggest that administering 6 days of daily low-dose prednisolone at the time of an upper respiratory tract infection does not reduce the risk of relapse of nephrotic syndrome in children in the UK. Further work is needed to investigate interethnic differences in treatment response. TRIAL REGISTRATION: isrctn.org Identifier: ISRCTN10900733; EudraCT 2012-003476-39

ObjectiveHypertrophic cardiomyopathy (HCM) is an important predictor of long-term outcomes in Friedreich’s ataxia (FA), but the clinical spectrum and survival in childhood is poorly described. This study aimed to describe the clinical characteristics of children with FA-HCM.Design and settingRetrospective, longitudinal cohort study of children with FA-HCM from the UK.Patients78 children (<18 years) with FA-HCM diagnosed over four decades.InterventionAnonymised retrospective demographic and clinical data were collected from baseline evaluation and follow-up.Main outcome measuresThe primary study end-point was all-cause mortality (sudden cardiac death, atrial arrhythmia-related death, heart failure-related death, non-cardiac death) or cardiac transplantation.ResultsThe mean age at diagnosis of FA-HCM was 10.9 (±3.1) years. Diagnosis was within 1 year of cardiac referral in 34 (65.0%) patients, but preceded the diagnosis of FA in 4 (5.3%). At baseline, 65 (90.3%) had concentric left ventricular hypertrophy and 6 (12.5%) had systolic impairment. Over a median follow-up of 5.1 years (IQR 2.4–7.3), 8 (10.5%) had documented supraventricular arrhythmias and 8 (10.5%) died (atrial arrhythmia-related n=2; heart failure-related n=1; non-cardiac n=2; or unknown cause n=3), but there were no sudden cardiac deaths. Freedom from death or transplantation at 10 years was 80.8% (95% CI 62.5 to 90.8).ConclusionsThis is the largest cohort of childhood FA-HCM reported to date and describes a high prevalence of atrial arrhythmias and impaired systolic function in childhood, suggesting early progression to end-stage disease. Overall mortality is similar to that reported in non-syndromic childhood HCM, but no patients died suddenly.

This article explores the theoretical and practical role(s) of humour in facilitating outreach about sexual and gender-based violence (SGBV) in Sierra Leone. While humour might be considered an insensitive way of approaching difficult issues, this project shows that incongruity can in fact be productive. Recognizing that humour itself can be a form of symbolic or physical violence in some contexts, we argue that humour is a means of opening up conversations about violence (in this case SGBV) in order to address the social and legal challenges associated with it. Our pilot project – devised by an interdisciplinary team and conducted in partnership with a Sierra Leonean access-to-justice NGO, Timap for Justice – used comedy and performance to meet two key challenges: to disseminate awareness about social and legal issues related to commonplace practices of SGBV, and to open up a broader discussion about experiences of SGBV. Using empirical evidence from focus groups and interviews, this article shows how a humorous approach proved to be a productive mode of engagement and examines key concepts including ‘the vicinity of laughter’ (involving the spatial and interpersonal aspects of humour), the connections between laughter and memory, and the paradoxical relationship between lived experience, humour and violence.

In malaria-endemic areas, residents of modern houses have less malaria than those living in traditional houses. We aimed to assess whether children in The Gambia received an incremental benefit from improved housing, where current best practice of insecticide-treated nets, indoor residual spraying, seasonal malaria chemoprevention in children younger than 5 years, and prompt treatment against clinical malaria was in place.

Purpose: Although guidelines can reduce postoperative opioid prescription, the problem of unused opioids persists. We assessed the pattern of opioid prescription and utilization after total hip arthroplasty (THA) and total knee arthroplasty (TKA). We hypothesized that opioid prescription patterns can influence opioid utilization. Methods: With institutional ethics approval, patients undergoing THA and TKA were enrolled prospectively. Surveys on opioid use were completed at two, six, and 12 weeks after surgery. Patients’ age, sex, American Society of Anesthesiologists’ Physical Status score, first 24-hr opioid consumption, quantity of opioid prescribed, and quantity of opioid utilized were analyzed to evaluate their effect on opioid consumption, unused opioid, and patient satisfaction. Results: Patients received prescriptions ranging from 200 morphine milligram equivalents (MME) to 800 MME. Three hundred and thirty THA and 230 TKA patients completed the surveys. Opioid utilization was influenced by the amount of prescribed opioids for both THA and TKA. The percentage of prescribed opioids used (~55% in THA and ~75% in TKA) and the proportion of patients using all prescribed opioids (~22% in THA and ~50% in TKA) were higher after TKA vsTHA (P&lt; 0.001 for both). Patients who used opioids for two days or less accounted for most (~50%) of the unused opioid. Patient satisfaction remained high and was not influenced by the amount of prescribed opioid. Conclusion: This study showed that larger prescriptions are associated with higher opioid consumption. A wide variation in opioid consumption requires approaches to minimize the initial opioid prescription and to provide additional prescriptions for patients that require higher levels of analgesia.

Speech pathologists (SLPs) are routinely called on to develop and deliver culturallyappropriate practices for working with Aboriginal clients. We posit that to create realchange in practices with Aboriginal clients, we need to shift the focus beyond the individual clinician. Aboriginal community partners, researchers, academics and linguists need to be engaged with SLPs in clinically applicable, collaborative, intercultural, interdisciplinary teamwork. To do this we ask the profession to reconsider the way our work is envisioned, and urge funding bodies and government agencies to better support teams engaged in implementation science. Shifting the focus from individual practising clinicians towards teamwork is a more generative solution to engaging in culturally responsive practices with Aboriginal clients and in line with the commitments made in Speech Pathology Australia's Apology to Aboriginal and Torres Strait Islander Peoples. We present three cases of interdisciplinary, collaborative work which might serve as informative practice examples for the profession.

Recessive mutations in diacylglycerol kinase epsilon (DGKE) display genetic pleiotropy, with pathological features reported as either thrombotic microangiopathy or membranoproliferative glomerulonephritis (MPGN), and clinical features of atypical hemolytic uremic syndrome (aHUS), nephrotic syndrome or both. Pathophysiological mechanisms and optimal management strategies have not yet been defined. In prospective and retrospective studies of aHUS referred to the United Kingdom National aHUS service and prospective studies of MPGN referred to the National Registry of Rare Kidney Diseases for MPGN we defined the incidence of DGKE aHUS as 0.009/million/year and so-called DGKE MPGN as 0.006/million/year, giving a combined incidence of 0.015/million/year. Here, we describe a cohort of sixteen individuals with DGKE nephropathy. One presented with isolated nephrotic syndrome. Analysis of pathological features reveals that DGKEmutations give an MPGN-like appearance to different extents, with but more often without changes in arterioles or arteries. In 15 patients presenting with aHUS, ten had concurrent substantial proteinuria. Identified triggering events were rare but coexistent developmental disorders were seen in six. Nine with aHUS experienced at least one relapse, although in only one did a relapse of aHUS occur after age five years. Persistent proteinuria was seen in the majority of cases. Only two individuals have reached end stage renal disease, 20 years after the initial presentation, and in one, renal transplantation was successfully undertaken without relapse. Six individuals received eculizumab. Relapses on treatment occurred in one individual. In four individuals eculizumab was withdrawn, with one spontaneously resolving aHUS relapse occurring. Thus we suggest that DGKE-mediated aHUS is eculizumab non-responsive and that in individuals who currently receive eculizumab therapy it can be safely withdrawn. This has important patient safety and economic implications.

The tumor microenvironment plays a critical role in the proliferation and chemoresistance of cancer cells. Growth factors (GFs) are known to interact with the extracellular matrix (ECM) viaheparin binding sites, and these associations influence cell behavior. In the present study, we demonstrate the ability to define signals presented by the scaffold by pre-mixing growth factors, such as epidermal growth factor, into the heparin-based (HP-B) hydrogel prior to gelation. In the 3D biomimetic microenvironment, breast cancer cells formed spheroids within 24 hours of initial seeding. Despite higher number of proliferating cells in 2D cultures, 3D spheroids exhibited a higher degree of chemoresistance after 72 hours. Further, our RNA sequencing results highlighted the phenotypic changes influenced by solid-phase GF presentation. Wnt/β-catenin and TGF-β signaling were upregulated in the cells grown in the hydrogel, while apoptosis, IL2-STAT5 and PI3K-AKT-mTOR signaling were downregulated. With emerging technologies for precision medicine in cancer, this nature of fine-tuning the microenvironment is paramount for cultivation and downstream characterization of primary cancer cells and rare circulating tumor cells (CTCs), and effective screening of chemotherapeutic agents.

Background: The treatment of acute myeloid leukemia (AML) in older and/or unfit patients consists of a combination of a hypomethylating agent (HMA), such as decitabine and azacitidine, with venetoclax, which can be safely administered in the ambulatory setting. In this study, we aimed to compare the outcomes of the treatment of patients with AML who received chemotherapy with venetoclax and an HMA in an ambulatory setting at an academic center or at a community practice with academic center support.

IMPORTANCE: Sudden cardiac death (SCD) is the most common mode of death in childhood hypertrophic cardiomyopathy (HCM), but there is no validated algorithm to identify those at highest risk. OBJECTIVE: To develop and validate an SCD risk prediction model that provides individualized risk estimates. DESIGN, SETTING, AND PARTICIPANTS: A prognostic model was developed from a retrospective, multicenter, longitudinal cohort study of 1024 consecutively evaluated patients aged 16 years or younger with HCM. The study was conducted from January 1, 1970, to December 31, 2017. EXPOSURES: The model was developed using preselected predictor variables (unexplained syncope, maximal left-ventricular wall thickness, left atrial diameter, left-ventricular outflow tract gradient, and nonsustained ventricular tachycardia) identified from the literature and internally validated using bootstrapping. MAIN OUTCOMES AND MEASURES: A composite outcome of SCD or an equivalent event (aborted cardiac arrest, appropriate implantable cardioverter defibrillator therapy, or sustained ventricular tachycardia associated with hemodynamic compromise). RESULTS: Of the 1024 patients included in the study, 699 were boys (68.3%); mean (interquartile range [IQR]) age was 11 (7-14) years. Over a median follow-up of 5.3 years (IQR, 2.6-8.3; total patient years, 5984), 89 patients (8.7%) died suddenly or had an equivalent event (annual event rate, 1.49; 95% CI, 1.15-1.92). The pediatric model was developed using preselected variables to predict the risk of SCD. The model’s ability to predict risk at 5 years was validated; the C statistic was 0.69 (95% CI, 0.66-0.72), and the calibration slope was 0.98 (95% CI, 0.59-1.38). For every 10 implantable cardioverter defibrillators implanted in patients with 6% or more of a 5-year SCD risk, 1 patient may potentially be saved from SCD at 5 years. CONCLUSIONS AND RELEVANCE: This new, validated risk stratification model for SCD in childhood HCM may provide individualized estimates of risk at 5 years using readily obtained clinical risk factors. External validation studies are required to demonstrate the accuracy of this model's predictions in diverse patient populations.

Continuing professional learning is vital to early childhood professionals, and the use of digital technology can potentially reduce costs and improve access. In this study, 74 educators across 17 early childhood services in Australian urban and regional locations completed a questionnaire about their personal and professional uses of digital technology to find resources. The results indicate most early childhood educators use digital technology to construct their own professional knowledge bases, and though they make some use of formal resources around national standards, they make greater use of informal resources and discussion groups. They tend to seek practical information and activity ideas and ways to connect with other professionals, although this varies somewhat by years of professional experience, age and the socioeconomic context they work in. Results highlight early childhood educators’ professional learning desires and the potential value of mobile learning for providing access to professional learning for early childhood educators working in resource-limited and geographically limited settings.

C9orf72repeat expansions are the most common genetic cause of frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). Poly(GR) proteins are toxic to neurons by forming cytoplasmic inclusions that sequester RNA-binding proteins including stress granule (SG) proteins. However, little is known of the factors governing poly(GR) inclusion formation. Here, we show that poly(GR) infiltrates a finely tuned network of protein-RNA interactions underpinning SG formation. It interacts with G3BP1, the key driver of SG assembly and a protein we found is critical for poly(GR) inclusion formation. Moreover, we discovered that N6-methyladenosine (m6A)-modified mRNAs and m6A-binding YTHDF proteins not only co-localize with poly(GR) inclusions in brains of c9FTD/ALS mouse models and patients with c9FTD, they promote poly(GR) inclusion formation via the incorporation of RNA into the inclusions. Our findings thus suggest that interrupting interactions between poly(GR) and G3BP1 or YTHDF1 proteins or decreasing poly(GR) altogether represent promising therapeutic strategies to combat c9FTD/ALS pathogenesis.

In order to meet the unique needs of local populations, health and care providers need to come together as a collective. A model of integration in line with the NHS Long Term Plan will support transformation, sustainability and meeting the increasing demands on the NHS. Due the complexity and variety of services in care communities, it is vital that organisations and the third sector acknowledge and understand one another with greater depth. Primary care networks (PCNs) support this by dissolving organisational boundaries, with services wrapping around each other and moving forward as one system. This article describes how one PCN in Wirral committed to appreciating each service's roles. By engaging regularly in different ways, members of the PCN were able build on professional relationships. The refocusing and reconnecting regularly as a collective team enabled a more streamlined approach to proactive, place-based patient care while providing professionals with improved working relationships, skill-sharing and increased job satisfaction.

Treatment guidelines recommend a stepwise approach to primary biliary cholangitis: all patients begin treatment with ursodeoxycholic acid (UDCA) monotherapy and those with an inadequate biochemical response after 12 months are subsequently considered for second-line therapies. However, as a result, patients at the highest risk can wait the longest for effective treatment. We determined whether UDCA response can be accurately predicted using pretreatment clinical parameters.

The radical mastectomy was the mainstay of breast cancer treatment through the majority of the twentieth century. However, as the understanding of breast cancer increased, the indications for more extensive surgical intervention decreased. The mastectomy has evolved so that skin-sparing or nipple-sparing mastectomy can be performed in the majority of women who undergo mastectomy currently. Today, nearly 40% of all women undergo mastectomy for breast cancer. The improved cosmetic appearance associated with skin- or nipple-sparing mastectomies does not compromise oncologic outcomes.

IMPORTANCE: Postoperative readmission data are used to measure hospital performance, yet the extent to which these readmissions reflect surgical quality is unknown. OBJECTIVE: To establish expert consensus on whether reasons for postoperative readmission are associated with the quality of surgery in the index admission. DESIGN, SETTING, AND PARTICIPANTS: In a modified Delphi process, a panel of 14 experts in medical and surgical readmissions comprising physicians and nonphysicians from Veterans Affairs (VA) and private-sector institutions reviewed 30-day postoperative readmissions from fiscal years 2008 through 2014 associated with inpatient surgical procedures performed at a VA medical center between October 1, 2007, and September 30, 2014. The consensus process was conducted from January through May 2017. Reasons for readmission were grouped into categories based on International Classification of Diseases, Ninth Revision (ICD-9) diagnosis codes. Panelists were given the proportion of readmissions coded by each reason and median (interquartile range) days to readmission. They answered the question, “Does the readmission reason reflect possible surgical quality of care problems in the index admission?” on a scale of 1 (never related) to 5 (directly related) in 3 rounds of consensus building. The consensus process was completed in May 2017 and data were analyzed in June 2017. MAIN OUTCOMES AND MEASURES: Consensus on proportion of ICD-9–coded readmission reasons that reflected quality of surgical procedure. RESULTS: In 3 Delphi rounds, the 14 panelists achieved consensus on 50 reasons for readmission; 12 panelists also completed group telephone calls between rounds 1 and 2. Readmissions with diagnoses of infection, sepsis, pneumonia, hemorrhage/hematoma, anemia, ostomy complications, acute renal failure, fluid/electrolyte disorders, or venous thromboembolism were considered associated with surgical quality and accounted for 25 521 of 39 664 readmissions (64% of readmissions; 7.5% of 340 858 index surgical procedures). The proportion of readmissions considered to be not associated with surgical quality varied by procedure, ranging from to 21% (613 of 2331) of readmissions after lower-extremity amputations to 47% (745 of 1598) of readmissions after cholecystectomy. CONCLUSIONS AND RELEVANCE: One-third of postoperative readmissions are unlikely to reflect problems with surgical quality. Future studies should test whether restricting readmissions to those with specific ICD-9 codes might yield a more useful quality measure.

To translate and study the factor structure of a Japanese version of the Stressors in Nursing Students scale.

This paper describes a small Mesolithic structure from the Cairngorm Mountains, Scotland. Excavations at Caochanan Ruadha identified a small oval structure (c. 3m×2.2m) with a central fire setting, in an upland valley (c.540masl). The site was occupied at c. 8200calBP and demonstrates hunter-gatherer use of the uplands during a period of significant climatic deterioration. The interpretation of the structure is primarily based on the distribution of the lithic assemblage, as the heavily podsolised soils have left no trace of light structural features. The lithic assemblage is specialised, dominated by microlith fragments, and functional analysis has identified different uses of different areas inside the structure. The identification of small, specialised Mesolithic sites is unusual and this paper will discuss the evidence for the presence of the structure and its use, compare it to other Mesolithic structures in Britain and highlight some methodological implications.

IMPORTANCE: Preoperative hyperglycemia is associated with adverse postoperative outcomes among patients who undergo surgery. Whether preoperative hemoglobin A1c (HbA1c) or postoperative glucose levels are more useful in predicting adverse events following surgery is uncertain in the current literature. OBJECTIVE: To examine the use of preoperative HbA1c and early postoperative glucose levels for predicting postoperative complications and readmission. DESIGN, SETTING, AND PARTICIPANTS: In this observational cohort study, inpatient gastrointestinal surgical procedures performed at 117 Veterans Affairs hospitals from 2007 to 2014 were identified, and cases of known infection within 3 days before surgery were excluded. Preoperative HbA1c levels were examined as a continuous and categorical variable (&lt;5.7%, 5.7%-6.5%, and >6.5%). A logistic regression modeled postoperative complications and readmissions with the closest preoperative HbA1c within 90 days and the highest postoperative glucose levels within 48 hours of undergoing surgery. MAIN OUTCOMES AND MEASURES: Postoperative complications and 30-day unplanned readmission following discharge. RESULTS: Of 21 541 participants, 1193 (5.5%) were women, and the mean (SD) age was 63.7 (10.6) years. The cohort included 23 094 operations with measurements of preoperative HbA1c levels and postoperative glucose levels. The complication and 30-day readmission rates were 27.2% and 14.7%, respectively. In logistic regression models adjusting for HbA1c, postoperative glucose levels, postoperative insulin use, diabetes, body mass index (calculated as weight in kilograms divided by height in meters squared), and other patient and procedural factors, peak postoperative glucose levels of more than 250 mg/dL were associated with increased 30-day readmissions (odds ratio, 1.18; 95% CI, 0.99-1.41; P = .07). By contrast, a preoperative HbA1c of more than 6.5% was associated with decreased 30-day readmissions (odds ratio, 0.85; 95% CI, 0.74-0.96; P = .01). As preoperative HbA1c increased, the frequency of 48-hour postoperative glucose checks increased (4.92, 6.89, and 9.71 for an HbA1c &lt;5.7%, 5.7%-6.4%, and >6.5%, respectively; P &lt; .001). Patients with a preoperative HbA1c of more than 6.5% had lower thresholds for postoperative insulin use. CONCLUSIONS AND RELEVANCE: Early postoperative hyperglycemia was associated with increased readmission, but elevated preoperative HbA1c was not. A higher preoperative HbA1c was associated with increased postoperative glucose level checks and insulin use, suggesting that heightened postoperative vigilance and a lower threshold to treat hyperglycemia may explain this finding.

Exposure to domestic violence and abuse (DVA) is a global public health issue associated with substantial morbidity and mortality. There are few high-quality studies that assess the impact of DVA exposure on the development of atopic disease.

IMPORTANCE: Frail patients are known to have poor perioperative outcomes. There is a paucity of literature investigating how the Modified Frailty Index (mFI), a validated measure of frailty, is associated with unplanned readmission among military veterans following surgery. OBJECTIVE: To understand the association between frailty and 30-day postoperative unplanned readmission. DESIGN, SETTING, AND PARTICIPANTS: A retrospective cohort study was conducted among adult patients who underwent surgery and were discharged alive from Veterans Affairs hospitals for orthopedic, general, and vascular conditions between October 1, 2007, and September 30, 2014, with a postoperative length of stay between 2 and 30 days. EXPOSURE: Frailty, as calculated by the 11 variables on the mFI. MAIN OUTCOMES AND MEASURES: The primary outcome of interest is 30-day unplanned readmission. Secondary outcomes included any 30-day predischarge or postdischarge complication, 30-day postdischarge mortality, and 30-day emergency department visit. RESULTS: The study sample included 236 957 surgical procedures (among 223 877 men and 13 080 women; mean [SD] age, 64.0 [11.3] years) from high-volume surgical specialties: 101 348 procedures (42.8%) in orthopedic surgery, 92 808 procedures (39.2%) in general surgery, and 42 801 procedures (18.1%) in vascular surgery. The mFI was associated with readmission (odds ratio [OR], 1.11; 95% CI, 1.10-1.12; R2 = 10.3%; C statistic, 0.71). Unadjusted rates of overall 30-day readmission (26 262 [11.1%]), postdischarge emergency department visit (34 204 [14.4%]), any predischarge (13 855 [5.9%]) or postdischarge (14 836 [6.3%]) complication, and postdischarge mortality (1985 [0.8%]) varied by frailty in a dose-dependent fashion. In analysis by individual mFI components using Harrell ranking, impaired functional status, identified as nonindependent functional status (OR, 1.16; 95% CI, 1.11-1.21; P &lt; .01) or having a residual deficit from a prior cerebrovascular accident (OR, 1.17; 95% CI, 1.11-1.22; P &lt; .01), contributed most to the ability of the mFI to anticipate readmission compared with the other components. Acutely impaired sensorium (OR, 1.12; 95% CI, 0.99-1.27; P = .08) and history of a myocardial infarction within 6 months (OR, 0.93; 95% CI, 0.81-1.06; P = .28) were not significantly associated with readmission. CONCLUSIONS AND RELEVANCE: The mFI is associated with poor surgical outcomes, including readmission, primarily due to impaired functional status. Targeting potentially modifiable aspects of frailty preoperatively, such as improving functional status, may improve perioperative outcomes and decrease readmissions.

Steroid Resistant Nephrotic Syndrome (SRNS) in children and young adults has differing etiologies with monogenic disease accounting for 2.9–30% in selected series. Using whole exome sequencing we sought to stratify a national population of children with SRNS into monogenic and non-monogenic forms, and further define those groups by detailed phenotypic analysis. Pediatric patients with SRNS were identified via a national United Kingdom Renal Registry. Whole exome sequencing was performed on 187 patients, of which 12% have a positive family history with a focus on the 53 genes currently known to be associated with nephrotic syndrome. Genetic findings were correlated with individual case disease characteristics. Disease causing variants were detected in 26.2% of patients. Most often this occurred in the three most common SRNS-associated genes: NPHS1, NPHS2,and WT1but also in 14 other genes. The genotype did not always correlate with expected phenotype since mutations in OCRL, COL4A3,and DGKEassociated with specific syndromes were detected in patients with isolated renal disease. Analysis by primary/presumed compared with secondary steroid resistance found 30.8% monogenic disease in primary compared with none in secondary SRNS permitting further mechanistic stratification. Genetic SRNS progressed faster to end stage renal failure, with no documented disease recurrence post-transplantation within this cohort. Primary steroid resistance in which no gene mutation was identified had a 47.8% risk of recurrence. In this unbiased pediatric population, whole exome sequencing allowed screening of all current candidate genes. Thus, deep phenotyping combined with whole exome sequencing is an effective tool for early identification of SRNS etiology, yielding an evidence-based algorithm for clinical management.

Background Acupuncture shows promise as a treatment for plantar heel pain (PHP) or plantar fasciitis (PF), but data heterogeneity has undermined demonstration of efficacy. Recognising that acupuncture is a diverse field of practice, the aim of this study was to gain a broader, global perspective on the different approaches and rationales used in the application of acupuncture in PHP.Methods We built upon an earlier systematic review (which was limited by the necessity of a methodological focus on efficacy) using the critical interpretive synthesis (CIS) method to draw upon a wider international sample of 25 clinical sources, including case reports and case series. Multiple tracks of analysis led to an emergent synthesis.Results Findings are presented at three levels: primary (summarised data); secondary (patterns observed); and tertiary (emergent synthesis). Multiple treatments and rationales were documented but no single approach dominated. Notable contradictions emerged such as the application of moxibustion by some authors and ice by others. Synthesis of findings revealed a ‘patchwork’ of factors influencing the approaches taken.Conclusions The complexity of the field of acupuncture was illustrated through the ‘lens’ of PHP. The ‘patchwork’ metaphor provides a unifying framework for a previously divergent community of practice and research. Several directions for future research were identified, such as: importance of prior duration; existence of diagnostic subgroups; and how practitioners make clinical decisions and report their findings. CIS was found to provide visibility for multiple viewpoints in developing theory and modelling the processes of ‘real world’ practice by acupuncturists addressing the problem of PHP.