Relationships between sodium, fats and carbohydrates on blood pressure, cholesterol and HbA1c: an umbrella review of systematic reviews.

Background: The relationship between nutrition and health is complex and the evidence to describe it broad and diffuse. This review brings together evidence for the effect of nutrients on cardiometabolic risk factors. Methods: An umbrella review identified systematic reviews of randomised controlled trials and meta-analyses estimating the effects of fats, carbohydrates and sodium on blood pressure, cholesterol and haemoglobin A1c (HbA1c). Medline, Embase, Cochrane Library and Science Citation Index were search through 26 May 2020, with supplementary searches of grey literature and websites. English language systematic reviews and meta-analyses were included that assessed the effect of sodium, carbohydrates or fat on blood pressure, cholesterol and HbA1c. Reviews were purposively selected using a sampling framework matrix. The quality of evidence was assessed with A MeaSurement Tool to Assess systematic Reviews 2 (AMSTAR2) checklist, evidence synthesised in a narrative review and causal pathways diagram. Results: Forty-three systematic reviews were included. Blood pressure was significantly associated with sodium, fibre and fat. Sodium, fats and carbohydrates were significantly associated with cholesterol. Monounsaturated fat, fibre and sugars were associated with HbA1c. Conclusion: Multiple relationships between nutrients and cardiometabolic risk factors were identified and summarised in an accessible way for public health researchers. The review identifies associations, inconsistencies and gaps in evidence linking nutrition to cardiometabolic health.

Iatrogenic open humeral shaft fractures following functional bracing.

INTRODUCTION: The treatment of closed humeral shaft fractures tends to be successful with functional bracing. Treatment failure due to iatrogenic conversion to an open fracture has not been described in the literature. We present a case series of patients that experienced open humeral shaft fractures after initially being treated with functional bracing for closed humeral shaft fractures and describe what factors are associated with this complication. MATERIALS AND METHODS: This was a retrospective case series performed at three level 1 trauma centers across North America. All nonoperatively treated humeral shaft fractures were reviewed from 2001 to 2023. Patients were included if they sustained a humeral shaft fracture, > 18 years old, were initially treated non-operatively with functional bracing which subsequently converted to an open fracture. Eight patients met inclusion criteria. All included patients were eventually treated with irrigation, debridement, and open reduction and internal fixation. Outcomes assessed included mortality rate, time until the fracture converted from closed to open, need for further surgery, and bony union. Descriptive statistics were used in analysis. RESULTS: The eight included patients on average were 65 ± 21.4 years old and had a body mass index (BMI) of 25.6 ± 5.2. Six patients were initially injured due to a fall. Time until the fractures became open on average was 5.2 ± 3.6 weeks. Three patients (37.5%) died within 1.8 ± 0.6 years after initial injury. The average Charlson Comorbidity Index (CCI) score was 4.5 ± 3.4. Three patients (37.5%) had dementia. Common characteristics among this cohort included a history of visual disturbances (50.0%), cerebrovascular accident (50.0%), smoking (50.0%), and alcohol abuse (50.0%). CONCLUSION: Conversion from a closed to open humeral shaft fracture after functional bracing is a potentially devastating complication. Physicians should be especially cognizant of patients with a low BMI, history of falling or visual disturbance, dementia, age ≥ 65, decreased sensorimotor protection, and significant smoking or alcohol history when choosing to use functional bracing as the final treatment modality. LEVEL OF EVIDENCE: IV.

Household food insecurity and child health outcomes: a rapid review of mechanisms and associations.

BACKGROUND: Household food insecurity (HHFI) has detrimental impact on child health outcomes. The primary aim of this work was to describe the mechanisms, defined as statistically quantified processes or systems, that explain the association between HHFI and poor child health outcomes. The secondary aim was to identify which child health outcomes were significantly associated with HHFI. METHODS: In this rapid review, we included real-world evidence studies in children and adolescents aged 3-24 years, from high-income countries. We searched peer-reviewed literature through the databases Medline, Embase, Web of Science and The Cochrane Library on March 10, 2022, with a 15-year time restriction. Key search terms included "food insecurity", "food poverty", "statistics", "structural equation model*", "regression", "conceptual model*", and "theoretical model*". We identified additional studies by searching citations and references. Papers were selected using pre-defined criteria and non-English Language studies were excluded. We extracted summary data of published studies using the Cochrane data extraction template as a guide. We included a broad range of health outcomes to identify what aspects of health are affected by HHFI, including metabolic risk factors (eg, BMI), conditions (eg, depression), biological processes (eg, sleep) and parent-child interactions (eg, feeding styles). We performed a narrative synthesis, as heterogeneity precluded statistical synthesis. We used the Quality in Prognosis Studies tool to assess the mechanism studies. FINDINGS: We included 70 systematic reviews (six mechanism and 64 association reviews) from the UK, Canada, USA, Australia, and Ireland (including 18 887 mechanism studies and 986 759 association studies). Low-to-moderate bias was detected in mechanism studies, and there was variability in HHFI measures. Maternal depression and parenting stress during childhood played a mechanistic role between HHFI and adolescent depression (b=0·008, 95% CI 0·002-0·016) and anxiety (b=0·012, 0·002-0·026). Maternal stress mediated the association between HHFI and child overweight (odds ratio [OR] 1·79, 0·82-3·92, p<0·01), via restrictive feeding styles (OR 1·81, 1·15-2·85, p=0·010) that had negative impact on diet (p<0·01). Ethnicity, income, employment, and education moderated the relationship between HHFI and child health outcomes (p<0·001). INTERPRETATION: Two key mechanistic pathways between HHFI and child health outcomes were diet and mental health of both child and parent, which appeared interrelated. Interventions targeting HHFI in children, should consider these pathways alongside sociodemographic factors. A strength of this review was that it was the first literature summary explaining the mechanisms between HHFI and child health, using evidence from high-income countries. A limitation was that HHFI measures were inconsistent between studies and countries, disallowing study comparisons. FUNDING: University of Sheffield.

Comparison of activity, structure, and dynamics of SF-1 and LRH-1 complexed with small molecule modulators.

Steroidogenic factor-1 (SF-1) is a phospholipid-sensing nuclear receptor expressed in the adrenal glands, gonads, and hypothalamus which controls steroidogenesis and metabolism. There is significant therapeutic interest in SF-1 because of its oncogenic properties in adrenocortical cancer. Synthetic modulators are attractive for targeting SF-1 for clinical and laboratory purposes due to the poor pharmaceutical properties of its native phospholipid ligands. While small molecule agonists targeting SF-1 have been synthesized, no crystal structures have been reported of SF-1 in complexes with synthetic compounds. This has prevented the establishment of structure-activity relationships that would enable better characterization of ligand-mediated activation and improvement in current chemical scaffolds. Here, we compare the effects of small molecules in SF-1 and its close homolog, liver receptor homolog-1 (LRH-1), and identify several molecules that specifically activate LRH-1. We also report the first crystal structure of SF-1 in complex with a synthetic agonist that displays low nanomolar affinity and potency for SF-1. We use this structure to explore the mechanistic basis for small molecule agonism of SF-1, especially compared to LRH-1, and uncover unique signaling pathways that drive LRH-1 specificity. Molecular dynamics simulations reveal differences in protein dynamics at the pocket mouth as well as ligand-mediated allosteric communication from this region to the coactivator binding interface. Our studies, therefore, shed important insight into the allostery driving SF-1 activity and show potential for modulation of LRH-1 over SF-1.

Measuring health-related quality of life measures in children: lessons from a pilot study.

There is a debate in the health outcomes literature regarding who the most appropriate respondent is when assessing children's health-related quality of life (HRQoL). In some cases, parent-proxy may be the only practical option where children are unable to self-complete an HRQoL questionnaire. However, children's self-reported values may be preferable because HRQoL is subjective and represents the respondent own perception of health. We collected the youth version of the EQ-5D-3L as part of a feasibility study comparing psychoanalytic child psychotherapy with usual care for children aged 5-11 years with treatment resistant conduct disorders. The questionnaires were completed at baseline and 4-month follow-up by the child via face-to-face researcher administration, and by one parent as a proxy respondent. We present percentages of completion at each time-point and investigate the level of agreement between child and proxy-respondent on the child's health. About two thirds of children (65.5%) were able to complete the EQ-5D-Y at baseline and 34.4% at follow-up. Children and primary carers were mostly concordant regarding overall child's health. Parents reported more problems in 'doing usual activities' and 'feeling worried, sad or unhappy' and fewer problems with 'pain' and 'looking after oneself' than children did. The reports regarding 'mobility' were very similar between children and proxy-respondents. The assessment of quality of life by children using selfreport questionnaires is possible with the help of a face-to-face researcher, providing evidence that children should be asked to self-complete HRQoL questionnaires in trial studies.

Sensitivity of chest X-ray for detecting lung cancer in people presenting with symptoms: a systematic review.

BACKGROUND: Despite increasing use of computed tomography (CT), chest X-ray remains the first-line investigation for suspected lung cancer in primary care in the UK. No systematic review evidence exists as to the sensitivity of chest X-ray for detecting lung cancer in people presenting with symptoms. AIM: To estimate the sensitivity of chest X-ray for detecting lung cancer in symptomatic people. DESIGN AND SETTING: A systematic review was conducted to determine the sensitivity of chest X-ray for the detection of lung cancer. METHOD: Databases including MEDLINE, EMBASE, and the Cochrane Library were searched; a grey literature search was also performed. RESULTS: A total of 21 studies met the eligibility criteria. Almost all were of poor quality. Only one study had the diagnostic accuracy of chest X-ray as its primary objective. Most articles were case studies with a high risk of bias. Several were drawn from non-representative groups, for example, specific presentations, histological subtypes, or comorbidities. Only three studies had a low risk of bias. Two primary care studies reported sensitivities of 76.8% (95% confidence interval [CI] = 64.5 to 84.2%) and 79.3% (95% CI = 67.6 to 91.0%). One secondary care study reported a sensitivity of 79.7% (95% CI = 72.7 to 86.8%). CONCLUSION: Though there is a paucity of evidence, the highest-quality studies suggest that the sensitivity of chest X-ray for symptomatic lung cancer is only 77% to 80%. GPs should consider if further investigation is necessary in high-risk patients who have had a negative chest X-ray.

Clinical decision support for high-cost imaging: A randomized clinical trial.

There is widespread concern over the health risks and healthcare costs from potentially inappropriate high-cost imaging. As a result, the Centers for Medicare and Medicaid Services (CMS) will soon require high-cost imaging orders to be accompanied by Clinical Decision Support (CDS): software that provides appropriateness information at the time orders are placed via a best practice alert for targeted (i.e. likely inappropriate) imaging orders, although the impacts of CDS in this context are unclear. In this randomized trial of 3,511 healthcare providers at Aurora Health Care, we study the impacts of CDS on the ordering behavior of providers. We find that CDS reduced targeted imaging orders by a statistically significant 6%, however there was no statistically significant change in the total number of high-cost scans or of low-cost scans. The results suggest that the impending CMS mandate requiring healthcare systems to adopt CDS may modestly increase the appropriateness of high-cost imaging.

TIGA-CUB-manualised psychoanalytic child psychotherapy versus treatment as usual for children aged 5-11 with treatment-resistant conduct disorders and their primary carers: results from a randomised controlled feasibility trial.

BACKGROUND: Parenting programmes are recommended for conduct disorders in 5-11 year olds, but ineffective for 25-33%. A feasibility trial was needed to determine whether a confirmatory trial of second-line, manualised short-term psychoanalytic child psychotherapy (mPCP) versus treatment as usual (TaU) is practicable. METHOD: This was a two-arm, pragmatic, parallel-group, multi-centre, individually-randomised controlled feasibility trial with blinded outcome assessment. Child-primary carer dyads were recruited from National Health Service Child and Adolescent Mental Health Services and mPCP delivered by routine child psychotherapists. RESULTS: Thirty-two dyads (50% of eligible, 95% CI 37 to 63%) were recruited, with 16 randomised to each arm. Eleven (69%) completed ≥50% of 12 week mPCP and 13 (81%) . Follow-up was obtained for 24 (75%) at 4 months and 14/16 (88%) at 8 months. Teacher follow-up was 16 (50%) ≥1 session. Manual adherence was good. Baseline candidate primary outcomes were 37.4 (SD 11.4) and 18.1 (SD 15.7) on the Child Behaviour Checklist/Teacher Report Form externalising scale and 102.8 (SD 28.4) and 58.8 (SD 38.9) on the total score. Health economics data collection was feasible and the trial acceptable to participants. CONCLUSION: Recruitment, teacher follow-up and the manual need some refinement. A confirmatory trial is feasible, subject to funding of research child psychotherapists.

Gaps in Guidelines for the Management of Diabetes in Low- and Middle-Income Versus High-Income Countries-A Systematic Review.

OBJECTIVE: The extent to which diabetes (DM) practice guidelines, often based on evidence from high-income countries (HIC), can be implemented to improve outcomes in low- and middle-income countries (LMIC) is a critical challenge. We carried out a systematic review to compare type 2 DM guidelines in individual LMIC versus HIC over the past decade to identify aspects that could be improved to facilitate implementation. RESEARCH DESIGN AND METHODS: Eligible guidelines were sought from online databases and websites of diabetes associations and ministries of health. Type 2 DM guidelines published between 2006 and 2016 with accessible full publications were included. Each of the 54 eligible guidelines was assessed for compliance with the Institute of Medicine (IOM) standards, coverage of the cardiovascular quadrangle (epidemiologic surveillance, prevention, acute care, and rehabilitation), translatability, and its target audiences. RESULTS: Most LMIC guidelines were inadequate in terms of applicability, clarity, and dissemination plan as well as socioeconomic and ethical-legal contextualization. LMIC guidelines targeted mainly health care providers, with only a few including patients (7%), payers (11%), and policy makers (18%) as their target audiences. Compared with HIC guidelines, the spectrum of DM clinical care addressed by LMIC guidelines was narrow. Most guidelines from the LMIC complied with less than half of the IOM standards, with 12% of the LMIC guidelines satisfying at least four IOM criteria as opposed to 60% of the HIC guidelines (P < 0.001). CONCLUSIONS: A new approach to the contextualization, content development, and delivery of LMIC guidelines is needed to improve outcomes.

Patient Experience After Receiving a Diagnosis of Gastric Cancer in the USA.

PURPOSE: This study investigated the patient perspective during cancer treatment and throughout the survivorship period and to understand how the patient experience may be related to choices for the treatment of gastric cancer. METHODS: Eligible patients in the Vector Oncology electronic medical records database were ≥18 years of age, diagnosed with gastric cancer, and received active treatment. Quality of life (QOL) was collected using the Patient Care Monitor (PCM). Time to deterioration in QOL and overall survival were measured, adjusting for demographic and baseline clinical characteristics. Logistic regression model and classification and regression trees (CART) were used to identify factors associated with treatment choice. RESULTS: There were 776 patients in this study, of whom 301 (38.8%) reported QOL data. Most patients reported problems on all PCM subscales; problems were more common during the treatment period. Median time to deterioration of PCM subscales ranged from 42 days for treatment side effects to 331 days for impaired performance. Median survival was low: 6.9 and 5.5 months from the start of first- and second-line therapy, respectively. The choices made between therapeutic options were primarily associated with the site at which the oncologist practiced. CONCLUSIONS: Patients with gastric cancer report a considerable number of concerns on all subscales of the PCM, particularly during active treatment periods. The treatment heterogeneity and relative lack of clinical and symptom- or QOL-related factors associated with treatment choice suggest a gap in evidence that must be filled.

Investigation of Classical Organic and Ionic Liquid Cosolvents for Early-Stage Screening in Fragment-Based Inhibitor Design with Unrelated Bacterial and Human Dihydrofolate Reductases.

Drug design by methods such as fragment screening requires effective solubilization of millimolar concentrations of small organic compounds while maintaining the properties of the biological target. We investigate four organic solvents and three 1-butyl-3-methylimidazolium (BMIm)-based ionic liquids (ILs) as cosolvents to establish conditions for screening two structurally unrelated dihydrofolate reductases (DHFRs) that are prime drug targets. Moderate concentrations (10%-15%) of cosolvents had little effect on inhibition of the microbial type II R67 DHFR and of human DHFR (hDHFR), while higher concentrations of organic cosolvents generally decreased activity of both DHFRs. In contrast, a specific IL conserved the activity of one DHFR, while severely reducing the activity of the other, and vice versa, illustrating the differing effect of ILs on distinct protein folds. Most of the cosolvents investigated preserved the fold of R67 DHFR and had little effect on binding of the cofactor NADPH, but reduced the productive affinity for its substrate. In contrast, cosolvents resulted in modest structural destabilization of hDHFR with little effect on productive affinity. We conclude that the organic cosolvents, methanol, dimethylformamide, and dimethylsulfoxide, offer the most balanced conditions for early-stage compound screening as they maintain sufficient biological activity of both DHFRs while allowing for compound dissolution in the millimolar range. However, IL cosolvents showed poor capacity to solubilize organic compounds at millimolar concentrations, mitigating their utility in early-stage screening. Nonetheless, ILs could provide an alternative to classical organic cosolvents when low concentrations of inhibitors are used, as when characterizing higher affinity inhibitors.

The Association Between Income and Life Expectancy in the United States, 2001-2014.

IMPORTANCE: The relationship between income and life expectancy is well established but remains poorly understood. OBJECTIVES: To measure the level, time trend, and geographic variability in the association between income and life expectancy and to identify factors related to small area variation. DESIGN AND SETTING: Income data for the US population were obtained from 1.4 billion deidentified tax records between 1999 and 2014. Mortality data were obtained from Social Security Administration death records. These data were used to estimate race- and ethnicity-adjusted life expectancy at 40 years of age by household income percentile, sex, and geographic area, and to evaluate factors associated with differences in life expectancy. EXPOSURE: Pretax household earnings as a measure of income. MAIN OUTCOMES AND MEASURES: Relationship between income and life expectancy; trends in life expectancy by income group; geographic variation in life expectancy levels and trends by income group; and factors associated with differences in life expectancy across areas. RESULTS: The sample consisted of 1,408,287,218 person-year observations for individuals aged 40 to 76 years (mean age, 53.0 years; median household earnings among working individuals, $61,175 per year). There were 4,114,380 deaths among men (mortality rate, 596.3 per 100,000) and 2,694,808 deaths among women (mortality rate, 375.1 per 100,000). The analysis yielded 4 results. First, higher income was associated with greater longevity throughout the income distribution. The gap in life expectancy between the richest 1% and poorest 1% of individuals was 14.6 years (95% CI, 14.4 to 14.8 years) for men and 10.1 years (95% CI, 9.9 to 10.3 years) for women. Second, inequality in life expectancy increased over time. Between 2001 and 2014, life expectancy increased by 2.34 years for men and 2.91 years for women in the top 5% of the income distribution, but by only 0.32 years for men and 0.04 years for women in the bottom 5% (P < .001 for the differences for both sexes). Third, life expectancy for low-income individuals varied substantially across local areas. In the bottom income quartile, life expectancy differed by approximately 4.5 years between areas with the highest and lowest longevity. Changes in life expectancy between 2001 and 2014 ranged from gains of more than 4 years to losses of more than 2 years across areas. Fourth, geographic differences in life expectancy for individuals in the lowest income quartile were significantly correlated with health behaviors such as smoking (r = -0.69, P < .001), but were not significantly correlated with access to medical care, physical environmental factors, income inequality, or labor market conditions. Life expectancy for low-income individuals was positively correlated with the local area fraction of immigrants (r = 0.72, P < .001), fraction of college graduates (r = 0.42, P < .001), and government expenditures (r = 0.57, P < .001). CONCLUSIONS AND RELEVANCE: In the United States between 2001 and 2014, higher income was associated with greater longevity, and differences in life expectancy across income groups increased over time. However, the association between life expectancy and income varied substantially across areas; differences in longevity across income groups decreased in some areas and increased in others. The differences in life expectancy were correlated with health behaviors and local area characteristics.