Genetic Analysis of Obesity-Induced Diabetic Nephropathy in BTBR Mice.

Diabetic nephropathy (DN) is the leading cause of end-stage renal disease in the U.S. and has a significant impact on human suffering. Leptin-deficient BTBR (BTBRob/ob) mice develop hallmark features of obesity-induced DN, whereas leptin-deficient C57BL/6J (B6ob/ob) mice do not. To identify genetic loci that underlie this strain difference, we constructed an F2 intercross between BTBRob/ob and B6ob/ob mice. We isolated kidneys from 460 F2 mice and histologically scored them for percent mesangial matrix and glomerular volume (∼50 glomeruli per mouse), yielding ∼45,000 distinct measures in total. The same histological measurements were made in kidneys from B6 and BTBR mice, either lean or obese (Lepob/ob), at 4 and 10 weeks of age, allowing us to assess the contribution of strain, age, and obesity to glomerular pathology. All F2 mice were genotyped for ∼5,000 single nucleotide polymorphisms (SNPs), ∼2,000 of which were polymorphic between B6 and BTBR, enabling us to identify a quantitative trait locus (QTL) on chromosome 7, with a peak at ∼30 Mbp, for percent mesangial matrix, glomerular volume, and mesangial volume. The podocyte-specific gene nephrin (Nphs1) is physically located at the QTL and contains high-impact SNPs in BTBR, including several missense variants within the extracellular immunoglobulin-like domains.

Introducing advanced paramedics into the rural general practice team in Ireland - general practitioners' attitudes.

INTRODUCTION: As Ireland's population increases and chronic disease becomes more prevalent, demand on limited general practice services will increase. Nursing roles within general practice are now considered to be standard, yet alternative non-medical professional roles are underexplored within an Irish context. Non-medical personnel such as Advanced Paramedics (APs) may have the capability to provide support to general practice. AIM: To explore GPs' attitudes and opinions about integrating Advanced Paramedics into rural general practice in Ireland. METHODS: A sequential explanatory mixed methodology was adopted. A questionnaire was designed and distributed to a purposeful sample of GPs attending a rural conference followed by semi-structured interviews. Data were recorded and transcribed verbatim and thematically analysed. RESULTS: In total, n=27 GPs responded to the survey and n=13 GPs were interviewed. Most GPs were familiar with APs and were receptive to the concept of closely collaborating with APs within a variety of settings, including out-of-hours services, home visits, nursing homes and even roles within the general practice surgery. DISCUSSION: GP and AP clinical practice dovetail within many facets of primary care and emergency care. GPs recognise that current rural models are unsustainable, and they realise the potential of integrating APs into the general practice team to help support and sustain the future of rural general practice services in Ireland. These interviews provided an exclusive, detailed insight into the world of general practice in Ireland that has not been previously documented in this way.

Design and Evaluation of Interprofessional Training Program for Healthcare Students from Collectivistic Culture.

Background: Healthcare is team-based, and with increased mobility of healthcare workers, most of them will work with team members from all over the globe. Interprofessional education (IPE) research has mostly focused on specially designed programs in academic health institutions to prepare students for multidisciplinary work. Few IPE programs aim to integrate students with mixed disciplines from collectivist cultures. Methods: This mixed-methods study was conducted between June and August 2019. Surveys and an e-portfolio were recorded of 33 final-year and graduated health professional students' participation in an 8-week IPE summer program at a medical school in Ireland. Survey results are described, and the content of portfolios was analyzed based on the deductive analysis of qualitative data derived from questions. Results: Students reported the greatest improvement in presentation skills (63.6%), followed by communication (54.5%), team working skills (93.9%), and interprofessional learning (42.4%), respectively. Qualitative findings highlighted challenges for students from a collectivist culture adapting to an IPE: uncomfortable verbally expressing themselves in problem-based learning (PBL) and how to work with other sex. Positive themes about IPE that emerged were enjoyment in sharing ideas and building trust with PBL groups. We learned that the program had to be flexible enough to meet the educational requirements of a target community with mixed English language ability and adaptability to IPE. Conclusion: The authors propose that an international PBL-based summer program is effective in improving healthcare students' attitudes towards IPE. This study provides valuable insights to facilitate the development of further IPE programs to increased collaboration between students across various healthcare disciplines. Supplementary Information: The online version contains supplementary material available at 10.1007/s40670-022-01536-7.

A Comparison of the Mid-Size Male THOR and Hybrid III ATDs in Vehicle Frontal Crash Tests.

In order to evaluate the THOR-50M as a front impact Anthropomorphic Test Device (ATD) for vehicle safety design, the ATD was compared to the H3-50M in matching vehicle crash tests for 20 unique vehicle models from 2 vehicle manufacturers. For the belted driver condition, a total of fifty-four crash tests were investigated in the 56.3 km/h (35 mph) front rigid barrier impact condition. Four more tests were compared for the unbelted driver and right front passenger at 40.2 km/h (25 mph) in the flat frontal and 30-degree right oblique rigid barrier impact conditions. The two ATDs were also evaluated for their ability to predict injury risk by comparing their fleet average injury risk to Crash Investigation Sampling System (CISS) accident data for similar conditions. The differences in seating position and their effect on ATD responses were also investigated. This study showed that the belted THOR-50M injury responses were higher than the H3-50M by 25%-180%, in all reported ATD responses, except chest acceleration. For one unbelted condition, the THOR-50M reported 200%-300% higher neck responses than the H3-50M, primarily due to head contact to the roof structure in a mid-sized sedan. The THOR-50M overpredicted the injury risk based on chest deflection compared to the CISS accident data by at least a factor of 4 times. The THOR-50M also overpredicted the injury risk based on BrIC by at least a factor of 10 times. Future work is needed to investigate these overpredictions with respect to ATD construction, injury risk curves, and seating procedures.

The Role of Hope and Resilience in Protecting Against Suicidal thoughts and Behaviors During the COVID-19 Pandemic.

OBJECTIVE: The COVID-19 pandemic has impacted the mental health and wellbeing of populations across the world. This study aimed to examine: (1) which specific aspects of the COVID-19 pandemic were associated with the presence of suicidal thoughts and behaviors, and (2) the extent to which participants' hopelessness and resilience moderated the relationship between COVID-19 related stress and suicidal thoughts and behaviors. METHOD: We administered an online survey to 12,989 adult (16+) participants across Wales from the 9th June to the 13th July 2020. Participants completed a series of questionnaires measuring the stressors they had experienced during the COVID-19 pandemic, their levels of hopelessness over the past two weeks, their levels of resilience, and whether they had experienced suicidal thoughts or behaviors since the onset of the COVID-19 pandemic. RESULTS: Our findings revealed that: (1) food insecurity, domestic abuse, relationship problems, redundancy, social isolation and financial problems were the COVID-19 related stressors most strongly associated with suicidal thoughts and behaviors, and (2) that both hopelessness and resilience moderated the relationship between COVID-19 stress and suicidal thoughts, such that the relationship between COVID-19 stress and the presence of suicidal thoughts was much stronger for individuals with high hopelessness and low resilience. CONCLUSIONS: These results highlight the aspects of the COVID-19 pandemic that are closely related to suicidal thoughts and behaviors and demonstrate the important role that hope for the future and resilience play in protecting individuals against the negative effects of the COVID-19 pandemic.HighlightsStressors caused by the pandemic are linked to increased suicidal thoughts.Hope protects individuals against the negative impact of the COVID-19 pandemic.Resilience also protects people from the negative impact of the COVID-19 pandemic.

Examination of a Canada-Wide Collaboration Platform for Order Sets: Retrospective Analysis.

BACKGROUND: Knowledge translation and dissemination are some of the main challenges that affect evidence-based medicine. Web 2.0 platforms promote the sharing and collaborative development of content. Executable knowledge tools, such as order sets, are a knowledge translation tool whose localization is critical to its effectiveness but a challenge for organizations to develop independently. OBJECTIVE: This paper describes a Web 2.0 resource, referred to as the collaborative network (TCN), for order set development designed to share executable knowledge (order sets). This paper also analyzes the scope of its use, describes its use through network analysis, and examines the provision and use of order sets in the platform by organizational size. METHODS: Data were collected from Think Research's TxConnect platform. We measured interorganization sharing across Canadian hospitals using descriptive statistics. A weighted chi-square analysis was used to evaluate institutional size to share volumes based on institution size, with post hoc Cramer V score to measure the strength of association. RESULTS: TCN consisted of 12,495 order sets across 683 diagnoses or processes. Between January 2010 and March 2015, a total of 131 health care organizations representing 360 hospitals in Canada downloaded order sets 105,496 times. Order sets related to acute coronary syndrome, analgesia, and venous thromboembolism were most commonly shared. COVID-19 order sets were among the most actively shared, adjusting for order set lifetime. A weighted chi-square analysis showed nonrandom downloading behavior (P<.001), with medium-sized institutions downloading content from larger institutions acting as the most significant driver of this variance (chi-gram=124.70). CONCLUSIONS: In this paper, we have described and analyzed a Web 2.0 platform for the sharing of order set content with significant network activity. The robust use of TCN to access customized order sets reflects its value as a resource for health care organizations when they develop or update their own order sets.

Psychological distress and resilience in first responders and health care workers during the COVID-19 pandemic.

During the COVID-19 pandemic, first responders and health care workers faced elevated virus-related risks through prolonged contacts with the public. Research suggests that these workers already experienced lower levels of psychological well-being linked to occupational risks. Thus, the pandemic's impact might have particularly affected mental health in these groups. This paper analysed data from a large-scale Welsh population study (N = 12,989) from June to July 2020. Levels of psychological distress were compared across various occupations, including police, fire and rescue, and NHS health care workers. Resilience was also indexed, and its role considered as a protective factor for psychological distress. Surprisingly, health care workers reported lower distress levels than the general population. Further, fire and rescue and police groups had lower distress than most groups and significantly higher resilience. Within police officers, higher resilience levels were protective for distress. Fire and rescue workers were half as likely as others to report distress, even accounting for demographic factors and resilience. The findings offer an optimistic view of psychological resilience in these critical occupations. They illustrate potential benefits to one's mental health of playing a crucial societal role during crises and reiterate the importance of enhancing resilience within groups who encounter high-risk situations daily. Practitioner points: Our findings provide evidence that health care workers and first responders showed lower levels of psychological distress than the general population during the first period of lockdown due to the COVID-19 pandemic in the United Kingdom. This may indicate that playing a critical role in society during an episode of crisis, and acting to help others, may be protective of one's own mental health.The research also provides an optimistic view of the psychological resilience of critical first responders and health care workers during a period early on in the COVID-19 pandemic (June-July 2020). This highlights the benefits of fostering resilience in those working within high-risk first responder and health care occupations.

Cardiac Rehabilitation for Patients With Heart Failure: JACC Expert Panel.

Cardiac rehabilitation is defined as a multidisciplinary program that includes exercise training, cardiac risk factor modification, psychosocial assessment, and outcomes assessment. Exercise training and other components of cardiac rehabilitation (CR) are safe and beneficial and result in significant improvements in quality of life, functional capacity, exercise performance, and heart failure (HF)-related hospitalizations in patients with HF. Despite outcome benefits, cost-effectiveness, and strong practice guideline recommendations, CR remains underused. Clinicians, health care leaders, and payers should prioritize incorporating CR as part of the standard of care for patients with HF.

The Influence of the COVID-19 Pandemic on Mental Well-Being and Psychological Distress: Impact Upon a Single Country.

The COVID-19 pandemic is likely to have affected the psychological well-being and mental health of many people. Data on prevalence rates of mental health problems are needed for mental health service planning. Psychological well-being and prevalence of clinically significant mental distress were measured in a large sample from Wales 11-16 weeks into lockdown and compared to population-based data collected in 2019 before the COVID-19 pandemic. Data were collected using an online survey disseminated across Wales and open to adults (age 16+) from 9th June to 13th July 2020. Psychological well-being was indexed via the Warwick-Edinburgh Mental Well-being Scale, and psychological distress was indexed via the K10. Data from 12,989 people who took part in this study were compared to that from April 2018 - March 2019, gathered by the National Survey for Wales (N = 11,922). Well-being showed a large decrease from 2019 levels. Clinically significant psychological distress was found in around 50% of the population (men = 47.4%, women = 58.6%), with around 20% showing "severe" effects (men = 17.0%, women = 20.9%): a 3-4-fold increase in prevalence. Most affected were young people, women, and those in deprived areas. By June-July 2020 the COVID-19 pandemic had dramatic effects on the mental health of people living in Wales (and by implication those in the UK and beyond). The effects are larger than previous reports. This probably reflects that the current data were taken deeper into the lockdown period than previous evaluations. Mental health services need to prepare for this wave of mental health problems with an emphasis on younger adults, women, and in areas of greater deprivation.

John's Campaign is starting to gain ground.

My trust has joined John's Campaign, which advocates for the right to stay with people who have dementia in hospital.

The use of wireless e-mail to improve healthcare team communication.

OBJECTIVE: To assess the impact of using wireless e-mail for clinical communication in an intensive care unit (ICU). DESIGN: The authors implemented push wireless e-mail over a GSM cellular network in a 26-bed ICU during a 6-month study period. Daytime ICU staff (intensivists, nurses, respiratory therapists, pharmacists, clerical staff, and ICU leadership) used handheld devices (BlackBerry, Research in Motion, Waterloo, ON) without dedicated training. The authors recorded e-mail volume and used standard methods to develop a self-administered survey of ICU staff to measure wireless e-mail impact. MEASUREMENTS: The survey assessed perceived impact of wireless e-mail on communication, team relationships, staff satisfaction and patient care. Answers were recorded on a 7-point Likert scale; favorable responses were categorized as Likert responses 5, 6, and 7. RESULTS: Staff sent 5.2 (1.9) and received 8.9 (2.1) messages (mean [SD]) per day during 5 months of the 6-month study period; usage decreased after study completion. Most (106/125 [85%]) staff completed the questionnaire. The majority reported that wireless e-mail improved speed (92%) and reliability (92%) of communication, improved coordination of ICU team members (88%), reduced staff frustration (75%), and resulted in faster (90%) and safer (75%) patient care; Likert responses were significantly different from neutral (p < 0.001 for all). Staff infrequently (18%) reported negative effects on communication. There were no reports of radiofrequency interference with medical devices. CONCLUSIONS: Interdisciplinary ICU staff perceived wireless e-mail to improve communication, team relationships, staff satisfaction, and patient care. Further research should address the impact of wireless e-mail on efficiency and timeliness of staff workflow and clinical outcomes.

Medical admission order sets to improve deep vein thrombosis prophylaxis rates and other outcomes.

BACKGROUND: The value of order sets for clinical decision support has not been established. OBJECTIVE: To determine whether introduction of admission order sets increases the proportion of inpatients receiving deep venous thrombosis (DVT) prophylaxis. DESIGN: Before-after study. SETTING: Community hospital. PATIENTS: General medical patients admitted to hospital. INTERVENTION: Paper-based admission order sets (instead of free-text orders) for voluntary use by internists, without any education or behavior change interventions. MEASUREMENTS: Primary outcome was proportion of medical admissions ordered DVT prophylaxis. Secondary outcomes included overall utilization of DVT prophylaxis in medical inpatients and other admission order care quality measures. RESULTS: Prior to introduction of order sets, DVT prophylaxis was ordered in 10.9% of patients. Patients admitted with order sets were more likely to be ordered DVT prophylaxis than patients admitted with free-text orders (44.0% versus 20.6%, by months 14 and 15, P<0.0001). Hospital-wide DVT prophylaxis in medical inpatients increased from 12.8% to 25.8% of patient-days (P<0.0001). Order set use improved many other secondary outcomes (P<0.05 for all), including allied health consultations (62.8% versus 12.7%), use of standardized diabetic diet (17.0% versus 5.1%), insulin sliding scale (19.1% versus 7.6%), potassium replacement protocol (63.8% versus 0.51%), documentation of allergies (54.3% versus 9.6%) and resuscitation status (57.4% versus 10.2%), and reduced orders for inappropriate laboratory tests such as blood urea nitrogen (39.4% versus 59.0%). CONCLUSIONS: The broad impact of order sets and minimal organizational resources required for their implementation suggests that order sets may have wide applicability as a clinical decision support tool.

Weight change after myocardial infarction--the Enhancing Recovery in Coronary Heart Disease patients (ENRICHD) experience.

BACKGROUND: The relationship of changes in weight to outcomes in patients after myocardial infarction (MI) is controversial. METHODS: From the ENRICHD trial data, we assessed weight change, and the associations of baseline weight and change at follow-up with outcomes and interactions between psychosocial factors. RESULTS: At baseline, 73.6% of patients (n = 1706) were overweight or obese; 134 patients had body mass index of > or = 40. Underweight patients were more likely to die or have nonfatal recurrent MI. After controlling for covariates, overweight and obese patients had similar outcomes to normal-weight patients. Eighteen percent of patients gained > 5%, 27% lost > 5%, and 55% had < or = 5% change in weight. Compared with weight loss of < or = 5%, the risk of death (adjusted hazard ratio 1.74, P = .01) and cardiovascular death (hazard ratio 1.79, P = .04) increased with weight loss of > 5%. After propensity matching, weight loss of > 5% remained as a significant risk factor for death and cardiovascular death. There was no interaction between weight change and depression and/or social support at baseline or follow-up. Weight change was not associated with recurrent MI or cardiovascular hospitalizations. CONCLUSIONS: A large proportion of patients lose or gain > 5% of body weight after an MI. The association between obesity and lower mortality is modulated by comorbidities. Weight loss after MI is associated with worse outcomes and is not related to depression or social support.

Extent of coronary artery disease as a predictor of outcomes in acute myocardial infarction complicated by heart failure, left ventricular dysfunction, or both.

BACKGROUND: Left ventricular systolic dysfunction (LVSD) and heart failure (HF) are powerful predictors of poor outcome after acute myocardial infarction (MI). It is not known, however, whether the extent of coronary artery disease (CAD) independently influences cardiovascular (CV) outcomes in these high-risk patients. METHODS: In the VALIANT, 14703 patients were randomly assigned to receive either captopril monotherapy, valsartan monotherapy, or a valsartan and captopril combination between 0.5 and 10 days after acute MI complicated by LVSD, HF, or both. Cox proportional hazards models were used to evaluate the relation between the extent of CAD (the number of diseased vessels as assessed by angiography) and a range of CV outcomes and all-cause mortality. RESULTS: Coronary angiography data were available on 5742 (40%) of the 14703 randomized patients. Single-vessel disease was reported in 1955 patients (34%), 2-vessel disease in 1598 (28%), and 3-vessel disease in 2189 (38%). For all CV outcomes, the risk increased with the severity of CAD (P for trend < .002). A comparison of single-, 2-, and 3-vessel disease showed that, after adjusting for all known covariates, including revascularization and ejection fraction, 2-vessel disease was associated with a 40% increased hazard (P = .008) and 3-vessel disease was associated with an 85% increased hazard (P < .001) for all-cause mortality. The fully adjusted hazard ratios for death and other CV outcomes increased significantly with increasing extent of CAD. CONCLUSIONS: Increasing extent of CAD, as detected by angiography, is a significant and independent risk factor for adverse CV outcomes after MI complicated by HF, LVSD, or both. The observed risk was apparent even after excluding patients who had undergone revascularization.

Organized Program to Initiate Lifesaving Treatment in Hospitalized Patients with Heart Failure (OPTIMIZE-HF): rationale and design.

Heart failure (HF) affects >5 million patients in the United States, and its prevalence is increasing every year. Despite the compelling scientific evidence that angiotensin-converting enzyme inhibitors and beta-blockers reduce hospitalizations and mortality rates in patients with HF, these lifesaving therapies continue to be underused. Several studies in a variety of clinical settings have documented that a significant proportion of eligible patients with HF are not receiving treatment with these guideline-recommended, evidence-based therapies. In patients hospitalized with HF, who are at particularly high risk for re-hospitalization and death, the initiation of beta-blockers is often delayed because of concern that early initiation of these agents may exacerbate HF. Recent studies suggest that beta-blockers can be safely and effectively initiated in patients with HF before hospital discharge and that clinical outcomes are improved. The Initiation Management Predischarge Process for Assessment of Carvedilol Therapy for Heart Failure (IMPACT-HF) trial demonstrated that pre-discharge initiation of carvedilol was associated with a higher rate of beta-blocker use after hospital discharge, with no increase in hospital length of stay. In addition, there was no increase in the risk of worsening of HF. Studies of hospital-based management systems that rely on early (pre-discharge) initiation of evidence-based therapies for patients with cardiovascular disease have also found increases in post-discharge use of therapy and a reduction in the rates of mortality and hospitalization. On the basis of these pivotal studies, the Organized Program to Initiate Lifesaving Treatment in Hospitalized Patients with Heart Failure (OPTIMIZE-HF) program is designed to improve medical care and education of hospitalized patients with HF and accelerate the initiation of evidence-based HF guideline recommended therapies by administering them before hospital discharge. A registry component, planned as the most comprehensive database of the hospitalized HF population focusing on admission to discharge and 60- to 90-day follow-up, is designed to evaluate the demographic, pathophysiologic, clinical, treatment, and outcome characteristics of patients hospitalized with HF. The ultimate aim of this program is to improve the standard of HF care in the hospital and outpatient settings and increase the use of evidence-based therapeutic strategies to save lives.

Diuretic resistance predicts mortality in patients with advanced heart failure.

BACKGROUND: In patients with chronic heart failure (CHF), diuretic requirements increase as the disease progresses. Because diuretic resistance can be overcome with escalating doses, the evaluation of CHF severity and prognosis may be incomplete without considering the intensity of therapy. METHODS: The prognostic importance of diuretic resistance (as evidenced by a high-dose requirement) was retrospectively evaluated in 1153 patients with advanced CHF who were enrolled in the Prospective Randomized Amlodipine Survival Evaluation (PRAISE). The relation of loop diuretic and angiotensin-converting enzyme inhibitor doses (defined by their median values) and other baseline characteristics to total and cause-specific mortality was determined by proportion hazards regression. RESULTS: High diuretic doses were independently associated with mortality, sudden death, and pump failure death (adjusted hazard ratios [HRs] 1.37 [P =.004], 1.39 [P =.042], and 1.51 [P =.034], respectively). Use of metolazone was an independent predictor of total mortality (adjusted HR = 1.37, P =.016) but not of cause-specific mortality. Low angiotensin-converting enzyme inhibitor dose was an independent predictor of pump failure death (adjusted HR = 2.21, P =.0005). Unadjusted mortality risks of congestion and its treatment were additive and comparable to those of established risk factors. CONCLUSIONS: The independent association of high diuretic doses with mortality suggests that diuretic resistance should be considered an indicator of prognosis in patients with chronic CHF. These retrospective observations do not establish harm or rule out a long-term benefit of diuretics in CHF, because selection bias may entirely explain the relation of prescribed therapy to death.