Geriatric proximal femur fracture updates.

Proximal femur fractures in the aging population present a variety of challenges. Physiologically, patients incurring this fracture are typically frail, with significant medical comorbidities, yet require early surgical treatment to restore mobility to prevent deterioration. Socioeconomically, the occurrence of a fragility fracture may be the beginning of the loss of independence, and the burdens of rehabilitation and support are borne by the individual patient and health care systems.

Effects of the Sodium-Glucose Cotransporter Inhibitors on Cardiovascular Death and All-Cause Mortality: A Systematic Review and Meta-analysis of Randomized Placebo-Controlled Clinical Trials.

BACKGROUND: Patients with diabetes mellitus are at an increased risk of cardiovascular morbidity and all-cause mortality. Heart failure and type 2 diabetes often occur concomitantly, and each disease independently increases the risk for the other. OBJECTIVE: Emerging data have revealed that some sodium-glucose cotransporter inhibitors (SGLTi) improve cardiovascular and renal outcomes, particularly in patients with type 2 diabetes. The magnitude of this effect in patients without any underlying condition remains unclear. As a result, we conducted a meta-analysis of the mortality outcomes of available SGLTi in patients with or without cardiovascular diseases, type 2 diabetes, cardiovascular risk factors, and heart failure. METHODS: We performed a systematic review and meta-analysis of randomized, placebo-controlled major cardiovascular outcome trials of SGLTi in patients regardless of their cardiovascular disease or risk status. PubMed, Cochrane, Google Scholar, MEDLINE, and EMBASE were searched for the relevant studies. Three reviewers extracted study data and three reviewers summarized the strength of the evidence. Efficacy outcomes included all-cause mortality, major adverse cardiovascular events (myocardial infarction, stroke, or cardiovascular death), the composite of all-cause mortality, cardiovascular death, or hospitalization for heart failure. Odds ratios with 95% confidence intervals were pooled across trials to calculate the overall effect size. RESULTS: A total of 5043 all-cause mortality events were observed in the study groups. In 42,050 patients who received SGLTi, 2581 events were reported, and 2462 events were reported in 35,491 patients who received placebo (odds ratio = 0.86, 95% confidence interval 0.80-0.93, p = 0.0003). The use of SGLTi significantly reduced cardiovascular mortality compared with control across the patients' population (odds ratio = 0.86, 95% confidence interval 0.79-0.93, p = 0.0001). There was a consistent pattern of mortality beneficial estimates for all patients with different co-morbid conditions in the SGLTi-treated arm compared with the placebo-treated group. The presence or absence of significant cardiovascular disease risk factors (including a family history of premature coronary artery disease, baseline estimated glomerular filtration rate, dyslipidemia, hypertension, smoking, history of cardiovascular disease, and older age) did not affect the estimated mortality benefits. CONCLUSIONS: Sodium-glucose cotransporter inhibitors significantly reduced major adverse cardiovascular events, including hospitalization and all-cause mortality in patients with or without established atherosclerotic cardiovascular disease. We observed a beneficial trend in patients with heart failure with preserved ejection fraction, and no benefits in patients with stroke or myocardial infarction.

Patients with diabetes are at increased risk of cardiac illness and mortality. Heart failure (HF) and type II diabetes mellitus (DM II) often occur concurrently, and each disease independently increases the risk for the other. Evolving data have revealed that medications utilized for diabetes management, specifically, sodium-glucose cotransporter inhibitors (SGLTi) improve cardiac and renal health, particularly in patients with DM II. The impact of this effect in other patients remains unclear. Therefore, we conducted a comprehensive review of the mortality and other benefits of available SGLTi in patients with or without cardiac diseases, DM II, cardiac risk factors, and HF. A total of 5043 mortality events were observed in the study groups. The use of SGLTi significantly reduced cardiac death compared with placebo. There was a reduction in the number of deaths for patients with different conditions in the SGLTi treated arm compared with the placebo group. The presence or absence of cardiac disease, or risk factors did not affect mortality benefits. SGLTi significantly reduced major adverse cardiac events, including hospitalization and mortality in patients with or without cardiac disease.

Human immunomodulatory ligand B7-1 mediates synaptic remodeling via the p75 neurotrophin receptor.

Cell surface receptors, ligands, and adhesion molecules underlie development, circuit formation, and synaptic function of the central nervous system and represent important therapeutic targets for many neuropathologies. The functional contributions of interactions between cell surface proteins of neurons and nonneuronal cells have not been fully addressed. Using an unbiased protein-protein interaction screen, we showed that the human immunomodulatory ligand B7-1 (hB7-1) interacts with the p75 neurotrophin receptor (p75NTR) and that the B7-1:p75NTR interaction is a recent evolutionary adaptation present in humans and other primates, but absent in mice, rats, and other lower mammals. The surface of hB7-1 that engages p75NTR overlaps with the hB7-1 surface involved in CTLA-4/CD28 recognition, and these molecules directly compete for binding to p75NTR. Soluble or membrane-bound hB7-1 altered dendritic morphology of cultured hippocampal neurons, with loss of the postsynaptic protein PSD95 in a p75NTR-dependent manner. Abatacept, an FDA-approved therapeutic (CTLA-4-hFc fusion) inhibited these processes. In vivo injection of hB7-1 into the murine subiculum, a hippocampal region affected in Alzheimer's disease, resulted in p75NTR-dependent pruning of dendritic spines. Here, we report the biochemical interaction between B7-1 and p75NTR, describe biological effects on neuronal morphology, and identify a therapeutic opportunity for treatment of neuroinflammatory diseases.

New graduate registered nurses: Risk mitigation strategies to ensure safety and successful transition to practice.

The COVID-19 pandemic has impacted traditional pathways for new graduate registered nurses (NGRN's) transition to practice. In response to stay at home emergency orders in 2020, NGRN's experienced changes in pre-licensure curriculum, clinical practicums, NCLEX testing, and licensure, all which influence preparedness for professional practice. The adverse impact on education and clinical training extends to all nursing students who attended higher education institutions of learning during 2020 to present and is a significant consideration with new graduates over the long-term, whom will be caring for patients in healthcare settings. Well before this pandemic, literature identified that NGRN's were predisposed to knowledge-practice gaps and lacked situational awareness. Recent nursing research emerging from the pandemic reveals a potentiating negative impact of the abbreviated pre-licensure experiences on patient safety in the clinical setting. In the current healthcare environment, it is preemptive for healthcare institutions and schools of nursing to work cohesively to ensure patient safety through an increased emphasis on evidence-based approaches to reduce patient harm and mitigate harm when it does occur. Further, in response to the increased demand for nurses by healthcare organizations, considerations for safety, risk management, and ethical care must be considered during the transition to practice for NGRN's.

The Impact of a Mobile App on Participation in Cardiac Rehabilitation and Understanding Barriers to Success: Comparative Cohort Study.

BACKGROUND: Poor patient uptake of cardiac rehabilitation (CR) remains a challenge for multiple reasons including geographic, time, cultural, cost, and psychological constraints. OBJECTIVE: We evaluated the impact on CR participation rates associated with the addition of the option of mobile app-based CR (Cardihab) for patients declining conventional CR. METHODS: A total of 204 consecutive patients were offered CR following angioplasty; of these, 99 were in cohort 1 (offered conventional CR only) and 105 were in cohort 2 (app-based CR offered to those declining conventional CR). Patients in each cohort were followed throughout a 6-week CR program and participation rates were compared for both groups. Patients in cohort 2 declining both forms of CR were interviewed to assess reasons for nonparticipation. RESULTS: CR participation improved from 21% (95% CI 14%-30%) to 63% (95% CI 53%-71%) with the addition of the app (P<.001). Approximately 25% (9/39) of the group declining the app-based program identified technology issues as the reason for nonparticipation. The remainder declined both CR programs or were ineligible due to frailty or comorbidities. CONCLUSIONS: Providing patients with the additional option of an app-based CR program substantially improved CR participation. Technology and psychological barriers can limit CR participation. Further innovation in CR delivery systems is required to improve uptake.

The dedicated iron deficiency anaemia clinic: a 15-year experience.

OBJECTIVE: To report our cumulative experience from a dedicated iron deficiency anaemia (IDA) clinic over the last 15 years-with particular emphasis on referral rate, uptake of investigation, impact on endoscopy services, diagnostic yield of gastrointestinal (GI) investigation and the issue of recurrent IDA. METHOD: A series of analyses of a register of 2808 referrals to the Poole IDA clinic between 2004 and 2018. RESULTS: The study population of 2808 had a sex ratio of 1.9 (female/male ratio) and a median age of 72 years (IQR: 60-79). A rising referral rate over the study period appears to be plateauing at around 2 cases per 1000 population per annum. On the basis of a snapshot audit, investigation of IDA may now account for over 20% of all diagnostic endoscopies.Overall, 86% of cases underwent examination of the upper and lower GI tract. Significant GI pathology was identified in 27% of the investigated cohort. Adenocarcinoma of the upper or lower GI tract was found in 8.3%, the majority in the right colon. The prevalence of recurrent IDA was estimated at 12.4%, and the results of investigation of this subgroup are reported. CONCLUSION: Unexplained IDA is common, particularly in those over 60 years, and may be the first indication of underlying GI malignancy in over 8% of cases. Unresolved challenges include accommodating the resulting endoscopy workload, establishing a risk/benefit ratio for investigating those with major comorbidities and the management of recurrent IDA.

The Impact of Anticoagulation on COVID-19 (SARS CoV-2) Patient Outcomes: A Systematic Review.

BACKGROUND: Emerging data suggest that coagulopathy, cytokine storm, and acute respiratory distress syndrome are associated with the 2019 coronavirus disease (COVID-19). The prevalence of hypercoagulable state in these patients is unknown, but appears to be higher compared to those with other critically ill patients. Elevated D-dimer, large blood vessels clots, deep vein thrombosis, pulmonary embolism and disseminated intravascular coagulation have been reported in patients diagnosed with COVID-19 either on admission or during hospitalization and may be predictors of poor outcomes. METHODS: We performed a comprehensive literature review using the search terms of COVID-19; severe acute respiratory syndrome coronavirus-2, coagulopathy, thrombosis and anticoagulation in PubMed, Ovid, google scholar, Medline and EMBASE databases from December 2019 to May 30, 2020. RESULTS: A total of 64 relevant studies were reviewed; of which, 4 studies met the inclusion criteria and were included for analysis. The majority of the studies were retrospective involving 525 critically ill COVID-19 patients. The most commonly studied anticoagulant administered was low molecular weight heparins. Anticoagulation dosing varied throughout the studies and may be classified as standard venous thromboembolism prophylaxis, intermediate dosing, or full dose anticoagulation. The most studied objective was improvement in coagulopathy. Significant reduction in D-dimer, improvement in coagulopathy markers such as Interlukin-6, fibrinogen degradation product level, as well as lymphocyte count were reported. CONCLUSION: Despite the limited quality of studies analyzed, prophylaxis and higher intensity dosed anticoagulation is associated with improved pulmonary oxygenation, decreased coagulopathy markers and decreased mortality in COVID-19 patients.

Refinement and validation of the IDIOM score for predicting the risk of gastrointestinal cancer in iron deficiency anaemia.

OBJECTIVE: To refine and validate a model for predicting the risk of gastrointestinal (GI) cancer in iron deficiency anaemia (IDA) and to develop an app to facilitate use in clinical practice. DESIGN: Three elements: (1) analysis of a dataset of 2390 cases of IDA to validate the predictive value of age, sex, blood haemoglobin concentration (Hb), mean cell volume (MCV) and iron studies on the probability of underlying GI cancer; (2) a pilot study of the benefit of adding faecal immunochemical testing (FIT) into the model; and (3) development of an app based on the model. RESULTS: Age, sex and Hb were all strong, independent predictors of the risk of GI cancer, with ORs (95% CI) of 1.05 per year (1.03 to 1.07, p<0.00001), 2.86 for men (2.03 to 4.06, p<0.00001) and 1.03 for each g/L reduction in Hb (1.01 to 1.04, p<0.0001) respectively. An association with MCV was also revealed, with an OR of 1.03 for each fl reduction (1.01 to 1.05, p<0.02). The model was confirmed to be robust by an internal validation exercise. In the pilot study of high-risk cases, FIT was also predictive of GI cancer (OR 6.6, 95% CI 1.6 to 51.8), but the sensitivity was low at 23.5% (95% CI 6.8% to 49.9%). An app based on the model was developed. CONCLUSION: This predictive model may help rationalise the use of investigational resources in IDA, by fast-tracking high-risk cases and, with appropriate safeguards, avoiding invasive investigation altogether in those at ultra-low predicted risk.

Development and perception of a multiple-site nontraditional postgraduate year 1 residency program.

PURPOSE: To describe the development and perception of a multiple-site nontraditional postgraduate year 1 (PGY1) residency program from the resident and preceptor perspectives. SUMMARY: A multiple-site nontraditional residency program was developed within a Florida health system to increase the education level and clinical responsibilities of hospital staff pharmacists. The program provided pharmacists interested in residency training an opportunity to pursue postgraduate credentials while maintaining their current position. The nontraditional residency program was implemented at 1 site and subsequently expanded across multiple affiliated hospital sites due to its success. Pharmacists currently working in the health system's network of hospitals for at least 2 years were eligible to enter into the 24-month program after successfully completing the application, interview, and matching process. The number of nontraditional resident positions available has varied by residency year and site. Offering this opportunity has increased the clinical knowledge of pharmacists, exposed them to a variety of practice areas, and increased their departmental contributions. In response to a request for feedback regarding the multiple-site nontraditional program, both residents and preceptors have reported benefits and challenges. CONCLUSION: Adequate resources are needed and a number of factors must be considered in developing a multiple-site nontraditional PGY1 residency program. Although there are potential challenges, it is perceived that the benefits justify continuation of the program.

Identification, Localization, and Quantification of HIV Reservoirs Using Microscopy.

The major barrier to eradicating human immunodeficiency virus-1 (HIV) infection is the generation and extended survival of HIV reservoirs. In order to eradicate HIV infection, it is essential to detect, quantify, and characterize circulating and tissue-associated viral reservoirs in infected individuals. Currently, PCR-based technologies and Quantitative Viral Outgrowth Assays (Q-VOA) are the gold standards to detect viral reservoirs. However, these methods are limited to detecting circulating viral reservoirs, and it has been shown that they misrepresent the size of the reservoirs, largely because they detect only one component of the HIV life cycle and are unable to detect viral reservoirs in tissues. Here, we described the use of multiple detection systems to identify integrated HIV DNA or viral mRNA and several HIV proteins in circulating and tissue reservoirs using improved staining and microscopy techniques. We believe that this imaging-based approach for detecting HIV reservoirs will lead to breakthroughs necessary to eradicate these reservoirs. © 2018 by John Wiley & Sons, Inc.

A Randomized Controlled Trial to Reduce HIV-Related Risk in African American Men Who Have Sex with Men and Women: the Bruthas Project.

African American men who have sex with men and women (MSMW) are among the populations with the highest need for HIV prevention programs in the USA. We tested a theory-based, community participatory behavioral intervention aiming to reduce sexual risk for HIV transmission in this population. A randomized clinical trial involving 396 African American MSMW who were assigned to a 4-session intervention involving HIV testing and counseling (n = 199) or to a HIV testing and counseling only (n = 197) control. In the 4-session intervention program, counselors provided education on HIV and STI risk, condom use, HIV testing, interpersonal sexual dynamics with both male and female partners, and motivational "triggers" of condomless sex. Participants completed baseline, 6-month, and 9-month assessments, and changes in HIV behavioral risk indicators were examined by condition and time. There were no statistically significant differences in sexual risk between the intervention condition and the control condition. Regardless of condition, participants reported significant reductions in mean number of condomless sex events with female casual partners from baseline (6.04) to 6 months (2.58) and 9 months (1.47), and with male casual partners from baseline (2.61) to 6 months (1.18) and 9 months (0.60). Condition-by-time interaction effects and condition main effects were non-significant. Although there were no significant differences by condition, findings support the effects of brief behavioral counseling and HIV testing on reducing condomless sex with casual female and male partners among African American MSMW. Future research should examine further the potential for brief behavioral counseling to promote biomedical HIV prevention and to reduce co-morbid health issues such as substance use among African American MSMW.

The Development of a Counseling-Based HIV Prevention Intervention for African American Men Who Have Sex With Men and Women: The Bruthas Project.

African American men who have sex with both men and women (AAMSMW) are at high risk for acquiring and transmitting HIV, yet few interventions exist to address their unique prevention needs. We conducted 3 focus groups, 21 in-depth interviews, and a pilot test of our intervention with = 61 AAMSMW, which showed significant reductions in sexual risk behavior after 6 months. The intervention is currently being tested in a randomized controlled trial (RCT). We discuss the development of a culturally tailored, theoretically grounded counseling intervention for AAMSMW, presenting findings from our formative research, intervention development process, pilot study, and the implementation of our RCT. We describe the content of each session, our protocol for merging Bruthas with HIV testing, and best practices for recruiting AAMSMW. If Bruthas is found to be efficacious, the intervention will reach a vulnerable population to encourage uptake of regular HIV testing and reduced sexual risk taking.

Glucagon-reactive islet-infiltrating CD8 T cells in NOD mice.

Type 1 diabetes is characterized by T-cell-mediated destruction of the insulin-producing ß cells in pancreatic islets. A number of islet antigens recognized by CD8 T cells that contribute to disease pathogenesis in non-obese diabetic (NOD) mice have been identified; however, the antigenic specificities of the majority of the islet-infiltrating cells have yet to be determined. The primary goal of the current study was to identify candidate antigens based on the level and specificity of expression of their genes in mouse islets and in the mouse ß cell line MIN6. Peptides derived from the candidates were selected based on their predicted ability to bind H-2K(d) and were examined for recognition by islet-infiltrating T cells from NOD mice. Several proteins, including those encoded by Abcc8, Atp2a2, Pcsk2, Peg3 and Scg2, were validated as antigens in this way. Interestingly, islet-infiltrating T cells were also found to recognize peptides derived from proglucagon, whose expression in pancreatic islets is associated with α cells, which are not usually implicated in type 1 diabetes pathogenesis. However, type 1 diabetes patients have been reported to have serum autoantibodies to glucagon, and NOD mouse studies have shown a decrease in α cell mass during disease pathogenesis. Our finding of islet-infiltrating glucagon-specific T cells is consistent with these reports and suggests the possibility of α cell involvement in development and progression of disease.

Developing and using a partnership covenant to guide a study of late HIV diagnosis.

BACKGROUND: Late diagnosis of HIV is an important problem in the United States, particularly in ethnically and socially diverse communities. OBJECTIVES: We created and used a partnership covenant to ensure our adherence to community-based participatory research (CBPR) principles as we began studying and addressing individual and structural barriers to timely HIV testing. METHODS: Sample CBPR principles were used to help develop a partnership covenant that in turn was used in steering committee (SC) meetings to gauge our adherence to CBPR in our work together and in the field. RESULTS: Continuing dialogue around our fidelity to the covenant resulted in concrete changes including a "crash course" on sampling for community partners and development of a community advisory board (CAB). Our ability to meet the project's specific aims was enhanced by using the covenant. CONCLUSIONS: Although time consuming, development and use of a CBPR covenant can improve high-level engagement and help to accomplish a study's specific aims.

Improving the efficiency of HIV testing with peer recruitment, financial incentives, and the involvement of persons living with HIV infection.

BACKGROUND: The authors piloted an HIV testing and counseling (HTC) approach using respondent-driven sampling (RDS), financial incentives, and persons living with HIV infection (PLHIV). METHODS: Eligible participants were aged 30-60 years, African American or black, and residents of Oakland, CA. Participants were tested for HIV infection and asked to refer up to 3 others. The authors compared the efficiency of RDS to conventional outreach-based HTC with the number needed to screen (NNS). They evaluated the effect of 2 randomly allocated recruitment incentives on the enrollment of high-risk or HIV-positive network associates: a flat incentive ($20) for eligible recruits or a conditional incentive ($10-35) for eligible recruits in priority groups, such as first-time testers. RESULTS: Forty-eight participants (10 PLHIV and 38 HIV negative) initiated recruitment chains resulting in 243 network associates. Nine (3.7%) participants tested HIV positive, of whom 7 (78%) were previously recognized. RDS was more efficient than conventional HTC at identifying any PLHIV (new or previously recognized; RDS: NNS = 27, 95% CI: 14 to 59; conventional: NNS = 154, 95% CI: 95 to 270). There was no difference between the 2 incentive groups in the likelihood of recruiting at least 1 high-risk HIV-negative or HIV-positive network associate (adjusted odds ratio = 0.89, 95% CI: 0.06 to 13.06) or in total number of high-risk HIV-negative or HIV-positive associates (adjusted odds ratio = 0.79, 95% CI: 0.23 to 2.71). CONCLUSIONS: Social network HTC strategies may increase demand for HTC and efficiently identify PLHIV. The flat incentive was as successful as the conditional incentive for recruiting high-risk individuals. Unexpectedly, this method also reidentified PLHIV aware of their status.

Beyond HLA-A*0201: new HLA-transgenic nonobese diabetic mouse models of type 1 diabetes identify the insulin C-peptide as a rich source of CD8+ T cell epitopes.

Type 1 diabetes is an autoimmune disease characterized by T cell responses to ß cell Ags, including insulin. Investigations employing the NOD mouse model of the disease have revealed an essential role for ß cell-specific CD8(+) T cells in the pathogenic process. As CD8(+) T cells specific for ß cell Ags are also present in patients, these reactivities have the potential to serve as therapeutic targets or markers for autoimmune activity. NOD mice transgenic for human class I MHC molecules have previously been employed to identify T cell epitopes having important relevance to the human disease. However, most studies have focused exclusively on HLA-A*0201. To broaden the reach of epitope-based monitoring and therapeutic strategies, we have looked beyond this allele and developed NOD mice expressing human ß(2)-microglobulin and HLA-A*1101 or HLA-B*0702, which are representative members of the A3 and B7 HLA supertypes, respectively. We have used islet-infiltrating T cells spontaneously arising in these strains to identify ß cell peptides recognized in the context of the transgenic HLA molecules. This work has identified the insulin C-peptide as an abundant source of CD8(+) T cell epitopes. Responses to these epitopes should be of considerable utility for immune monitoring, as they cannot reflect an immune reaction to exogenously administered insulin, which lacks the C-peptide. Because the peptides bound by one supertype member were found to bind certain other members also, the epitopes identified in this study have the potential to result in therapeutic and monitoring tools applicable to large numbers of patients and at-risk individuals.