"You Need to Keep It Going, Mind, Body, and Spirit": Older Adults' Perspectives on Aging in Place in Subsidized Housing.

In the U.S., more than one million older adults with low incomes live in apartment buildings subsidized by the Low-Income Housing Tax Credit. Although this population experiences disproportionate rates of nursing home admission, little is known about residents' perspectives on factors that influence their ability to live independently in these settings. Fifty-eight residents aged 62 and older and eight study partners participated in qualitative interviews about their perspectives on living independently in subsidized housing, including barriers and facilitators. We analyzed transcripts using a hybrid inductive and deductive approach to qualitative thematic analysis. Barriers and facilitators for living independently in subsidized housing related to the influence of the social and physical environment on individuals' experiences of living independently, including factors unique to subsidized housing. Findings suggest how interventions to optimize functional status and promote independence among older adults living in subsidized housing can build on existing strengths of the subsidized housing environment to improve outcomes.

Spatiotemporal distribution and bionomics of Anopheles stephensi in different eco-epidemiological settings in Ethiopia.

BACKGROUND: Malaria is a major public health concern in Ethiopia, and its incidence could worsen with the spread of the invasive mosquito species Anopheles stephensi in the country. This study aimed to provide updates on the distribution of An. stephensi and likely household exposure in Ethiopia. METHODS: Entomological surveillance was performed in 26 urban settings in Ethiopia from 2021 to 2023. A kilometer-by-kilometer quadrant was established per town, and approximately 20 structures per quadrant were surveyed every 3 months. Additional extensive sampling was conducted in 50 randomly selected structures in four urban centers in 2022 and 2023 to assess households' exposure to An. stephensi. Prokopack aspirators and CDC light traps were used to collect adult mosquitoes, and standard dippers were used to collect immature stages. The collected mosquitoes were identified to species level by morphological keys and molecular methods. PCR assays were used to assess Plasmodium infection and mosquito blood meal source. RESULTS: Catches of adult An. stephensi were generally low (mean: 0.15 per trap), with eight positive sites among the 26 surveyed. This mosquito species was reported for the first time in Assosa, western Ethiopia. Anopheles stephensi was the predominant species in four of the eight positive sites, accounting for 75-100% relative abundance of the adult Anopheles catches. Household-level exposure, defined as the percentage of households with a peridomestic presence of An. stephensi, ranged from 18% in Metehara to 30% in Danan. Anopheles arabiensis was the predominant species in 20 of the 26 sites, accounting for 42.9-100% of the Anopheles catches. Bovine blood index, ovine blood index and human blood index values were 69.2%, 32.3% and 24.6%, respectively, for An. stephensi, and 65.4%, 46.7% and 35.8%, respectively, for An. arabiensis. None of the 197 An. stephensi mosquitoes assayed tested positive for Plasmodium sporozoite, while of the 1434 An. arabiensis mosquitoes assayed, 62 were positive for Plasmodium (10 for P. falciparum and 52 for P. vivax). CONCLUSIONS: This study shows that the geographical range of An. stephensi has expanded to western Ethiopia. Strongly zoophagic behavior coupled with low adult catches might explain the absence of Plasmodium infection. The level of household exposure to An. stephensi in this study varied across positive sites. Further research is needed to better understand the bionomics and contribution of An. stephensi to malaria transmission.

Proceedings of the annual meeting of the European Consortium of Lipodystrophies (ECLip), Pisa, Italy, 28-29 September 2023.

Lipodystrophy syndromes are rare diseases primarily affecting the development or maintenance of the adipose tissue but are also distressing indirectly multiple organs and tissues, often leading to reduced life expectancy and quality of life. Lipodystrophy syndromes are multifaceted disorders caused by genetic mutations or autoimmunity in the vast majority of cases. While many subtypes are now recognized and classified, the disease remains remarkably underdiagnosed. The European Consortium of Lipodystrophies (ECLip) was founded in 2014 as a non-profit network of European centers of excellence working in the field of lipodystrophies aiming at promoting international collaborations to increase basic scientific understanding and clinical management of these syndromes. The network has developed a European Patient Registry as a collaborative research platform for consortium members. ECLip and ECLip registry activities involve patient advocacy groups to increase public awareness and to seek advice on research activities relevant from the patients perspective. The annual ECLip congress provides updates on the research results of various network groups members.

Using risk-adjusted cumulative sum to evaluate surgeon, divisional, and institutional outcomes-a feasibility study.

BACKGROUND: Few objective, real-time measurements of surgeon performance exist. The risk-adjusted cumulative sum is a novel method that can track surgeon-level outcomes on a continuous basis. The objective of this study was to demonstrate the feasibility of using risk-adjusted cumulative sum to monitor outcomes after colorectal operations and identify clinically relevant performance variations. METHODS: The National Surgical Quality Improvement Program was queried to obtain patient-level data for 1,603 colorectal operations at a high-volume center from 2011 to 2020. For each case, expected risks of morbidity, mortality, reoperation, readmission, and prolonged length of stay were estimated using the National Surgical Quality Improvement Program risk calculator. Risk-adjusted cumulative sum curves were generated to signal observed-to-expected odds ratios of 1.5 (poor performance) and 0.5 (exceptional performance). Control limits were set based on a false positive rate of 5% (α = 0.05). RESULTS: The cohort included data on 7 surgeons (those with more than 20 cases in the study period). Institutional observed versus expected outcomes were the following: morbidity 12.5% (vs 15.0%), mortality 2.5% (vs 2.0%), prolonged length of stay 19.7% (vs 19.1%), reoperation 11.1% (vs 11.3%), and 30-day readmission 6.1% (vs 4.8%). Risk-adjusted cumulative sum accurately demonstrated within- and between-surgeon performance variations across these metrics and proved effective when considering division-level data. CONCLUSION: Risk-adjusted cumulative sum adjusts for patient-level risk factors to provide real-time data on surgeon-specific outcomes. This approach enables prompt identification of performance outliers and can contribute to quality assurance, root-cause analysis, and incentivization not only at the surgeon level but at divisional and institutional levels as well.

Caring for Patients with Functional Impairment in Middle Age: Perspectives from Primary Care Providers and Geriatricians.

BACKGROUND: The prevalence of functional impairment is increasing among middle-aged adults and is associated with adverse health outcomes. Primary care providers (PCPs) and geriatricians may have important insights about optimal approaches to caring for these patients, but little is known about their perspectives. OBJECTIVE: To examine PCPs' and geriatricians' perspectives on clinical needs and optimal approaches to care for middle-aged patients with functional impairment. DESIGN: Qualitative study using semi-structured interviews. PARTICIPANTS: PCPs and geriatricians from outpatient practices in the San Francisco Bay area. APPROACH: Interviews focused on characteristics and care needs of middle-aged patients with functional impairment and models of care to address these needs. We analyzed interviews using hybrid deductive-inductive qualitative thematic analysis. KEY RESULTS: Clinicians (14 PCPs, 15 geriatricians) described distinct characteristics of functional impairment in middle-aged versus older adults, such as different rates of onset, but similar clinical needs. Despite these similar needs, clinicians identified age-specific barriers to delivering optimal care to middle-aged patients. These included system-level challenges such as limited access to insurance and social services; practice- and clinician-level barriers including inadequate clinician training; and patient-level factors including less access to family caregivers and perceptions of stigma. To overcome these challenges, clinicians suggested clinical approaches including addressing health-related social needs within healthcare systems; implementing practice-based models that are multi-disciplinary, team-based, and coordinated; training clinicians to effectively manage functional impairment; and expanding community-based services and supports to help patients navigate the medical system. Identified needs, challenges, and solutions were generally similar across geriatricians and PCPs. CONCLUSIONS: Clinicians face challenges in delivering optimal care to middle-aged patients who have functional impairments similar to their older counterparts but lack access to services and supports available to older people. These findings suggest the importance of increasing access to care models that address functional impairment regardless of age.

Envelope protein-specific B cell receptors direct lentiviral vector tropism in vivo.

While studying transgene expression after systemic administration of lentiviral vectors, we found that splenic B cells are robustly transduced, regardless of the types of pseudotyped envelope proteins. However, the administration of two different pseudotypes resulted in transduction of two distinct B cell populations, suggesting that each pseudotype uses unique and specific receptors for its attachment and entry into splenic B cells. Single-cell RNA sequencing analysis of the transduced cells demonstrated that different pseudotypes transduce distinct B cell subpopulations characterized by specific B cell receptor (BCR) genotypes. Functional analysis of the BCRs of the transduced cells demonstrated that BCRs specific to the pseudotyping envelope proteins mediate viral entry, enabling the vectors to selectively transduce the B cell populations that are capable of producing antibodies specific to their envelope proteins. Lentiviral vector entry via the BCR activated the transduced B cells and induced proliferation and differentiation into mature effectors, such as memory B and plasma cells. BCR-mediated viral entry into clonally specific B cell subpopulations raises new concepts for understanding the biodistribution of transgene expression after systemic administration of lentiviral vectors and offers new opportunities for BCR-targeted gene delivery by pseudotyped lentiviral vectors.

Metabolic and other morbid complications in congenital generalized lipodystrophy type 4.

Morbidity and mortality rates in patients with autosomal recessive, congenital generalized lipodystrophy type 4 (CGL4), an ultra-rare disorder, remain unclear. We report on 30 females and 16 males from 10 countries with biallelic null variants in CAVIN1 gene (mean age, 12 years; range, 2 months to 41 years). Hypertriglyceridemia was seen in 79% (34/43), hepatic steatosis in 82% (27/33) but diabetes mellitus in only 21% (8/44). Myopathy with elevated serum creatine kinase levels (346-3325 IU/L) affected all of them (38/38). 39% had scoliosis (10/26) and 57% had atlantoaxial instability (8/14). Cardiac arrhythmias were detected in 57% (20/35) and 46% had ventricular tachycardia (16/35). Congenital pyloric stenosis was diagnosed in 39% (18/46), 9 had esophageal dysmotility and 19 had intestinal dysmotility. Four patients suffered from intestinal perforations. Seven patients died at mean age of 17 years (range: 2 months to 39 years). The cause of death in four patients was cardiac arrhythmia and sudden death, while others died of prematurity, gastrointestinal perforation, and infected foot ulcers leading to sepsis. Our study highlights high prevalence of myopathy, metabolic abnormalities, cardiac, and gastrointestinal problems in patients with CGL4. CGL4 patients are at high risk of early death mainly caused by cardiac arrhythmias.

Lipodystrophy in methylmalonic acidemia associated with elevated FGF21 and abnormal methylmalonylation.

A distinct adipose tissue distribution pattern was observed in patients with methylmalonyl-CoA mutase deficiency, an inborn error of branched-chain amino acid (BCAA) metabolism, characterized by centripetal obesity with proximal upper and lower extremity fat deposition and paucity of visceral fat, that resembles familial multiple lipomatosis syndrome. To explore brown and white fat physiology in methylmalonic acidemia (MMA), body composition, adipokines, and inflammatory markers were assessed in 46 patients with MMA and 99 matched controls. Fibroblast growth factor 21 levels were associated with acyl-CoA accretion, aberrant methylmalonylation in adipose tissue, and an attenuated inflammatory cytokine profile. In parallel, brown and white fat were examined in a liver-specific transgenic MMA mouse model (Mmut-/- TgINS-Alb-Mmut). The MMA mice exhibited abnormal nonshivering thermogenesis with whitened brown fat and had an ineffective transcriptional response to cold stress. Treatment of the MMA mice with bezafibrates led to clinical improvement with beiging of subcutaneous fat depots, which resembled the distribution seen in the patients. These studies defined what we believe to be a novel lipodystrophy phenotype in patients with defects in the terminal steps of BCAA oxidation and demonstrated that beiging of subcutaneous adipose tissue in MMA could readily be induced with small molecules.

Early Implementation of Robotic Training in Surgical and Surgical Subspecialty Residency.

BACKGROUND: Robotic surgery has emerged as an operative tool for many elective and urgent surgical procedures. The purpose of this study was to evaluate early surgical trainees' experiences and opinions of robotic surgery. METHODS: An introductory robotic training course consisting of online da Vinci Xi/X training and in-person, hands on training was implemented for residents and medical students across surgical subspecialties at a single institution. A voluntary survey evaluating perceptions of and interest in robotic surgery and prior robotic surgery experience, as well as a basics of robotics quiz, was distributed to participants prior to the start of the in-person session. Descriptive statistics were used to evaluate the cohort. RESULTS: 85 trainees participated in the course between 2020 and 2023, including 58 first- and second-year surgical residents (general surgery, urology, OB/GYN, and thoracic surgery) and 27 fourth-year medical students. 9.4% of participants reported any formal robotic surgery training prior to the session, with only 19% of participants reporting robotic operative experience. 52% of the participants knew of and/or had completed the da Vinci online course modules prior to the scheduled training session. Participants unanimously (100%) agreed that robotic surgery should be implemented into surgical training. CONCLUSIONS: There is rising enthusiasm for robotic surgery, yet early exposure and training remain infrequent and inconsistent amongst medical students and new surgical residents. A standardized introduction of multi-disciplinary robotic surgery training should be incorporated into medical school and/or early residency education to ensure surgical residents receive appropriate exposure and training to achieve competency.

Experimental assessment of laser scarecrows for reducing avian damage to sweet corn.

BACKGROUND: Birds damage crops, costing millions of dollars annually, and growers utilize a variety of lethal and nonlethal deterrents in an attempt to reduce crop damage by birds. We experimentally tested laser scarecrows for their effectiveness at reducing sweet corn (Zea mays) damage. We presented 18 captive flocks of free-flying European starlings (Sturnus vulgaris) with fresh sweet corn ears distributed on two plots where laser and control treatments were alternated each day and allowed each flock to forage over 5 days. In 16 trials, fresh sweet corn ears were mounted on wooden sticks distributed from 0 to 32 m from laser units (Stick Trials), and in two trials birds foraged on ripe corn grown from seed in the flight pen (Natural Trials). We aimed to determine if laser-treated plots had significantly less damage overall and closer to the laser unit, and whether birds became more or less likely to forage in laser-treated plots over time. RESULTS: Lasers reduced damage overall, marginally in Stick Trials and dramatically in Natural Trials. Damage increased during each week in both trial types. Damage increased significantly with distance from lasers, and significant treatment effects occurred up to ~20 m from lasers. CONCLUSION: Our results concur with recent field trials demonstrating strong reductions in sweet corn damage when lasers are deployed. This study provides a first look at how birds respond to repeated laser exposure and whether damage increases with distance from lasers. Key differences between pen and field trials are discussed. © 2023 Society of Chemical Industry. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.

"I'll fill in the gaps": perspectives of HHAs on promoting aging in place for older adults with low incomes.

Older adults with low incomes experience disproportionate rates of cognitive and functional impairment and an elevated risk of nursing home admission. Home health aides (HHAs) may have insight into how to optimize aging in place for this population, yet little is known about HHAs' perspectives on this topic. We conducted 6 focus groups with 21 English-speaking and 10 Spanish-speaking HHAs in Pennsylvania and New Jersey. Transcripts were analyzed using qualitative thematic analysis, and three themes emerged. First, HHAs described the uniqueness of their role within multidisciplinary care teams. Second, HHAs shared concrete interventions they employ to help their clients improve their function at home. Third, HHAs discussed barriers they face when helping clients age in place. Our findings suggest that HHAs have important insights into improving aging in place for older adults with low incomes and that their perspectives should be incorporated into care planning and intervention delivery.

Mortality Among Older Medical Patients at Flagship Hospitals and Their Affiliates.

BACKGROUND: We define a "flagship hospital" as the largest academic hospital within a hospital referral region and a "flagship system" as a system that contains a flagship hospital and its affiliates. It is not known if patients admitted to an affiliate hospital, and not to its main flagship hospital, have better outcomes than those admitted to a hospital outside the flagship system but within the same hospital referral region. OBJECTIVE: To compare mortality at flagship hospitals and their affiliates to matched control patients not in the flagship system but within the same hospital referral region. DESIGN: A matched cohort study PARTICIPANTS: The study used hospitalizations for common medical conditions between 2018-2019 among older patients age ≥ 66 years. We analyzed 118,321 matched pairs of Medicare patients admitted with pneumonia (N=57,775), heart failure (N=42,531), or acute myocardial infarction (N=18,015) in 35 flagship hospitals, 124 affiliates, and 793 control hospitals. MAIN MEASURES: 30-day (primary) and 90-day (secondary) all-cause mortality. KEY RESULTS: 30-day mortality was lower among patients in flagship systems versus control hospitals that are not part of the flagship system but within the same hospital referral region (difference= -0.62%, 95% CI [-0.88%, -0.37%], P<0.001). This difference was smaller in affiliates versus controls (-0.43%, [-0.75%, -0.11%], P=0.008) than in flagship hospitals versus controls (-1.02%, [-1.46%, -0.58%], P<0.001; difference-in-difference -0.59%, [-1.13%, -0.05%], P=0.033). Similar results were found for 90-day mortality. LIMITATIONS: The study used claims-based data. CONCLUSIONS: In aggregate, within a hospital referral region, patients treated at the flagship hospital, at affiliates of the flagship hospital, and in the flagship system as a whole, all had lower mortality rates than matched controls outside the flagship system. However, the mortality advantage was larger for flagship hospitals than for their affiliates.

Identifying Barriers and Facilitators to Veterans Affairs Whole Health Integration Using the Updated Consolidated Framework for Implementation Research.

BACKGROUND: Veterans Affairs (VA) implemented the Veteran-centered Whole Health System initiative across VA sites with approaches to implementation varying by site. PURPOSE: Using the Consolidated Framework for Implementation Research (CFIR), we aimed to synthesize systemic barriers and facilitators to Veteran use with the initiative. Relevance to healthcare quality, systematic comparison of implementation procedures across a national healthcare system provides a comprehensive portrait of strengths and opportunities for improvement. METHODS: Advanced fellows from 11 VA Quality Scholars sites performed the initial data collection, and the final report includes CFIR-organized results from six sites. RESULTS: Key innovation findings included cost, complexity, offerings, and accessibility. Inner setting barriers and facilitators included relational connections and communication, compatibility, structure and resources, learning centeredness, and information and knowledge access. Finally, results regarding individuals included innovation deliverers, implementation leaders and team, and individual capability, opportunity, and motivation to implement and deliver whole health care. DISCUSSION AND IMPLICATIONS: Examination of barriers and facilitators suggest that Whole Health coaches are key components of implementation and help to facilitate communication, relationship building, and knowledge access for Veterans and VA employees. Continuous evaluation and improvement of implementation procedures at each site is also recommended.

Parental leave policies in general surgery residencies.

BACKGROUND: Prospective residents use program websites to glean information regarding parental leave policies. This study investigates the online availability and content of parental leave policies for general surgery residency programs. METHODS: Parental leave policy information was collected from general surgery residency program and Graduate Medical Education (GME) websites. Descriptive statistics and multivariable logistic regression were used for analysis. RESULTS: Of the 344 general surgery residency programs, parental leave policies were found on 6% of program and 52% of GME websites. Family Medical Leave Act policies were reported the most, followed by maternity, then paternity, and then adoption/other clauses. Academic programs, program location in the Southeastern US and larger program size were all significant predictors of online policy availability. CONCLUSIONS: General surgery parental leave policies vary and are not readily available online. These findings identify a significant opportunity for surgery residency programs to improve the disclosure of parental leave policy information.

Epigenetic age and socioeconomic status contribute to racial disparities in cognitive and functional aging between Black and White older Americans.

Epigenetic age, a biological aging marker measured by DNA methylation, is a potential mechanism by which social factors drive disparities in age-related health. Epigenetic age gap is the residual between epigenetic age measures and chronological age. Previous studies showed associations between epigenetic age gap and age-related outcomes including cognitive capacity and performance on some functional measures, but whether epigenetic age gap contributes to disparities in these outcomes is unknown. We use data from the Health and Retirement Study to examine the role of epigenetic age gap in racial disparities in cognitive and functional outcomes and consider the role of socioeconomic status (SES). Epigenetic age measures are GrimAge or Dunedin Pace of Aging methylation (DPoAm). Cognitive outcomes are cross-sectional score and two-year change in Telephone Interview for Cognitive Status (TICS). Functional outcomes are prevalence and incidence of limitations performing Instrumental Activities of Daily Living (IADLs). We find, relative to White participants, Black participants have lower scores and greater decline in TICS, higher prevalence and incidence rates of IADL limitations, and higher epigenetic age gap. Age- and gender-adjusted analyses reveal that higher GrimAge and DPoAm gap are both associated with worse cognitive and functional outcomes and mediate 6-11% of racial disparities in cognitive outcomes and 19-39% of disparities in functional outcomes. Adjusting for SES attenuates most DPoAm associations and most mediation effects. These results support that epigenetic age gap contributes to racial disparities in cognition and functioning and may be an important mechanism linking social factors to disparities in health outcomes.

TEG-based transfusion protocol is associated with decreased blood product use without increased risk of hemoperitoneum.

BACKGROUND: Thromboelastography (TEG) informs the need for blood product transfusions to prevent procedural bleeding complications in patients with cirrhosis. We aimed to evaluate the impact of using a TEG-based transfusion protocol on blood product utilization before paracentesis and the post-paracentesis hemoperitoneum (PPH) incidence. METHODS: We conducted an ambispective analysis of patients with cirrhosis who underwent paracentesis from 2017 to 2021. In May 2019, we enacted a TEG-based transfusion protocol to guide pre-paracentesis blood product use. Patients with platelets < 20,000 or international normalized ratio ≥ 4 underwent TEG and received blood products if r value > 10 min or MA <30 mm. Patients were divided into pre-TEG and post-TEG protocol cohorts based on the date of paracentesis. Pre-paracentesis blood product transfusions in the form of platelets, fresh frozen plasma, and cryoprecipitates were recorded. PPH was defined as a decrease in hemoglobin of ≥1 g and the presence of blood on diagnostic imaging and/or the need for therapeutic intervention. RESULTS: A total of 483 patients underwent 1281 paracenteses. The main etiologies of cirrhosis were alcohol (43%) and NASH (25%), and the mean MELD-sodium was 22±6. Pre-TEG and post-TEG protocol cohort sizes were similar: 253 patients and 607 paracenteses versus 230 patients and 674 paracenteses. After TEG-protocol implementation, blood product transfusions decreased significantly (228 vs. 49 products, p<0.001) with associated cost savings. One patient in each cohort developed PPH. CONCLUSION: Implementation of a pre-paracentesis TEG-based transfusion protocol for patients with cirrhosis successfully resulted in decreased blood product use with no associated increase in incidence of PPH.

Management of Central and Peripheral Nervous System Tumors in Patients with Neurofibromatosis.

Neurofibromatosis type I (NF1), neurofibromatosis type 2 (NF2), and schwannomatosis represent a diverse group of genetic tumor predisposition syndromes with a shared feature of tumors affecting the peripheral nerve sheaths. PURPOSE OF REVIEW: Many advancements have been made in understanding the biologic underpinnings of these conditions, and in 2016 the first drug was approved by the FDA to treat pediatric symptomatic unresectable plexiform neurofibromas. RECENT FINDINGS: Mek inhibitors have provided a much-needed therapeutic avenue for NF1 patients with unresectable plexiform neurofibromas (PN), both for reduction of tumor bulk and for improvement in symptoms. Selumetinib is the first FDA approved drug for PN, but is only approved for children. Some research suggests that alternative Mek inhibitors and other mixed tyrosine kinase inhibitors may have better efficacy in adults. Vascular endothelial growth factor (VEGF) inhibitor bevacizumab can prolong hearing and delay the need for surgery in NF2 patients with bilateral vestibular schwannomas. This article provides an update regarding considerations and approaches when treating the tumors associated with the neurofibromatoses (NF), including risk and prognosis metrics, clinical trial results, surgical techniques, and radiation therapy recommendations.

Genotype-stratified treatment for monogenic insulin resistance: a systematic review.

BACKGROUND: Monogenic insulin resistance (IR) includes lipodystrophy and disorders of insulin signalling. We sought to assess the effects of interventions in monogenic IR, stratified by genetic aetiology. METHODS: Systematic review using PubMed, MEDLINE and Embase (1 January 1987 to 23 June 2021). Studies reporting individual-level effects of pharmacologic and/or surgical interventions in monogenic IR were eligible. Individual data were extracted and duplicates were removed. Outcomes were analysed for each gene and intervention, and in aggregate for partial, generalised and all lipodystrophy. RESULTS: 10 non-randomised experimental studies, 8 case series, and 23 case reports meet inclusion criteria, all rated as having moderate or serious risk of bias. Metreleptin use is associated with the lowering of triglycerides and haemoglobin A1c (HbA1c) in all lipodystrophy (n = 111), partial (n = 71) and generalised lipodystrophy (n = 41), and in LMNA, PPARG, AGPAT2 or BSCL2 subgroups (n = 72,13,21 and 21 respectively). Body Mass Index (BMI) is lowered in partial and generalised lipodystrophy, and in LMNA or BSCL2, but not PPARG or AGPAT2 subgroups. Thiazolidinediones are associated with improved HbA1c and triglycerides in all lipodystrophy (n = 13), improved HbA1c in PPARG (n = 5), and improved triglycerides in LMNA (n = 7). In INSR-related IR, rhIGF-1, alone or with IGFBP3, is associated with improved HbA1c (n = 17). The small size or absence of other genotype-treatment combinations preclude firm conclusions. CONCLUSIONS: The evidence guiding genotype-specific treatment of monogenic IR is of low to very low quality. Metreleptin and Thiazolidinediones appear to improve metabolic markers in lipodystrophy, and rhIGF-1 appears to lower HbA1c in INSR-related IR. For other interventions, there is insufficient evidence to assess efficacy and risks in aggregated lipodystrophy or genetic subgroups.

The hormone insulin stimulates nutrient uptake from the bloodstream into tissues. In insulin resistance (IR), this action is blunted. Some rare gene alterations cause severe IR, diabetes that is difficult to control, and early complications. Many treatments have been suggested, but reliable evidence of their risks and benefits is sparse. We analysed all available reports describing treatment outcomes in severe IR. We found that the evidence is of low to very low quality overall. Injections of leptin, a hormone from fat tissue, or thiazolidinedione tablets that increase fat tissue both appear to improve diabetes control in people with reduced ability to make fat tissue. Injections of another treatment, insulin-like growth factor, appear to improve diabetes control in people with direct blockage of insulin action. There is a pressing need to improve evidence for treatment in these rare and severe conditions.