Perinatal mental health and pregnancy-associated mortality: opportunities for change.

Perinatal mental health conditions have been associated with adverse pregnancy outcomes, including maternal death. This quality improvement project analyzed pregnancy-associated death among veterans with mental health conditions in order to identify opportunities to improve healthcare and reduce maternal deaths. Pregnancy-associated deaths among veterans using Veterans Health Administration (VHA) maternity care benefits between fiscal year 2011 and 2020 were identified from national VHA databases. Deaths among individuals with active mental health conditions underwent individual chart review using a standardized abstraction template adapted from the Centers for Disease Control and Prevention (CDC). Thirty-two pregnancy-associated deaths were identified among 39,720 paid deliveries with 81% (n = 26) occurring among individuals with an active perinatal mental health condition. In the perinatal mental health cohort, most deaths (n = 16, 62%) occurred in the late postpartum period and 42% (n = 11) were due to suicide, homicide, or overdose. Opportunities to improve care included addressing (1) racial disparities, (2) mental health effects of perinatal loss, (3) late postpartum vulnerability, (4) lack of psychotropic medication continuity, (5) mental health conditions in intimate partners, (6) child custody loss, (7) lack of patient education or stigmatizing patient education, and (8) missed opportunities for addressing reproductive health concerns in mental health contexts. Pregnancy-associated deaths related to active perinatal mental health conditions can be reduced. Mental healthcare clinicians, clinical teams, and healthcare systems have opportunities to improve care for individuals with perinatal mental health conditions.

Cannabis use disorder contributes to cognitive dysfunction in Veterans with traumatic brain injury.

Background: While emerging evidence supports a link between traumatic brain injury (TBI) and progressive cognitive dysfunction in Veterans, there is insufficient information on the impact of cannabis use disorder (CUD) on long-term cognitive disorders. This study aimed to examine the incidences of cognitive disorders in Veterans with TBI and CUD and to evaluate their relationship. Methods: This retrospective cohort study used the US Department of Veterans Affairs and Department of Defense administrative data from the Long-term Impact of Military-Relevant Brain Injury Consortium-Chronic Effects of Neurotrauma Consortium Phenotype study. Diagnoses suggesting cognitive disorders after a TBI index date were identified using inpatient and outpatient data from 2003 to 2022. We compared the differential cognitive disorders incidence in Veterans who had the following: (1) no CUD or TBI (control group), (2) CUD only, (3) TBI only, and (4) comorbid CUD+TBI. Kaplan-Meier analyses were used to estimate the overall cognitive disorders incidence in the above study groups. The crude and adjusted Cox proportional hazards models were used to estimate crude and adjusted hazard ratios (HRs) for cognitive disorders. Results: A total of 1,560,556 Veterans [82.32% male, median (IQR) age at the time of TBI, 34.51 (11.29) years, and 61.35% white] were evaluated. The cognitive disorder incidence rates were estimated as 0.68 (95% CI, 0.62, 0.75) for CUD only and 1.03 (95% CI, 1.00, 1.06) for TBI only per 10,000 person-months of observations, with the highest estimated cognitive disorder incidence observed in participants with both TBI and CUD [1.83 (95% CI, 1.72, 1.95)]. Relative to the control group, the highest hazard of cognitive disorders was observed in Veterans with CUD+TBI [hazard ratio (HR), 3.26; 95% CI, 2.91, 3.65], followed by those with TBI only (2.32; 95 CI%, 2.13, 2.53) and with CUD (1.79; 95 CI%, 1.60, 2.00). Of note, in the CUD only subgroup, we also observed the highest risk of an early onset cognitive disorder other than Alzheimer's disease and Frontotemporal dementia. Discussion: The results of this analysis suggest that individuals with comorbid TBI and CUD may be at increased risk for early onset cognitive disorders, including dementia.

Racial/Ethnic and Geographic Disparities in Comorbid Traumatic Brain Injury-Renal Failure in US Veterans and Associated Veterans Affairs Resource Costs, 2000-2020.

Studies have identified disparities by race/ethnicity and geographic status among veterans with traumatic brain injury (TBI) and renal failure (RF). We examined the association of race/ethnicity and geographic status with RF onset in veterans with and without TBI, and the impact of disparities on Veterans Health Administration resource costs. METHODS: Demographics by TBI and RF status were assessed. We estimated Cox proportional hazards models for progression to RF and generalized estimating equations for inpatient, outpatient, and pharmacy cost annually and time since TBI + RF diagnosis, stratified by age. RESULTS: Among 596,189 veterans, veterans with TBI progressed faster to RF than those without TBI (HR 1.96). Non-Hispanic Black veterans (HR 1.41) and those in US territories (HR 1.71) progressed faster to RF relative to non-Hispanic Whites and those in urban mainland areas. Non-Hispanic Blacks (-$5,180), Hispanic/Latinos ($-4,984), and veterans in US territories (-$3,740) received fewer annual total VA resources. This was true for all Hispanic/Latinos, while only significant for non-Hispanic Black and US territory veterans < 65 years. For veterans with TBI + RF, higher total resource costs only occurred ≥ 10 years after TBI + RF diagnosis ($32,361), independent of age. Hispanic/Latino veterans ≥ 65 years received $8,248 less than non-Hispanic Whites and veterans living in US territories < 65 years received $37,514 less relative to urban veterans. CONCLUSION: Concerted efforts to address RF progression in veterans with TBI, especially in non-Hispanic Blacks and those in US territories, are needed. Importantly, culturally appropriate interventions to improve access to care for these groups should be a priority of the Department of Veterans Affairs priority for these groups.

Costs of implementing a multi-site facilitation intervention to increase access to medication treatment for opioid use disorder.

BACKGROUND: The United States has been grappling with the opioid epidemic, which has resulted in over 75,000 opioid-related deaths between April 2020 and 2021. Evidence-based pharmaceutical interventions (buprenorphine, methadone, and naltrexone) are available to reduce opioid-related overdoses and deaths. However, adoption of these medications for opioid use disorder has been stifled due to individual- and system-level barriers. External facilitation is an evidence-based implementation intervention that has been used to increase access to medication for opioid use disorder (MOUD), but the implementation costs of external facilitation have not been assessed. We sought to measure the facility-level direct costs of implementing an external facilitation intervention for MOUD to provide decision makers with estimates of the resources needed to implement this evidence-based program. METHODS: We performed a cost analysis of the pre-implementation and implementation phases, including an itemization of external facilitation team and local site labor costs. We used labor estimates from the Bureau of Labor and Statistics, and sensitivity analyses were performed using labor estimates from the Veterans Health Administration (VHA) Financial Management System general ledger data. RESULTS: The average total costs for implementing an external facilitation intervention for MOUD per site was $18,847 (SD 6717) and ranged between $11,320 and $31,592. This translates to approximately $48 per patient with OUD. Sites with more encounters and participants with higher salaries in attendance had higher costs. This was driven mostly by the labor involved in planning and implementation activities. The average total cost of the pre-implementation and implementation activities were $1031 and $17,816 per site, respectively. In the sensitivity analysis, costs for VHA were higher than BLS estimates likely due to higher wages. CONCLUSIONS: Implementing external facilitation to increase MOUD prescribing may be affordable depending on the payer's budget constraints. Our study reported that there were variations in the time invested at each phase of implementation and the number and type of participants involved with implementing an external facilitation intervention. Participant composition played an important role in total implementation costs, and decision makers will need to identify the most efficient and optimal number of stakeholders to involve in their implementation plans.

Improving the Maternity Care Safety Net: Establishing Maternal Mortality Surveillance for Non-Obstetric Providers and Institutions.

The siloed nature of maternity care has been noted as a system-level factor negatively impacting maternal outcomes. Veterans Health Administration (VA) provides multi-specialty healthcare before, during, and after pregnancy but purchases obstetric care from community providers. VA providers may be unaware of perinatal complications, while community-based maternity care providers may be unaware of upstream factors affecting the pregnancy. To optimize maternal outcomes, the VA has initiated a system-level surveillance and review process designed to improve non-obstetric care for veterans experiencing a pregnancy. This quality improvement project aimed to describe the VA-based maternal mortality review process and to report maternal mortality (pregnancy-related death up to 42 days postpartum) and pregnancy-associated mortality (death from any cause up to 1 year postpartum) among veterans who use VA maternity care benefits. Pregnancies and pregnancy-associated deaths between fiscal year (FY) 2011-2020 were identified from national VA databases. All deaths underwent individual chart review and abstraction that focused on multi-specialty care received at the VA in the year prior to pregnancy until the time of death. Thirty-two pregnancy-associated deaths were confirmed among 39,720 pregnancies (PAMR = 80.6 per 100,000 live births). Fifty percent of deaths occurred among individuals who had experienced adverse social determinants of health. Mental health conditions affected 81%. Half (n = 16, 50%) of all deaths occurred in the late postpartum period (43-365 days postpartum) after maternity care had ended. More than half of these late postpartum deaths (n = 9, 56.2%) were related to suicide, homicide, or overdose. Integration of care delivered during the perinatal period (pregnancy through postpartum) from primary, mental health, emergency, and specialty care providers may be enhanced through a system-based approach to pregnancy-associated death surveillance and review. This quality improvement project has implications for all healthcare settings where coordination between obstetric and non-obstetric providers is needed.

The economic impact of cannabis use disorder and dementia diagnosis in veterans diagnosed with traumatic brain injury.

Background: Studies have demonstrated that individuals diagnosed with traumatic brain injury (TBI) frequently use medical and recreational cannabis to treat persistent symptoms of TBI, such as chronic pain and sleep disturbances, which can lead to cannabis use disorder (CUD). We aimed to determine the Veterans Health Administration (VHA) healthcare utilization and costs associated with CUD and dementia diagnosis in veterans with TBI. Methods: This observational study used administrative datasets from the population of post-9/11 veterans from the Long-term Impact of Military-Relevant Brain Injury Consortium-Chronic Effects of Neurotrauma Consortium and the VA Data Warehouse. We compared the differential VHA costs among the following cohorts of veterans: (1) No dementia diagnosis and No CUD group, (2) Dementia diagnosis only (Dementia only), (3) CUD only, and (4) comorbid dementia diagnosis and CUD (Dementia and CUD). Generalized estimating equations and negative binomial regression models were used to estimate total annual costs (inflation-adjusted) and the incidence rate of healthcare utilization, respectively, by dementia diagnosis and CUD status. Results: Data from 387,770 veterans with TBI (88.4% men; median [interquartile range (IQR)] age at the time of TBI: 30 [14] years; 63.5% white) were followed from 2000 to 2020. Overall, we observed a trend of gradually increasing healthcare costs 5 years after TBI onset. Interestingly, in this cohort of veterans within 5 years of TBI, we observed substantial healthcare costs in the Dementia only group (peak = $46,808) that were not observed in the CUD and dementia group. Relative to those without either condition, the annual total VHA costs were $3,368 higher in the CUD only group, while no significant differences were observed in the Dementia only and Dementia and CUD groups. Discussion: The findings suggest that those in the Dementia only group might be getting their healthcare needs met more quickly and within 5 years of TBI diagnosis, whereas veterans in the Dementia and CUD group are not receiving early care, resulting in higher long-term healthcare costs. Further investigations should examine what impact the timing of dementia and CUD diagnoses have on specific categories of inpatient and outpatient care in VA and community care facilities.

Long-Term Benzodiazepine Use and Discontinuation Among Patients in the U.S. Veterans Health Administration.

Objective: Although long-term benzodiazepine use is not recommended, patients are often prescribed benzodiazepines for >30 days (long-term use). Data from the Veterans Health Administration (VHA) may inform efforts to discontinue such use. This study sought to describe benzodiazepine use and discontinuation among VHA patients and compared patients who continued and discontinued use. Methods: The study used nationwide electronic health record data for all VHA-enrolled patients (age ≥18) from fiscal year (FY) 2019 (N=6,032,613). The primary outcome, benzodiazepine discontinuation, was defined as no prescription refill for 120 days. Results: In FY2019, 3.5% of VHA enrollees were prescribed benzodiazepines for >30 days, which was 72.0% of those prescribed benzodiazepines. One-third of veterans prescribed long-term benzodiazepines discontinued use. Continuation was more likely among patients who were older, not Black, taking benzodiazepines longer, and taking higher doses. When demographic factors were controlled, patients who continued long-term use were more likely to have a diagnosis of anxiety, posttraumatic stress disorder (PTSD), bipolar disorder, or psychosis and less likely to have depression or an alcohol or drug use disorder. Continuation was associated with a lower likelihood of sleep and cardiopulmonary disorders and of dementia. Conclusions: Higher discontinuation prevalence among patients with substance use disorders, dementia, or cardiopulmonary disorders is encouraging. However, the challenge remains of discontinuing long-term use among patients who are White, older, or diagnosed as having anxiety, PTSD, bipolar disorder, or psychosis. There is a need to identify provider, patient, and contextual factors driving long-term benzodiazepine use in these patient groups to effectively apply evidence-based discontinuation strategies.

Economic impact of comorbid TBI-dementia on VA facility and non-VA facility costs, 2000-2020.

OBJECTIVE: There is evidence Traumatic Brain Injury (TBI) is associated with increased risk of dementia (D). We compared VA and non-VA facility costs associated with TBI+D and each diagnosis alone, relative to neither diagnosis, annually and over time, 2000-2020. METHODS: We estimated adjusted panel models of annual VHA costs in VA and non-VA facilities, stratified by age, and by TBI-dementia status. We also estimated cost for the TBI+D cohort by time since TBI and dementia diagnoses. All costs were 2021 inflation adjusted. RESULTS: Veterans <65 ($30,736) and ≥65 ($15,650) with TBI+D, while veterans <65 ($3,379) and ≥65 ($4,252) with TBI-only had higher annual total VHA costs, relative to neither diagnosis. Veterans with TBI+D < 65 ($42,864) and ≥65 ($72,424) had higher costs in years≥15 after TBI diagnosis, while <65 ($36,431) and ≥65 ($37,589) had higher costs in years ≥10 after dementia diagnosis. CONCLUSIONS: The main cost driver was inpatient non-VA facility costs. Veterans had continuously increasing inpatient care costs in non-VA facilities over time since their TBI and dementia diagnoses. Given budget constraints on the VA system, quality of care in non-VA facilities warrants comparison with VA facilities to make informed decisions regarding referrals to non-VA facilities.

Family members' experience improves with care preference documentation in home based primary care.

BACKGROUND: The Veterans Health Administration (VA) implemented the comprehensive life-sustaining treatment (LST) Decisions Initiative to provide training and standardize documentation of goals of care and LST preferences for seriously ill Veterans to improve end-of-life (EOL) outcomes. LST documentation is expected for all Home-Based Primary Care (HBPC) Veterans because they are at high risk of hospitalization and mortality. METHODS: A retrospective, cross-sectional analysis compared associations between Bereaved Family Survey (BFS) EOL care ratings and LST documentation. Participants were Veterans who died August 1, 2018 through September 30, 2019 in one of 55 VA HBPC programs. Regression modeling generated odds for key BFS outcomes. LST template completion rate was plotted by month to understand the interaction between time, LST completion rate, and EOL care family ratings. RESULTS: LST preferences were documented for 39% of HBPC Veterans. Family members rated overall EOL care as excellent for 53% of Veterans but significant divergence in BFS ratings occurred during the last 7 months of the study with 60% of family members of LST completers rating care as excellent compared with 48% for Veterans lacking LST documentation (p = 0.003). The adjusted odds of rating overall care in the final month of life as excellent was higher among those with a completed LST template (1.64 95% CI 1.19, 2.26). CONCLUSIONS: Higher rates of LST documentation were associated with more favorable ratings of EOL but not in initial months following implementation of the comprehensive initiative; however, LST documentation rates were lower than expected among HBPC Veterans. Following an initial period of implementation of a comprehensive national initiative to promote Veteran choice about care during serious illness, documented LST preferences were associated with better family ratings of EOL care. HBPC clinicians may improve the bereaved family experience by using LSDTI tools and training to elicit and document preferences.

Outcomes of a randomized quality improvement trial for high-risk Veterans in year two.

OBJECTIVE: The Veterans Health Administration (VHA) conducted a randomized quality improvement evaluation to determine whether augmenting patient-centered medical homes with Primary care Intensive Management (PIM) decreased utilization of acute care and health care costs among patients at high risk for hospitalization. PIM was cost-neutral in the first year; we analyzed changes in utilization and costs in the second year. DATA SOURCES: VHA administrative data for five demonstration sites from August 2013 to March 2019. DATA SOURCES: Administrative data extracted from VHA's Corporate Data Warehouse. STUDY DESIGN: Veterans with a risk of 90-day hospitalization in the top 10th percentile and recent hospitalization or emergency department (ED) visit were randomly assigned to usual primary care vs primary care augmented by PIM. PIM included interdisciplinary teams, comprehensive patient assessment, intensive case management, and care coordination services. We compared the change in mean VHA inpatient and outpatient utilization and costs (including PIM expenses) per patient for the 12-month period before randomization and 13-24 months after randomization for PIM vs usual care using difference-in-differences. PRINCIPAL FINDINGS: Both PIM patients (n = 1902) and usual care patients (n = 1882) had a mean of 5.6 chronic conditions. PIM patients had a greater number of primary care visits compared to those in usual care (mean 4.6 visits/patient/year vs 3.7 visits/patient/year, p < 0.05), but ED visits (p = 0.45) and hospitalizations (p = 0.95) were not significantly different. We found a small relative increase in outpatient costs among PIM patients compared to those in usual care (mean difference + $928/patient/year, p = 0.053), but no significant differences in mean inpatient costs (+$245/patient/year, p = 0.97). Total mean health care costs were similar between the two groups during the second year (mean difference + $1479/patient/year, p = 0.73). CONCLUSIONS: Approaches that target patients solely based on the high risk of hospitalization are unlikely to reduce acute care use or total costs in VHA, which already offers patient-centered medical homes.

Prevalence and correlates of initiating injection drug use before the age of 18 years in Iran: results of a national survey.

Background: In this study, we sought to determine factors relating to initiating injection drug use before the age of 18 years in Iran.Methods: In this cross-sectional survey, people who inject drugs were recruited using facility-based sampling in 10 cities in Iran in 2014. Adults (≥18 year) who reported injecting drugs at least one time during the last year were included. A structured questionnaire collected behaviors related to injection, sexual risk, and HIV testing. Based on the reported age of first injection, we grouped participants into that initiating injection drug use by before 18-year old versus 18- and after 18-year old.Results: Of 2356 participants, 199 (8.5%, 95% CI 7.4-9.6) started injecting before the age of 18 years. Initiating injection drug use before the age of 18 years were more likely to be <30-year old (39.4% vs. 19.7%, p < .001), report syringe and needle sharing (15.0% vs. 5.4%, p < .001), have sex with other men (24.3% vs. 15.6%, p < .001), and have complete knowledge about HIV (92.5% vs. 86.4%, p < .001).Conclusion: People who started injection at younger ages had higher risk profiles and should be prioritized for substance use treatment, harm reduction, and HIV prevention programs.

Sex Discrepancies in the Protective Effect of Opioid Agonist Therapy on Incident Hepatitis C Infection.

BACKGROUND: While opioid agonist therapy (OAT) reduces the risk of hepatitis C virus (HCV) acquisition among people who inject drugs (PWID), protective effects may be attenuated in females. We used pooled data from an international collaboration of prospective cohorts to assess sex disparities in HCV incidence among PWID exposed to OAT. METHODS: Independent predictors of HCV infection were identified using Cox regression models with random effects after accounting for the clustering effect of study sites. Unadjusted and adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) are presented in sex-specific analyses. RESULTS: Among 701 participants exposed to OAT, HCV incidence was 16.5/100 person-years of observation (PYO) (95% CI, 13.1-20.7) in females and 7.6/100 PYO (95% CI, 6.0-9.5) in males (female:male adjusted HR [aHR], 1.80 [95% CI, 1.37-2.22]; P < .001). Factors associated with HCV acquisition among females exposed to OAT included nonwhite race (aHR, 1.79 [95% CI, 1.25-2.56]; P = .001), unstable housing (aHR, 4.00 [95% CI, 3.62-4.41]; P < .001), daily or more frequent injection (aHR, 1.45 [95% CI, 1.01-2.08]; P = .042), and receptive syringe sharing (aHR, 1.43 [95% CI, 1.33-1.53]; P < .001). CONCLUSIONS: Female PWID exposed to OAT are twice as likely as their male counterparts to acquire HCV. While there is a need for better understanding of sex differences in immune function and opioid pharmacokinetic and pharmacodynamic parameters, structural and behavioral interventions that target women are required to bolster the efficacy of OAT in preventing HCV transmission.

Dual Unsafe Injection and Sexual Behaviors for HIV Infection Among People Who Inject Drugs in Iran.

We used two national surveys (2010: N = 1597; 2013: N = 1057) of people who inject drugs (PWID) in past-month to assess the prevalence and population size of PWID with either safe or unsafe injection and sex behaviors, overall and by HIV status. In 2013, only 27.0% (vs. 32.3% in 2010) had safe injection and sex, 24.6% (vs. 23.3% in 2010) had unsafe injection and sex, 26.4% (vs. 26.5% in 2010) had only unsafe injection, and 22.0% (vs. 18.0% in 2010) had unsafe sex only. Among HIV-positive PWID in 2013, only 22.1% (~ 2200 persons) had safe injection and sex, 14.2% (~ 1400 persons) had unsafe injection and sex, 53.1% (~ 5200 persons) had unsafe injection, and 10.6% had unsafe sex (~ 1100 persons). Among HIV-negative PWID in 2013, only 27.5% (~ 22,200 persons) had safe injection and sex, 25.9% (~ 20,900 PWID) had unsafe injection and sex, 23.2% (~ 18,700 persons) had unsafe injection, and 23.3% (~ 18,800 persons) had unsafe sex. HIV-positive and -negative PWID in Iran continue to be at risk of HIV acquisition or transmission which calls for targeted preventions services.

Using Pyruvate Kinase as a Predictor for Patient With Endometrial Cancer Having Complex Hyperplasia With Atypia to Prevent Hysterectomy and Preserve Fertility: Retrospective Immunohistochemical Study.

OBJECTIVES: To explore whether the metabolic switches proceed or succeed the histological changes in precancerous lesions. To validate pyruvate kinase isoform 1 (PKM1) and pyruvate kinase isoform 2 (PKM2) as a histological biomarker to predict the progression of endometrial hyperplasia into invasive cancer status. METHODS: The records of 56 patients with a primary diagnosis of complex hyperplasia with atypia after endometrial biopsy were selected and analyzed retrospectively. A set of 3 consecutive sections at 4-µm thickness were cut and studied with immunohistochemical stains. From each case, 2 to 3 fields with a diagnosis of complex hyperplasia with atypia were selected and compared. A single pathologist blinded to the final diagnosis assigned the scoring. RESULTS: Positive immunostaining for PKM1 was observed in 31.25% (10 out of 32) of initial endometrial biopsy with the diagnosis of complex hyperplasia with atypia and final diagnosis of endometrial cancer, while 91.67% (out of 24) of patients with final diagnosis of negative endometrial cancer had endometrial biopsy with positive PKM1 staining ( P < .001). Positive immunostaining for PKM2 was observed in 100% of patient with endometrial biopsy result of endometrial hyperplasia with atypia (56 of 56). CONCLUSIONS: Lack of staining with PKM1 expression may help to predict the fate of endometrial hyperplasia. The disappearance of this marker is associated with the progression of hyperplasia toward cancer phenotype. Further studies are needed to understand the causes and potential mechanisms for suppressing Pyruvate Kinase Isoform 1 expression in endometrial hyperplasia.

The Effect of Female Sex on Hepatitis C Incidence Among People Who Inject Drugs: Results From the International Multicohort InC3 Collaborative.

Background: The objective of this study was to assess differences in hepatitis C virus (HCV) incidence by sex in people who inject drugs (PWID), using a large international multicohort set of pooled biological and behavioral data from prospective observational studies of incident human immunodeficiency virus (HIV) and HCV infections in high-risk cohorts (the InC3 Collaborative). Methods: HCV infection date was estimated based on a hierarchy of successive serological (anti-HCV), virological (HCV RNA), and clinical (symptoms and/or liver function tests) data. We used a Cox proportional hazards model to calculate the crude and adjusted female to male (F:M) hazard ratio (HR) for HCV incidence using biological sex as the main exposure. Results: A total of 1868 PWID were observed over 3994 person-years of observation (PYO). Unadjusted F:M HR was 1.38 (95% confidence interval [CI], 1.15-1.65) and remained significant after adjusting for behavioral and demographic risk factors (1.39 [95% CI, 1.12-1.72]). Although syringe and equipment sharing were associated with the highest HCV incidence rate in women (41.62 and 36.83 PYO, respectively), we found no sex differences attributed to these risk factors. Conclusions: Our findings indicate that women who inject drugs may be at greater risk of HCV acquisition than men, independent of demographic characteristics and risk behaviors. Multiple factors, including biological (hormonal), social network, and differential access to prevention services, may contribute to increased HCV susceptibility in women who inject drugs.

Comparative Accuracy of 17 Point-of-Care Glucose Meters.

BACKGROUND: The accuracy of point-of-care blood glucose (BG) meters is important for the detection of dysglycemia, calculation of insulin doses, and the calibration of continuous glucose monitors. The objective of this study was to compare the accuracy of commercially available glucose meters in a challenging laboratory study using samples with a wide range of reference BG and hemoglobin values. METHODS: Fresh, discarded blood samples from a hospital STAT laboratory were either used without modification, spiked with a glucose solution, or incubated at 37°C to produce 347 samples with an even distribution across reference BG levels from 20 to 440 mg/dl and hemoglobin values from 9 to 16 g/dl. We measured the BG of each sample with 17 different commercially available glucose meters and the reference method (YSI 2300) at the same time. We determined the mean absolute relative difference (MARD) for each glucose meter, overall and stratified by reference BG and by hemoglobin level. RESULTS: The accuracy of different meters widely, exhibiting a range of MARDs from 5.6% to 20.8%. Accuracy was lower in the hypoglycemic range, but was not consistently lower in samples with anemic blood hemoglobin levels. CONCLUSIONS: The accuracy of commercially available glucose meters varies widely. Although the sample mix in this study was much more challenging than those that would be collected under most use conditions, some meters were robust to these challenges and exhibited high accuracy in this setting. These data on relative accuracy and robustness to challenging samples may be useful in informing the choice of a glucose meter.

Home use of a bihormonal bionic pancreas versus insulin pump therapy in adults with type 1 diabetes: a multicentre randomised crossover trial.

BACKGROUND: The safety and effectiveness of a continuous, day-and-night automated glycaemic control system using insulin and glucagon has not been shown in a free-living, home-use setting. We aimed to assess whether bihormonal bionic pancreas initialised only with body mass can safely reduce mean glycaemia and hypoglycaemia in adults with type 1 diabetes who were living at home and participating in their normal daily routines without restrictions on diet or physical activity. METHODS: We did a random-order crossover study in volunteers at least 18 years old who had type 1 diabetes and lived within a 30 min drive of four sites in the USA. Participants were randomly assigned (1:1) in blocks of two using sequentially numbered sealed envelopes to glycaemic regulation with a bihormonal bionic pancreas or usual care (conventional or sensor-augmented insulin pump therapy) first, followed by the opposite intervention. Both study periods were 11 days in length, during which time participants continued all normal activities, including athletics and driving. The bionic pancreas was initialised with only the participant's body mass. Autonomously adaptive dosing algorithms used data from a continuous glucose monitor to control subcutaneous delivery of insulin and glucagon. The coprimary outcomes were the mean glucose concentration and time with continuous glucose monitoring (CGM) glucose concentration less than 3·3 mmol/L, analysed over days 2-11 in participants who completed both periods of the study. This trial is registered with ClinicalTrials.gov, number NCT02092220. FINDINGS: We randomly assigned 43 participants between May 6, 2014, and July 3, 2015, 39 of whom completed the study: 20 who were assigned to bionic pancreas first and 19 who were assigned to the comparator first. The mean CGM glucose concentration was 7·8 mmol/L (SD 0·6) in the bionic pancreas period versus 9·0 mmol/L (1·6) in the comparator period (difference 1·1 mmol/L, 95% CI 0·7-1·6; p<0·0001), and the mean time with CGM glucose concentration less than 3·3 mmol/L was 0·6% (0·6) in the bionic pancreas period versus 1·9% (1·7) in the comparator period (difference 1·3%, 95% CI 0·8-1·8; p<0·0001). The mean nausea score on the Visual Analogue Scale (score 0-10) was greater during the bionic pancreas period (0·52 [SD 0·83]) than in the comparator period (0·05 [0·17]; difference 0·47, 95% CI 0·21-0·73; p=0·0024). Body mass and laboratory parameters did not differ between periods. There were no serious or unexpected adverse events in the bionic pancreas period of the study. INTERPRETATION: Relative to conventional and sensor-augmented insulin pump therapy, the bihormonal bionic pancreas, initialised only with participant weight, was able to achieve superior glycaemic regulation without the need for carbohydrate counting. Larger and longer studies are needed to establish the long-term benefits and risks of automated glycaemic management with a bihormonal bionic pancreas. FUNDING: National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health, and National Center for Advancing Translational Sciences.

Probiotics in Human Immunodeficiency Virus Infection: A Systematic Review and Evidence Synthesis of Benefits and Risks.

People living with human immunodeficiency virus frequently use dietary supplements, including probiotics, but concern exists about ingesting live organisms. We performed a systematic review of the benefits of probiotics and a meta-analysis of sepsis risk. We undertook a protocol-driven, comprehensive review to identify all relevant studies, assess their quality, and summarize the evidence. Of 2068 references, 27 were analyzed. The data suggest possible benefits for CD4 count, recurrence or management of bacterial vaginosis, and diarrhea management. We examined randomized, controlled studies explicitly assessing sepsis in any patient population, and we found zero cases of supplement-associated bacteremia or fungemia in 39 randomized controlled trials comprising 9402 subjects. The estimated number needed to harm is 7369 in Bayesian approach (95% credible interval: 1689, ∞), which should reassure clinicians. No or mild adverse effects were reported. Longer duration studies investigating different individual and mixed strains for plausible indications are needed to establish best practices.

Correction: Micronutrients in HIV: A Bayesian Meta-Analysis.

[This corrects the article DOI: 10.1371/journal.pone.0120113.].

Micronutrients in HIV: a Bayesian meta-analysis.

BACKGROUND: Approximately 28.5 million people living with HIV are eligible for treatment (CD4<500), but currently have no access to antiretroviral therapy. Reduced serum level of micronutrients is common in HIV disease. Micronutrient supplementation (MNS) may mitigate disease progression and mortality. OBJECTIVES: We synthesized evidence on the effect of micronutrient supplementation on mortality and rate of disease progression in HIV disease. METHODS: We searched MEDLINE, EMBASE, the Cochrane Central, AMED and CINAHL databases through December 2014, without language restriction, for studies of greater than 3 micronutrients versus any or no comparator. We built a hierarchical Bayesian random effects model to synthesize results. Inferences are based on the posterior distribution of the population effects; posterior distributions were approximated by Markov chain Monte Carlo in OpenBugs. PRINCIPAL FINDINGS: From 2166 initial references, we selected 49 studies for full review and identified eight reporting on disease progression and/or mortality. Bayesian synthesis of data from 2,249 adults in three studies estimated the relative risk of disease progression in subjects on MNS vs. control as 0.62 (95% credible interval, 0.37, 0.96). Median number needed to treat is 8.4 (4.8, 29.9) and the Bayes Factor 53.4. Based on data reporting on 4,095 adults reporting mortality in 7 randomized controlled studies, the RR was 0.84 (0.38, 1.85), NNT is 25 (4.3, ∞). CONCLUSIONS: MNS significantly and substantially slows disease progression in HIV+ adults not on ARV, and possibly reduces mortality. Micronutrient supplements are effective in reducing progression with a posterior probability of 97.9%. Considering MNS low cost and lack of adverse effects, MNS should be standard of care for HIV+ adults not yet on ARV.