Risk of depression in persons with Alzheimer's disease: A national cohort study.

INTRODUCTION: Depression is a risk factor and possible prodromal symptom of Alzheimer's disease (AD), but little is known about subsequent risk of developing depression in persons with AD. METHODS: National matched cohort study was conducted of all 129,410 persons diagnosed with AD and 390,088 with all-cause dementia during 1998-2017 in Sweden, and 3,900,880 age- and sex-matched controls without dementia, who had no prior depression. Cox regression was used to compute hazard ratios (HRs) for major depression through 2018. RESULTS: Cumulative incidence of major depression was 13% in persons with AD and 3% in controls. Adjusting for sociodemographic factors and comorbidities, risk of major depression was greater than two-fold higher in women with AD (HR, 2.21; 95% confidence interval [CI], 2.11-2.32) or men with AD (2.68; 2.52-2.85), compared with controls. Similar results were found for all-cause dementia. DISCUSSION: Persons diagnosed with AD or related dementias need close follow-up for timely detection and treatment of depression. Highlights: In a large cohort, women and men with AD had >2-fold subsequent risk of depression.Risks were highest in the first year (>3-fold) but remained elevated ≥3 years later.Risk of depression was highest in persons aged ≥85 years at AD diagnosis.Persons with AD need close follow-up for detection and treatment of depression.

Personality correlates of past-year alcohol use in individuals with severe alcohol use disorder and a lifetime history of involvement in alcoholics anonymous.

BACKGROUND: Alcohol use disorder (AUD) is a highly impairing condition with important public health impacts. Despite the availability of treatment options for AUD, research shows that few people receive treatment, and even fewer can maintain abstinence/low-drinking levels. This study investigated the role of personality traits in past-year alcohol use among individuals with severe AUD who ever attended Alcoholics Anonymous (AA), a widespread and easily accessible self-help group for alcohol problems. METHODS: Univariable and multivariable regressions were performed separately in females and males with alcohol consumption as an outcome. Socioeconomic factors, genetic liability, and psychopathology were included as covariates in the analyses. RESULTS: Results from the multivariable model indicated that in females who attended AA, greater alcohol use was related to both positive and negative urgency and low sensation seeking, while in males, greater alcohol use was related to positive urgency. Results also showed that, in both sexes, younger age and lower educational levels were associated with greater alcohol use. Moreover, single males and individuals with lower AUD severity were at higher risk of using alcohol in the past year. CONCLUSIONS: These findings highlight sex-specific correlates of drinking in individuals with AUD who engaged in self-help groups. These findings may help to improve treatment options, as personality encompasses modifiable traits that can be targeted in psychological interventions.

Splice site and de novo mutations can cause mixed dominant negative/gain of function PLCG2-associated immune dysregulation with cold urticaria (CU-PLAID).

Background: Phospholipase Cγ2 (PLCγ2) is an important signaling molecule that receives and transmits signals from various cell surface receptors in most hematopoietic lineages. Variants of PLCG2 cause PLCγ2-associated immune dysregulation (PLAID), a family of conditions that are classified by mutational effect. PLAID with cold urticaria (CU-PLAID) is caused by in-frame deletions of PLCG2 that are dominant negative at physiologic temperatures but become spontaneously active at sub-physiologic temperatures. Objective: To identify genetic lesions that cause PLAID by combining RNA sequencing of full-length PLCG2 with whole genome sequencing. Methods: We studied nine probands with antibody deficiency and a positive evaporative cooling test, together with two known CU-PLAID patients and three healthy subjects. Illumina sequencing was performed on full-length PLCG2 cDNA synthesized from peripheral blood mononuclear cell RNA and whole genome sequencing was used to identify genetic lesions. Novel alternate transcripts were overexpressed in the Plcg2-deficient DT40 cell overexpression system. ERK phosphorylation was quantified by flow cytometry with and without BCR crosslinking. Results: Two probands expressed novel alternative transcripts of PLCG2 with in-frame deletions. The first, expressing PLCG2 without exons 18-19, carried a splice site mutation in intron 19. The second, expressing PLCG2 without exons 19-22, carried a 14kb de novo deletion of PLCG2. DT40 cells overexpressing the exon 18-19 or exon 19-22 deletions failed to phosphorylate ERK in response to BCR crosslinking. Conclusion: In addition to autosomal dominant genomic deletions, de novo deletions and splice site mutations of PLCG2 can also cause CU-PLAID. All of these can be identified by cDNA-based sequencing.

Recessive variants in the intergenic NOS1AP-C1orf226 locus cause monogenic kidney disease responsive to anti-proteinuric treatment.

In genetic disease, an accurate expression landscape of disease genes and faithful animal models will enable precise genetic diagnoses and therapeutic discoveries, respectively. We previously discovered that variants in NOS1AP , encoding nitric oxide synthase 1 (NOS1) adaptor protein, cause monogenic nephrotic syndrome (NS). Here, we determined that an intergenic splice product of N OS1AP / Nos1ap and neighboring C1orf226/Gm7694 , which precludes NOS1 binding, is the predominant isoform in mammalian kidney transcriptional and proteomic data. Gm7694 -/- mice, whose allele exclusively disrupts the intergenic product, developed NS phenotypes. In two human NS subjects, we identified causative NOS1AP splice variants, including one predicted to abrogate intergenic splicing but initially misclassified as benign based on the canonical transcript. Finally, by modifying genetic background, we generated a faithful mouse model of NOS1AP -associated NS, which responded to anti-proteinuric treatment. This study highlights the importance of intergenic splicing and a potential treatment avenue in a mendelian disorder.

Fetal neuroimaging applications for diagnosis and counseling of brain anomalies: Current practice and future diagnostic strategies.

Advances in fetal brain neuroimaging, especially fetal neurosonography and brain magnetic resonance imaging (MRI), allow safe and accurate anatomical assessments of fetal brain structures that serve as a foundation for prenatal diagnosis and counseling regarding fetal brain anomalies. Fetal neurosonography strategically assesses fetal brain anomalies suspected by screening ultrasound. Fetal brain MRI has unique technological features that overcome the anatomical limits of smaller fetal brain size and the unpredictable variable of intrauterine motion artifact. Recent studies of fetal brain MRI provide evidence of improved diagnostic and prognostic accuracy, beginning with prenatal diagnosis. Despite technological advances over the last several decades, the combined use of different qualitative structural biomarkers has limitations in providing an accurate prognosis. Quantitative analyses of fetal brain MRIs offer measurable imaging biomarkers that will more accurately associate with clinical outcomes. First-trimester ultrasound opens new opportunities for risk assessment and fetal brain anomaly diagnosis at the earliest time in pregnancy. This review includes a case vignette to illustrate how fetal brain MRI results interpreted by the fetal neurologist can improve diagnostic perspectives. The strength and limitations of conventional ultrasound and fetal brain MRI will be compared with recent research advances in quantitative methods to better correlate fetal neuroimaging biomarkers of neuropathology to predict functional childhood deficits. Discussion of these fetal sonogram and brain MRI advances will highlight the need for further interdisciplinary collaboration using complementary skills to continue improving clinical decision-making following precision medicine principles.

Venous Thromboembolism Risk Factors in Women With Obesity Who Undergo Cesarean Delivery.

Venous thromboembolism (VTE) is a leading cause of maternal mortality. Obesity and cesarean delivery are established risk factors for pregnancy-related VTE. We identified additional risk factors among patients with obesity who underwent a cesarean delivery to identify those who need VTE prophylaxis. We conducted a secondary analysis of data from the Maternal-Fetal Medicine Units Network (MFMU) Cesarean Registry Database using a case-control design. Cases were identified as women with obesity having a pre-pregnancy body mass index of >30 kg/m2, who underwent cesarean delivery and subsequently developed deep venous thrombosis (DVT) or pulmonary embolism (PE). These women were compared to a control group of women with obesity who underwent cesarean delivery but did not develop DVT or PE. Analysis of risk factors associated with VTE was performed using Chi-Square test and Fisher's exact test. We identified 43 VTE cases and 172 controls in the MFMU database. Increased risk of VTE was noted in women with endometritis (OR of 4.58 [95% CI: 1.86-11.2, P = .0004]), receiving a blood transfusion (OR 17.07 [95% CI: 4.46-65.3, P = .0001]), having a coagulopathy (OR 27.73 [95% CI: 3.24-237.25, P = .0003]), and urinary tract infection (OR 2.39 [95% CI: 1.08-5.28, P = .03]). Important risk factors for VTE in women with obesity who undergo cesarean delivery include endometritis, intra- or post-operative transfusion, coagulopathy, and urinary tract infection. The presence of one or more of these factors may help guide provider decision-making regarding whether to administer thromboprophylaxis.

Lac-Phe mediates the effects of metformin on food intake and body weight.

Metformin is a widely prescribed anti-diabetic medicine that also reduces body weight. There is ongoing debate about the mechanisms that mediate metformin's effects on energy balance. Here, we show that metformin is a powerful pharmacological inducer of the anorexigenic metabolite N-lactoyl-phenylalanine (Lac-Phe) in cells, in mice and two independent human cohorts. Metformin drives Lac-Phe biosynthesis through the inhibition of complex I, increased glycolytic flux and intracellular lactate mass action. Intestinal epithelial CNDP2+ cells, not macrophages, are the principal in vivo source of basal and metformin-inducible Lac-Phe. Genetic ablation of Lac-Phe biosynthesis in male mice renders animals resistant to the effects of metformin on food intake and body weight. Lastly, mediation analyses support a role for Lac-Phe as a downstream effector of metformin's effects on body mass index in participants of a large population-based observational cohort, the Multi-Ethnic Study of Atherosclerosis. Together, these data establish Lac-Phe as a critical mediator of the body weight-lowering effects of metformin.

Challenges, risks, and opportunities of antiretroviral drugs in women of reproductive potential.

INTRODUCTION: The HIV/AIDS epidemic has been one of the greatest challenges in global health, significantly affecting women of reproductive potential. Considerable advances in antiretroviral therapy for women living with HIV have contributed to improvements in quality of life, better reproductive and birth outcomes, and a reduced risk of perinatal transmission. AREAS COVERED: Despite the progress made, persistent challenges in access and adherence to antiretroviral drugs may limit their benefits for some women. More pharmacokinetic and safety studies in pregnant and lactating women are urgently needed, as are prospective surveillance systems to evaluate associations between fetal and infant antiretroviral exposures, drug-drug interactions, and pregnancy outcomes. EXPERT OPINION: Multipurpose technologies, such as combined HIV and other STI or unintended pregnancy prevention, and innovative delivery methods, such as the development of long-acting antiretrovirals, have the potential to reduce adherence challenges and enhance quality of life for women with HIV. Parallel advances in drug safety testing and surveillance are needed to ensure the health and safety of women with or at risk for HIV and children at risk for perinatal transmission.

Associations between polygenic liability to psychopathology and non-suicidal versus suicidal self-injury.

Little is known about how non-suicidal and suicidal self-injury are differentially genetically related to psychopathology and related measures. This research was conducted using the UK Biobank Resource, in participants of European ancestry (N = 2320 non-suicidal self-injury [NSSI] only; N = 2648 suicide attempt; 69.18% female). We compared polygenic scores (PGS) for psychopathology and other relevant measures within self-injuring individuals. Logistic regressions and likelihood ratio tests (LRT) were used to identify PGS that were differentially associated with these outcomes. In a multivariable model, PGS for anorexia nervosa (odds ratio [OR] = 1.07; 95% confidence intervals [CI] 1.01; 1.15) and suicidal behavior (OR = 1.06; 95% CI 1.00; 1.12) both differentiated between NSSI and suicide attempt, while the PGS for other phenotypes did not. The LRT between the multivariable and base models was significant (Chi square = 11.38, df = 2, p = 0.003), and the multivariable model explained a larger proportion of variance (Nagelkerke's pseudo-R2 = 0.028 vs. 0.025). While NSSI and suicidal behavior are similarly genetically related to a range of mental health and related outcomes, genetic liability to anorexia nervosa and suicidal behavior is higher among those reporting a suicide attempt than those reporting NSSI-only. Further elucidation of these distinctions is necessary, which will require a nuanced assessment of suicidal versus non-suicidal self-injury in large samples.

Alcohol use disorder and risk of specific methods of suicide death in a national cohort.

INTRODUCTION: Alcohol use disorder (AUD) is among the strongest correlates of suicide death, but it is unclear whether AUD status is differentially associated with risk of suicide by particular methods. METHODS: The authors used competing risks models to evaluate the association between AUD status and risk of suicide by poisoning, suffocation, drowning, firearm, instruments, jumping, or other means in a large Swedish cohort born 1932-1995 (total N = 6,581,827; 48.8% female). Data were derived from Swedish national registers, including the Cause of Death Register and a range of medical registers. RESULTS: After adjusting for sociodemographic factors and familial liability to suicidal behavior, AUD was positively associated with risk of suicide for each method evaluated (cumulative incidence differences: 0.006-1.040 for females, 0.046-0.680 for males), except the association with firearm suicide in females. AUD was most strongly associated with risk of suicide by poisoning. Sex differences in the effects of AUD and family liability were observed for some, but not all, methods. Furthermore, high familial liability for suicidal behavior exacerbated AUD's impact on risk for suicide by poisoning (both sexes) and suffocation and jumping (males only), while the inverse interaction was observed for firearm suicide (males only). CONCLUSIONS: AUD increases risk of suicide by all methods examined and is particularly potent with respect to risk of suicide by poisoning. Differences in risk related to sex and familial liability to suicidal behavior underscore AUD's nuanced role in suicide risk. Future research should investigate targeted means restriction effectiveness among persons with AUD.

Divorce, genetic risk, and suicidal thoughts and behaviors in a sample with recurrent major depressive disorder.

BACKGROUND: Theories of risk for suicidal thoughts and behaviors (STB) implicate both interpersonal and biological factors. Divorce/separation and aggregate genetic liability are robustly associated with STB, but have seldom been evaluated in conjunction with one another. Furthermore, whether these factors are effective predictors in high-risk populations is not clear. METHODS: Analyses were conducted in a sample of Han Chinese women with severe recurrent major depressive disorder (maximum N = 4380). Logistic regressions were used to evaluate the associations between divorce/separation and polygenic scores (PGS) for suicidal ideation or behavior with STB. Where appropriate, additive interactions between divorce and PGS were tested. RESULTS: Divorce/separation was significantly associated with increased risk of suicidal ideation, plans, and attempts (odds ratios = 1.28-1.61). PGS for suicidal ideation were not associated with STB, while PGS for suicidal behavior were associated with ideation and plans (odds ratios = 1.08-1.09). There were no significant interactions between divorce/separation and PGS. CONCLUSIONS: Consistent with theories of suicidality, the disruption or end of an important interpersonal relationship is an indicator of risk for STB. Aggregate genetic liability for suicidal behavior more modestly contributes to risk, but does not exacerbate the negative impact of divorce. Thus, even within a high-risk sample, interpersonal and biological exposures distinguish between those who do and do not experience STB, and could motivate targeted screening. Further research is necessary to evaluate whether and how the context of divorce contributes to variation in its effect on STB risk.

Socioeconomic position indicators and risk of alcohol-related medical conditions: A national cohort study from Sweden.

BACKGROUND: Alcohol consumption contributes to excess morbidity and mortality in part through the development of alcohol-related medical conditions (AMCs, including alcoholic cardiomyopathy, hepatitis, cirrhosis, etc.). The current study aimed to clarify the extent to which risk for these outcomes differs as a function of socioeconomic position (SEP), as discrepancies could lead to exacerbated health disparities. METHODS AND FINDINGS: We used longitudinal Swedish national registries to estimate the individual and joint associations between 2 SEP indicators, educational attainment and income level, and risk of AMC based on International Classification of Diseases codes, while controlling for other sociodemographic covariates and psychiatric illness. We conducted Cox proportional hazards models in sex-stratified analyses (N = 1,162,679 females and N = 1,196,659 males), beginning observation at age 40 with follow-up through December 2018, death, or emigration. By the end of follow-up, 4,253 (0.37%) females and 11,183 (0.93%) males had received an AMC registration, corresponding to overall AMC incidence rates among females and males of 2.01 and 5.20, respectively. In sex-stratified models adjusted for birth year, marital status, region of origin, internalizing and externalizing disorder registrations, and alcohol use disorder (AUD) registration, lower educational attainment was associated with higher risk of AMC in both females (hazard ratios [HRs] = 1.40 to 2.46 for low- and mid-level educational attainment across 0 to 15 years of observation) and males (HRs = 1.13 to 1.48). Likewise, risk of AMC was increased for those with lower income levels (females: HRs = 1.10 to 5.86; males: HRs = 1.07 to 6.41). In secondary analyses, we further adjusted for aggregate familial risk of AUD by including family genetic risk scores for AUD (FGRSAUD), estimated using medical, pharmacy, and criminal registries in extended families, as covariates. While FGRSAUD were associated with risk of AMC in adjusted models (HR = 1.17 for females and HR = 1.21 for males), estimates for education and income level remained largely unchanged. Furthermore, FGRSAUD interacted with income level, but not education level, such that those at higher familial liability to AUD were more susceptible to the adverse effect of low income. Limitations of these analyses include the possibility of false negatives for psychiatric illness registrations, changes in income after age 40 that were not accounted for due to modeling restrictions, restriction to residents of a high-income country, and the inability to account for individual-level alcohol consumption using registry data. CONCLUSIONS: Using comprehensive national registry data, these analyses demonstrate that individuals with lower levels of education and/or income are at higher risk of developing AMC. These associations persist even when accounting for a range of sociodemographic, psychiatric, and familial risk factors. Differences in risk could contribute to further health disparities, potentially warranting increased screening and prevention efforts in clinical and public health settings.

Colonic malakoplakia in a pediatric renal transplant recipient case report.

Malakoplakia is a rare, chronic granulomatous disease that mainly affects the genitourinary system of immunocompromised adults. It is caused by a bactericidal deficit in macrophages and, therefore, the treatment includes antimicrobials that reach high concentrations in macrophages. To our knowledge, we present the first case of malakoplakia in a pediatric solid organ transplant recipient. Our patient is a 15-year-old male renal transplant recipient who presented with recurrent diarrhea. Blood, urine, and gastrointestinal pathogen panel testing were positive for enteroaggregative Escherichia coli. A colonoscopy revealed diffuse malakoplakia. He had a complete resolution of symptoms with trimethoprim-sulfamethoxazole therapy. Unfortunately, his malakoplakia recurred after 9 months prompting the transition of therapy to oral gentamicin with subsequent remission. Malakoplakia should be considered in the differential of solid organ transplant recipients with recurrent gastrointestinal infections.

"DIEP Flap vs PAP Flap vs LAP Flap: A Propensity Matched Analysis of Aesthetic Outcomes, Complications, and Satisfaction".

INTRODUCTION: As free breast reconstruction options evolve, a patient and body centric approach can distinguish refined aesthetic outcomes. While DIEP, PAP, and LAP flaps are all safe and effective options for breast reconstruction, a head-to-head analysis of these three flaps has not been performed. We aim to compare these three flaps based on outcomes, BREAST-Q, and aesthetic results. METHODS: After IRB approval, a retrospective review in a REDCap database guided analysis of patients who underwent simultaneous bilateral DIEP, PAP, or LAP flaps at a single academic institution. Propensity matching was performed to match 50 patients (100 flaps) in each group. Post-operative complications and BREAST-Q satisfaction survey scores were documented, and crowdsourcing was carried out to determine aesthetic preference in the general population. RESULTS: Overall patient post-operative breast satisfaction was insignificantly different across the three flap groups(p>0.05). Associations were seen with LAP flap donor site seromas, PAP flap donor site infections and wounds, and DIEP flap breast wounds and flap necrosis(p<0.05). DIEP flaps had a higher raw score average on crowdsourcing survey, although LAP flaps were rated significantly higher aesthetically than DIEP and PAP flaps when undergoing a matched head-to-head analysis(p<0.05). CONCLUSION: DIEP, PAP, and LAP flaps all have favorable outcomes with insignificantly different long-term satisfaction, with comparable complication profiles. While DIEP flaps may initially score higher, LAP flaps score higher frequently when analyzed in a head-to-head analysis. For these reasons, tailoring breast reconstruction to the patient's anatomy and morphology provides optimal outcomes.

A Swedish population-based study to evaluate the usefulness of resting heart rate in the prediction of suicidal behavior among males.

INTRODUCTION: Resting heart rate has been distinctly related to both internalizing (high pulse) and externalizing (low pulse) disorders. We aimed to explore the associations between resting heart rate and suicidal behavior (nonfatal suicide attempt [SA] and suicide death [SD]) and evaluate if such associations exist beyond the effects of internalizing/externalizing symptomatology. METHOD: We used Cox proportional hazards models to evaluate the associations between resting heart rate (age 19) and later SA/SD in 357,290 Swedish men. Models were controlled for internalizing disorders, externalizing disorders, and resilience (the ability to deal with adversity). Co-relative analysis (comparing pairs of different genetic relatedness) was used to control for unmeasured family confounders and improve causal inference. RESULTS: In baseline models, low resting heart rate was associated with SA (HR = 0.96; 95% CI: 0.95,0.98) and high resting heart rate with SD (HR = 1.04; 95% CI: 1.002,1.07). The association with SA remained after adjustment for all confounders (HR = 0.98). However, the association with SD did not persist after controlling for covariates. Co-relative analysis did not support causal associations. CONCLUSIONS: Our findings raise interesting etiological questions for the understanding of suicidal behaviors but do not support the usefulness of resting heart rate in suicide prediction.

Functional EPAS1/HIF2A missense variant is associated with hematocrit in Andean highlanders.

Hypoxia-inducible factor pathway genes are linked to adaptation in both human and nonhuman highland species. EPAS1, a notable target of hypoxia adaptation, is associated with relatively lower hemoglobin concentration in Tibetans. We provide evidence for an association between an adaptive EPAS1 variant (rs570553380) and the same phenotype of relatively low hematocrit in Andean highlanders. This Andean-specific missense variant is present at a modest frequency in Andeans and absent in other human populations and vertebrate species except the coelacanth. CRISPR-base-edited human cells with this variant exhibit shifts in hypoxia-regulated gene expression, while metabolomic analyses reveal both genotype and phenotype associations and validation in a lowland population. Although this genocopy of relatively lower hematocrit in Andean highlanders parallels well-replicated findings in Tibetans, it likely involves distinct pathway responses based on a protein-coding versus noncoding variants, respectively. These findings illuminate how unique variants at EPAS1 contribute to the same phenotype in Tibetans and a subset of Andean highlanders despite distinct evolutionary trajectories.

Frequency of Treatment Failure of UTIs in Children With Congenital Urinary Tract Anomalies.

OBJECTIVES: Children with certain congenital anomalies of the kidney and urinary tract and neurogenic bladder (CAKUT/NGB) are at higher risk of treatment failure for urinary tract infections (UTIs) than children with normal genitourinary anatomy, but the literature describing treatment and outcomes is limited. The objectives of this study were to describe the rate of treatment failure in children with CAKUT/NGB and compare duration of antibiotics between those with and without treatment failure. METHODS: Multicenter retrospective cohort of children 0 to 17 years old with CAKUT/NGB who presented to the emergency department with fever or hypothermia and were diagnosed with UTI between 2017 and 2018. The outcome of interest was treatment failure, defined as subsequent emergency department visit or hospitalization for UTI because of the same pathogen within 30 days of the index encounter. Descriptive statistics and univariates analyses were used to compare covariates between groups. RESULTS: Of the 2014 patient encounters identified, 482 were included. Twenty-nine (6.0%) of the 482 included encounters had treatment failure. There was no difference in the mean duration of intravenous antibiotics (3.4 ± 2.5 days, 3.5 ± 2.8 days, P = .87) or total antibiotics between children with and without treatment failure (10.2 ± 3.8 days, 10.8 ± 4.0 days, P = .39) Of note, there was a higher rate of bacteremia in children with treatment failure (P = .04). CONCLUSIONS: In children with CAKUT/NGB and UTI, 6.0% of encounters had treatment failure. Duration of antibiotics was not associated with treatment failure. Larger studies are needed to assess whether bacteremia modifies the risk of treatment failure.

Health-system specialty pharmacist intervention types, acceptance, and associated actions for patients with multiple sclerosis.

DISCLAIMER: In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time. PURPOSE: Health-system specialty pharmacy (HSSP) pharmacists play an integral role in the care of patients with multiple sclerosis (PwMS) by facilitating medication access, providing counseling, improving adherence, and decreasing provider workload. However, current literature detailing pharmacist interventions and their acceptance rates in this population is limited. The purpose of this study was to identify the types and acceptance rate of clinical interventions completed by pharmacists for PwMS. METHODS: To evaluate the acceptance rate of HSSP pharmacist interventions, we conducted a retrospective, multicenter, observational, descriptive study for the period from October 2019 to August 2022. Intervention types were categorized into reasons for intervention, recommendations from the pharmacists, and their acceptance rates. RESULTS: For 225 patients enrolled in HSSP services, 449 interventions were completed with an average of 2.0 interventions per patient. Most interventions identified were associated with medication adherence (28.7%), medication regimen (27.6%), adverse drug reaction (ADR) (20.7%), and laboratory values (15.1%). The average adherence, defined by the proportion of days covered, was 94%. The most common recommendations were to continue therapy (14.9%), schedule laboratory tests (12.7%), and follow up with providers (11.8%). Recommendations had an acceptance rate of 85.3%, with 3.8% of recommendations declined and 10.9% requiring follow-up with providers. CONCLUSION: P Pharmacists impact patient outcomes through the completion of clinical interventions that improve adherence, identify medication regimen problems, manage ADRs, and coordinate proper laboratory testing. Pharmacist recommendations were most often accepted for interventions related to medication regimen and ADRs. Proper identification and management of medication regimen concerns, as well as tolerability of medications, can positively impact adherence and improve overall patient outcomes.

Clarifying the relationship between physical injuries and risk for suicide attempt in a Swedish national sample.

INTRODUCTION: The Interpersonal-Psychological Theory of Suicide proposes that capability for suicide is acquired through exposure to painful and provocative events (PPEs). Although there is robust evidence for a positive association between aggregate measures of PPEs and risk for suicidal behavior, little is known about the contributions of physical injuries. The present study investigated the relationship between injuries and risk of subsequent suicide attempt (SA). METHODS: Data were from Swedish population-based registers. All individuals born in Sweden between 1970 and 1990 were included (N = 1,011,725 females and 1,067,709 males). We used Cox regression models to test associations between 10 types of injuries (eye injury; fracture; dislocation/sprain/strain; injury to nerves and spinal cord; injury to blood vessels; intracranial injury; crushing injury; internal injury; traumatic amputation; and other or unspecified injuries) and risk for later SA. Analyses were stratified by sex and adjusted for year of birth and parental education. Additional models tested for differences in the pattern of associations based on age group and genetic liability for SA. In co-relative models, we tested the association between each injury type and risk for SA in relative pairs of varying genetic relatedness to control for unmeasured familial confounders. RESULTS: All 10 injury types were associated with elevated risk for SA (hazard ratios [HRs] = 1.2-7.0). Associations were stronger in the first year following an injury (HRs = 1.8-7.0), but HRs remained above 1 more than 1 year after injury exposure (HRs = 1.2-2.6). The strength of associations varied across injury type, sex, age, and genetic liability for SA. For example, the magnitude of the association between crushing injury and risk for SA was larger in females than males, whereas other injuries showed a similar pattern of associations across sex. Moreover, there was evidence to support positive additive interaction effects between several injury types and aggregate genetic liability for SA (relative excess risk due to interaction [RERI] = 0.1-0.3), but the majority of these interactions became non-significant or changed direction after accounting for comorbid psychiatric and substance use disorders. In co-relative models, the pattern of associations differed by injury type, such that there was evidence to support a potential causal effect of eye injury, fracture, dislocation/sprain/strain, intracranial injury, and other and unspecified injuries on risk for SA. For the remaining injury types, HRs were not significantly different from 1 in monozygotic twins, which is consistent with confounding by familial factors. CONCLUSIONS: Injuries are associated with increased risk for subsequent SA, particularly in the first year following an injury. While genetic and familial environmental factors may partly explain these associations, there is also evidence to support a potential causal effect of several injury types on future risk for SA.