Characteristics and outcomes of pregnancies among women with phenylketonuria from the NBS Connect registry.

Women with phenylketonuria (PKU) should maintain blood phenylalanine (phe) concentration within the recommended range before and during pregnancy to prevent maternal PKU syndrome (MPKUS) in their offspring. Women who gave birth to children with MPKUS symptoms were more likely to report elevated phe concentration before pregnancy, and barriers to accessing components of their dietary management during pregnancy, including blood phe testing, medical food, modified low-protein foods, and healthcare visits with PKU specialists.

The efficacy of Carbamylglutamate impacts the nutritional management of patients with N-Acetylglutamate synthase deficiency.

BACKGROUND: The autosomal recessive disorder N-acetylglutamate synthase (NAGS) deficiency is the rarest defect of the urea cycle, with an incidence of less than one in 2,000,000 live births. Hyperammonemic crises can be avoided in individuals with NAGS deficiency by the administration of carbamylglutamate (also known as carglumic acid), which activates carbamoyl phosphatase synthetase 1 (CPS1). The aim of this case series was to introduce additional cases of NAGS deficiency to the literature as well as to assess the role of nutrition management in conjunction with carbamylglutamate therapy across new and existing cases. METHODS: We conducted retrospective chart reviews of seven cases of NAGS deficiency in the US and Canada, focusing on presentation, diagnosis, medication management, nutrition management, and outcomes. RESULTS: Five new and two previously published cases were included. Presenting symptoms were consistent with previous reports. Diagnostic confirmation via molecular testing varied in protocol across cases, with consecutive single gene tests leading to long delays in diagnosis in some cases. All patients responded well to carbamylglutamate therapy, as indicated by normalization of plasma ammonia and citrulline, as well as urine orotic acid in patients with abnormal levels at baseline. Although protein restriction was not prescribed in any cases after carbamylglutamate initiation, two patients continued to self-restrict protein intake. One patient experienced two episodes of hyperammonemia that resulted in poor long-term outcomes. Both episodes occurred after a disruption in access to carbamylglutamate, once due to insurance prior authorization requirements and language barriers and once due to seizure activity limiting the family's ability to administer carbamylglutamate. CONCLUSIONS: Follow-up of patients with NAGS deficiency should include plans for illness and for disruption of carbamylglutamate access, including nutrition management strategies such as protein restriction. Carbamylglutamate can help patients with NAGS deficiency to liberalize their diets, but the maximum safe level of protein intake to prevent hyperammonemia is not yet known. Patients using this medication should still monitor their diet closely and be prepared for any disruptions in medication access, which might require immediate dietary adjustments or medical intervention to prevent hyperammonemia.

Nutrition management of PKU with pegvaliase therapy: update of the web-based PKU nutrition management guideline recommendations.

BACKGROUND: The web-based GMDI/SERN PKU Nutrition Management Guideline, published before approval of pegvaliase pharmacotherapy, offers guidance for nutrition management of individuals with phenylketonuria (PKU) treated with dietary therapy and/or sapropterin. An update of this guideline aims to provide recommendations that improve clinical outcomes and promote consistency and best practice in the nutrition management of individuals with PKU receiving pegvaliase therapy. Methodology includes: formulation of a research question; review, critical appraisal, and abstraction of peer-reviewed studies and unpublished practice literature; expert input through Delphi surveys and a Nominal Group process; and external review by metabolic experts. RESULTS: Recommendations, summary statements, and strength of evidence are included for each of the following topics: (1) initiating a pegvaliase response trial, (2) monitoring therapy response and nutritional status, (3) managing pegvaliase treatment after response to therapy, (4) education and support for optimal nutrition with pegvaliase therapy, and (5) pegvaliase therapy during pregnancy, lactation, and adolescence. Findings, supported by evidence and consensus, provide guidance for nutrition management of individuals receiving pegvaliase therapy for PKU. Recommendations focus on nutrition management by clinicians, as well as the challenges for individuals with PKU as a result of therapy changes. CONCLUSIONS: Successful pegvaliase therapy allows the possibility for individuals with PKU to consume an unrestricted diet while still maintaining the benefits of blood phenylalanine control. This necessitates a perspective change in education and support provided to individuals in order to achieve healthy nutrient intake that supports optimal nutritional status. The updated guideline, and companion Toolkit for practical implementation of recommendations, is web-based, allowing for utilization by health care providers, researchers, and collaborators who advocate and care for individuals with PKU. These guidelines are meant to be followed always taking into account the provider's clinical judgement and considering the individual's specific circumstances. Open access is available at the Genetic Metabolic Dietitians International ( https://GMDI.org ) and Southeast Regional Genetics Network ( https://managementguidelines.net ) websites.

Primary Care Providers' Use of Genetic Services in the Southeast United States: Barriers, Facilitators, and Strategies.

INTRODUCTION/OBJECTIVES: Collectively, genetic diseases are not that rare, and with increasing availability of genetics-informed healthcare management, primary care providers (PCPs) are more often asked to screen for or provide genetic services. Previous studies have identified barriers that impact PCPs' ability to provide genetic services, including limited knowledge, training, and time/resources. This study set out to identify specific barriers limiting genetics service provision by PCPs within the Southeastern Regional Genetics Network (SERN) and resources that would help eliminate those barriers. METHODS: PCPs were recruited through provider networks and invited to participate in semi-structured interviews, conducted via Zoom, recorded, and transcribed verbatim. Interview transcripts were independently coded by 2 coders using MAXQDA software. Thematic analysis was conducted. RESULTS: Eleven interviews were conducted. Three predominant themes emerged from the data regarding factors impacting use of genetic services: system-wide factors, provider-specific factors, and patient factors. System-wide barriers included a lack of genetics providers and logistic challenges, which led to some PCPs coordinating referrals with other specialists or independently managing patients. Regarding provider-specific barriers, PCPs reported lack of genetics knowledge making referrals challenging. When possible, many PCPs contacted genetics providers for assistance. When not possible, some PCPs reached out to other colleagues or specialists for guidance. Patient-specific barriers included concerns or lack of information regarding genetics and unmet social needs. Many PCPs provided additional education regarding genetics appointments or testing benefits to their patients. Assistance from genetic counselors, electronic medical record systems that support referral to genetics, prior experience referring to genetics, established communication channels with genetics professionals, and highly motivated patients all facilitated improved collaboration with genetic services. PCPs provided suggestions for future resources to support interactions with genetics, including clear referral guidelines, increased access to genetics providers, improved test ordering processes, increased access to genetic education, and communication systems. CONCLUSIONS: PCPs face barriers at 3 different levels when engaging with genetic services: systems, providers, and patients. This study identified strategies that PCPs use to address these barriers, which are dependent on individual resources and practice settings. These strategies demonstrate resourcefulness in working to incorporate genetics into clinics operating at maximum capacity. By targeting barriers that uniquely impact providers, systems, and patients, as well as building upon strategies that PCPs are already using, medical providers can support PCPs to help with the provision of genetic services.

Breastfeeding practices for infants with inherited metabolic disorders: A survey of registered dietitians in the United States and Canada.

Background: Breast milk is considered the optimal first food for infants. Breastfeeding infants with inherited metabolic disorders (IMDs) is complex due to the critical need to manage intake of specific macronutrients depending on the type of IMD. Objective: To describe current practices of registered dietitians (RD) who treat patients with IMDs regarding the incorporation of breastmilk into disease management. Design: Cross-sectional survey.Participants/setting:online survey conducted in December 2020 of 66 RDs who treat patients with IMDs in the United States and Canada.Main outcome measures:the survey focused on personal demographics, clinic characteristics, institutional feeding protocols for infants with IMDs, confidence in working with breastfeeding parents of infants with IMDs, and knowledge about breastfeeding with questions derived from the Iowa Infant Feeding Attitudes Scale.Statistical analysis performed:.Fisher's exact test was used for comparisons. Results: Most RDs were confident or very confident in their ability to provide nutritional guidance for breastfeeding infants with IMDs. Half of the participants reported that they had received training on breastfeeding of infants of IMDs. For infants with phenylketonuria (PKU), most RDs include breastfeeding as part of nutritional management. Breastfeeding is less likely to be used in the management of infants with other aminoacidopathies and fatty acid oxidation disorders. Use of measured expressed breastmilk was preferred, including for aminoacidopathies other than PKU, organic acidemias, and fatty acid oxidation disorders. Knowledge about breastfeeding varied. Less than half of RDs referred mothers to a lactation specialist somewhat regularly or frequently. Conclusions: Our survey found variation in experience, training, and use of breastfeeding-related nutritional management protocols in IMDs. A lack of formal training programs for the nutritional management of IMDs may account for some of this variation. Future research, including the collection of more detailed disorder-specific data, could help contribute to the development of clinical practice guidelines.

Natural history of children and adults with phenylketonuria in the NBS-PKU Connect registry.

PURPOSE: Phenylalanine hydroxylase deficiency, or phenylketonuria (PKU), is a rare autosomal recessive metabolic disorder. Early diagnosis via newborn screening (NBS) and initiation of treatment prevent the development of cognitive impairment and other co-morbidities. The purpose of this study is to describe the natural history of PKU in the United States, including prevalence of co-morbidities and predictors of outcomes. METHODS: We analyzed data from a self-report survey in the NBS-PKU Connect online registry. We describe the participants' nutrition management strategies, barriers to management, outcomes of bone disorders, skin, and psychological co-morbidities, and the use of special education or other special services. Predictors of outcomes were identified and assessed, including the impact of sex, age, age at diagnosis, blood phenylalanine concentration, use of sapropterin, use of medical food, adherence to prescribed diet, use of low protein modified foods, whether they had ever been off-diet, and use of tyrosine supplementation. RESULTS: The 219 respondents included individuals with PKU or hyperphenylalanemia (n = 78), or their caregivers (n = 141). Most (84.3%) started treatment before the age of two weeks. About one-third indicated that they had been off-diet at some point in their lives, and 81.4% reported that they currently adhered to their prescribed diet, with adherence to prescribed diet decreasing with age. Blood phenylalanine concentration was under the recommended threshold of 360 µmol/L for 68.5% of participants. One-quarter of respondents reported psychological co-morbidities, with anxiety and ADD/ADHD being the most common. The incidence of psychological co-morbidities increased with age and with ever having been off diet. Special education or other special services were more likely to be reported by individuals who were diagnosed after one week of age. Skin disorders such as acne and eczema were more common in females than males, and a minority of participants reported bone disorders. CONCLUSIONS: Despite recommendations to maintain blood phenylalanine concentrations in the therapeutic range throughout life, it is not uncommon for adults with PKU to discontinue dietary management of their disorder. Early diagnosis was associated with reduced need for special education or other special services, and continuous treatment was associated with decreased psychological co-morbidities.

Genetic Referral Patterns and Responses to Clinical Scenarios: A Survey of Primary Care Providers and Clinical Geneticists.

INTRODUCTION: Primary care physicians (PCPs) are considered the gatekeepers of genetic services, but they often underutilize or inappropriately utilize such services, leading to lack of early treatment, incorrect diagnoses, and unnecessary procedures. This study aims to delineate PCP referral patterns, including the frequency of, motivators for, and barriers to genetic referrals and testing in the present landscape of genomics. METHODS: A 34-item online survey was distributed to PCPs in the United States (US). PCP demographics, practice characteristics, and referral patterns, motivators, and barriers were analyzed. Six hypothetical clinical scenarios included in the survey also were presented to a cohort of clinical geneticists. We calculated PCPs' rates of ordering genetic tests and of referral to genetics services in the past year. Rates and responses to clinical scenarios were compared based on respondents' personal and practice characteristics. RESULTS: A total of 95 PCPs and 25 clinical geneticists participated. Among the PCPs, 79% reported referring and 50% reported ordering genetic testing in the last year. PCPs with genetic counselors (GCs) in their clinic referred at significantly higher rates than those without (P = .008). White PCPs referred at significantly higher rates compared to Black or African American PCPs (P = .009). The most commonly reported motivators for referring patients to genetic services were preference for specialist coordination, lack of knowledge, and family's desire for risk information. The most commonly reported barriers were patient refusal, provider concerns about costs to patients, and uncertainty of when a genetic referral is appropriate. In response to clinical scenarios, clinical geneticists were in agreement about the need for genetic testing or referral for 2 of the scenarios. For these 2 scenarios, only 48% and 71% of PCPs indicated that they would offer genetic testing or referral, respectively. CONCLUSIONS: Responses to clinical scenarios suggest that it is not clear to PCPs when referrals or testing are needed. Collaboration with GCs is one approach to reducing barriers to and improving PCPs' utilization of genetic services. Clear guidelines from clinical geneticists may help facilitate appropriate use of genetics services by PCPs. Additional research is needed to further describe barriers that PCPs face in genetic testing/referrals.

The Use of Telemedicine and Other Strategies by Registered Dietitians for the Medical Nutrition Therapy of Patients With Inherited Metabolic Disorders During the COVID-19 Pandemic.

The clinical management of patients with inherited metabolic disorders (IMDs) includes medical nutrition therapy (MNT) by a registered dietitian (RD). We utilized an online quantitative and qualitative survey to characterize the practices of RDs treating patients with IMDs during the COVID-19 pandemic and to identify challenges and unmet needs. We received responses from 117 RDs. Results indicate that RDs are using alternate methods to engage this vulnerable population and provide MNT during the pandemic, including offering telemedicine appointments. Barriers to implementation of telemedicine include the limitations of virtual visits (inability to conduct physical exams and collect blood samples), time, patient knowledge of technology, audio problems, and patient access to internet, computers, or smartphones. RDs have addressed these barriers by extending prescriptions without a medical exam, relying on local facilities for blood draws, increasing the number of patients that use at-home filter papers for blood monitoring, and expanding the use of phone calls and emails. RDs identified patient education materials to facilitate telemedicine visits as a primary unmet need. Despite the reported barriers and limitations of telemedicine for MNT of IMDs, there was widespread satisfaction with the approach among RDs, with 96.9% reporting that they were somewhat or very satisfied with telemedicine. Although this survey focused on barriers, benefits of telemedicine for both RDs and patients were also reported. Identification of barriers and unmet needs can help clinics plan strategies to maximize telemedicine delivery models, to improve efficiency and patient outcomes, and to support sustained use of telemedicine post-pandemic.

Presentation and management of N-acetylglutamate synthase deficiency: a review of the literature.

BACKGROUND: N-Acetylglutamate synthase (NAGS) deficiency is an extremely rare autosomal recessive metabolic disorder affecting the urea cycle, leading to episodes of hyperammonemia which can cause significant morbidity and mortality. Since its recognition in 1981, NAGS deficiency has been treated with carbamylglutamate with or without other measures (nutritional, ammonia scavengers, dialytic, etc.). We conducted a systematic literature review of NAGS deficiency to summarize current knowledge around presentation and management. METHODS: Case reports and case series were identified using the Medline database, as well as references from other articles and a general internet search. Clinical data related to presentation and management were abstracted by two reviewers. RESULTS: In total, 98 cases of NAGS deficiency from 79 families, in 48 articles or abstracts were identified. Of these, 1 was diagnosed prenatally, 57 were neonatal cases, 34 were post-neonatal, and 6 did not specify age at presentation or were asymptomatic at diagnosis. Twenty-one cases had relevant family history. We summarize triggers of hyperammonemic episodes, diagnosis, clinical signs and symptoms, and management strategies. DNA testing is the preferred method of diagnosis, although therapeutic trials to assess response of ammonia levels to carbamylglutamate may also be helpful. Management usually consists of treatment with carbamylglutamate, although the reported maintenance dose varied across case reports. Protein restriction was sometimes used in conjunction with carbamylglutamate. Supplementation with citrulline, arginine, and sodium benzoate also were reported. CONCLUSIONS: Presentation of NAGS deficiency varies by age and symptoms. In addition, both diagnosis and management have evolved over time and vary across clinics. Prompt recognition and appropriate treatment of NAGS deficiency with carbamylglutamate may improve outcomes of affected individuals. Further research is needed to assess the roles of protein restriction and supplements in the treatment of NAGS deficiency, especially during times of illness or lack of access to carbamylglutamate.

Genetic testing experiences and genetics knowledge among families with inherited metabolic diseases.

We surveyed individuals with inherited metabolic diseases (IMDs) or their caregivers to explore experiences with genetic testing. Pursuit of knowledge, benefit to science, clinician recommendations, cascade testing, and cost were important considerations for pursuing genetic testing. Knowledge about inheritance patterns was limited, even for those who had received genetic testing. Future studies should further examine knowledge of IMDs and genetic testing among families, and factors that impact clinicians' decisions to offer genetic testing for IMDs.

Chagas Disease in Southern Coastal Ecuador: Coinfections with Arboviruses and a Comparison of Serological Assays for Chagas Disease Diagnosis.

Occurrence of Chagas disease and arbovirus coinfections is unknown, despite the vast co-endemic areas throughout the Americas. This study examined the proportion of individuals positive for Trypanosoma cruzi and coinfections with dengue, chikungunya, and Zika viruses in Machala, Ecuador (January 2014-December 2015). Chagas seropositivity was evaluated with five commercially available assays. Dengue infections were identified by nonstructural protein 1 rapid test and enzyme linked immunosorbent assay (ELISA), immunoglobulin M ELISA, and reverse transcription PCR (RT-PCR); chikungunya and Zika infections were identified by RT-PCR. Of 658 individuals, six were positive for T. cruzi (0.91%), including one T. cruzi/dengue coinfection and one T. cruzi/chikungunya/dengue coinfection. The clinical manifestations of coinfected individuals corresponded to severe dengue and dengue with warning signs, respectively. We observed discrepant results by using the Hemagen Chagas kit and the rapid test Chagas Detect Plus (false positives: 3.9% and 15.4%), highlighting the need to assess diagnostic assays in geographic regions with distinct taxonomic units of T. cruzi.

The Burden of Dengue Fever and Chikungunya in Southern Coastal Ecuador: Epidemiology, Clinical Presentation, and Phylogenetics from the First Two Years of a Prospective Study.

Here, we report the findings from the first 2 years (2014-2015) of an arbovirus surveillance study conducted in Machala, Ecuador, a dengue-endemic region. Patients with suspected dengue virus (DENV) infections (index cases, N = 324) were referred from five Ministry of Health clinical sites. A subset of DENV-positive index cases (N = 44) were selected, and individuals from the index household and four neighboring homes within 200 m were recruited (N = 400). Individuals who entered the study, other than the index cases, are referred to as associates. In 2014, 70.9% of index cases and 35.6% of associates had acute or recent DENV infections. In 2015, 28.3% of index cases and 12.8% of associates had acute or recent DENV infections. For every DENV infection captured by passive surveillance, we detected an additional three acute or recent DENV infections in associates. Of associates with acute DENV infections, 68% reported dengue-like symptoms, with the highest prevalence of symptomatic acute infections in children aged less than 10 years. The first chikungunya virus (CHIKV) infections were detected on epidemiological week 12 in 2015; 43.1% of index cases and 3.5% of associates had acute CHIKV infections. No Zika virus infections were detected. Phylogenetic analyses of isolates of DENV from 2014 revealed genetic relatedness and shared ancestry of DENV1, DENV2, and DENV4 genomes from Ecuador with those from Venezuela and Colombia, indicating the presence of viral flow between Ecuador and surrounding countries. Enhanced surveillance studies, such as this, provide high-resolution data on symptomatic and inapparent infections across the population.

Case Report: An Acute Chikungunya Infection and a Recent Secondary Dengue Infection in a Peripartum Case in Ecuador.

Dengue virus (DENV) and chikungunya virus (CHIKV) are transmitted by the same mosquito vectors and now co-circulate in many parts of the world; however, coinfections and serial infections are not often diagnosed or reported. A 38-week pregnant woman was admitted to the hospital with a diagnosis of suspected DENV and CHIKV in southern coastal Ecuador. The pregnancy was complicated by mild polyhydramnios and fetal tachycardia, and a healthy newborn was born. The patient was positive for a recent secondary DENV infection (Immunoglobulin M and Immunoglobulin G positive) and an acute CHIKV infection (real-time reverse transcriptase polymerase chain reaction positive) (Asian genotype). The newborn was not tested for either virus. This case resulted in a benign clinical course with a favorable pregnancy outcome.

Social-ecological factors and preventive actions decrease the risk of dengue infection at the household-level: Results from a prospective dengue surveillance study in Machala, Ecuador.

BACKGROUND: In Ecuador, dengue virus (DENV) infections transmitted by the Aedes aegypti mosquito are among the greatest public health concerns in urban coastal communities. Community- and household-level vector control is the principal means of controlling disease outbreaks. This study aimed to assess the impact of knowledge, attitudes, and practices (KAPs) and social-ecological factors on the presence or absence of DENV infections in the household. METHODS: In 2014 and 2015, individuals with DENV infections from sentinel clinics in Machala, Ecuador, were invited to participate in the study, as well as members of their household and members of four neighboring households located within 200 meters. We conducted diagnostic testing for DENV on all study participants; we surveyed heads of households (HOHs) regarding demographics, housing conditions and KAPs. We compared KAPs and social-ecological factors between households with (n = 139) versus without (n = 80) DENV infections, using bivariate analyses and multivariate logistic regression models with and without interactions. RESULTS: Significant risk factors in multivariate models included proximity to abandoned properties, interruptions in piped water, and shaded patios (p<0.05). Significant protective factors included the use of mosquito bed nets, fumigation inside the home, and piped water inside the home (p<0.05). In bivariate analyses (but not multivariate modeling), DENV infections were positively associated with HOHs who were male, employed, and of younger age than households without infections (p<0.05). DENV infections were not associated with knowledge, attitude, or reported barriers to prevention activities. DISCUSSION: Specific actions that can be considered to decrease the risk of DENV infections in the household include targeting vector control in highly shaded properties, fumigating inside the home, and use of mosquito bed nets. Community-level interventions include cleanup of abandoned properties, daily garbage collection, and reliable piped water inside houses. These findings can inform interventions to reduce the risk of other diseases transmitted by the Ae. aegypti mosquito, such as chikungunya and Zika fever.

Psychological Distress and Zika, Dengue and Chikungunya Symptoms Following the 2016 Earthquake in Bahía de Caráquez, Ecuador.

On 16 April 2016, a 7.8 magnitude earthquake struck coastal Ecuador, resulting in significant mortality and morbidity, damages to infrastructure, and psychological trauma. This event coincided with the first outbreak of Zika virus (ZIKV) and co-circulation with dengue virus (DENV) and chikungunya virus (CHIKV). We tested whether the degree of psychological distress was associated with the presence of suspected DENV, CHIKV, ZIKV (DCZ) infections three months after the earthquake. In July 2016, 601 household members from four communities in Bahía de Caráquez, Manabí Province, Ecuador, were surveyed in a post-disaster health evaluation. Information was collected on demographics, physical damages and injuries, chronic diseases, self-reported psychological distress, and DCZ symptoms. We calculated the prevalence of arbovirus and distress symptoms by community. ANOVA was used to compare the mean number of psychological distress symptoms between people with versus without suspected DCZ infections by age, gender, community and the need to sleep outside of the home due to damages. The prevalence of suspected DCZ infections was 9.7% and the prevalence of psychological distress was 58.1%. The average number of psychological distress symptoms was significantly higher among people with suspected DCZ infections in the periurban community of Bella Vista, in women, in adults 40-64 years of age and in individuals not sleeping at home (p < 0.05). The results of this study highlight the need to investigate the interactions between psychological distress and arboviral infections following natural disasters.

Patatin-like phospholipase domain-containing protein 3 (PNPLA3): A potential role in the association between liver disease and bipolar disorder.

OBJECTIVE: Due to the increased prevalence of liver disease in patients with bipolar disorder, we examined the potential role of the patatin-like phospholipase domain-containing protein 3 (PNPLA3) variant among individuals with bipolar disorder and those with no mood disorder. METHODS: We used the National Health and Nutrition Examination Survey (NHANES) database (aged 15-39 years) to identify a group of individuals with a bipolar diagnosis and a control group of individuals with no mood disorder. A total of 1931 individuals were randomly selected, one from each family containing information on the PNPLA3 genotype to be used in the analysis. RESULTS: Analyses revealed individuals with the recessive variant genotype (MM) had an adjusted odds ratio for bipolar disorder of about 4.6 compared to individuals with either IM or II genotypes of the PNPLA3 variant. LIMITATIONS AND CONCLUSIONS: Limitations of this study include the use of a lay-administered survey in for diagnosis of bipolar disorder in NHANES. The association between the PNPLA3 variant and bipolar disorder may help guide further work on medication effectiveness, treatment options, prevention approaches, and understanding potential medication side effects among specific subgroups of individuals with the MM genotype.

Clinical course of alcohol use in veterans following an AUDIT-C Positive Screen.

There is little known regarding the typical trajectory of alcohol use following a positive screen for hazardous alcohol use. This information would help primary care providers as they attempt to determine the best use of patient visits that might include brief alcohol interventions versus other competing medical demands. This longitudinal observational study included 98 Veterans who screened positive on the Alcohol Use Disorders Identification Test-Consumption (>3) and were asked to report on their alcohol use every 3 months for 1 year. Using latent class growth modeling, we identified the best fitting latent class structure for each outcome of high-risk and heavy drinking, respectively. There was a class of participants with increased probability of having a high-risk week or episode of heavy drinking as well as a group of participants who appeared to maintain their current drinking pattern. Although the latent class growth modeling suggested that none of the groups of participants reduced the likelihood of occurrence of heavy drinking days, two groups did significantly reduce the probability of having a hazardous alcohol use week. These results suggest that there are specific classes of patients who are less likely to change their alcohol use following a positive screen, especially those patients who report engaging in heavy drinking.

Identifying classes of veterans with multiple risk factors.

As researchers examine the efficacy of interventions that simultaneously target more than 1 symptom, it is important to identify ways to help guide research and program development. This study used electronic medical record data to examine the covariation of multiple risk factors regularly assessed among primary care patients. It also examined the health care utilization of those patients identifying where the health care system came in contact with them to help identify the ideal locations these interventions may be most often used. We obtained data for six risk factors, as well as the number of primary care, mental health, and emergency department visits, from Veteran patients with a primary care visit. There were three main groups of primary care patients, identified using latent class analysis and regression. Although the smallest group, the "High Treatment Need" group, had an increased probability of screening positive for all four risk factors, the post-traumatic stress disorder screen was a significant discriminator of this group from the others. Results show that this group had the greatest number of encounters in all health care locations suggesting significant opportunities for intervention. However, future research is needed to examine the current interventions offered and potential avenues where risk factors may be addressed simultaneously.

Substance use disorders increase the odds of subsequent mood disorders.

BACKGROUND: There is a well-known association between mood disorders and substance use disorders (SUD), but little research has been conducted on SUDs as risk factors for the development of subsequent mood disorders. METHODS: We analyzed data from the National Comorbidity Survey Replication study. Diagnoses were determined using DSM-IV criteria. Odds ratios (aORs) of subsequently developing mood disorders were adjusted for age, sex and race/ethnicity. RESULTS: Data from 5217 individuals were included (6.6% male; mean age 45.3 years; 72.6% White, 11.2% Black, 12.5% Hispanic and 3.7% other). Subsequent mood disorders developed in 26.4% of individuals with primary adolescent-onset SUD (12-17 years), 21.7% of those with SUD onset at 18-25 years, and 14.0% of those with SUD onset between the ages of 26 and 34 years. The mean lagtime between SUD onset and development of a mood disorder was about 11 years. Controlling for demographic variables, the aORs of developing a mood disorder in these three age groups were 2.44, 3.65, and 3.25. Substance dependence was associated with higher odds of mood disorders than was abuse. Among the specific mood disorders, the increased odds of developing bipolar disorder were particularly high among individuals with drug dependence. CONCLUSIONS: Individuals with adolescent and young adult-onset SUD had increased odds of developing a secondary mood disorder. This indicates that adolescents and young adults with SUD should be closely monitored for both positive and negative mood symptoms. SUD treatment and aftercare offer opportunities for the early identification of secondary mood disorders.