Approved but Unavailable: A Mystery-Caller Survey of Mifepristone Access in a Large Ontario City.

OBJECTIVES: Mifepristone/misoprostol (mife/miso) has been approved in Canada since 2017, and is available since 2018. Mife/miso does not require witnessed administration in Canada, and therefore most patients obtain a prescription for home use. We sought to determine the proportion of pharmacies in Hamilton, Ontario, Canada, a city of over 500 000, that had combination mife/miso in stock at any given time. METHODS: A mystery-caller approach was used to survey all pharmacies (n = 218) in Hamilton, Ontario, Canada between June 2022 and September 2022. RESULTS: Of the 208 pharmacies that were successfully contacted, only 13 (6%) pharmacies had mife/miso in stock. The most commonly cited reasons for the medication being unavailable were low patient demand (38%), cost (22%), lack of familiarity with medication (13%), supplier issues (9%), training requirements (8%), and medication expiry (7%). CONCLUSIONS: These findings suggest that while mife/miso has been available in Canada since 2017, significant barriers remain to patients accessing this medication. This study clearly demonstrates a need for further advocacy and clinician education to ensure mife/miso is accessible to the patients who require it.

Energy optimization during walking involves implicit processing.

Gait adaptations, in response to novel environments, devices or changes to the body, can be driven by the continuous optimization of energy expenditure. However, whether energy optimization involves implicit processing (occurring automatically and with minimal cognitive attention), explicit processing (occurring consciously with an attention-demanding strategy) or both in combination remains unclear. Here, we used a dual-task paradigm to probe the contributions of implicit and explicit processes in energy optimization during walking. To create our primary energy optimization task, we used lower-limb exoskeletons to shift people's energetically optimal step frequency to frequencies lower than normally preferred. Our secondary task, designed to draw explicit attention from the optimization task, was an auditory tone discrimination task. We found that adding this secondary task did not prevent energy optimization during walking; participants in our dual-task experiment adapted their step frequency toward the optima by an amount and at a rate similar to participants in our previous single-task experiment. We also found that performance on the tone discrimination task did not worsen when participants were adapting toward energy optima; accuracy scores and reaction times remained unchanged when the exoskeleton altered the energy optimal gaits. Survey responses suggest that dual-task participants were largely unaware of the changes they made to their gait during adaptation, whereas single-task participants were more aware of their gait changes yet did not leverage this explicit awareness to improve gait adaptation. Collectively, our results suggest that energy optimization involves implicit processing, allowing attentional resources to be directed toward other cognitive and motor objectives during walking.

Breastfeeding Associated with Lower Prevalence of Metabolic Syndrome in Women with Gestational Diabetes in the Very Early Postpartum Period.

OBJECTIVE: The aim of this study is to examine the association of breastfeeding with metabolic syndrome (MetS) in women with recent gestational diabetes mellitus (GDM) in the very early postpartum (PP) period. STUDY DESIGN: We performed a secondary analysis of the Balance After Baby Intervention (BABI) study which enrolled women with recent GDM. Data collected during an early (∼8 weeks) PP visit were used in this analysis. At this visit, weight, height, waist circumference (WC), blood pressure (BP), fasting plasma glucose (FPG), and lipids were obtained. MetS was classified per National Cholesterol Education Program Adult Treatment Program III (NCEP-ATP III) criteria. We defined breastfeeding as currently breastfeeding or not currently breastfeeding for the main analysis. RESULTS: Of 181 women enrolled in BABI, 178 were included in this analysis (3 excluded for missing lipids). Thirty-four percent were Hispanic. Of non-Hispanics, 31.5% were White, 18.5% Asian, and 12.9% Black/African American. The prevalence of MetS was 42.9% in women not breastfeeding versus 17.1% in women breastfeeding (p < 0.001; adjusted odds ratio [aOR] = 0.16 [95% confidence interval (CI): 0.06-0.41]). Breastfeeding women had significantly lower odds of FPG ≥100 mg/dL (aOR = 0.36 [95% CI: 0.14-0.95], p = 0.039), HDL < 50 mg/dL (aOR = 0.19 [95% CI: 0.08-0.46], p < 0.001), and triglycerides (TG) ≥ 150 mg/dL (aOR = 0.26 [95% CI: 0.10-0.66], p = 0.005). When evaluated as continuous variables, WC, FPG, and TG were significantly lower and HDL significantly higher in women breastfeeding in the very early PP period (vs. not breastfeeding). CONCLUSION: In a diverse population of women with recent GDM, there was lower prevalence of MetS in women breastfeeding compared with those not breastfeeding in the very early PP period. This study extends the findings of an association of breastfeeding with MetS previously reported at time points more remote from pregnancy to the very early PP period and to an ethnically and racially diverse population. KEY POINTS: · MetS prevalence in women with recent GDM was lower in breastfeeding than not breastfeeding women.. · FPG, HDL, WC, and TG were improved in the breastfeeding group.. · This study extends prior findings to the very early PP period and to a diverse population..

Retrospective Comparison of PGE2 Vaginal Insert and Foley Catheter for Outpatient Cervical Ripening.

OBJECTIVE: To compare the efficacy of two methods of outpatient cervical ripening (CR): an intracervical Foley catheter and a prostaglandin E2 (PGE)2 slow-release vaginal insert. METHODS: All records of women receiving outpatient CR at a tertiary care hospital from January 2017 to June 2018 were retrospectively reviewed. We compared time from insertion of first CR agent until delivery between groups using a Cox proportional hazards (CPH) model. Exclusion criteria included age <18 years, multiple gestation, or contraindication to either CR method. Secondary outcomes included time from removal of agent and time from admission until delivery, additional CR used, uterine tachysystole, labour and delivery complications, type of delivery, and adverse neonatal outcomes. RESULTS: A total of 153 patients were included (82 Foley; 71 PGE2). Baseline characteristics were comparable except for lower dilation in the PGE2 group (16% vs. 38% <1cm dilated; P < 0.05). In the CPH model, time from insertion to delivery was not different between PGE2 and Foley catheter groups (median 27 vs. 33 h), controlling for parity, gestational age, initial dilation, and use of oxytocin (HR 1.13, 95% confidence interval 0.77-1.68). Patients in the PGE2 group were more likely to experience uterine tachysystole (9% vs. 0%; P < 0.01) and require another method of CR (34% vs. 1%; P < 0.001). There were no differences in neonatal or maternal adverse outcomes between groups. CONCLUSION: Our results suggest that outpatient Foley catheter and PGE2 CR are comparable in time from insertion to delivery; however, PGE2 inserts are associated with higher rates of tachysystole and the need for second CR method. A prospective study is warranted to further investigate these findings.

The Use of Non-insulin Agents in Gestational Diabetes: Clinical Considerations in Tailoring Therapy.

PURPOSE OF REVIEW: To assess evidence to date for use of non-insulin agents in treatment of gestational diabetes mellitus. RECENT FINDINGS: There has been increasing interest in the use of non-insulin agents, primarily metformin and glyburide (which both cross the placenta). Metformin has been associated with less maternal weight gain; however, recent studies have shown a trend toward increased weight in offspring exposed to metformin in utero. Glyburide has been associated with increased neonatal hypoglycemia. Glycemic control during pregnancy is essential to optimize both maternal and fetal outcomes. There are a myriad of factors to consider when designing treatment programs including patient preference, phenotype, and glucose patterns. While insulin is typically recommended as first-line, some women refuse or cannot afford insulin and in those cases, non-insulin agents may be used. Further studies are needed to assess treatment in pregnancy, perinatal outcomes, and particularly long-term metabolic profiles in mothers and offspring.

Management of Preexisting Diabetes in Pregnancy: A Review.

Importance: The presence of preexisting type 1 or type 2 diabetes in pregnancy increases the risk of adverse maternal and neonatal outcomes, such as preeclampsia, cesarean delivery, preterm delivery, macrosomia, and congenital defects. Approximately 0.9% of the 4 million births in the United States annually are complicated by preexisting diabetes. Observations: Women with diabetes have increased risk for adverse maternal and neonatal outcomes, and similar risks are present with type 1 and type 2 diabetes. Both forms of diabetes require similar intensity of diabetes care. Preconception planning is very important to avoid unintended pregnancies and to minimize risk of congenital defects. Hemoglobin A1c goals are less than 6.5% at conception and less than 6.0% during pregnancy. It is also critical to screen for and manage comorbid illnesses, such as retinopathy and nephropathy. Medications known to be unsafe in pregnancy, such as angiotensin-converting enzyme inhibitors and statins, should be discontinued. Women with obesity should be screened for obstructive sleep apnea, which is often undiagnosed and can result in poor outcomes. Blood pressure goals must be considered carefully because lower treatment thresholds may be required for women with nephropathy. During pregnancy, continuous glucose monitoring can improve glycemic control and neonatal outcomes in women with type 1 diabetes. Insulin is first-line therapy for all women with preexisting diabetes; injections and insulin pump therapy are both effective approaches. Rates of severe hypoglycemia are increased during pregnancy; therefore, glucagon should be available to the patient and close contacts should be trained in its use. Low-dose aspirin is recommended soon after 12 weeks' gestation to minimize the risk of preeclampsia. The importance of discussing long-acting reversible contraception before and after pregnancy, to allow for appropriate preconception planning, cannot be overstated. Conclusions and Relevance: Preexisting diabetes in pregnancy is complex and is associated with significant maternal and neonatal risk. Optimization of glycemic control, medication regimens, and careful attention to comorbid conditions can help mitigate these risks and ensure quality diabetes care before, during, and after pregnancy.

REDUCED IMPACT OF DIABETES CLINIC REFERRAL ON HIGH-FREQUENCY EMERGENCY DEPARTMENT USERS.

OBJECTIVE: The patterns of emergency department (ED) visits in patients with diabetes are not well understood. The Emergency Department Diabetes Rapid-referral Program (EDRP) allows direct booking of ED patients presenting with urgent diabetes needs into a diabetes specialty clinic within 1 day of ED discharge. The objective of this secondary analysis was to examine characteristics of patients with diabetes who have frequent ED visits and determine reasons for revisits. METHODS: A single-center analysis was conducted comparing patients referred to the EDRP (n = 420) to historical unexposed controls (n = 791). The primary outcome was the proportion of patients in each frequency group of ED revisits (none, 1 to 3 [infrequent], 4 to 10 [frequent], or >10 [superfrequent]) in the year after the ED index visit. Secondary outcomes were hospitalization rates and International Classification of Diseases-Ninth Revision (ICD-9) diagnoses at ED revisits. RESULTS: Superfrequent users, responsible for >20% of total ED visits, made up small but not significantly different proportions of EDRP and control populations, 3.6% and 5.2%, respectively. Superfrequent groups had lower hospital admission rates at ED revisits compared to frequent groups. Mental health disorders (including substance abuse) were the primary, secondary, or tertiary ICD-9 codes in 30.6% (95% confidence interval [CI], 27.7% to 33.5%) and 6.6% (95% CI, 5.1% to 8.2%) in the superfrequent and infrequent groups, respectively. CONCLUSION: Direct access to diabetes specialty care from the ED is effective in reducing ED recidivism but not amongst a small subgroup of superfrequent ED users. This group was more likely to have mental health disorders recorded at ED revisits, suggesting that more comprehensive approaches are needed for this population. ABBREVIATIONS: EDRP = Emergency Department Diabetes Rapid-referral Program; ED = emergency department; HbA1c = hemoglobin A1c; ICD-9 = International Classification of Diseases-Ninth Revision.

Mutations in the essential arabinosyltransferase EmbC lead to alterations in Mycobacterium tuberculosis lipoarabinomannan.

The Mycobacterium tuberculosis cell wall is a complex structure essential for the viability of the organism and its interaction with the host. The glycolipid lipoarabinomannan (LAM) plays an important role in mediating host-bacteria interactions and is involved in modulation of the immune response. The arabinosyltransferase EmbC required for LAM biosynthesis is essential. We constructed recombinant strains of M. tuberculosis expressing a variety of alleles of EmbC. We demonstrated that EmbC has a functional signal peptide in M. tuberculosis. Over- or underexpression of EmbC resulted in reduced or increased sensitivity to ethambutol, respectively. The C-terminal domain of EmbC was essential for activity because truncated alleles were unable to mediate LAM production in Mycobacterium smegmatis and were unable to complement an embC deletion in M. tuberculosis. The C-terminal domain of the closely related arabinosyltransferase EmbB was unable to complement the function of the EmbC C-terminal domain. Two functional motifs were identified. The GT-C motif contains two aspartate residues essential for function in the DDX motif. The proline-rich region contains two highly conserved asparagines (Asn-638 and Asn-652). Mutation of these residues was tolerated, but loss of Asn-638 resulted in the synthesis of truncated LAM, which appeared to lack arabinose branching. All embC alleles that were incapable of complementing LAM production in M. smegmatis were not viable in M. tuberculosis, supporting the hypothesis that LAM itself is essential in M. tuberculosis.

From doing to leading: PGY-1 to PGY-2 transition.

BACKGROUND: Clinical trainees experience several professional transitions throughout their career, which can be exciting, anxiety-provoking or both. The first to second post-graduate year (PGY) transition for residents (junior doctors) in North America involves assuming new roles such as team leader, clinical supervisor, and teacher, often with minimal preparation. We explored resident experiences and emotions during this transition, and obtained their strategies for navigating this transition, through the lens of Bridges' transition model. This model has three stages: (1) ending, losing and letting go, (2) the neutral zone and (3) the new beginning. METHODS: We conducted one in-person focus group and subsequent one-on-one virtual semistructured interviews (due to COVID-19) of PGY-2 and PGY-3 residents who had previously undergone the transition. These sessions were recorded and transcribed, and thematic analysis was performed. FINDINGS: Four residents participated in the focus group, and 14 participated in one-on-one interviews. We identified five key themes: (1) not just a cog in the wheel, (2) contributing to growth of near-peers, (3) being flexible and adaptive, (4) emulating resident role models and (5) relationships with attendings. Residents suggested a transitions-focused retreat, simulation training to lead clinical emergencies, supervised opportunities for PGY-1s to act as PGY-2s coached by senior residents, and pairing PGY-1s with senior residents to help prepare for the transition. CONCLUSION: Professional transitions are both anxiety-provoking and exciting. Clinical trainees need preparation to successfully navigate multiple transitions. The Bridges' transition model could be useful in conceptualising transitions and planning curricula.

An Overview of Specialist Services for Huntington's Disease in the United Kingdom.

BACKGROUND: Huntington's disease (HD) is a rare inherited neurodegenerative disorder characterized by complex evolving needs that change as the condition progresses. There is limited understanding about the organization of HD clinical services and their resourcing in the United Kingdom (UK). OBJECTIVE: To understand the organization and resourcing of specialist HD services for people with HD (PwHD) in the UKMethods:This cross-sectional study collected quantitative data via on online survey, and qualitative data via telephone semi-structured interviews. Descriptive statistics were used to describe quantitative outcomes, and qualitative results were analyzed using content analysis. RESULTS: A total of 31 specialist services for HD were identified. Of the 27 services that completed the online survey, 23 had an active multidisciplinary team of healthcare professionals (HCPs) and were led primarily by a mental health trust (26%) or tertiary referral hospital (26%). Specialist services offered outpatient clinics (96%), outreach in the community (74%), telemedicine (70%), inpatient beds (26%) and satellite clinics (26%). Many services indicated that their capacity (ability to see patients as often as needed with current resources) was difficult, with some services reporting more difficulty at the early or later stages of HD. Key resourcing gaps were identified with access to facilities, HCPs and referral networks. CONCLUSIONS: This research highlights the variation in organization and capacity within individual HD services as well as current resourcing and gaps in access that influence this capacity. Further research should be done to understand the impact of service organization and current resourcing gaps in access on the quality of care provided for PwHD in the UK.

Development and Usability of a Text Messaging Program for Women With Gestational Diabetes: Mixed Methods Study.

BACKGROUND: Gestational diabetes mellitus (GDM) affects 5%-10% of pregnancies and can lead to serious fetal and maternal complications. SMS text messaging is an effective way to improve diabetes management outside of pregnancy, but has not been well studied in GDM. OBJECTIVE: This study aimed to perform user experience testing and assess usability and acceptability of an SMS text messaging program (Text 4 Success) for women with GDM. METHODS: An automated 2-way texting program was developed. It included (1) reminders to check blood glucose levels, (2) positive feedback to user-reported glucose levels, (3) weekly educational messages, and (4) weekly motivational messages. For the user experience testing, women received simulated messages. For the usability study, women were enrolled in the program and received messages for 2 weeks. All women participated in semistructured interviews. For women in the usability study, data from glucose measuring devices were downloaded to assess adherence to self-monitoring of blood glucose (SMBG), measured as the percentage of recommended SMBG checks performed (a secondary outcome). RESULTS: Ten women participated in user experience testing. Suggestions for optimization included further customization of message timing and minimization of jargon, which were incorporated. Ten women participated in the usability study. All 10 would recommend the program to other women with GDM. Participants liked the immediate feedback to glucose values. Suggestions included further flexibility of messages related to mealtimes and the ability to aggregate blood glucose data into a table or graph. Overall, adherence to SMBG testing was high at baseline (222/238 recommended checks, 93%). In comparing the week prior to the trial with the 2 weeks during the trial, there was a small but statistically insignificant difference (P=.48) in the percentage of recommended SMBG performed (median 93% [25th-75th IQR 89%-100%] vs median 97% [25th-75th IQR 92%-100%]). CONCLUSIONS: Overall, women with GDM would recommend the Text 4 Success in GDM program and think it is helpful for GDM self-management. The program was usable and acceptable. The program may be better suited to those who have low levels of adherence to SMBG at baseline or to women at time of their diagnosis of GDM. Adaptations to the program will be made based on user suggestions. Further study of SMS text messaging to improve SMBG in GDM is needed.

An exploration of clinical, behavioral, and community factors associated with sleep duration and efficiency among middle-aged Black/African American smokers.

STUDY OBJECTIVES: We examined the most important correlates to sleep duration and efficiency from a comprehensive array of multilevel factors. METHODS: Baseline data from a cohort of 216 Black/African American smokers aged 40-65 years were examined. The binary outcomes of healthy sleep duration (6-8 h/night) and efficiency (≥85%) were ascertained from 14 consecutive days of actigraphy. Seventy-three independent variables from socio-demographic, individual behavioral, individual physiological, interpersonal, and community domains were assessed. Random survival forest decision trees were generated for each outcome, and variable importance metrics used to rank the predictive abilities of exposure variables. The 5 most predictive exposure variables for each outcome were entered into a regression model of the respective outcome (with age and sex). RESULTS: Study participants (N = 216) had a mean age of 54.57 years (SD = 6.17) and 57% were male. Healthy sleep duration was achieved by 56.5% and healthy sleep efficiency by 13.6% of the sample. Regression models showed every additional minute of light physical activity was associated with 1% increased odds, while every unit decrease in the inflammation marker of interleukin-8 was associated with 12% increased odds, of achieving a healthy sleep duration. Every unit increase in total social support was associated with a 34% increased odds, while every unit increase in the hazardous drinking score corresponded with 30% decreased odds, of achieving healthy sleep efficiency. CONCLUSIONS: Light physical activity, social support, and alcohol consumption may be key modifiable intervention targets to improving sleep duration and sleep efficiency in this population.

A flipped classroom in graduate medical education.

BACKGROUND: The role of the flipped classroom model in graduate medical education (GME) is not yet defined. We set out to evaluate the feasibility, acceptability and outcomes of a flipped classroom instructional model in an internal medicine curriculum. METHODS: This pilot study was carried out in an academic medical centre in the USA with 43 second-year internal medicine postgraduate trainees. Trainees watched videos on the pharmacological treatment of type 2 diabetes outside of the classroom, followed by an in-class session in which they engaged in case-based discussions. The intervention was evaluated using surveys and a knowledge test before, immediately after and 6 months after the intervention. RESULTS: The mean number of correct answers for a 10-question knowledge test was 5.25 before the intervention, 8.00 in the immediate post-intervention test, and 7.10 in the 6-month follow-up test (p < 0.001). Six months after the intervention, 57.1% of participants reported prescribing an antidiabetic medication discussed at the session. In a focus group, trainees reported their preference for interactive, case-based learning, concern about the time required for preparation and interest in incorporating real patient cases. DISCUSSION: Trainees preferred the flipped classroom, which also resulted in increased knowledge and self-reported prescribing changes; however, the required preparatory time may limit its feasibility in GME.

Assessment of Second-Generation Diabetes Medication Initiation Among Medicare Enrollees From 2007 to 2015.

Importance: Little is known about how new and expensive drugs diffuse into practice affects health care costs. Objective: To describe the variation in second-generation diabetes drug use among Medicare enrollees between 2007 and 2015. Design, Setting, and Participants: This population-based, cross-sectional study included data from 100% of Medicare Parts A, B, and D enrollees who first received diabetes drug therapy from January 1, 2007, to December 31, 2015. Patients with type 1 diabetes were excluded. Data were analyzed beginning in the spring of 2018, and revisions were completed in 2019. Exposures: For each patient, the initial diabetes drug choice was determined; drugs were classified as first generation (ie, approved before 2000) or second generation (ie, approved after 2000, including dipeptidyl peptidase 4 [DPP-4] inhibitors, glucagon-like peptide-1 [GLP-1] receptor agonists, and sodium-glucose cotransporter-2 [SGLT-2] inhibitors). Main Outcomes and Measures: The primary outcome was the between-practice variation in use of second-generation diabetes drugs between 2007 and 2015. Practices with use rates of second-generation diabetes drugs more than 1 SD above the mean were considered high prescribing, while those with use rates more than 1 SD below the mean were considered low prescribing. Results: Among 1 182 233 patients who initiated diabetes drug therapy at 42 977 practices between 2007 and 2015, 1 104 718 (93.4%) were prescribed a first-generation drug (mean [SD] age, 75.4 [6.7] years; 627 134 [56.8%] women) and 77 515 (6.6%) were prescribed a second-generation drug (mean [SD] age, 76.5 [7.2] years; 44 697 [57.7%] women). By December 2015, 22 457 practices (52.2%) had used DPP-4 inhibitors once, compared with 3593 practices (8.4%) that had used a GLP-1 receptor agonist once. Furthermore, 17 452 practices (40.6%) were using DPP-4 inhibitors in 10% of eligible patients, while 1286 practices (3.0%) were using GLP-1 receptor agonists in 10% of eligible patients, and SGLT-2 inhibitors, available after March 2013, were used at least once by 1716 practices (4.0%) and used in 10% of eligible patients by 872 practices (2.0%) by December 2015. According to Poisson random-effect regression models, beneficiaries in high-prescribing practices were more than 3-fold more likely to receive DPP-4 inhibitors (relative risk, 3.55 [95% CI, 3.42-3.68]), 24-fold more likely to receive GLP-1 receptor agonists (relative risk, 24.06 [95% CI, 14.14-40.94]) and 60-fold more likely to receive SGLT-2 inhibitors (relative risk, 60.41 [95% CI, 15.99-228.22]) compared with beneficiaries in low-prescribing practices. Conclusions and Relevance: These findings suggest that there was substantial between-practice variation in the use of second-generation diabetes drugs between 2007 and 2015, with a concentration of use among a few prescribers and practices responsible for much of the early diffusion.

Sleep Duration and Efficiency Associated With Better Functional Exercise Capacity in Black Smokers at Risk for COPD.

BACKGROUND: Black smokers have earlier development of lung disease as well as poorer sleep health than whites. RESEARCH QUESTION: In a sample of black smokers, to what extent does sleep health modify the association between smoking level and functional exercise capacity? DESIGN AND METHODS: Cross-sectional data from 209 black smokers (≥ 1 cigarette in last month), aged 40 to 65 years with no evidence of sleep-disordered breathing (apnea-hypopnea index < 15) or severe COPD (FEV1 > 50%), were used for the current study. Self-reported smoking rate, objectively measured sleep efficiency (SE), total sleep time (TST), and the 6-min walk test (6MWT) for functional exercise capacity were the key assessments. RESULTS: The mean age was 54.8 years (SD, 5.96), and mean cigarettes smoked per day (cpd) was 8.71 (SD, 6.78). Mean SE was 69.9% (SD, 12.3%), and mean TST was 307.99 min (SD 92.2). In adjusted linear regression models of the 6MWT (meters), TST (slope estimate, -0.14; P = .14) and SE (slope estimate, -1.0; P = .19) were negatively associated with 6MWT. The smoking rate × SE interaction was highly significant (slope estimate, 0.18; P = .007) such that in individuals who smoked ≥ 10 cpd, every additional percentage of SE garnered an additional distance of 0.83 to 6.62 m. Similarly, the smoking rate × TST interaction was significant (slope estimate, 0.019; P = .03) such that in smokers who smoked ≥ 10 cpd, every additional minute of TST garnered an additional distance of 0.04 to 0.60 m. INTERPRETATION: Higher SE and, to a lesser extent, longer TST, in black adults who smoke ≥ 10 cpd is associated with better 6MWT performance. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov; No.: NCT03534076; URL: www.clinicaltrials.gov.

A Microbe Associated with Sleep Revealed by a Novel Systems Genetic Analysis of the Microbiome in Collaborative Cross Mice.

The microbiome influences health and disease through complex networks of host genetics, genomics, microbes, and environment. Identifying the mechanisms of these interactions has remained challenging. Systems genetics in laboratory mice (Mus musculus) enables data-driven discovery of biological network components and mechanisms of host-microbial interactions underlying disease phenotypes. To examine the interplay among the whole host genome, transcriptome, and microbiome, we mapped QTL and correlated the abundance of cecal messenger RNA, luminal microflora, physiology, and behavior in a highly diverse Collaborative Cross breeding population. One such relationship, regulated by a variant on chromosome 7, was the association of Odoribacter (Bacteroidales) abundance and sleep phenotypes. In a test of this association in the BKS.Cg-Dock7m +/+ Leprdb/J mouse model of obesity and diabetes, known to have abnormal sleep and colonization by Odoribacter, treatment with antibiotics altered sleep in a genotype-dependent fashion. The many other relationships extracted from this study can be used to interrogate other diseases, microbes, and mechanisms.

A case of severe hypothyroidism due to lenalidomide.

Lenalidomide, an immunomodulatory drug often used to treat multiple myeloma, can cause hypo- or hyperthyroidism. We present a patient being treated with lenalidomide for 2 years who developed severe hypothyroidism that was complicated by rhabdomyolysis and acute kidney injury. Thyroid function tests should be serially monitored in patients taking lenalidomide.

Physical education teachers' and principals' perspectives on the use of FitnessGram.

OBJECTIVES: FitnessGram is commonly used to measure physical fitness and improve physical activity and health in youth. However, little is known about its use for informing physical activity and health promotion policy within schools and school districts, especially from the perspective of key decision-makers like principals. Therefore, this study examined physical education teachers' and principals' perceptions of FitnessGram use and its relationship with school and district efforts to promote physical activity. METHODS: Principal and physical education teacher surveys were developed, converted to an online format, and then emailed along with a project description and instructions to all Delaware public and charter school physical education teachers (N = 183) and principals (N = 193) with a valid email. RESULTS: Completed surveys were received from 35.5% of the teachers and 21.2% of the principals. All teachers and 95.1% of the principals reported their school used FitnessGram the past academic year. FitnessGram was significantly more likely to be used if FitnessGram results better aligned with school/district policies (r = 0.39) and were considered important in the school's decision-making process (r = 0.53). Significantly more principals than teachers said that FitnessGram results were important in their school's decision-making process and that FitnessGram results were used to inform policy-/decision-making. CONCLUSION: Use of FitnessGram was correlated with how well it related to school/district policy. Unfortunately, most of the physical education teachers and principals did not think FitnessGram was adequately integrated into the policy-/decision-making process.

National Rates of Initiation and Intensification of Antidiabetic Therapy Among Patients With Commercial Insurance.

OBJECTIVE: Prompt initiation and intensification of antidiabetic therapy can delay or prevent complications from diabetes. We sought to understand the rates of and factors associated with the initiation and intensification of antidiabetic therapy among commercially insured patients in the U.S. RESEARCH DESIGN AND METHODS: Using 2008-2015 commercial claims linked with laboratory and pharmacy data, we created an initiation cohort with no prior antidiabetic drug use and an HbA1c ≥8% (64 mmol/mol) and an intensification cohort of patients with an HbA1c ≥8% (64 mmol/mol) who were on a stable dose of one noninsulin diabetes drug. Using multivariable logistic regression, we determined the rates of and factors associated with initiation and intensification. In addition, we determined the percent of variation in treatment patterns explained by measurable patient factors. RESULTS: In the initiation cohort (n = 9,799), 63% of patients received an antidiabetic drug within 6 months of the elevated HbA1c test. In the intensification cohort (n = 10,941), 82% had their existing antidiabetic therapy intensified within 6 months of the elevated HbA1c test. Higher HbA1c levels, lower generic drug copayments, and more frequent office visits were associated with higher rates of both initiation and intensification. Better patient adherence prior to the elevated HbA1c level, existing therapy with a second-generation antidiabetic drug, and lower doses of existing therapy were also associated with intensification. Patient factors explained 7.96% of the variation in initiation and 7.35% of the variation in intensification. CONCLUSIONS: Approximately two-thirds of patients were newly initiated on antidiabetic therapy, and four-fifths of those already receiving antidiabetic therapy had it intensified within 6 months of an elevated HbA1c in a commercially insured population. Patient factors explain 7-8% of the variation in diabetes treatment patterns.

Actual neighborhood-level crime predicts body mass index z-score changes in a multi-racial/ethnic sample of children.

Longitudinal studies are warranted to clarify the influence crime has on health outcomes in children especially children representing multiple racial/ethnic backgrounds. To address this need, the current study examined whether neighborhood-level crime predicted changes in body mass index z (BMIz) scores in 373 White (W), 627 African American (AA), 1020 Hispanic (H), and 88 Asian (A), five to ten year-old boys and girls living in urban neighborhoods. Heights and weights were assessed at baseline (2012) and three-years later and used to calculate BMIz scores. Characteristics of zip codes where students lived during the three-year period were obtained at baseline from various sources. The Crime Risk Index (CRI) for each zip code was calculated using actual crime statistics. Multiple linear regression analyses were conducted to examine associations between baseline CRI and follow-up BMIz scores while controlling for other variables including BMIz at baseline. The CRI and BMIz scores differed significantly by race/ethnicity with the highest values for both noted in H. Regression analyses indicated that the CRI accounted for a significant percentage of the variance in follow-up BMIz scores in the overall sample. When race/ethnicity was considered, the CRI predicted follow-up BMIz scores only in W children. The CRI was not significantly associated with BMIz scores in the other races/ethnicities. The impact actual, neighborhood-level crime has on BMI in children is complex. Based on the existing evidence, considering actual crime as a primary target in obesity prevention would be premature especially in racial/ethnicity minority children living in urban areas.