Performance of a computable phenotype for identification of patients with diabetes within PCORnet: The Patient-Centered Clinical Research Network.

PURPOSE: PCORnet, the National Patient-Centered Clinical Research Network, represents an innovative system for the conduct of observational and pragmatic studies. We describe the identification and validation of a retrospective cohort of patients with type 2 diabetes (T2DM) from four PCORnet sites. METHODS: We adapted existing computable phenotypes (CP) for the identification of patients with T2DM and evaluated their performance across four PCORnet sites (2012-2016). Patients entered the cohort on the earliest date they met one of three CP categories: (CP1) coded T2DM diagnosis (ICD-9/ICD-10) and an antidiabetic prescription, (CP2) diagnosis and glycosylated hemoglobin (HbA1c) ≥6.5%, or (CP3) an antidiabetic prescription and HbA1c ≥6.5%. We required evidence of health care utilization in each of the 2 prior years for each patient, as we also developed an incident T2DM CP to identify the subset of patients without documentation of T2DM in the 365 days before t0 . Among a systematic sample of patients, we calculated the positive predictive value (PPV) for the T2DM CP and incident-T2DM CP using electronic health record (EHR) review as reference. RESULTS: The CP identified 50 657 patients with T2DM. The PPV of patients randomly selected for validation was 96.2% (n = 1572; CI:95.1-97.0) and was consistently high across sites. The PPV for the incident-T2DM CP was 5.8% (CI:4.5-7.5). CONCLUSIONS: The T2DM CP accurately and efficiently identified patients with T2DM across multiple sites that participate in PCORnet, although the incident T2DM CP requires further study. PCORnet is a valuable data source for future epidemiological and comparative effectiveness research among patients with T2DM.

Evaluation of sulphadoxine-pyrimethamine for intermittent preventive treatment of malaria in pregnancy: a retrospective birth outcomes study in Mansa, Zambia.

BACKGROUND: Intermittent preventive treatment of malaria in pregnancy (IPTp) with sulphadoxine-pyrimethamine (SP) decreases placental parasitaemia, thus improving birth outcomes. Zambian policy recommends monthly SP-IPTp doses given presumptively during pregnancy at each antenatal examination, spaced one month apart after 16 weeks of gestation. The effectiveness of SP-IPTp was evaluated in Zambia where a recent study showed moderate prevalence of Plasmodium falciparum parasites with genetic mutations that confer SP resistance. METHODS: HIV-negative women were enrolled at the time of delivery at two facilities in Mansa, Zambia, an area of high malaria transmission. Women were interviewed and SP exposure was determined by antenatal card documentation or self-reports. Using Poisson regression modelling, the effectiveness of SP-IPTp was evaluated for outcomes of parasitaemia (microscopic examination of maternal peripheral, cord, and placental blood films), maternal anaemia (Hb < 11 g/dl), placental infection (histopathology), and infant outcomes (low birth weight (LBW), preterm delivery, and small for gestational age) in women who took 0-4 doses of SP-IPTp. RESULTS: Participants included 435 women, with a median age of 23 years (range 16-44). Thirty-four women took zero doses of SP-IPTp, while 115, 142 and 144 women took one, two, or ≥ three doses, respectively. Multivariate Poisson regression models considering age, mosquito net usage, indoor residual spraying, urban home, gravidity, facility, wet season delivery, and marital status showed that among paucigravid women ≥ two doses of SP-ITPp compared to one or less doses was associated with a protective effect on LBW (prevalence ratio (PR) 0.33, 95% confidence interval (CI) 0.12-0.91) and any infection (PR 0.76, CI 0.58-0.99). Multivariate models considering SP-IPTp as a continuous variable showed a protective dose-response association with LBW (paucigravid women: PR 0.54, CI 0.33-0.90, multigravid women: PR 0.63, CI 0.41-0.97). CONCLUSIONS: In Mansa, Zambia, an area of moderate SP resistance, ≥ two doses of SP-IPTp were associated with a protective effect from malaria in pregnancy, especially among paucigravid women. Each dose of SP-IPTp contributed to a 46 and 37% decrease in the frequency of LBW among paucigravid and multigravid women, respectively. SP-IPTp remains a viable strategy in this context.

ROLE OF INSULIN SENSITIZERS ON CARDIOVASCULAR RISK FACTORS IN POLYCYSTIC OVARIAN SYNDROME: A META-ANALYSIS.

OBJECTIVE: Polycystic ovarian syndrome (PCOS) is associated with an increase in cardiovascular (CV) risk factors such as insulin resistance, with accompanying hyperinsulinemia and hyperlipidemia, which are predisposing factors for type 2 diabetes mellitus and CV disease. The aim of this meta-analysis is to examine the effect of insulin sensitizers on clinical and biochemical features of PCOS and risk factors for CV disease. METHODS: A systematic literature review was conducted, and randomized controlled clinical trials were identified by a search of bibliographic databases: Medline database (from 1966 forward), EMBASE (January 1985 forward), and Cochrane Central Register of Controlled Trials. Reviews of reference lists further identified candidate trials. Data was independently abstracted in duplicate by 2 investigators using a standardized data-collection form. Articles without a comparison group and randomization allocation were excluded. Reviewers worked independently and in duplicate to determine the methodological quality of trials, then collected data on patient characteristics, interventions, and outcomes. RESULTS: Of 455 studies, 44 trials were eligible. A random effects model was used. Significant unadjusted results favoring treatment with insulin sensitizers were obtained for body mass index (BMI) (effect size [ES] of 0.58), waist to hip ratio (WHR) (ES of 0.02), low-density-lipoprotein cholesterol (LDL-C) (ES of 0.11), fasting insulin (ES of 2.82), fasting glucose (ES of 0.10), free testosterone (ES of 1.88), and androstenedione level (ES of 0.76). CONCLUSION: Treatment with insulin sensitizers in women with PCOS results in improvement in CV factors such as BMI, WHR, LDL-C, fasting insulin, glucose, free testosterone, and androstenedione.

Efficacy of sulphadoxine-pyrimethamine for intermittent preventive treatment of malaria in pregnancy, Mansa, Zambia.

BACKGROUND: Intermittent preventive treatment of malaria in pregnancy (IPTp) with sulphadoxine-pyrimethamine (SP) decreases adverse effects of malaria during pregnancy. Zambia implemented its IPTp-SP programme in 2003. Emergence of SP-resistant Plasmodium falciparum threatens this strategy. The quintuple mutant haplotype (substitutions in N51I, C59R, S108N in dhfr and A437G and K540E in dhps genes), is associated with SP treatment failure in non-pregnant patients with malaria. This study examined efficacy of IPTp-SP and presence of the quintuple mutant among pregnant women in Mansa, Zambia. METHODS: In Mansa, an area with high malaria transmission, HIV-negative pregnant women presenting to two antenatal clinics for the 1st dose of IPTp-SP with asymptomatic parasitaemia were enrolled and microscopy for parasitaemia was done weekly for five weeks. Outcomes were parasitological failure and adequate parasitological response (no parasitaemia during follow-up). Polymerase chain reaction assays were employed to distinguish recrudescence from reinfection, and identify molecular markers of SP resistance. Survival analysis included those who had reinfection and incomplete follow-up (missed at least one follow-up). RESULTS: Of the 109 women included in the study, 58 (53%) completed all follow-up, 34 (31%) had incomplete follow-up, and 17 (16%) were lost to follow-up after day 0. Of those who had complete follow-up, 15 (26%, 95% confidence interval [CI] [16-38]) had parasitological failure. For the 92 women included in the survival analysis, median age was 20 years (interquartile range [IQR] 18-22), median gestational age was 22 weeks (IQR range 20-24), and 57% were primigravid. There was no difference in time to failure in primigravid versus multigravid women. Of the 84 women with complete haplotype data for the aforementioned loci of the dhfr and dhps genes, 53 (63%, 95% CI [50-70]) had quintuple mutants (two with an additional mutation in A581G of dhps). Among women with complete follow-up and quintuple mutants, 22% had parasitological failure versus 0% without (p = 0.44). CONCLUSIONS: While underpowered, this study found 26% failure rates of SP given the moderate prevalence of the quintuple mutant haplotype. Despite the presence of resistance, SP retained some efficacy in clearing parasites in pregnant women, and may remain a viable option for IPTp in Zambia.

Qualitative Review of Organizational Responses to Rumors in the 2014-2016 Ebola Virus Disease Outbreak in Liberia and Sierra Leone.

INTRODUCTION: Rumors and misperceptions were a persistent challenge in the response to the 2014-2016 Ebola Virus Disease (EVD) outbreak in West Africa. This study aimed to document organizational approaches to identifying and addressing rumors and provide practical recommendations for future outbreaks. METHODS: We conducted semistructured interviews with 34 individuals who participated in the EVD response in Liberia and/or Sierra Leone. Interviews focused on the general organizational approach and organizational response to specific rumors. Interviews were recorded and transcribed verbatim. RESULTS: Most respondents reported that rumors were considered an organizational priority and their importance increased over time. Formal rumor identification systems using community-level reporters were described in Liberia and Sierra Leone as well as varied informal systems. A wide range of approaches was used to address rumors including Community Led Ebola Action, Community Led Total Sanitation, drama performances, Ebola Treatment Center/Unit-based approaches, radio, leveraging community leaders as an information source, and organization change. Interpersonal and community-led approaches were described most often. Staff whose professional roles did not involve rumor management reported informally addressing rumors with colleagues and beneficiaries. Rumors reflecting valid concerns with the EVD response, such as potential infection in health care facilities, were addressed through organizational change and improvement. DISCUSSION: Interpersonal and community-led approaches were considered effective by participants and hold promise for future outbreaks. Informal systems developed at Ebola Treatment Centers/Units highlighted how these facilities may be utilized as an information hub. Professionals who interact with beneficiaries, especially local staff, are likely to address rumors informally and organizations may benefit from considering local staff an asset in rumor management. Rumors alerted responders to issues in the EVD response, but this may not be the most efficient mechanism to receive and address concerns.

Racial and sex differences in the polymorphisms of the endocannabinoid receptor genes in obesity.

BACKGROUND: Obesity is a global epidemic and prevalence of obesity is higher in African Americans (AAs) compared to Caucasians. The endocannabinoid system (EC) and polymorphism in the endocannabinoid receptor type 1 (CNR1) gene 3813A/G and 4895A/G and in the fatty acid amide hydrolase (FAAH) are associated with obesity. The objective was to explore racial and sex differences in these polymorphisms and the biochemical abnormalities seen in obesity. METHODS: A cross-sectional study of 667 subjects (53.67% female; 49.18% AA; 69.72% were obese (body mass index [BMI] ≥30)) were screened for CNR1 3813, 4895 and FAAH 385 polymorphisms using a real-time polymerase chain reaction (PCR) system. RESULTS: Subjects with FAAH 385 polymorphisms were more likely to be obese (75.14% vs. 67.81, P = 0.046). There were no significant sex differences for CNR1 3813 and CNR1 4895; or between obese and control group. AAs had higher prevalence of CNR1 3813 (OR, 2.80, 95% CI, 1.95-4.04) and FAAH 385 (OR, 2.48, 95% CI, 1.82-3.38). Association between African American race and the three genotypes persisted after adjustment of all the variables (P < 0.001). CONCLUSION: FAAH 385 polymorphism is more likely seen in obese and in older subjects. AAs had higher prevalence of CNR1 3813 and FAAH 385 polymorphisms; and lower prevalence of CNR1 4895 polymorphism. These findings may explain some of the racial differences, but not the sex differences in the clinical expression of obesity.

Diabetes medication regimens and patient clinical characteristics in the national patient-centered clinical research network, PCORnet.

We used electronic medical record (EMR) data in the National Patient-Centered Clinical Research Network (PCORnet) to characterize "real-world" prescription patterns of Type 2 diabetes (T2D) medications. We identified a retrospective cohort of 613,203 adult patients with T2D from 33 datamarts (median patient number: 12,711) from 2012 through 2017 using a validated computable phenotype. We characterized outpatient T2D prescriptions for each patient in the 90 days before and after cohort entry, as well as demographics, comorbidities, non-T2D prescriptions, and clinical and laboratory variables in the 730 days prior to cohort entry. Approximately half of the individuals in the cohort were females and 20% Black. Hypertension (60.3%) and hyperlipidemia (50.5%) were highly prevalent. Most patients were prescribed either a single T2D drug class (42.2%) or had no evidence of a T2D prescription in the EMR (42.4%). A smaller percentage was prescribed multiple T2D drug types (15.4%). Among patients prescribed a single T2D drug type, metformin was the most common (42.6%), followed by insulin (18.2%) and sulfonylureas (13.9%). Newer classes represented approximately 13% of single T2D drug type prescriptions (dipeptidyl peptidase-4 inhibitors [6.6%], glucagon-like peptide-1 receptor agonists [2.5%], thiazolidinediones [2.0%], and sodium-glucose cotransporter-2 inhibitors [1.6%]). Among patients prescribed multiple T2D drug types, the most common combination was metformin and sulfonylureas (63.5%). Metformin-based regimens were highly prevalent in PCORnet's T2D population, whereas newer agents were prescribed less frequently. PCORnet is a novel source for the potential conduct of observational studies among patients with T2D.

Conjugated Estrogens and Bazedoxifene Improve ß Cell Function in Obese Menopausal Women.

CONTEXT: Studies suggest that menopausal hormone therapy (MHT) prevents type 2 diabetes (T2D). The combination of conjugated estrogens (CE) with the selective estrogen receptor modulator bazedoxifene (BZA) is an MHT that improves obesity and T2D in preclinical models of menopausal metabolic syndrome. The effect of CE/BZA on adiposity and glucose homeostasis in obese postmenopausal women is unknown. OBJECTIVE: To investigate the effect of CE/BZA on body composition, glucose homeostasis, and markers of inflammation in obese postmenopausal women. RESEARCH DESIGN INTERVENTION AND PARTICIPANTS: Randomized, double-blind, placebo-controlled pilot trial of 12 obese menopausal women assigned to 12-week treatment with CE 0.45 mg/BZA 20 mg (n = 7) or placebo (n = 5). At baseline and after 12 weeks, we assessed body composition (dual-energy X-ray absorptiometry), glucose homeostasis (IV glucose tolerance test), and inflammation biomarkers. RESULTS: Women treated with CE/BZA exhibited increased ß cell function using homeostatic model assessment-B [median (interquartile range) CE/BZA vs placebo: 18.5 (-0.9 to 320.6) µU/mM vs -25.5 (-39.9 to -0.1) µU/mM; P = 0.045], and decreased basal glucose concentrations (Gb) [-5.2 (-9.2 to -1.7) mg/dL vs 2.7 (0.9 to 4.9) mg/dL; P = 0.029]. Insulin sensitivity was higher in the placebo arm [1.35 (1.12 to 1.82) (µU/mL) min-1 vs -0.24 (-1.50 to 0.19) (µU/mL) min-1; P = 0.029]. No changes between treatment groups were observed for the acute insulin response to glucose (AIRg), the disposition index (DI), body composition, and inflammatory biomarkers. CONCLUSIONS: A 12-week treatment of obese postmenopausal women with CEs/BZA improves fasting ß cell function and glucose concentrations without change in AIRg, HOMA-IR, DI, body composition, or markers of inflammation.

Evaluation of a Remote Monitoring System for Diabetes Control.

PURPOSE: The use of technology to implement cost-effective health care management on a large scale may be an alternative for diabetes management but needs to be evaluated in controlled trials. This study assessed the utility and cost-effectiveness of an automated Diabetes Remote Monitoring and Management System (DRMS) in glycemic control versus usual care. METHODS: In this randomized, controlled study, patients with uncontrolled diabetes on insulin were randomized to use of the DRMS or usual care. Participants in both groups were followed up for 6 months and had 3 clinic visits at 0, 3, and 6 months. The DRMS used text messages or phone calls to remind patients to test their blood glucose and to report results via an automated system, with no human interaction unless a patient had severely high or low blood glucose. The DRMS made adjustments to insulin dose(s) based on validated algorithms. Participants reported medication adherence through the Morisky Medication Adherence Scale-8, and diabetes-specific quality of life through the diabetes Daily Quality of Life questionnaire. A cost-effectiveness analysis was conducted based on the estimated overall costs of DRMS and usual care. FINDINGS: A total of 98 patients were enrolled (59 [60%] female; mean age, 59 years); 87 participants (89%) completed follow-up. HbA1c was similar between the DRMS and control groups at 3 months (7.60% vs 8.10%) and at 6 months (8.10% vs 7.90%). Changes from baseline to 6 months were not statistically significant for self-reported medication adherence and diabetes-specific quality of life, with the exception of the Daily Quality of Life-Social/Vocational Concerns subscale score (P = 0.04). IMPLICATIONS: An automated system like the DRMS may improve glycemic control to the same degree as usual clinic care and may significantly improve the social/vocational aspects of quality of life. Cost-effectiveness analysis found DRMS to be cost-effective when compared to usual care and suggests DRMS has a good scale of economy for program scale up. Further research is needed to determine how to sustain the benefits seen with the automated system over longer periods.

Case of thyrotoxic periodic paralysis in a caucasian male and review of literature.

Objective. Thyrotoxic periodic paralysis (TPP), a known condition in Asian men, is becoming increasingly common in men from Western countries. Since suspicion for TPP as a differential in diagnosis is of utmost importance to avoid overcorrection of hypokalemia and other complications, we are reporting a case of TPP in a 25-year-old Caucasian male. Methods. The patient presented with intermittent lower extremity weakness after consumption of a large high-carbohydrate meal. Clinical examination revealed diffusely enlarged thyroid gland, no muscle power in lower extremities, tremors, and brisk deep tendon reflexes. Results. Clinical and laboratory findings were consistent with Graves' disease and the patient had hypokalemia. The patient responded to potassium repletion and was treated with propylthiouracil and propranolol. After treatment with radioactive iodine, the patient developed postablative hypothyroidism for which he was treated with levothyroxine. Conclusion. Since this condition is overlooked by physicians in Western countries, we present a case of TPP in a Caucasian male thus showing the importance of consideration of TPP in Caucasians despite its rare occurrence and the need for prompt diagnosis to avoid the danger of hyperkalemia in management of the paralytic attack in TPP patients.

The effects of gastroretentive gabapentin (Gralise®) on spinal stenosis patients with radicular pain.

BACKGROUND: The health and efficacy profiles of Gralise® in the treatment of pain from spinal stenosis and radicular symptomatology have not been measured. A review of the current literature indicates that no studies exist that evaluate the safety and efficacy profiles of Gralise® in the treatment of pain from spinal stenosis and radicular symptomatology. OBJECTIVE: Our study is aimed at determining whether Gralise is a safe and effective pharmacotherapy for the pain from spinal stenosis and radicular symptomatology. STUDY DESIGN: A 4-week prospective open label single arm and single center study of patients with MRI diagnosis of spinal stenosis with radicular pain. METHODS: The primary measure of efficacy was a change in average daily pain (ADP) score from baseline to completion of Gralise therapy for 4 weeks. The secondary efficacy endpoints were the patients' Patients Global Impression of Change Scale (PGIC), the clinician's Clinical Global Impression of Change Scale (CGI) reports, and the Medical Outcomes Study (MOS) sleep scale of improvement from baseline to completing 4 weeks of Gralise therapy. The safety and tolerability were evaluated by the incidence of adverse events reported while on Gralise therapy. SETTING: The study was performed at the Clinical Research Facilities at Tulane Medical Center, New Orleans, Louisiana, in the period from December 1, 2012, to August 30, 2013. RESULTS: Thirty-five patients achieved an efficacy point of one-week Gralise medication treatment. Twenty-seven of 35 (77.2%) patients completed all 5 visits. The PGIC noted a significant positive change in: (1) activity limitations; (2) symptoms; (3) emotions and overall quality of life when related to their condition from first visit as well as improved degree of change when related to their condition from first to last visit. The MOS sleep scale and sleep diaries noted a significant increase of hours slept on average (an increase in over one hour per night--5.8 hours versus 6.86 hours) from the beginning of the study to the end. The CGI noted a majority of 10 out of 27 with marked significant therapeutic effect with no side effects. The ADP rating from pain intensity scale and pain diaries noted significant improvement of lesser levels of pain experienced (P =.5907 and P =.8547 respectively). No significant adverse effects were noted in the study. LIMITATIONS: Variation in degree of spinal stenosis, small sample size. CONCLUSIONS: Gralise demonstrated moderate efficacy with reduced pain intensity and increased sleep and was well tolerated in spinal stenosis patients with radicular symptoms.