Basal Insulin Initiation and Maintenance in Adults with Type 2 Diabetes Mellitus in the United States.

OBJECTIVE: A survey of US adults with type 2 diabetes mellitus was conducted to better understand patients' insulin initiation experiences and treatment persistence behaviors. RESEARCH DESIGN AND METHODS: Participants were recruited from consumer panels and grouped by basal insulin treatment pattern: continuers (no gap of ≥7 days within 6 months of initiation); interrupters (gap ≥7 days, resumed treatment); discontinuers (stopped for ≥7 days, not resumed). A quota of approximately 50 respondents per persistence category was set. RESULTS: A total of 154 respondents (52 continuers, 52 interrupters, 50 discontinuers) completed the survey. Mean age was 51.4 years; 51.9% male. Continuers were more likely to report their views being considered during initiation, and less likely to report a sense of failure. Concerns included insulin dependence (64.3% agree/strongly agree), frequent blood glucose monitoring (55.2%), costs/ability to pay (53.9%), fears of or mistakes during self-injection (52.6%), and weight gain (52.6%). Continuers were motivated by benefits of insulin therapy; experienced or potential side effects were notable factors for interruption/discontinuation. Healthcare provider instruction was indicated as a reason for continuing, stopping, and restarting therapy. CONCLUSION: Benefits of basal insulin therapy motivated continuers while side effects impacted interruption/discontinuation. Persistence on basal insulin is often influenced by provider actions. Earlier provider intervention upon signs of treatment discontinuation may promote persistence.

Successful Health Care Provider Strategies to Overcome Psychological Insulin Resistance in United States and Canada.

PURPOSE: To identify specific actions and characteristics of health care providers (HCPs) in the United States and Canada that influenced patients with type 2 diabetes who were initially reluctant to begin insulin. METHODS: Patients from the United States (n = 120) and Canada (n = 74) were recruited via registry, announcements, and physician referrals to complete a 30-minute online survey based on interviews with patients and providers regarding specific HCP actions that contributed to the decision to begin insulin. RESULTS: The most helpful HCP actions were patient-centered approaches to improve patients' understanding of the injection process (ie, "My HCP walked me through the whole process of exactly how to take insulin" [helped moderately or a lot, United States: 79%; Canada: 83%]) and alleviate concerns ("My HCP encouraged me to contact his/her office immediately if I ran into any problems or had questions after starting insulin" [United States: 76%; Canada: 82%]). Actions that were the least helpful included referrals to other sources (ie, "HCP referred patient to a class to help learn more about insulin" [United States: 40%; Canada: 58%]). CONCLUSIONS: The study provides valuable insight that HCPs can use to help patients overcome psychological insulin resistance, which is a critical step in the design of effective intervention protocols.

Challenges in insulin initiation among Hispanics/Latinos with diabetes in the United States.

PURPOSE: The prevalence of diagnosed diabetes in the United States (U.S.) is particularly high among people of Hispanic/Latino ethnicity, placing this population at risk of developing diabetes-related complications. We conducted a systematic literature review to understand and communicate the current gaps and disparities, including myths and misconceptions, regarding insulin initiation among the Hispanic/Latino population in the U.S. METHODS: We searched MEDLINE and MEDLINE In-process, e-pubs ahead of print (OvidSP), EMBASE (OvidSP), and the Cochrane Central Register of Controlled Trials (CENTRAL). The search strategy combined free text and controlled vocabulary terms and was developed to identify challenges associated with insulin use and initiation, as well as myths/misconceptions associated with insulin use. The quality of included studies was assessed using the National Institutes of Health (NIH) quality assessment tool. PRINCIPAL RESULTS: In total, 777 articles were identified, with 13 articles included for data synthesis. Frequently reported barriers to initiating diabetes treatment among the Hispanic/Latino community related to socioeconomic and sociocultural factors. In particular, limited health literacy and access to health care, as well as low education and economic status, were common factors preventing treatment initiation for diabetes. Cultural factors, including language, food preferences, and lack of family support were also evident, with misconceptions and fears concerning insulin being commonly reported. Patients also described barriers concerning health care providers, including interpersonal issues and difficulties with communication and language. MAJOR CONCLUSIONS: Overall, the current literature highlights many obstacles facing Hispanic/Latino patients in initiating insulin treatment for diabetes. Although limited research was identified, we describe common barriers and themes among this minority population. Awareness of these barriers is important for health care providers, enabling them to identify and address insulin-related fears and misconceptions and to be mindful of their cultural competency. Additionally, knowledge of current barriers will guide further research aimed at developing tailored strategies and tools to improve long-term health outcomes and quality of life in this population.

Understanding the impact of five major determinants of health (genetics, biology, behavior, psychology, society/environment) on type 2 diabetes in U.S. Hispanic/Latino families: Mil Familias - a cohort study.

BACKGROUND: In the United States (U.S.), the prevalence of both diagnosed and undiagnosed type 2 diabetes (T2D) is nearly twice as high among Mexican-origin Hispanic/Latino adults compared to non-Hispanic Whites. Rates of diabetes-related complications, e.g., acute stroke and end-stage renal disease, are also higher among Hispanic/Latino adults compared to their non-Hispanic/Latino White counterparts. Beyond genetic and biological factors, it is now recognized that sociocultural influences are also important factors in determining risk for T2D and the associated complications. These influences include ethnicity, acculturation, residence, education, and economic status. The primary objective of this study is to determine the influence of the 5 major determinants of human health (genetics, biology, behavior, psychology, society/environment) on the burden of T2D for Latino families. To achieve this objective, Mil Familias (www.milfamilias.sansum.org/) is establishing an observational cohort of 1000 Latino families, with at least one family member living with T2D. METHODS: Specially trained, bilingual Latino/a community health workers (Especialistas) recruit participant families and conduct research activities. Each individual family member will contribute data annually on over 100 different variables relating to their genetics, biology, psychology, behavior, and society/environment, creating a Latino-focused biobank ("Living Information Bank"). This observational cohort study is cross-sectional and longitudinal. Participants are divided into 4 groups: adults age ≥ 18 years with and without T2D, and children age ≥ 7 and < 18 years with and without T2D. Study activities take place through encounters between families and their Especialista. Encounters include screening/enrollment, informed consent, health promotion assessment, laboratory tests, questionnaires, physical activity monitoring, and reflection. DISCUSSION: By creating and providing the framework for the Cohort Establishment study, we intend to inform new approaches regarding equity and excellence in diabetes research and care. We will examine the complex set of factors that contribute to the burden of diabetes in Latino families and assess if cardio-metabolic disease risks go beyond the traditional biological and genetic factors. Breaking the code on the interplay of cardio-metabolic risk factors may help not only this fast growing segment of the U.S. population, but also other high-risk populations. TRIAL REGISTRATION: Study retrospectively registered at ClinicalTrials.gov (NCT03830840), 2/5/2019 (enrollment began 2/1/2019).

Racial and Ethnic Disparities in the Burden and Cost of Diabetes for US Medicare Beneficiaries.

Purpose: To examine the burden and cost of diabetes among fee-for-service Medicare beneficiaries. Methods: Medicare 5% File data for type 1 diabetes (T1D) and type 2 diabetes (T2D) consisting of 1,397,933 enrollees in fee-for-service without Medicare Advantage during the period 2012-2013 were analyzed by race and ethnicity. Results: Although non-Hispanic whites (nHWs) comprised most of this population (86%), prevalence of T1D and T2D was higher for Hispanics than nHWs (3.4% vs. 1.8%, p=0.0006, for T1D and 33.4% vs. 21.9%, p<0.0001, for T2D). Hispanics also had more acute hospital admissions (p=0.0235 for T1D and p=0.0009 for T2D) and longer lengths of stay (7.5 vs. 6.9 days for T1D, p=0.0105, and 6.7 vs. 6.2 days for T2D, p<0.0001) compared with nHWs. Allowed and paid costs per member per month adjusted for confounding were higher for Hispanics than nHWs for T2D (both p<0.0001) and lower for those with T1D (both p<0.0001). Mean number of chronic diseases in patients with diabetes was higher in Hispanics than nHWs (both T1D and T2D, p<0.0000). For T2D, Hispanics were more likely to have glycated hemoglobin (HbA1c) and lipid testing as well as nephropathy screening (all p<0.0001). Hispanics with T1D were also more likely to have HbA1c and lipid tests (p=0.0014 and p=0.0011, respectively); retinopathy and nephropathy screening rates did not differ significantly from rates among nHWs. Conclusion: Diabetes disproportionately impacts US seniors, with Hispanics almost twice as likely as nHWs to be diagnosed. Racial and ethnic disparities exist in the burden and cost of diabetes care for Medicare recipients.

Estrogen-regulated miRNA-27b is altered by bisphenol A in human endometrial stromal cells.

MicroRNAs (miRs) are small molecules important for regulation of transcription and translation. The objective was to identify hormonally regulated miRs in human endometrial stromal cells and to determine the impact of the endocrine disruptor, bisphenol A (BPA), on those miRs. miR microarray analysis and multiple confirmatory cell preparations treated with 17ß-estradiol (E2) and BPA altered miR-27b, let-7c, let-7e and miR-181b. Further, decidualization downregulated miR-27b. VEGFB and VEGFC were validated as targets of miR-27b. Identification of miR-27b target genes suggests that BPA and E2 downregulate miR-27b thereby leading to upregulation of genes important for vascularization and angiogenesis of the endometrium during the menstrual cycle and decidualization.

Use of Clomiphene Citrate in minimal stimulation in vitro fertilization negatively impacts endometrial thickness: an argument for a freeze-all approach.

OBJECTIVE: Minimal stimulation IVF is a treatment option that uses clomiphene citrate (CC). We sought to evaluate how CC impacts endometrial thickness during minimal stimulation IVF cycles. METHODS: We retrospectively analyzed a cohort of 230 cycles in 119 poor ovarian response patients. The IVF cycles were studied in three groups: 130 minimal stimulation cycles, 29 mild stimulation cycles, and 30 conventional high dose gonadotropin releasing hormone (GnRH) antagonist cycles. Thirty-three minimal stimulation IVF patients had 41 frozen embryo transfers (FET) which allowed us to study whether the CC effects were prolonged. RESULTS: Endometrial thickness in the minimal stimulation group was significantly lower than the mild and conventional stimulation groups (7.3±2.2mm versus 11.4±3.3mm versus 12.9±3.8mm, respectively, p<0.0001). In patients who underwent minimal stimulation IVF followed by FET, significantly thicker endometrial thickness was achieved during their FET cycles as compared to their minimal stimulation cycles (7.95±2.1mm versus 10.3±1.8mm, p<0.0001). CONCLUSION: We concluded that endometrial thickness is impacted during minimal stimulation IVF cycles. Since negative effects on endometrial thickness are not observed in the patients' subsequent FET cycle, a freeze-all approach is justified to mitigate adverse endometrial effects of CC in minimal stimulation IVF cycles.

Primary care physician perspectives on basal insulin initiation and maintenance in patients with type 2 diabetes mellitus.

AIMS: To describe primary care physicians' (PCPs) perceptions of patient reactions and concerns about insulin initiation and identify opportunities for increased support. METHODS: Cross-sectional, online survey of PCPs prescribing basal insulin to adults with type 2 diabetes mellitus (T2DM). PCPs were identified from administrative claims of a large commercial health plan and descriptive results of PCP responses were reported. RESULTS: PCPs (N=100) treated an average of 17 patients receiving insulin during a typical week. More than 85% of insulin initiation recommendations originated with PCPs. Most offered glucose monitoring instructions (96%) and advice on diet, exercise, and diabetes management (96%); 35% provided insulin titration algorithms; 93% reported that patients often or always took their insulin daily within 3 months of initiation; 31% of PCPs reported monthly office contacts with patients for the first 3 months; 16% reported no outreach efforts; fewer than 20% connected patients with support groups. When starting basal insulin, PCPs reported patients feeling personal failure regarding their diabetes treatment (33% often/always) and lacking confidence in their ability to manage insulin therapy (38% often/always). CONCLUSIONS: Study results identify additional opportunities for assisting patients in making the transition to insulin, including more frequent direct outreach to monitor insulin usage.

Hot Topics in Primary Care: Demystifying the Differences: Follow-on Biologics, Biosimilars, and Generics.

Sponsors of follow-on biologics can submit their applications for approval by the US Food and Drug Administration (FDA) under 2 distinct pathways. The submission pathway is determined by the pathway previously used by the reference biologic product, which is the biologic product upon which the follow-on product relies for evidence of safety and efficacy.

Economic Impact of Treatment Duration and Persistence with Basal Insulin in Previously Insulin-Naive Users.

BACKGROUND: Although insulin is a well-established therapy that is associated with improved clinical outcomes, adherence and persistence with insulin regimens are poor in patients with type 2 diabetes mellitus (T2DM). Diabetes-related health care costs and the impact of insulin persistence patterns on these health care costs have been previously studied; however, these aspects of insulin therapy have limited data beyond the first year of use and have not been characterized among patients previously naive to basal insulin. OBJECTIVES: To (a) describe and compare medical- and pharmacy-related costs, health care resource utilization, and comorbidities and complications during the initial year and second (experienced) year of basal insulin therapy, and (b) describe and compare the impact of continuous versus interrupted basal insulin use during each year. METHODS: This was a retrospective observational database analysis using claims from multiple U.S. commercial health plans (Truven Health MarketScan) in previously insulin-naive patients with T2DM who were initiated on basal insulin. Data collected included all-cause and diabetes-related medical and pharmacy costs, health care resource utilization (i.e., number and type of outpatient visits, hospitalization, emergency department [ED] visits), medication use, and preselected comorbidities and complications. This cost analysis described and compared health care costs and resource use between the initial and experienced years and further compared health care costs and resource use between continuers and interrupters within each of those years. RESULTS: A total of 23,645 patients were included in the analysis; 12,224 were classified as continuers and 11,421 were classified as interrupters. Among all patients, mean increases from the initial year to the experienced year were observed for all-cause medical costs ($12,690-$13,408; P = 0.048), all-cause pharmacy costs ($6,253-$6,559; P < 0.001), and all-cause health care costs ($18,943-$19,967; P = 0.006), after adjusting for inflation. All-cause pharmacy costs were significantly higher for continuers versus interrupters, but total diabetes-related medical care costs, all-cause ED costs, and all-cause medical costs were significantly lower, resulting in similar all-cause health care costs between continuers and interrupters in both the initial and experienced years. Among all patients, diabetes-related inpatient visits and outpatient primary care physician (PCP) visits, total medical inpatient visits, and total medical outpatient PCP visits were significantly higher in the initial year than in the experienced year; however, there were fewer diabetes-related ED visits in the initial year. CONCLUSIONS: Initiation of basal insulin appears to be associated with increased health care costs, and treatment persistence pattern (continuers vs. interrupters) is further correlated with health care expenditures. Although associated with decreased pharmacy costs, interruption of therapy increases medical costs, underscoring the importance of addressing persistence to therapy. DISCLOSURES: This study was funded by Eli Lilly and Company and Boehringer Ingelheim. Eli Lilly reviewed and approved this manuscript for submission. All the authors are employees and minor shareholders of Eli Lilly and Company. Study concept and design were contributed by Kalirai, Duan, and Reed. Duan and Liu collected the data, and data interpretation was performed by Kalirai. The manuscript was written by all the authors and revised by Kalirai.

Has testosterone passed the test in premenopausal women with low libido? A systematic review.

BACKGROUND: There are limited evaluation and treatment options for low libido in premenopausal women. This review sought to evaluate the available evidence supporting the evaluation of testosterone serum levels and testosterone treatment of premenopausal women with low libido. METHODS: MEDLINE, PubMed, and ClinicalTrials.gov were searched for articles that referenced the evaluation of testosterone serum level and/or testosterone treatment on premenopausal women with low libido from 1995 to 2015. Additional references were obtained from the reference sections of other papers and from peer review. Studies that included only postmenopausal women were excluded. A total of 13 studies were reviewed in detail. Nine studies examined the relationship between testosterone serum levels and sexuality, an additional three studies examined the effect of testosterone treatment on premenopausal women with low libido, and one study examined both the topics. RESULTS: Six of the ten testosterone serum evaluation studies failed to show a significant association between testosterone serum level and libido. Only one out of four studies examining testosterone treatment in premenopausal women was able to show any clear improvement in libido; however, the effect was limited to only the intermediate dose of testosterone, with the low and high doses of testosterone not producing any effect. CONCLUSION: The currently available evidence does not support testosterone serum evaluation or treatment in premenopausal women with low libido. Hence, further studies are warranted.

Postoperative Urinary Retention With Gross Vulvar Edema After Use of 4% Icodextrin.

BACKGROUND: 4% icodextrin is a fluid that can be instilled laparoscopically to prevent adhesion formation. There are few complications reported in the literature associated with its use. CASE: A 38-year-old woman, gravida 2, para 0, abortus 2 underwent laparoscopic salpingectomy. 4% icodextrin was instilled in an effort to prevent adhesion formation. Postoperatively, the patient experienced urinary retention and gross vulvar edema that required foley catheter use until the 4% icodextrin solution had absorbed. CONCLUSION: Postoperative complications that may be associated with the use of 4% icodextrin include urinary retention and vulvar edema.

Shifting paradigms in diminished ovarian reserve and advanced reproductive age in assisted reproduction: customization instead of conformity.

As women are increasingly delaying childbearing into their 30s and beyond, diminished ovarian reserve (DOR) and advanced reproductive age (ARA) patients are bound to become a large proportion of all assisted reproductive technology practices. Traditional controlled ovarian stimulation (COS) protocols for DOR and/or ARA have had some limited success, but pregnancy rates are lower and cycle cancellation rates are higher than their younger counterparts with normal ovarian reserve. Though many physicians have a selection of favorite standard protocols that they use, patients with DOR may require closer monitoring and customization of the treatment cycle to address the common problems that come with low ovarian reserve. Frequent issues that surface in women with DOR and/or ARA include poor follicular response, premature luteinizing hormone surge, and poor embryo quality. Limited published evidence exists to guide treatment for DOR. However, use of minimal or mild doses of gonadotropins, avoidance of severe pituitary suppression, and consideration for luteal phase stimulation and a "freeze all" approach are possible customized treatment options that can be considered for such patients who have failed more traditional COS protocols.

Vulvar pyoderma gangrenosum originating from a healed obstetric laceration.

BACKGROUND: Pyoderma gangrenosum is a rare dermatologic disorder that can occur on the vulva. CASE: A 25-year-old woman, gravida 2 para 1 abortus 1, had development of pain and subsequent ulceration at the location of her previously healed vulvar obstetric laceration. The ulceration and pain continued to worsen despite wound management. Once the diagnosis of vulvar pyoderma gangrenosum was made, cyclosporine was started and the wound rapidly healed. CONCLUSION: Vulvar pyoderma gangrenosum should be considered when a vulvar wound is not healing with conservative measures. Cyclosporine can be considered as an alternative to steroids for treatment.

Malignant pericardial effusion and pericardial tumor involvement secondary to cervical cancer.

BACKGROUND: Antemortem discovery of a malignant pericardial effusion secondary to cervical cancer is uncommon and management should focus on symptom control. CASE: A patient was diagnosed with widely metastatic cervical cancer following a simple hysterectomy for presumed benign etiology. Sixteen months later, she was diagnosed with pericardial tumor involvement and a malignant pericardial effusion resulting in severe dyspnea. The patient underwent a pericardial window procedure that temporarily alleviated her symptoms. She again developed symptoms 2 weeks following the procedure and ultimately elected supportive care. CONCLUSION: Malignant pericardial effusion is a challenging clinical scenario. Although multiple treatment options exist, prognosis is poor and usually limited.

Peripartum cardiomyopathy and acute fatty liver of pregnancy: one patient with two zebras.

OBJECTIVE: Peripartum cardiomyopathy (PPCM) and acute fatty liver of pregnancy (AFLP) are rare complications of pregnancy affecting approximately 1/10,000 pregnancies each. We describe a patient who had biopsy-proven AFLP complicated by PPCM. METHODS: Chart review and literature search. RESULTS: The patient is a 22-year-old G5P1213 obese African-American female who presented at 30 weeks gestation with abdominal pain. She had normal blood pressures and mildly elevated liver enzymes. After completion of a 24 hour urine protein collection that was consistent with pre-eclampsia, an induction of labor with uncomplicated vaginal delivery was accomplished. Following delivery, a computed tomography scan of the abdomen revealed significant cardiomegaly. An echocardiogram revealed global dysfunction with an ejection fraction of 10%. Liver biopsy showed AFLP. Attempts to establish a unifying etiology were unrevealing. The PPCM was treated with diuretics and intravenous immunoglobulin. The patient's clinical status deteriorated, eventually requiring continuous dialysis, intubation, pharmacologic and mechanical inotropic support, and a feeding tube. The patient was discharged to a long-term care facility where she subsequently passed away from multiorgan failure. CONCLUSION: AFLP and PPCM are rare complications of pregnancy. We present a patient who had both. Both diseases carry a high mortality rate, and together, are likely fatal.

Surgically managed stage I endometrial cancer in a low-volume center: outcomes and complications in a military residency program.

OBJECTIVE: The purpose of this study was to compare operative outcomes and complications for patients with endometrial cancer who underwent staging by laparoscopy vs laparotomy in a low-volume facility. STUDY DESIGN: Research was conducted with a retrospective cohort of surgical patients with clinical stage I endometrial cancer from 2004-2009. RESULTS: Eighty-six demographically similar patients (50 laparotomy and 36 laparoscopy) were identified. Laparoscopy had less estimated blood loss (339 vs 558 mL; P = .013) and lower rates of transfusion (5.6% vs 24%; P = .02). Laparoscopy was longer (281 vs 202 minutes; P < .0005) but required a shorter hospital stay (2.2 vs 5.5 days; P < .0005). Laparoscopy patients had fewer overall complications (16.7% vs 32%; P = .11). No differences in final surgical stage or lymph node yields between the groups were present. CONCLUSION: Although a longer procedure, laparoscopy had fewer complications and shorter hospital stays. Prolonged operative time, compared with published experience, is potentially the result of unique factors in our center.

Hospice enrollment for terminally ill patients with gynecologic malignancies: impact on outcomes and interventions.

OBJECTIVE: To determine survival and interventions for patients with non-curative gynecologic malignancies based on supportive care enrollment. METHODS: An IRB approved retrospective review identified patients with recurrent/persistent gynecologic cancers from 2002 to 2008. Demographics, therapy, clinicopathologic data, hospice utilization, surgical/invasive procedures and survival were collected. Patients were considered hospice enrollees if they enrolled following recommendation from their provider (HOSPICE); however, patients that declined hospice when recommended were considered (NO HOSPICE), regardless if they ultimately received supportive care. Standard statistical tests including: t-test and Kaplan-Meier with Log Rank were used. RESULTS: Eighty-one patients were identified: 29 patients (36%) NO HOSPICE and 52 (64%) HOSPICE. Mean age was 61. Most patients had ovarian cancer (54.3%), were white (61.7%) and had disease recurrence (72%). Patients utilized a median of 3 anti-neoplastic therapies (range 0-10) for recurrent or progressive/persistent disease. Median time receiving hospice care was 1week for NO HOSPICE patients versus 8weeks HOSPICE patients (p<0.0005). In a subset of patients with recurrent disease, median overall survival for NO HOSPICE patients was 9months (95% CI 5.9-12.1months) versus 17months (95% CI 11.1-22.9months) for HOSPICE patients (p=0.002). NO HOSPICE patients were more likely to have a procedure performed (55% vs. 31%) within 4weeks of their death, including the administration of chemotherapy OR 2.4 (95% CI 1.1-7.1, p=0.036). CONCLUSIONS: While retrospective reviews evaluating hospice are challenging, our data suggest no detrimental impact on survival for hospice patients. Continued evaluation for patients at the end-of-life is necessary in order to optimize resource utilization.