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Organizational Project Management (OPM) is not a "thing" or a "procedure" rather, it can almost be described as a "state of being" or "harmony" in the alignment of what an organization does and how it gets there. OPM has the responsibility to enhance and improve how an organization achieves its strategic goals. It provides organizations with an intelligent approach to deal effectively with the various projects and programs required by the market, its organizational stakeholders, and regulatory agencies, all within the organization's limited resources. OPM has the responsibility to support the alignment between the organization's business strategy and its projects to achieve the organization's goals. It is also responsible for managing risks and dealing with the uncertainty that may prevent the organization from achieving its objectives. In addition, it enables the organization to measure its capabilities, then plan and implement improvements to seek the systematic achievement of best practices. Moreover, it ensures organizational learnings from both knowledge management and lessons learned. The purpose of the research is to illustrate the important role that OPM must or needs to play within the organization. This research utilizes the current knowledge base in the project management environment to answer the question of "Why does an organization need to establish OPM?" In addition to describing OPM's responsibility in the organization, the paper will briefly explore four categories, Portfolio Management, Project Sponsor, Effective Programs and Projects Management, and Strategic Project Management Office (PMO) for establishing OPM in an organization.

This study investigated the safety and efficacy of IDegLira as add-on to SGLT2i. In this 26-week, phase 3b, open-label trial, 420 patients with T2D uncontrolled on SGLT2i ± OADs were randomized 1:1 to receive add-on therapy of IDegLira or IGlar U100 (100 units [U]/mL). Starting doses were 10 U in both treatment arms. Doses were titrated twice-weekly to a fasting glucose target of 72 to 90 mg/dL; only IDegLira had a maximum dose (50 U). Mean A1C decreased from 8.2% at baseline to 6.3% at week 26 for IDegLira and from 8.4 to 6.7% for IGlar U100; IDegLira superiority confirmed (p In conclusion, superiority of IDegLira vs. IGlar U100 as add-on to SGLT2i was confirmed for glycemic control, body weight, hypoglycemia rate and total daily insulin dose. Disclosure A. Philis-Tsimikas: Research Support; Self; Dexcom, Inc.. Advisory Panel; Self; Dexcom, Inc., Eli Lilly and Company, Merck & Co., Inc., Novo Nordisk A/S, Sanofi. Research Support; Self; Novo Nordisk A/S, Sanofi, Mylan. Stock/Shareholder; Spouse/Partner; Novo Nordisk A/S. Employee; Spouse/Partner; Ionis Pharmaceuticals, Inc.. Stock/Shareholder; Spouse/Partner; Esperion Therapeutics, Ionis Pharmaceuticals, Inc.. Advisory Panel; Self; AstraZeneca. L. Billings: Advisory Panel; Self; Novo Nordisk A/S, Sanofi. Consultant; Self; Novo Nordisk A/S. Research Support; Self; Novo Nordisk A/S. Speaker's Bureau; Self; Novo Nordisk A/S, Dexcom, Inc. R.S. Busch: Speaker's Bureau; Self; AbbVie Inc., AstraZeneca. Research Support; Self; Bayer AG, Intarcia Therapeutics, Inc.. Advisory Panel; Self; Janssen Pharmaceuticals, Inc.. Speaker's Bureau; Self; Amgen Inc.. Research Support; Self; Sanofi US. Speaker's Bureau; Self; Eli Lilly and Company, Boehringer Ingelheim Pharmaceuticals, Inc.. Research Support; Self; Amarin Corporation. C. Morales Portillo: Advisory Panel; Self; Novo Nordisk A/S, Sanofi, Eli Lilly and Company, Boehringer Ingelheim GmbH, Merck Sharp & Dohme Corp., Janssen Pharmaceuticals, Inc., AstraZeneca, Abbott. Research Support; Self; Novo Nordisk A/S, Sanofi, Eli Lilly and Company, Boehringer Ingelheim GmbH, Merck Sharp & Dohme Corp., Janssen Pharmaceuticals, Inc., AstraZeneca, Theracos, Inc., Lexicon Pharmaceuticals, Inc.. Speaker's Bureau; Self; Novo Nordisk A/S, Sanofi, Eli Lilly and Company, Boehringer Ingelheim GmbH, Merck Sharp & Dohme Corp., Janssen Pharmaceuticals, Inc., AstraZeneca, Abbott. R. Sahay: Advisory Panel; Self; Boehringer Ingelheim, Sanofi, Eli Lilly and Company, Novo Nordisk A/S. Advisory Panel; Spouse/Partner; Intas Pharmaceuticals Ltd., Pfizer Inc.. Speaker's Bureau; Self; Sanofi, Eli Lilly and Company, Boehringer Ingelheim, Dr. Reddys Laboratories, USV Private Limited, Glenmark. Speaker's Bureau; Spouse/Partner; Boehringer Ingelheim. N. Halladin: Employee; Self; Novo Nordisk A/S. R. Juhl: Employee; Self; Novo Nordisk A/S. S. Harris: Advisory Panel; Self; Novo Nordisk A/S, Sanofi, Merck, AstraZeneca, Amgen Inc., Lilly/Boehringer Ingelheim, Abbott, Janssen. Consultant; Self; Novo Nordisk A/S, Sanofi, Merck, AstraZeneca, Lilly/Boehringer Ingelheim, Abbott, Janssen. Research Support; Self; Novo Nordisk A/S, Sanofi, Merck, Abbott, AstraZeneca, Janssen. Other Relationship; Self; CIHR, CDA, The Lawson Foundation.

Body weight (BW) changes may affect muscle mass and thus creatinine (Cr) levels. Estimating glomerular filtration rate (eGFR) by Cr-based equations may not accurately reflect changes in kidney function when BW changes. Dulaglutide (DU) treatment was associated with BW loss and lesser eGFR (Cr-CKD-EPI) decline in people with T2D and moderate to severe CKD compared to insulin glargine (IG) (Table). The aim was to evaluate if the lesser eGFR decline observed with DU is related to BW loss. eGFR was evaluated with Cr-based equations (MDRD, CKD-EPI) compared to cystatin C-CKD-EPI equation. Cystatin C is not affected by muscle mass changes. CrCL was evaluated with the Cockcroft-Gault equation. BL characteristics were similar between treatments ([mean±SD] eGFR (Cr-CKD-EPI): 38.3±12.8 mL/min/1.73m2, A1c: 8.6±1.0%, age: 64.6±8.6 y, T2D duration: 18.1±8.7 y). All equations consistently show that eGFR remained stable with DU, but significantly decreased with IG regardless of BW loss in DU or gain in IG (Table). Since BW is a factor in CrCL calculations, compared to eGFR equations, BW loss in DU led to bias toward greater reductions in CrCL. This bias disappeared when using lean BW (Table). In conclusion, compared to IG, DU was associated with lesser eGFR decline in people with T2D and moderate to severe CKD regardless of BW changes. Disclosure K.R. Tuttle: Consultant; Self; Eli Lilly and Company, Boehringer Ingelheim GmbH, AstraZeneca, Gilead Sciences, Inc. M. Lakshmanan: Employee; Self; Eli Lilly and Company. Stock/Shareholder; Self; Eli Lilly and Company. Stock/Shareholder; Spouse/Partner; Eli Lilly and Company. B.L. Rayner: Advisory Panel; Self; Boehringer Ingelheim Pharmaceuticals, Inc.. Speaker's Bureau; Self; Novartis AG, Servier. Advisory Panel; Self; AstraZeneca. R.S. Busch: Speaker's Bureau; Self; AbbVie Inc., AstraZeneca. Research Support; Self; Bayer AG, Intarcia Therapeutics, Inc.. Advisory Panel; Self; Janssen Pharmaceuticals, Inc.. Speaker's Bureau; Self; Amgen Inc.. Research Support; Self; Sanofi US. Speaker's Bureau; Self; Eli Lilly and Company, Boehringer Ingelheim Pharmaceuticals, Inc.. Research Support; Self; Amarin Corporation. A.G. Zimmermann: Employee; Self; Eli Lilly and Company. Stock/Shareholder; Self; Eli Lilly and Company. Employee; Spouse/Partner; Eli Lilly and Company. Stock/Shareholder; Spouse/Partner; Eli Lilly and Company. B. Woodward: Employee; Self; Eli Lilly and Company. F.T. Botros: Employee; Self; Eli Lilly and Company.

Purpose: This is a pre-post observational study from an endocrinology ambulatory care practice assessing the effectiveness and safety of a single injectable combination antidiabetic agent, the basal insulin, insulin glargine, and the glucagon-like peptide-1 (GLP-1) receptor agonist, lixisenatide, to background therapy for patients with type 2 diabetes mellitus (T2DM). Methods: The study population will consist of subjects with T2DM who have failed to achieve adequate glycemic control and require the addition of once-daily insulin glargine-lixisenatide (iGlarLixi). Five groups will be assessed: patients initiating iGlarLixi, patients on a basal insulin at baseline, patients on a GLP-1 receptor agonist at baseline, patients on basal insulin and GLP-1 receptor agonist (single-entity products) at baseline and patients only on oral antidiabetic agents at baseline. Potential subjects will be identified via a computerized text search of medication lists from patients’ electronic medical records, which will be reviewed to ascertain if study criteria are met. Outcome: The primary study outcome is change in HbA1c. Secondary outcomes include percentage of patients achieving an HbA1c of < 7% or ≤ 6.5%, change in weight, change in systolic and diastolic blood pressures and change in lipid parameters. Safety will be assessed via collection of reported adverse effects. Results: Thirty subjects initiated therapy with iGlarLixi and 23 had follow-up data. The mean duration of T2DM was 11.3 years and baseline HbA1c was 8.27%. The median starting dose of iGlarLixi was 30 units and the mean dose at follow-up was 41 units. After an average of about 4 months on therapy, HbA1c decreased by 0.94% in the entire cohort (p = 0.02). Fifty-seven percent of subjects achieved an HbA1c < 7% and 26% achieved an HbA1c ≤ 6.5%. iGlarLixi was well tolerated and discontinuation was low (3 subjects) and mainly due to medication cost. Disclosure M.D. Stryker: Other Relationship; Self; Amgen Inc.. Research Support; Self; AstraZeneca. Other Relationship; Self; Novo Nordisk Inc.. Speaker's Bureau; Self; Regeneron Pharmaceuticals, Inc.. C.A. Blow: None. E.B. Friedman: None. R.S. Busch: Speaker's Bureau; Self; AbbVie Inc., AstraZeneca. Research Support; Self; Bayer AG, Intarcia Therapeutics, Inc.. Advisory Panel; Self; Janssen Pharmaceuticals, Inc.. Speaker's Bureau; Self; Amgen Inc.. Research Support; Self; Sanofi US. Speaker's Bureau; Self; Eli Lilly and Company, Boehringer Ingelheim Pharmaceuticals, Inc.. Research Support; Self; Amarin Corporation. M.P. Kane: None.

In DUAL IX, a 26-week, phase 3b, treat-to-target, open-label trial, patients with uncontrolled T2D on SGLT2i ± OADs (N=420) were randomized 1:1 to once-daily IDegLira or IGlar U100 (100 units [U]/mL) add-on therapy. IDegLira was superior to IGlar U100 for A1C (1.9 vs. 1.7% reduction), body weight (0.0 vs. 2.0 kg gain) and hypoglycemia rate (58% lower with IDegLira). PROs were measured at baseline and week 26 with the 5-domain Treatment Related Impact Measure-Diabetes (TRIM-D) questionnaire, with higher scores indicating better outcomes. After 26 weeks, improvements were significantly greater with IDegLira vs. IGlar U100 in total TRIM-D, Treatment Burden domain and especially Diabetes Management domain (Table), including 4 of the 5 individual items (estimated treatment ratio [95% confidence interval]): help you control your diabetes: 2.17 [1.47; 3.21], p In conclusion, vs. IGlar U100, IDegLira treatment resulted in better clinical and treatment management outcomes. Disclosure M. Brod: Consultant; Self; Novo Nordisk A/S. L.K. Billings: Advisory Panel; Self; Novo Nordisk A/S, Sanofi. Consultant; Self; Novo Nordisk A/S. Research Support; Self; Novo Nordisk A/S. Speaker's Bureau; Self; Novo Nordisk A/S, Dexcom, Inc. R.S. Busch: Speaker's Bureau; Self; AbbVie Inc., AstraZeneca. Research Support; Self; Bayer AG, Intarcia Therapeutics, Inc.. Advisory Panel; Self; Janssen Pharmaceuticals, Inc.. Speaker's Bureau; Self; Amgen Inc.. Research Support; Self; Sanofi US. Speaker's Bureau; Self; Eli Lilly and Company, Boehringer Ingelheim Pharmaceuticals, Inc.. Research Support; Self; Amarin Corporation. S. Harris: Advisory Panel; Self; Novo Nordisk A/S, Sanofi, Merck, AstraZeneca, Amgen Inc., Lilly/Boehringer Ingelheim, Abbott, Janssen. Consultant; Self; Novo Nordisk A/S, Sanofi, Merck, AstraZeneca, Lilly/Boehringer Ingelheim, Abbott, Janssen. Research Support; Self; Novo Nordisk A/S, Sanofi, Merck, Abbott, AstraZeneca, Janssen. Other Relationship; Self; CIHR, CDA, The Lawson Foundation. C. Morales Portillo: Advisory Panel; Self; Novo Nordisk A/S, Sanofi, Eli Lilly and Company, Boehringer Ingelheim GmbH, Merck Sharp & Dohme Corp., Janssen Pharmaceuticals, Inc., AstraZeneca, Abbott. Research Support; Self; Novo Nordisk A/S, Sanofi, Eli Lilly and Company, Boehringer Ingelheim GmbH, Merck Sharp & Dohme Corp., Janssen Pharmaceuticals, Inc., AstraZeneca, Theracos, Inc., Lexicon Pharmaceuticals, Inc.. Speaker's Bureau; Self; Novo Nordisk A/S, Sanofi, Eli Lilly and Company, Boehringer Ingelheim GmbH, Merck Sharp & Dohme Corp., Janssen Pharmaceuticals, Inc., AstraZeneca, Abbott. R. Sahay: Advisory Panel; Self; Boehringer Ingelheim, Sanofi, Eli Lilly and Company, Novo Nordisk A/S. Advisory Panel; Spouse/Partner; Intas Pharmaceuticals Ltd., Pfizer Inc.. Speaker's Bureau; Self; Sanofi, Eli Lilly and Company, Boehringer Ingelheim, Dr. Reddys Laboratories, USV Private Limited, Glenmark. Speaker's Bureau; Spouse/Partner; Boehringer Ingelheim. A. Busk: Employee; Self; Novo Nordisk A/S. Stock/Shareholder; Self; Novo Nordisk A/S. Stock/Shareholder; Spouse/Partner; Novo Nordisk A/S. S. Eggert: Employee; Self; Novo Nordisk A/S. N. Halladin: Employee; Self; Novo Nordisk A/S. A. Philis-Tsimikas: Research Support; Self; Dexcom, Inc.. Advisory Panel; Self; Dexcom, Inc., Eli Lilly and Company, Merck & Co., Inc., Novo Nordisk A/S, Sanofi. Research Support; Self; Novo Nordisk A/S, Sanofi, Mylan. Stock/Shareholder; Spouse/Partner; Novo Nordisk A/S. Employee; Spouse/Partner; Ionis Pharmaceuticals, Inc.. Stock/Shareholder; Spouse/Partner; Esperion Therapeutics, Ionis Pharmaceuticals, Inc.. Advisory Panel; Self; AstraZeneca.

Summary Background Many antihyperglycaemic drugs, including insulin, are primarily cleared by the kidneys, restricting treatment options for patients with kidney disease. Dulaglutide is a long-acting glucagon-like peptide-1 receptor agonist that is not cleared by the kidneys, and confers a lower risk of hypoglycaemia than does insulin. We assessed the efficacy and safety of dulaglutide in patients with type 2 diabetes and moderate-to-severe chronic kidney disease. Methods AWARD-7 was a multicentre, open-label trial done at 99 sites in nine countries. Eligible patients were adults with type 2 diabetes and moderate-to-severe chronic kidney disease (stages 3–4), with an HbA 1c of 7·5–10·5%, and who were being treated with insulin or insulin plus an oral antihyperglycaemic drug and were taking a maximum tolerated dose of an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker. Participants were randomly assigned (1:1:1) by use of a computer-generated random sequence with an interactive response system to once-weekly injectable dulaglutide 1·5 mg, once-weekly dulaglutide 0·75 mg, or daily insulin glargine as basal therapy, all in combination with insulin lispro, for 52 weeks. Insulin glargine and lispro doses were titrated as per an adjustment algorithm; dulaglutide doses were masked to participants and investigators. The primary outcome was HbA 1c at 26 weeks, with a 0·4% non-inferiority margin. Secondary outcomes included estimated glomerular filtration rate (eGFR) and urine albumin-to-creatinine ratio (UACR). The primary analysis population was all randomly assigned patients who received at least one dose of study treatment and had at least one post-randomisation HbA 1c measurement. The safety population was all patients who received at least one dose of study treatment and had any post-dose data. This study is registered with ClinicalTrials.gov, number NCT01621178. Findings Between Aug 15, 2012, and Nov 30, 2015, 577 patients were randomly assigned, 193 to dulaglutide 1·5 mg, 190 to dulaglutide 0·75 mg, and 194 to insulin glargine. The effects on HbA 1c change at 26 weeks of dulaglutide 1·5 mg and 0·75 mg were non-inferior to those of insulin glargine (least squares mean [LSM] −1·2% [SE 0·1] with dulaglutide 1·5 mg [183 patients]; −1·1% [0·1] with dulaglutide 0·75 mg [180 patients]; −1·1% [0·1] with insulin glargine [186 patients]; one-sided p≤0·0001 for both dulaglutide doses vs insulin glargine). The differences in HbA 1c concentration at 26 weeks between dulaglutide and insulin glargine treatments were LSM difference −0·05% (95% CI −0·26 to 0·15, p 1c -lowering effects persisted to 52 weeks (LSM −1·1% [SE 0·1] with dulaglutide 1·5 mg; −1·1% [0·1] with dulaglutide 0·75 mg; −1·0% [0·1] with insulin glargine). At 52 weeks, eGFR was higher with dulaglutide 1·5 mg (Chronic Kidney Disease Epidemiology Collaboration equation by cystatin C geometric LSM 34·0 mL/min per 1·73 m 2 [SE 0·7]; p=0·005 vs insulin glargine) and dulaglutide 0·75 mg (33·8 mL/min per 1·73 m 2 [0·7]; p=0·009 vs insulin glargine) than with insulin glargine (31·3 mL/min per 1·73 m 2 [0·7]). At 52 weeks, the effects of dulaglutide 1·5 mg and 0·75 mg on UACR reduction were not significantly different from that of insulin glargine (LSM −22·5% [95% CI −35·1 to −7·5] with dulaglutide 1·5 mg; −20·1% [–33·1 to −4·6] with dulaglutide 0·75 mg; −13·0% [–27·1 to 3·9] with insulin glargine). Proportions of patients with any serious adverse events were similar across groups (20% [38 of 192] with dulaglutide 1·5 mg, 24% [45 of 190] with dulaglutide 0·75 mg, and 27% [52 of 194] with insulin glargine). Dulaglutide was associated with higher rates of nausea (20% [38 of 192] with dulaglutide 1·5 mg and 14% [27 of 190] with 0·75 mg, vs 5% [nine of 194] with insulin glargine) and diarrhoea (17% [33 of 192] with dulaglutide 1·5 mg and 16% [30 of 190] with 0·75 mg, vs 7% [14 of 194] with insulin glargine) and lower rates of symptomatic hypoglycaemia (4·4 events per patient per year with dulaglutide 1·5 mg and 4·3 with dulaglutide 0·75 mg, vs 9·6 with insulin glargine). End-stage renal disease occurred in 38 participants: eight (4%) of 192 with dulaglutide 1·5 mg, 14 (7%) of 190 with dulaglutide 0·75 mg, and 16 (8%) of 194 with insulin glargine. Interpretation In patients with type 2 diabetes and moderate-to-severe chronic kidney disease, once-weekly dulaglutide produced glycaemic control similar to that achieved with insulin glargine, with reduced decline in eGFR. Dulaglutide seems to be safe to use to achieve glycaemic control in patients with moderate-to-severe chronic kidney disease. Funding Eli Lilly and Company.

JMJD1C, a member of the Jumonji-domain containing histone demethylases protein family, has been associated with levels of sex-hormone binding globulin (SHBG) and testosterone in men, and knock-out rodent models show age-dependent infertility. The objective of this study was to investigate whether single nucleotide polymorphisms (SNPs) nearby JMJD1C are associated with pubertal onset in boys and with male reproduction. 671 peri-pubertal boys, 1,027 young men, 315 fertile men, and 252 infertile men were genotyped for two JMJD1C SNPs (rs7910927 and rs10822184). rs7910927 and rs10822184 showed high linkage. Boys with the rs7910927 TT genotype entered puberty 3.6 months earlier than their peers (p = 2.5 × 10−2). In young men, the number of T alleles was associated with decreased levels of SHBG, follicle-stimulating hormone (FSH), testosterone, and testosterone x luteinizing hormone, as well as increased levels of Inhibin B, Inhibin B/FSH ratio, and testis size. No significant associations with semen parameters were observed and the genotype distribution was comparable among fertile and infertile men. In conclusion, genetic variation in the vicinity of JMJD1C had a surprisingly large impact on the age at pubertal onset in boys as well as levels of reproductive hormones and testis size in men, emphasizing the relationship between JMJD1C and reproductive functions.

Fragestellung: Was sind die demographischen und klinischen Merkmale sowie zeitlichen Trends der Versorgung von Typ-2-Diabetespatienten (T2D) in Deutschland (2008-2016)? Methodik: In einer retrospektiven Analyse wurden demographische Merkmale, Diagnosen, Therapien, und Laborwerte von T2D-Patienten[zum vollständigen Text gelangen Sie über die oben angegebene URL], 16. Deutscher Kongress für Versorgungsforschung (DKVF)

BACKGROUND: Fluid retention is a common adverse event in patients who receive endothelin (ET) receptor antagonist therapy, including the highly selective ETA receptor antagonist, atrasentan.OBJECTIVE: We performed longitudinal assessments of thoracic bioimpedance in patients with type 2 diabetes mellitus and nephropathy to determine whether a decrease in bioimpedance accurately reflected fluid retention during treatment with atrasentan.STUDY DESIGN: We conducted a randomized, double-blind, placebo-controlled study in 48 patients with type 2 diabetes mellitus and nephropathy who were receiving stable doses of renin angiotensin system inhibitors and diuretics.METHODS: Patients were randomized 1:1:1 to placebo, atrasentan 0.5 mg, or atrasentan 1.25 mg once daily for 8 weeks. Thoracic bioimpedance, vital signs, clinical exams, and serologies were taken at weeks 1, 2, 4, 6, and 8, with the exception of serum hemoglobin, which was not taken at week 1, and serum brain natriuretic peptide, which was only taken at baseline, week 4, and week 8.RESULTS: Alterations in bioimpedance were more often present in those who received atrasentan than in those who received placebo, though overall differences were not statistically significant. Transient declines in thoracic bioimpedance during the first 2 weeks of atrasentan exposure occurred before or during peak increases in body weight and hemodilution (decreased serum hemoglobin).CONCLUSIONS: We conclude that thoracic bioimpedance did not reflect changes in weight gain or edema with atrasentan treatment in this study. However, the sample size was small, and it may be of interest to explore the use of thoracic bioimpedance in a larger population to understand its potential clinical use in monitoring fluid retention in patients with chronic kidney disease who receive ET receptor antagonists.

Among persons with type 2 diabetes (t2d), the development of glucose intolerance involves dysfunction in several organs and tissues, including the muscle, liver, pancreas, kidney, gastrointestinal tract, adipose tissue, and brain. individuals with t2d typically have a number of comorbidities, including hypertension, hyperlipidemia, and being overweight or obese, and are, consequently, at high cardiovascular risk. guidelines recommend a comprehensive care strategy that includes treatment of diabetes-related complications and comorbidities beyond those related to hyperglycemia. use of glucose-lowering therapies with complementary activities that address multiple facets of the disease may improve long-term outcomes for patients with t2d. two recent drug classes developed for use in t2d, glucagon-like peptide-1 receptor agonists (glp-1ras) and sodium glucose cotransporter 2 (sglt2) inhibitors, have been shown in clinical trials to have beneficial effects on glycemic control, body weight, cardiovascular risk factors, and (for liraglutide, semaglutide, and empagliflozin) cardiovascular outcomes, while having an acceptable safety profile. between them, these drug classes directly or indirectly affect many of the organs and tissues involved in the pathogenesis of t2d, and their beneficial effects on glycemic- and cardiovascular-related parameters are likely to be complementary and potentially additive. in the largest clinical trial of a glp-1ra and an sglt2 inhibitor in combination (duration-8), patients with t2d (n = 685) who received exenatide plus dapagliflozin added to their treatment regimen for 28 weeks had significantly greater reductions from baseline in glycated hemoglobin, body weight, and systolic blood pressure compared with patients who received either drug as monotherapy. this review summarizes the complementary aspects of these drug classes and presents the available data among patients receiving dual therapy with a glp-1ra and an sglt2 inhibitor.

Clinical use of single serum gonadotropin measurements in children is limited by the pulsatile secretion of follicle-stimulating hormone (FSH) and luteinizing hormone (LH). However, first morning voided (FMV) urine may integrate the fluctuating gonadotropin serum levels.We aimed to evaluate urinary and serum gonadotropin levels according to age, sex, and pubertal stage in healthy children and to assess the clinical use of FMV urinary gonadotropins in children with disordered puberty.Cross-sectional part of the COPENHAGEN Puberty Study and longitudinal study of patients.Population-based and outpatient clinic.Eight hundred forty-three healthy children from the COPENHAGEN Puberty Study and 25 girls evaluated for central precocious puberty (CPP).Clinical pubertal staging, including serum and urinary gonadotropin levels.Urinary gonadotropins increased with advancing age and pubertal development and were detectable in FMV urine before physical signs of puberty. FMV urinary LH correlated strongly with basal (r = 0.871, P0.001) and gonadotropin-releasing hormone (GnRH)-stimulated serum LH (r = 0.82, P0.001). Urinary LH was superior to urinary FSH in differentiating the pubertal stage. Receiver operating curve analysis revealed that a cut-off standard deviation (SD) score of 2 for urinary LH (IU/L) gave a sensitivity of 75% and a specificity of 92% in predicting a positive GnRH stimulation test (LHmax5 IU/L). Urinary concentrations of LH decreased after 3 months of GnRH treatment to levels below +2 SDs.Urinary gonadotropin levels increased before the onset of puberty and were elevated in girls with CPP. We suggest urinary LH as an alternative noninvasive method to improve diagnosing and therapeutic management of children with disordered puberty.

Background The effect of physician‐staffed helicopter emergency medical service ( HEMS ) on ST ‐elevation myocardial infarction ( STEMI ) patient transfer is unknown. The purpose of this study was to evaluate the characteristics and outcomes of physician‐staffed HEMS (Physician‐ HEMS ) versus non‐physician‐staffed (Standard‐ HEMS ) in patients with STEMI . Methods and Results We studied 398 STEMI patients transferred by either Physician‐ HEMS (n=327) or Standard‐ HEMS (n=71) for primary or rescue percutaneous coronary intervention at 2 hospitals between 2006 and 2014. Data were collected from electronic medical records and each institution's contribution to the National Cardiovascular Data Registry. Baseline characteristics were similar between groups. Median electrocardiogram‐to‐balloon time was longer for the Standard‐ HEMS group than for the Physician‐ HEMS group (118 vs 107 minutes; P =0.002). The Standard‐ HEMS group was more likely than the Physician‐ HEMS group to receive nitroglycerin (37% vs 15%; P P HEMS group (25.4% vs 11.3%; P =0.002). After adjusting for age, sex, Killip class, and transport time, patients transferred by Standard‐ HEMS had increased risk of any serious in‐hospital adverse event (odds ratio=2.91; 95% CI =1.39–6.06; P =0.004). In‐hospital mortality was not statistically different between the 2 groups (9.9% in the Standard‐ HEMS group vs 4.9% in the Physician‐ HEMS group; P =0.104). Conclusions Patients with STEMI transported by Standard‐ HEMS had longer transport times, higher rates of nitroglycerin and opioid administration, and higher rates of adjusted in‐hospital events. Efforts to better understand optimal transport strategies in STEMI patients are needed.

Objective To assess the real-world efficacy and safety of the first sodium-glucose cotransporter-2 inhibitor, canagliflozin, in the treatment of patients with type 2 diabetes mellitus (T2DM). Methods This observational study assessed the efficacy and tolerability of canagliflozin in T2DM patients. Primary study outcomes were changes in HbAlC and weight, and percentage of patients reporting adverse effects of therapy. Results The study criteria were met by 111 patient records. Baseline patient characteristics were: average age, 59 ± 9 years; mean duration of T2DM, 11.9 ± 7.3 years; 57.6% of patients were male; 92.8% were Caucasian; baseline BMI, 38.9 ± 11 kg/m2; and mean baseline HbAlC, 7.53 (58.8 mmol/mol) ± 1.08%. HbAlC and weight were significantly reduced by 0.37% and 4.4 kg, respectively. Adverse effects were reported by 21 patients, and 17 (15.3%) discontinued canagliflozin because of adverse reactions. Conclusion Canagliflozin was generally well tolerated and significantly reduced HbAlC levels and body weight in patients with T2DM when added to a regimen of other anti-hyperglycemic agents.

Fur die Versorgung von Schallleitungsschwerhorigkeiten stellen diverse Formen von Knochenleitungshorgeraten (perkutane und transkutane) eine erfolgreiche und erprobte Therapie dar. Will man aus medizinischen oder personlichen Grunden auf einen Eingriff verzichten, stehen Gerate mit Kopfbandern oder -bugeln und Knochenleitungsbrillen zur Verfugung. In der vorliegenden Studie wurde der zu erwartende audiologische Erfolg eines neuen Gerats (C.A.I. BC811, Fa. bruckhoff hannover, Hannover; C.A.I.: Concha Anchored Instrument) untersucht, das in der Concha fixiert wird und den Schall auf das Jochbein ubertragt. In der Cross-over-Studie wurden Patienten (n = 4) mit einer Schallleitungsschwerhorigkeit mit geringer sensorineuraler Komponente und vorhandener Versorgung mit einem Knochenleitungshorgerat versuchsweise mit einem BC811 versorgt. Die audiologischen Ergebnisse mit der optimierten bestehenden Versorgung und der Versorgung mit dem BC811 wurden in 2-Wochen-Intervallen untersucht und verglichen. Neben den versorgten und unversorgten Schwellen im Freifeld wurden das Freiburger Einsilberverstehen, das Horen im Storschall (OlSa) und die subjektive Bewertung des Versorgungserfolgs (APHAB-Fragebogen) untersucht. In den versorgten Freifeldschwellen, dem Functional Gain und dem Einsilberverstehen wurden keine signifikanten Unterschiede zwischen der bestehenden Versorgung und dem BC811 festgestellt. Die mittlere Verbesserung der Horschwelle betrug beim BC811 FF PTA4 29,4 ± 11,1 dB (Mittelwert ± Standardabweichung). Die Verbesserung im Einsilberverstehen war mit beiden Versorgungsvarianten signifikant und wies – ebenso wie das Verstehen im Storschall – keine signifikanten Differenzen untereinander auf. Die subjektive Bewertung beider Gerate mit dem APHAB war mit einer Verbesserung von 36,4 (Kontrollgerate) und 33,4 (BC811) Punkten im Global Score vergleichsweise positiv. Der Vergleich mit Knochenleitungshorgeraten zeigte, dass das BC811 bei Schallleitungsschwerhorigkeiten eine Alternative zu der herkommlichen Versorgung mit perkutanen Geraten darstellt.

A polymorphism in the FSHB promoter (-211G→T, rs10835638) was found to be associated with decreased FSH, elevated LH, reduced testosterone, and oligozoospermia in males. Although FSH is pivotal for ovarian function, no data on consequences of FSHB -211G→T are available in females.We studied the effects of FSHB -211G→T on the hypothalamic-pituitary-ovarian axis in women.In a university-based in vitro fertilization unit, women undergoing standardized diagnostics were genotyped and compared with a fertile control group.The study group consisted of 365 thoroughly characterized women with normal menstrual cycle intervals and proven ovulation, with predominantly male-factor infertility. The independently recruited control group included 438 women with proven fertility and no history of abortions.Distribution of alleles and genotypes were compared between the study group and controls. In the study group, associations of endocrine parameters with FSHB -211G→T were assessed.Allele and genotype frequencies were not significantly different between the study population and controls (T-allele: 14.4 vs. 16.6%; TT-homozygotes: 2.5 vs. 3.2%). The FSHB -211G→T TT-genotype was strongly associated with elevated FSH (TT-homozygosity effect 2.05 U/liter, P = 0.003). LH increased with the number of T-alleles (1.30 U/liter per T-allele, P0.001). Additionally, FSHB -211G→T was associated with reduced progesterone (-1.96 ng/ml per T-allele, P = 0.047).This is a report on phenotypic consequences of FSHB -211G→T on the hypothalamic-pituitary-ovarian axis in women. The findings, partially contradictory to those in men, point to a gender-specific compensatory mechanism of gonadotropin secretion, probably involving progesterone.

Puberty marks numerous physiological processes which are initiated by central activation of the hypothalamic–pituitary–gonadal axis, followed by development of secondary sexual characteristics. To a large extent, pubertal timing is heritable, but current knowledge of genetic polymorphisms only explains few months in the large inter-individual variation in the timing of puberty. We have analysed longitudinal genome-wide changes in DNA methylation in peripheral blood samples (n = 102) obtained from 51 healthy children before and after pubertal onset. We show that changes in single methylation sites are tightly associated with physiological pubertal transition and altered reproductive hormone levels. These methylation sites cluster in and around genes enriched for biological functions related to pubertal development. Importantly, we identified that methylation of the genomic region containing the promoter of TRIP6 was co-ordinately regulated as a function of pubertal development. In accordance, immunohistochemistry identified TRIP6 in adult, but not pre-pubertal, testicular Leydig cells and circulating TRIP6 levels doubled during puberty. Using elastic net prediction models, methylation patterns predicted pubertal development more accurately than chronological age. We demonstrate for the first time that pubertal attainment of secondary sexual characteristics is mirrored by changes in DNA methylation patterns in peripheral blood. Thus, modulations of the epigenome seem involved in regulation of the individual pubertal timing.

Puberty marks numerous physiological processes which are initiated by central activation of the hypothalamic–pituitary–gonadal axis, followed by development of secondary sexual characteristics. To a large extent, pubertal timing is heritable, but current knowledge of genetic polymorphisms only explains few months in the large inter-individual variation in the timing of puberty. We have analysed longitudinal genome-wide changes in DNA methylation in peripheral blood samples (n = 102) obtained from 51 healthy children before and after pubertal onset. We show that changes in single methylation sites are tightly associated with physiological pubertal transition and altered reproductive hormone levels. These methylation sites cluster in and around genes enriched for biological functions related to pubertal development. Importantly, we identified that methylation of the genomic region containing the promoter of TRIP6 was co-ordinately regulated as a function of pubertal development. In accordance, immunohistochemistry identified TRIP6 in adult, but not pre-pubertal, testicular Leydig cells and circulating TRIP6 levels doubled during puberty. Using elastic net prediction models, methylation patterns predicted pubertal development more accurately than chronological age. We demonstrate for the first time that pubertal attainment of secondary sexual characteristics is mirrored by changes in DNA methylation patterns in peripheral blood. Thus, modulations of the epigenome seem involved in regulation of the individual pubertal timing.

Single nucleotide polymorphisms altering FSH action (FSHB -211GT, FSHR -29GA, and FSHR 2039AG) are associated with peripubertal and adult levels of reproductive hormones and age at pubertal onset in girls.To investigate whether genetic polymorphisms altering FSH action affect serum levels of female reproductive hormones and breast development as early as during minipuberty.Longitudinal study.Population-based cohort study.A total of 402 healthy girls at 3 months of age.Analyses of single nucleotide polymorphisms by PCR using Kompetitive Allele Specific PCR genotyping assays; identification of glandular breast tissue by palpation and measurement of the diameter. Serum levels of anti-Müllerian hormone, FSH, LH, estradiol, inhibin B, and sex hormone-binding globulin were assessed by immunoassays.FSHR -29GA was associated with both FSH and anti-Müllerian hormone levels with an A allele effect size of -0.8 IU/L (P = .005) and 1.4 nmol/L (P = .003), respectively. FSHR 2039AG correlated with breast tissue size with a negative additive effect of minor alleles (P = .021), whereas the effect on estradiol levels was only present in homozygotes. FSHB -211T carriers had smaller breast tissue size than girls who without a minor allele; GT+TT 10.5 (confidence interval 9.4-11.5) mm vs GG 12.1 (confidence interval 11.4-12.8) mm, P = .014.Our study indicates that 3 genetic polymorphisms altering FSH action, especially FSHR -29GA and FSHR 2039AG, affect female hormone profile and glandular breast tissue development already during minipuberty. Thus, genetic variations of FSH signaling appear to determine the individual set point of the hypothalamic-pituitary-gonadal axis already early in life.

Background Glucocorticoid replacement is commonly required to treat secondary adrenal insufficiency after surgical resection of unilateral cortisol-secreting adrenocortical adenomas. Here, we describe a patient with unilateral cortisol-secreting adenomas in which the preoperative use of mifepristone therapy was associated with recovery of the hypothalamic–pituitary–adrenal (HPA) axis, eliminating the need for postoperative glucocorticoid replacement. Case Presentation A 66-year-old Caucasian man with type 2 diabetes mellitus, hyperlipidemia, hypertension, and obesity was hospitalized for Fournier's gangrene and methicillin-resistant Staphylococcus aureus sepsis. Abdominal computed tomography scan revealed three left adrenal adenomas measuring 1.4, 2.1, and 1.2 cm and an atrophic right adrenal gland. Twenty-four-hour urinary free cortisol level was elevated (237 µg/24 hours, reference range 0–50 µg/24 hours). Hormonal evaluation after resolution of the infection showed an abnormal 8 mg overnight dexamethasone suppression test (cortisol postdexamethasone 14.5 µg/dL), suppressed adrenocorticotropic hormone (ACTH; Conclusion Preoperative mifepristone therapy was associated with apparent recovery of the HPA axis prior to unilateral adrenalectomy in a patient with unilateral adrenal adenomas. Postoperatively, the patient experienced no signs or symptoms of adrenal insufficiency and no glucocorticoid replacement was required.

To determine the efficacy of at least 1 year of teriparatide therapy on bone mineral density (BMD), T-scores, and rates of occurrence of fractures in patients with a history of resolved secondary hyperparathyroidism due to vitamin D deficiency and to compare its efficacy with that in patients without a history of resolved secondary hyperparathyroidism.In this retrospective study based on a search of electronic medical records, we collected the following data: patient demographics, doses of calcium and vitamin D supplementation, duration of teriparatide treatment, history and treatment of secondary hyperparathyroidism, BMD information, T-scores, and any history of fractures. Paired and unpaired t tests, the Fisher exact test, and the Wilcoxon rank sum test were used for statistical analysis.Ninety-five patients (7 with a history of resolved secondary hyperparathyroidism due to vitamin D deficiency and 88 without such a history) fulfilled the study inclusion criteria. Baseline characteristics (demographics, median calcium and vitamin D supplementation doses, mean BMD, mean T-scores, and fracture rates before teriparatide therapy) were similar between the 2 groups. In comparison with baseline data, after a mean of 21 months of teriparatide therapy: (1) hip BMD and T-scores did not change in either study group (with no significant differences between the 2 groups), (2) spine BMD and T-scores significantly improved in both study groups (with no significant differences between them), and (3) wrist T-scores significantly worsened in both study groups (with wrist BMD significantly lower in patients without a history of secondary hyperparathyroidism). No patients with a history of secondary hyperparathyroidism sustained a fracture while receiving teriparatide therapy versus 6 of 88 patients without a history of secondary hyperparathyroidism (P = .624).Patients with a history of resolved secondary hyperparathyroidism attributable to vitamin D deficiency responded to teriparatide therapy in a fashion similar to patients without such a history.

Ainsworth, C. H., Samhouri, J. F., Busch, D. S., Cheung, W. W. L., Dunne, J., and Okey, T. A. 2011. Potential impacts of climate change on Northeast Pacific marine foodwebs and fisheries. – ICES Journal of Marine Science, 68: 1217–1229. Although there has been considerable research on the impacts of individual changes in water temperature, carbonate chemistry, and other variables on species, cumulative impacts of these effects have rarely been studied. Here, we simulate changes in (i) primary productivity, (ii) species range shifts, (iii) zooplankton community size structure, (iv) ocean acidification, and (v) ocean deoxygenation both individually and together using five Ecopath with Ecosim models of the northeast Pacific Ocean. We used a standardized method to represent climate effects that relied on time-series forcing functions: annual multipliers of species productivity. We focused on changes in fisheries landings, biomass, and ecosystem characteristics (diversity and trophic indices). Fisheries landings generally declined in response to cumulative effects and often to a greater degree than would have been predicted based on individual climate effects, indicating possible synergies. Total biomass of fished and unfished functional groups displayed a decline, though unfished groups were affected less negatively. Some functional groups (e.g. pelagic and demersal invertebrates) were predicted to respond favourably under cumulative effects in some regions. The challenge of predicting climate change impacts must be met if we are to adapt and manage rapidly changing marine ecosystems in the 21st century.

A dedicated media processor is used in many mobile consumer devices to accelerate video, image, graphics, and display processing. Increased demand for higher pixel resolution, higher quality image and video processing, more graphics performance necessitates dramatically increased signal processing capabilities. To provide the increased performance at acceptable cost and power requires redesign of the traditional architecture. By wisely partitioning algorithms across programmable and fixed-function blocks, the performance goals can be met while still maintaining flexibility for new feature requirements and new standards. For a better than acceptable user experience and playback time, all IPs (display, graphics, video, and imaging) have to be optimized as an ''end to end'' system. In this paper, an overview of the future trends of multimedia IP processor architectures is provided that describes the implications on system architecture, power, and performance.

Quick simple testing methods are needed to evaluate alternative wood materials for marine construction because traditional borer resistant materials are becoming scarce or are no longer permitted due to concerns over environmental emissions of preservatives. Laboratory tests can provide species-specific information on rates of wood biodeterioration by wood borers under optimum conditions, in contrast to field trials where more than one borer species may be present and conditions are variable. The methodology described herein relies on the assumption that faecal pellet production rate in limnoriids must match feeding rate quite closely. Thus, the number of faecal pellets produced by individual specimens of Limnoria quadripunctata, while feeding on a non-durable and non-toxic wood species – Pinus sylvestris sapwood – in different test conditions, was monitored over a period of 15 days. Mortality and moulting were also registered. Several variables likely to affect survival and feeding rates were investigated in order to optimise the test conditions. Temperature and salinity regime affected both survival and feeding rates while moulting cycle affected feeding rates. The optimisation of this test methodology aims to provide the basis for a standard laboratory test with the wood-boring crustacean Limnoria.

This study compared the accuracy and precision of five blood glucose (BG) meters.Diabetes patients undergoing venipuncture for glucose testing were randomized to one of two groups consisting of three meters: FreeStyle Flash (Abbott Diabetes Care, Alameda, CA), Accu-Chek Advantage (Roche Diagnostics Corp., Indianapolis, IN), and Accu-Chek Compact Plus (Roche Diagnostics) or FreeStyle Flash, Ascensia Contour (Bayer Healthcare, Diagnostic Division, Tarrytown, NY), and BD Logic (BD Diabetes Care, Franklin Lake, NJ). Within 5 min following venipuncture, duplicate finger BG measurements from three ipsilateral fingers were taken. Finger glucose measurements were compared with laboratory reference values. Accuracy was assessed by a Clarke error grid analysis (EGA) and within 10% of the laboratory value criteria. Meter precision was determined by calculating the absolute mean differences in glucose values between duplicate samples.Finger sticks were obtained from 202 patients. Mean venipuncture BG was 148 mg/dL (SD +/- mg/64 dL; range 25-439 mg/dL). Accuracy by Clarke EGA (Zone A results) was demonstrated in 69% of Advantage samples, 75% of Compact Plus, and 96% of the first group of Flash versus 88% of the Contour, 67% of the Logic, and 91% of the second Flash samples (P0.05 for both Flash and Contour). Meter accuracy using the 10% criteria was demonstrated in 30%, 38%, 70%, 46%, 48%, and 68% of the samples, respectively (P0.05 for both Flash groups compared to each of the other meters). There were no differences in meter precision.No statistically significant differences in accuracy were evident using the Clarke EGA criteria (pooled results of Zone A and B), though the more strict 20% accuracy criteria (Zone A results only) found the Flash and Contour to have significantly greater accuracy compared to the Advantage, Compact Plus, and the Logic. Using the 10% accuracy criteria found the Flash to have significantly greater accuracy than each of the other four meters. All five meters demonstrated similar precision.

To evaluate the 1-year efficacy and safety of treatment with exenatide in combination with insulin (a use not approved by the US Food and Drug Administration).Electronic medical records of 3 private-practice endocrinologists were reviewed to identify patients with type 2 diabetes mellitus (T2DM) receiving insulin who subsequently began exenatide therapy. Patients' baseline hemoglobin A1c (A1C) levels, weights, lipid profiles, blood pressures, and medication utilization were compared with corresponding data obtained after a minimal duration of 12 months.We identified 134 patients with T2DM initiating exenatide therapy in combination with insulin between April 2005 and April 2006. One-year follow-up information was available for 124 patients. Exenatide use resulted in a significant 0.87% reduction in A1C (P.001), despite a 45% discontinuation of premeal insulin use (P.001), a 9-U reduction in mean premeal insulin doses (P = .0066), a reduction in the median number of daily insulin injections from 2 to 1 (P = .0053), and a 59% discontinuation rate of sulfonylurea use (P = .0088). Exenatide use was associated with a mean weight loss of 5.2 kg (P.001), with 72% of evaluable patients losing weight. Forty-eight patients (36%) discontinued exenatide therapy during the first year, primarily attributable to gastrointestinal intolerance. Fourteen patients (10%) experienced hypoglycemia, most of which was mild.Exenatide in combination with insulin in patients with T2DM was associated with significant reductions in A1C and weight after 1 year of therapy. This was offset, however, by an exenatide discontinuation rate of 36%, primarily due to adverse gastrointestinal effects.

Summary Background In melanoma, several signalling pathways are constitutively activated. Among them, the RAS/RAF/MEK/ERK (MAPK) and PI3K/AKT (AKT) signalling pathways are activated through multiple mechanisms and appear to play a major role in melanoma development and progression. Objectives In this study, we examined whether targeting the MAPK and/or AKT signalling pathways would have therapeutic effects against melanoma. Methods Using a panel of pharmacological inhibitors (BAY 43-9006, PD98059, U0126, wortmannin, LY294002) we inhibited the MAPK and AKT signalling pathways at different levels and evaluated the effects on growth, survival and invasion of melanoma cells in monolayer and organotypic skin culture. Results Antiproliferative and proapoptotic effects of inhibitors alone in monolayer culture were disappointing and varied among the different cell lines. In contrast, combined targeting of the MAPK and AKT signalling pathways significantly inhibited growth and enhanced apoptosis in monolayer culture. To verify our data in a more physiological context we incorporated melanoma cells into regenerated human skin mimicking the microenvironment of human melanoma. Combinations of MAPK and AKT inhibitors completely suppressed invasive tumour growth of melanoma cells in regenerated human skin. Conclusions Combined targeting of MAPK and AKT signalling pathways is a promising strategy for melanoma treatment and should encourage further in-depth investigations.

Exenatide is an incretin mimetic agent that possesses multiple mechanisms of glucose lowering. It enhances glucose-dependent insulin secretion by the pancreatic β-cell, leading to insulin release in the presence of elevated glucose concentrations. It also moderates glucagon secretion and lowers serum glucagon concentrations during periods of hyperglycemia. Lower glucagon concentrations lead to decreased hepatic glucose output and decreased insulin demand. Exenatide also slows gastric emptying, thereby reducing the rate at which meal-derived glucose appears in the circulation, thereby further decreasing postprandial blood glucose levels. Finally, administration of exenatide has been shown to reduce subsequent food intake by increasing satiety, often resulting in weight loss.1 Exenatide is indicated as an adjunctive therapy to improve glycemic control in patients with type 2 diabetes who are taking metformin and/or a sulfonylurea but have not achieved adequate glycemic control.1 To decrease gastrointestinal intolerance, exenatide is initiated at 5 μg subcutaneously twice daily and increased after 1 month to a target maintenance dose of 10 μg twice daily. Three 30-week studies as add-on therapy to sulfonylurea, metformin, and sufonylurea/metformin have demonstrated hemoglobin A1c (A1C) reductions of ∼ 1% with an average weight loss of 1.4–1.8 kg.2–4 Therapy was generally well tolerated with the most frequent adverse events classified as mild or moderate and gastrointestinal in nature. Severe hypoglycemia was not observed during these studies.2–4 The concurrent use of exenatide with insulin, meglitinides, or α-glucosidase inhibitors has not been reported. Published information regarding the use of exenatide with thiazolidinediones (TZDs) is limited to two abstracts.5,6 The objective of this study was to determine the effectiveness and safety of off-label exenatide use in patients with type 2 diabetes. A retrospective review of the electronic medical records of one private-practice endocrinologist was conducted. The study was …