Adherence to antiretroviral treatment and correlation with risk of hospitalization among commercially insured HIV patients in the United States

Purpose

A lower daily pill burden may improve adherence to antiretroviral treatment (ART) and clinical outcomes in patients with human immunodeficiency virus (HIV). This study assessed differences in adherence using the number of pills taken per day, and evaluated how adherence correlated with hospitalization.

Methodology

Commercially insured patients in the LifeLink database with an HIV diagnosis (International Classification of Diseases, 9th Revision, Clinical Modification code 042.xx) between 6/1/2006 and 12/31/2008 and receipt of a complete ART regimen were selected for inclusion. Patients were grouped according to their daily pill count and remained on ART for at least 60 days. Outcomes included adherence and rates of hospitalization. Adherence was measured as the proportion of days between the start and end of the regimen in which the patient maintained supply of all initiated ART components. Logistic regressions assessed the relationship between pills per day, adherence, and hospitalization, controlling for demographics, comorbidities, and ART-naïve (vs. experienced) status.

Results

7,073 patients met the study inclusion criteria, and 33.4%, 5.8%, and 60.8% received an ART regimen comprising one, two, or three or more pills per day, respectively. Regression analysis showed patients receiving a single pill per day were significantly more likely to reach a 95% adherence threshold versus patients receiving three or more pills per day (odds ratio [OR] = 1.59; P<0.001). Regardless of the number of pills received per day, patients were over 40% less likely to have a hospitalization if they were adherent to therapy (OR = 0.57; P<0.001). Patients receiving a single pill per day were 24% less likely to have a hospitalization versus patients receiving three or more pills per day (OR = 0.76; P = 0.003).

Conclusions

ART consisting of a single pill per day was associated with significantly better adherence and lower risk of hospitalization in patients with HIV compared to patients receiving three or more pills per day.     

Treatment of Osteoporosis and Prevention of New Fractures: Role of Intravenously Administered Bisphosphonates

ObjectiveTo evaluate the usefulness of intravenously administered bisphosphonates for improving absorption, tolerability, adherence, and outcomes in the treatment and prevention of osteoporosis.MethodsData published from 1996 to 2009 relevant to the treatment of osteoporosis, with emphasis on bisphosphonates, fracture risk, adherence to therapy, frequency of dosing, intravenous treatment, tolerability, cost-effectiveness, and quality of life, were reviewed.ResultsAlthough bisphosphonates are currently the standard of care for treatment of postmenopausal osteoporosis and osteoporosis in men, oral formulations are associated with poor absorption and potential irritation of the upper gastrointestinal tract. These issues necessitate complicated and restrictive dosing regimens, which in turn lead to poor compliance and persistence. Intravenous formulations such as 3 mg of ibandronate given quarterly and 5 mg of zoledronic acid administered once yearly avoid problems relating to absorption and tolerability by bypassing the gastrointestinal tract. Intravenously administered ibandronate is presumed (by virtue of similar or superior improvements in bone mineral density) to have antifracture efficacy similar to that of orally administered ibandronate given daily, which has been shown to produce significant reductions in vertebral fractures during a 3-year period in comparison with placebo. Zoledronic acid, 5 mg once yearly, has been shown to produce a significant reduction in the risk of morphometric vertebral fractures, clinical vertebral fractures, hip fractures, and nonvertebral fractures versus placebo during a 3-year interval in patients with postmenopausal osteoporosis and also to yield a significantly decreased risk for new clinical fractures versus placebo in patients with recent low-trauma hip fracture. Both agents have favorable safety and tolerability profiles.ConclusionIntravenously administered bisphosphonates have the potential to increase compliance and persistence with therapy in patients with osteoporosis and to improve patient outcomes. (Endocr Pract. 2009;15:483-493)     

A 24-Week,Prospective, Randomized,Open-Label,Treat-To-Target Pilot Study of Obese Type 2 Diabetes Patients with Severe Insulin Resistance to Assess the Addition of Exenatide on the Efficacy of U-500 Regular Insulin Plus Metformin

ObjectiveTo compare the efficacy of 500 U/mL (U-500) regular insulin + metformin with U-500 regular insulin + metformin + exenatide in improving glycemic control in patients with severely insulin-resistant type 2 diabetes mellitus (T2DM).MethodsThirty patients with T2DM and severe insulin resistance were screened, and 28 were randomized to regular insulin U-500 + metformin or the GLP-1 analog exenatide, U-500, and metformin. Glycated hemoglobin (HbA_1c) levels, body weight, and insulin doses were documented at baseline and at 3 and 6 months. The number and severity hypoglycemic episodes were noted.ResultsThere were 7 males and 7 females in each group (U-500 + metformin and U-500 + metformin + exenatide). Overall, U-500 insulin + metformin, either alone or with the addition of exenatide, resulted in a significant improvement in HbA_1c in both groups, with no significant difference between the 2 groups. There was no meaningful weight change in those utilizing exenatide. Those on U-500 insulin and metformin alone had a tendency toward some weight gain. No severe hypoglycemia occurred during the study period. Symptomatic hypoglycemia was more common in the group on exenatide, but this occurred in only 5 patients, and the clinical significance of this is uncertain. Insulin dosage changes on U-500 regular insulin were variable but tended to be lower in those subjects on exenatide.ConclusionsU-500 regular insulin + metformin is effective for the treatment of T2DM patients with severe insulin resistance. The addition of exenatide may ameliorate potential weight gain but provides no additional improvement in glycemia. (Endocr Pract. 2014;20:1143-1150)     

Effectiveness and Long-Term Safety of Thiazolidinediones and Metformin in Renal Transplant Recipients

ObjectiveTo investigate the long-term safety and effectiveness of thiazolidinediones and metformin in renal transplant recipients with posttransplant diabetes mellitus (PTDM) or preexisting diabetes mellitus (DM).MethodsRetrospective chart review was performed for renal transplant recipients with PTDM or preexisting DM followed up during the years 2000-2006. Data collected included baseline characteristics; glomerular filtration rate (GFR); creatinine; hemoglobin A_1c; and development of congestive heart failure, edema, and liver function abnormalities. GFR was calculated using the Modification of Diet in Renal Disease study equation calculator.ResultsThirty-two patients comprised the metformin group (PTDM = 21, preexisting DM = 11), and 46 patients were included in the TZD group (PTDM = 33, preexisting DM = 13). Only 24 patients taking metformin and 31 patients taking TZDs were included for effectiveness analysis since the others required additional medications to control their DM. Mean follow-up was 16.4 months (range, 1-55 months) for patients treated with metformin and 37.1 months (range, 6-72 months) for patients treated with TZDs. GFR was decreased from baseline in all patients, but the only significant change was in patients with preexisting DM. While there was a significant change in creatinine levels in the metformin group, only 5 patients had to discontinue the drug because of this elevation (3 in preexisting DM group, 2 in PTDM group). Change in hemoglobin A_1c from baseline was not significant in either study group. Development of congestive heart failure or liver function abnormalities was not observed.ConclusionsMetformin appears to be safe in the renal transplant population for a mean duration of 16 months, although caution should be exercised using close monitoring in patients with preexisting DM. TZDs appear to be safe for a mean duration of 37 months after renal transplant. (Endocr Pract. 2008;14:979-984)     

Cost-Effectiveness of Empagliflozin and Metformin Combination Versus Standard Care as First-Line Therapy in Patients With Type 2 Diabetes Mellitus

ObjectiveSodium-glucose cotransporter 2 inhibitors have been shown to reduce cardiovascular events but are currently not used as the first-line therapy. This study was conducted to evaluate the cost-effectiveness of first-line empagliflozin plus metformin versus metformin monotherapy among Australians with type 2 diabetes mellitus (T2DM) and existing cardiovascular disease (CVD).MethodsA Markov model with 1-year cycles and a 5-year time horizon was constructed to simulate the occurrence of recurrent cardiovascular events among Australians aged 50 to 84 years with T2DM and CVD. Efficacy results were derived from the Empagliflozin Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients-Removing Excess Glucose trial. Costs and utilities were drawn from published sources. The evaluation adopted both health care and societal perspectives, with the latter ascribing the Australian government’s “value of statistical life year” (A$213 000) to each year lived by a person. Future outcomes were discounted at 5% annually. Sensitivity analyses were conducted to enhance the robustness of conclusions.ResultsCompared with metformin monotherapy, first-line empagliflozin plus metformin reduced overall cardiovascular events by 0.82% and overall deaths by 7.72% over 5 years. There were 0.2 years of life saved per person and 0.16 quality-adjusted life years gained, at a net health care cost of A$4408. These equated to incremental cost-effectiveness ratios of A$22 076 per year of life saved and A$28 244 per quality-adjusted life year gained. The gains in the value of statistical life year equated to A$42 530 per person, meaning that from a societal perspective, the intervention was cost-saving.ConclusionFirst-line empagliflozin plus metformin may represent a cost-effective strategy for the management of T2DM and CVD in Australia.     

Dose-Dependent Relationship Between Metformin and Colorectal Cancer Occurrence Among Patients with Type 2 Diabetes—A Nationwide Cohort Study

BACKGROUND: Increasing bodies of evidence suggest that metformin may be beneficial in the primary prevention of colorectal cancer (CRC), and a dose–response relationship has been reported. However, long-term epidemiological observations between the treatment period, cumulative dose, and intensity of metformin and CRC are rarely reported. The aim of this study was to identify the association between the effect of metformin and CRC development in a nationwide cohort study. METHODS: This nationwide population-based study examined a cohort of 1,000,000 patients randomly sampled from individuals enrolled in the Taiwan National Health Insurance system. Patients with newly diagnosed type 2 diabetes mellitus (DM) between 1997 and 2007 were enrolled. A statistical variables, including the demographic data, treatment period, cumulative dose, and intensity of metformin use, was compared between patients developing CRC and those without CRC. RESULTS: This study included 47,597 patients. The mean follow-time was 7.17 ± 3.21 years. After adjustment, metformin use was an independent protective factor against CRC development (P < .001). Although the protective ability of metformin against CRC development was reduced during long-term therapy, the risk of CRC decreased progressively with a higher cumulative dose or higher intensity of metformin use (both P < .001). CONCLUSION: This study revealed that metformin use significantly reduced the risk of CRC in a dose-dependent manner in patients with type 2 DM in the Taiwanese population. However, a gradual decline in medication adherence may reduce the protective ability of metformin against CRC development during long-term therapy.     

Association between Gastroenterological Malignancy and Diabetes Mellitus and Anti-Diabetic Therapy: A Nationwide,Population-Based Cohort Study

BackgroundThe relationship between diabetes mellitus (DM) and cancer incidence has been evaluated in limited kinds of cancer. The effect of anti-diabetic therapy (ADT) on carcinogenesis among diabetic patients is also unclear.ResultsIncidence of cancer at any site was significantly higher in patients with DM than in those without (p<0.001). The risk of carcinogenesis imparted by DM was greatest in gastroenterological malignancies (liver, pancreas, and colorectal cancer) as well as lung, breast and oral cancer (p<0.001). Among the oral types of ADT, metformin decreased the risk of lung and liver cancer, but had less effect on reducing the risk of colorectal cancer. α-glucosidase inhibitor decreased the risk of developing liver, colorectal, and breast cancer. Apart from intermediate-acting insulin, rapid-acting, long-acting, and combination insulin treatment significantly reduced the overall cancer risk among all DM patients. In subgroup analysis, long-acting insulin treatment significantly decreased the risk of lung, liver, and colorectal cancer.ConclusionOur results supported the notion that pre-existing DM increases the incidence of gastroenterological cancer. ADT, especially metformin, α-glucosidase inhibitor, and long-acting insulin treatment, may protect patients with DM against these malignancies. It is crucial that oncologists should closely collaborate with endocrinologists to provide an optimal cancer-specific therapy and diabetic treatment to patients simultaneously with cancer and DM.     

Metformin increases cancer specific survival in colorectal cancer patients—National cohort study

PurposeWe aimed to assess oncological outcomes in colorectal cancer patients with type 2 diabetes mellitus (T2DM) using metformin.MethodsPatients with colorectal cancer and T2DM during 2000–2012 period were identified form Lithuanian Cancer Registry and the National Health Insurance Fund database. Colorectal cancer-specific survival (CS) was the primary outcome. It was measured from date of colorectal cancer diagnosis to date of death due to colorectal cancer, or last known date alive.Results15,052 people who met eligibility criteria for this analysis, including 1094 (7.27%) with pre-existing type 2 diabetes (271 metformin never users and 823 metformin users) and 13 958 people without diabetes assessed. During follow-up (mean follow-up time was 4.4 years, with range from 1 day to 17 years) there were 10,927 deaths including 8559 from colorectal cancer. Significantly lower risk in CS between diabetic and non-diabetic people with lower risk of cancer-specific mortality (HR 0.87, 95% CI 0.80–0.94) in diabetic patient population was seen. After adjustment for age, stage at diagnosis and metformin usage, significant difference in colorectal CS between metformin users in diabetic patient population compared to non-diabetics and metformin non-users in diabetic patient population was found (0.80 (0.72–0.89) vs 1.00 and vs 1.05 (0.91–1.23)). Overall survival (OS) was better for diabetic patients with significant difference in diabetic metformin users (HR 0.91, 95% CI 0.79–0.94).ConclusionsColorectal cancer patients with T2DM treated with metformin as part of their diabetic therapy appear to have a superior OS and CS. However, prospective controlled studies are still needed to evaluate the efficacy of metformin as an anti-tumor agent.     

Colesevelam Hydrochloride Added to Background Metformin Therapy in Patients with Type 2 Diabetes Mellitus: A Pooled Analysis from 3 Clinical Studies

ObjectiveTo evaluate the glucose- and lipid-altering efficacy of colesevelam hydrochloride (HCl) when added to background metformin therapy in patients with inadequately controlled type 2 diabetes mellitus (T2DM).MethodsThis post hoc analysis included patients with T2DM from 3 randomized, double-blind, placebo- controlled pivotal studies who received metformin as part of their background antidiabetes therapy. In the pivotal studies, patients with T2DM were randomly assigned to receive colesevelam HCl (3.75 g/d) or placebo added to existing metformin (26 weeks), sulfonylurea (26 weeks), or insulin (16 weeks) monotherapy or combination therapy, wherein the combination therapies may have included metformin.ResultsIn this pooled analysis of 696 patients with T2DM who were receiving metformin monotherapy or metformin combined with other antidiabetes therapies, 355 were randomly assigned to receive colesevelam HCl and 341 to receive placebo. In comparison with placebo, colesevelam HCl significantly reduced hemoglobin A_1c (A1C) and fasting plasma glucose (mean treatment difference: -0.50% and -15.7 mg/dL, respectively; P < .001 for both), as well as significantly reduced levels of low-density lipoprotein cholesterol (LDL-C; mean treatment difference: -16.5%), total cholesterol (TC; -5.8%), non-high-density lipoprotein cholesterol (non-HDL-C; -8.2%), and apolipoprotein (apo) B (-7.6%) (P < .0001 for all). Median triglyceride levels were increased with colesevelam HCl (median treatment difference: + 12.8%; P < .0001). In comparison with placebo, colesevelam HCl significantly increased apo A-I (mean treatment difference: + 3.3%; P < .0001), whereas the mean increase in HDL-C with colesevelam HCl was not significant. Colesevelam HCl therapy was generally well tolerated.ConclusionWhen added to metformin-including therapy, colesevelam HCl significantly reduced A1C and fasting glucose, as well as levels of LDL-C, TC, non- HDL-C, and apo B in patients with inadequately controlled T2DM. (Endocr Pract. 2011;17:933-938)     

The Use of Pill Counts as a Facilitator of Adherence with Antiretroviral Therapy in Resource Limited Settings

Background

Pill counts are often used to measure adherence to ART, but there is little data on how they affect adherence. We previously showed a bivariate relationship between clinicians counting pills and adherence in patients receiving HIV care in Kenya. We present a secondary analysis of the relationship between numbers of pill counts and clinical outcomes in resource limited settings

Methods

Patients initiating ART at Kijabe Hospital were monitored for the number of discretionary pill counts performed by their clinician in the first 6 months of ART. Subjects were followed for at least 1 year after enrollment. The number of clinician pill counts was correlated to ART adherence. The primary endpoints were time to treatment failure, defined as a detectable HIV-1 viral load, death; or loss to follow-up.

Results

Clinician pill counts were done at 68% of clinic visits for 304 subjects. There was a positive correlation between the number of clinician pill counts and ART adherence (r = 0.21, p <0.001). Patients were divided into 3 groups (0 counts, 1 to 3 counts, 4 to 7 counts) and exhibited adherence of 76%, 84%, and 92%, respectively (p = 0.004). Time to treatment failure for these groups was 220 days, 438 days, and 497 days (P<0.01), respectively. Time to virologic failure in living patients remaining in the cohort was longer in those with more pill count (P =0.02). Multi-variate analysis adjusting for co-variates affecting time to treatment failure found that that clinician pill counts were associated with a decreased risk of treatment failure (HR = 0.69, p =0.04).

Conclusions

The number of clinician pill count performed was independently associated with better adherence and a decreased risk of treatment failure. The use of clinician pill counts should be further studied as an adherence promoter through a randomized clinical trial.     

The Hirsute Woman: Challenges in Evaluation and Management

ObjectiveTo review the etiology, pathogenesis, diagnostic approach, and management of hirsutism.MethodsWe discuss the clinical course of hirsutism and provide our recommendations on the various treatment options available.ResultsHirsutism is a common clinical problem characterized by the presence of increased terminal hair growth in androgen-dependent areas of the skin. The development of hirsutism depends on the presence of the pilosebaceous unit, which is genetically determined, as well as the presence of the androgen receptor and intracellular 5α-reductase activity, which converts testosterone to its more active metabolite, dihydrotestosterone. A detailed history and physical examination and the following laboratory tests can diagnose most causes of hirsutism: early-morning follicular phase measurement of total testosterone, testosterone not bound to sex hormone-binding globulin, dehydroepiandrosterone sulfate, 17-hydroxypro- gesterone, prolactin, and thyrotropin levels. Oral contraceptive preparations may be effective monotherapy formild hirsutism. For the treatment of more severe hirsutism, oral contraceptive pills combined with spironolactone are as effective as oral contraceptive pills containing cyproter- one acetate, which are not available in the United States. Because of teratogenicity, spironolactone should be used with caution in premenopausal women when it is administered without an oral contraceptive pill. Metformin is an alternative therapy for hirsutism in women with polycystic ovary syndrome who have other indications for metformin use. Metformin is not as effective as antiandrogens for the management of hirsutism. The use of glucocorticoids, finasteride, or flutamide is not recommended.ConclusionsHirsutism can be evaluated with a detailed history and physical examination and a limited number of hormonal tests. Serious disorders presenting as hirsutism are rare and can be excluded with the recommended evaluation. Treatment is targeted at reducing the production and bioavailability of testosterone, as well as blocking target tissue androgen action. (Endocr Pract. 2011;17:807-818)     

六味地黄丸联合二甲双胍对2型糖尿病患者血清载脂蛋白的影响及疗效研究

目的:探讨六味地黄丸联合二甲双胍片对2型糖尿病患者血清载脂蛋白的影响及临床疗效。方法:选择106例2型糖尿病患者并依照随机数表法分作对照组与观察组,各53例。对照组行二甲双胍治疗,观察组基于对照组加用六味地黄丸治疗,比较两组治疗前后载脂蛋白A、B(ApoA、ApoB)、ApoA/ApoB、空腹血糖(FPG)、餐后2 h血糖(2h PG)、空腹胰岛素(FINS)、胰岛素抵抗指数(HOMA-IR)、白细胞介素-6(IL-6)、超敏C反应蛋白(hs-CRP)、内皮素-1(ET-1)、一氧化氮(NO)水平的变化,临床疗效和不良反应的发生情况。结果:治疗后,两组ApoA、ApoA/ApoB、NO均较治疗前上升,但观察组ApoA、ApoA/ApoB、NO高于对照组,差异有统计学学意义(P0.05)。两组FPG、2PG、FINS、HOMA-IR、IL-6、hs-CRP、ET-1均较治疗前降低,但观察组FPG、2PG、FINS、HOMA-IR、IL-6、hs-CRP、ET-1低于对照组(P0.05)。观察组总有效率高于对照组(P0.05),两组不良反应的发生率比较差异无统计学学意义(P0.05)。结论:六味地黄丸联合二甲双胍的疗效治疗2型糖尿病患者的疗效较好,且可有效控制血糖、改善内皮功能并调节血清载脂蛋白水平。     

The Humanistic Burden of Type 1 Diabetes Mellitus in Europe: Examining Health Outcomes and the Role of Complications

AimsDiagnoses of Type 1 Diabetes Mellitus (T1DM) in Europe appear to be on the rise. Therefore it is imperative that researchers understand the potential impact that increases in prevalence could have on the affected individuals as well as on society as a whole. Accordingly this study examined the humanistic and economic burden of T1DM in patients relative to those without the condition across a number of health outcomes including health status, work productivity loss, activity impairment, and healthcare resource use.MethodsSurvey data from a large, representative sample of EU adults (The EU National Health and Wellness Survey) were examined.ResultsResults suggest that overall burden is higher for those diagnosed with T1DM than respondents without diabetes and that burden increases as complications associated with T1DM increase.ConclusionsTaken together, these results suggest that treatment strategies for T1DM should balance clinical, humanistic, and economic burden and patients should be educated on the role of complications in disease outcomes.     

体型肥胖2型糖尿病患者血清胆红素、胆汁酸、25(OH)D3水平及与胰岛素抵抗的关系研究

摘要 目的：探讨体型肥胖2型糖尿病（T2DM）患者血清胆红素、胆汁酸（BA）、25羟维生素D3[25(OH)D₃]水平及其与胰岛素抵抗（IR）的关系。方法：选取2018年1月-2019年12月我院就诊的240例T2DM患者,根据体重指数（BMI）将患者分为T2DM-N组84例,T2DM-OW组92例,T2DM-OB组64例。分别测定总胆红素（TBIL）、间接胆红素（IBIL）、直接胆红素（DBIL）、胆汁酸（BA）、25(OH)D₃等指标。以胰岛素抵抗指数（HOMA-IR）为因变量,行多元线性回归,分析IR的危险因素。结果：T2DM-OB组BMI、BA、甘油三酯（TG）、空腹血糖（FPG）、餐后2小时血糖（2hPG）、糖化血红蛋白（HbA1c）、空腹胰岛素（FINS）、胰岛素抵抗指数（HOMA-IR）、C反应蛋白（CRP）高于T2DM-N组,DBIL、25(OH)D₃低于T2DM-N组,差异均有统计学意义（P<0.05）。Pearson相关性分析显示,HOMA-IR与BMI、BA呈正相关（P<0.05),与DBIL、25(OH)D₃呈负相关（P<0.05);多元线性回归分析显示BMI升高,25(OH)D₃、DBIL下降为IR的危险因素（P<0.05）。结论：肥胖的T2DM患者存在IR及血脂紊乱,心血管疾病患病风险增加,BA水平升高,DBIL、25(OH)D₃水平下降,机体慢性低度炎症水平升高,除了BMI,25(OH)D₃、DBIL水平下降亦有可能是体型肥胖T2DM患者IR的重要危险因素。     

The influence of antidiabetic medications on the development and progression of prostate cancer

BackgroundThe development of prostate tumors has been linked to co-morbid diabetes mellitus (DM) in several studies, potentially through the stimulation of insulin-like growth factor receptor (IGFR). This study evaluates the effect of anti-diabetic medication use on the development of high grade tumors and time to tumor progression compared to non-diabetics.MethodsThis retrospective, nested case control study identified patients with prostate cancer (PCa) from the Kentucky Medicaid Database. Cases were diagnosed with PCa and DM and using at least one of the following antidiabetic medications; sulfonylureas, insulin, metformin or TZDs. Cases were further stratified on their insulin exposure resulting from therapy. Controls were those with PCa without DM or any anti-diabetic medications.ResultsThe use of metformin or TZDs trended toward decreased odds of high-grade tumors and decreased risk of progression, while sulfonylureas and high-dose insulin tended toward an increased odds of high-grade tumors and increase the risk of progression compared to non-diabetics.ConclusionsFuture studies should be conducted to further evaluate the effects of anti-diabetic medications on tumor grade and time to prostate cancer progression.     

Periodontal Disease in Type 1 Diabetes Mellitus: Influence of Pubertal Stage and Glycemic Control

ObjectiveThough gingivitis is common in children with type 1 diabetes mellitus (T1DM), the overall periodontal health in T1DM during the pubertal stage is less well-characterized. The study was undertaken to explore the possible influence of puberty and metabolic derangement on periodontal health in T1DM.MethodsIn this cross-sectional study, 110 subjects between 10-18 years with T1DM and 52 healthy siblings of similar age were evaluated for pubertal stage, glycosylated hemoglobin (HbA1c), and periodontal health. Simplified oral hygiene index (OHIS), gingival index (GI), plaque index (PI), bleeding on probing (BOP), and probing depth (PPD) were evaluated at 4 sites per tooth as per 6 Ramfjord index teeth used to assess periodontal disease (PD).ResultsPD not merely gingivitis was significantly higher in T1DM (84/110, 76.36%) than the control group (28/52, 53.8%) (P = .004). Irrespective of pubertal status, children with T1DM had worse GI, PI, BOP, and PPD than nondiabetic subjects, although OHIS was better in diabetes. In both T1DM and nondiabetic subjects, pubertal subjects showed significantly worse OHIS, PPD, BOP, and GI than prepubertal subjects. PD was correlated with pubertal stage, age, and HbA1c, although less strongly with the duration of diabetes. In logistic regression, pubertal stage was a stronger predictor of PD (OR = 14.26) than age (OR = 2.22), and HbA1c (OR = 1.5) rather than the presence of diabetes and its duration.ConclusionsThough pubertal status, age, and poor glycemic control rather than the presence of diabetes and its duration are associated with gingivitis and other forms of PD, puberty had a more profound effect in the pathogenesis of PD in T1DM.     

Caracterización y costes asociados al perfil del paciente con diabetes tipo 2 en tratamiento con metformina al que se le añade un segundo fármaco antidiabético oral: estudio de base poblacional

ObjectivesTo determine compliance, metabolic control, complications and healthcare costs of patients treated with metformin started a second antidiabetic drug in patients with type 2 diabetes (T2DM).Patients and methodsDesign multicenter observational retrospective. Patients were evaluated ≥30 years (age), treated with metformin and started a second antidiabetic treatment during 2008-2009. There were 4 patient groups (metformin and another antidiabetic): a) dipeptidyl peptidase-4 inhibitors (IDPP4), b) sulfonylureas, c) glitazones and d) insulin. Main measures: comorbidity, metabolic control, compliance and complications. Patients were followed for 2 years. The cost model differed direct health costs (primary care / specialist) and indirect (labor productivity). Statistical analysis: logistic regression models and ANCOVA, p < 0.05.Results2067 patients were included (mean age: 66.6 years male: 53.1%). 25.1% started a second treatment with IDPP4; 42.9% sulfonylureas, 14.0% glitazones and 18.0% insulin. At 2 years follow-up, patients treated with IDPP4 showed greater adherence vs. 70.3%. 59.9%, 60.3% and 58.4; better control of 64.3% vs. DM2. 62.6%, 62.8% and 50.5% and a decrease of 13.9% compared to hypoglycaemia 40.4%, 37.6% and 58.9% respectively (p < 0.001). The average / unit total costs was €2,321 vs. €2,475, €2,724 and €3,164, respectively, p < 0.001. Rates of cardiovascular events and renal failure were 3.7%, 6.4%, 7.6% and 10.2% respectively.ConclusionsSulfonylureas were the most commonly used drugs. Patients treated with IDPP4 had higher compliance and control of diabetes, with lower rates of hypoglycaemia and healthcare costs.     

Riboflavin as an independent and accurate biomarker for adherence in a randomized double-blind and placebo-controlled clinical trial

Background: Medication adherence is critical for success of clinical trials.

Objective: To assess oral riboflavin is an adherence marker.

Methods: Riboflavin was incorporated into active treatment and placebo pills for a clinical trial lasting for 2 years.

Results: The accuracy (area under the receiver operating curve) of urinary riboflavin was 0.91 as a binary classifier of adherence, and was similar or better than for two active study ingredients daidzein (0.92) and genistein (0.87) (all p?<?0.0001). Decreased adherence over time was similar in the two study groups.

Conclusion: Riboflavin is an accurate and useful biomarker for study pill ingestion.