Yoona Kim

Efficacy and Safety of Dipeptidyl Peptidase-4 Inhibitors in Type 2 Diabetes: Meta-Analysis

BACKGROUND: An up-to-date assessment of dipeptidyl peptidase-4 (DPP-4) inhibitors is needed to include newly available data. OBJECTIVE: To assess the efficacy and safety of DPP-4 inhibitors, including sitagliptin, saxagliptin, vildagliptin, and linagliptin, in type 2 diabetes. METHODS: We conducted a search of MEDLINE for randomized controlled trials (RCTs) of DPP-4 inhibitors in type 2 diabetes through November 2011, using the key terms sitagliptin, saxagliptin, vildagliptin, and linagliptin. We also searched for completed, but unpublished, trials at relevant web sites. RCTs were selected for meta-analysis if they (1) compared DPP-4 inhibitors with placebo or an antihyperglycemic agent; (2) had study duration of 12 or more weeks; (3) had 1 or more baseline and posttreatment efficacy and/or safety outcome; and (4) were published in English. RESULTS: In 62 evaluated articles, DPP-4 inhibitors lowered hemoglobin A1c (A1C) significantly more than placebo (weighted mean difference [WMD] −0.76%; 95% CI −0.83 to −0.68); however, heterogeneity was substantial (I2 = 82%). Exclusion of Japanese trials (n = 7) resulted in a reduction of heterogeneity (I2 = 59%). In the non-Japanese RCTs (n = 55), DPP-4 inhibitors were associated with a reduction in A1C (WMD −0.65%; 95% CI −0.71 to −0.60) but higher risk of hypoglycemia (odds ratio [OR] 1.30; 95% CI 1.00 to 1.68) compared to placebo. The 7 Japanese-specific RCTs showed a greater reduction in A1C (WMD −1.67%; 95% CI −1.89 to −1.44) and a nonsignificant increase in risk of hypoglycemia (OR 1.41; 95% CI 0.51 to 3.88) with DPP-4 inhibitors versus placebo. When comparing DPP-4 inhibitors to active comparators, the I2 was still high after deleting Japanese studies. In these 17 active comparator trials, there was no significant difference in A1C reduction (WMD 0.04%; 95% CI −0.09 to 0.16) or risk of hypoglycemia (OR 0.60; 95% CI 0.22 to 1.61) for DPP-4 inhibitors compared to other antihyperglycemics. There were similar odds of any or serious adverse events with DPP-4 inhibitors compared to placebo, but a decreased risk compared to other antihyperglycemics. CONCLUSIONS: DPP-4 inhibitors were associated with a reduction in A1C with comparable safety profiles compared to placebo, but no significant difference in A1C compared to other hyperglycemics. Differences in efficacy and safety were observed between Japanese and non-Japanese patients.

Reduction of chronic hepatitis B-related hepatocellular carcinoma with anti-viral therapy, including low risk patients

Anti‐viral therapy in chronic hepatitis B (CHB) is associated with a reduced risk of hepatocellular carcinoma (HCC) primary described in patients with cirrhosis.

Retrospective Evaluation of the Impact of Copayment Increases for Specialty Medications on Adherence and Persistence in an Integrated Health Maintenance Organization System

BACKGROUND Specialty drugs are generally defined as high-cost injectable, infused, oral, or inhaled drugs that require close monitoring. Specialty drugs account for an increasing percentage of total drug expenditures, and management of specialty drugs has become a priority. A Central Texas-based integrated health maintenance organization system implemented a specialty drug benefit to manage expensive specialty drug costs. OBJECTIVES Our objective was to measure and compare the change in adherence and persistence after implementation of copayment increases for select specialty medications used on a long-term basis (at least 2 years). METHODS Patients who were long-term users of anti-inflammatory, immunosuppressant, cancer, and multiple sclerosis medications were selected. The intervention group consisted of those whose out-of-pocket payment for specialty medications increased, and the control group consisted of those whose out-of-pocket costs did not change. Adherence, defined by proportion of days covered, was measured every 3 months for 12 months before and after the change. Individual growth model analysis evaluated the changes in adherence. Cox regression analysis determined the difference in persistence between groups. RESULTS There were 178 and 202 patients in the intervention and control groups, respectively. The growth model showed a small but statistically significant decrease in proportion of days covered of 0.040 after copay changes in the intervention versus control group (P < 0.001) for immunosuppressants. The Cox regression analysis indicated a higher probability of intervention patients on anti-inflammatory drugs (hazard ratio [HR] = 2.53; 95% CI, 1.38-4.62) and immunosuppressants (HR = 3.01; 95% CI, 1.20-7.56) would be nonpersistent compared with those in their control groups. CONCLUSIONS The move to the specialty formulary allows for closer scrutiny of specialty utilization by pharmacists, who actively monitor utilization and access. Despite the minimal adherence decrease and significant persistence changes with certain drug types, the results indicated relatively more stability with specialty drug use than reported with traditional pharmaceuticals.

Medication adherence and activity patterns underlying uncontrolled hypertension: Assessment and recommendations by practicing pharmacists using digital health care

OBJECTIVES This report summarizes the first use of a digital health feedback system (DHFS) by practicing pharmacists to establish evidence-based blood pressure (BP) management recommendations. SETTING Fifteen commercial pharmacies and 39 patients in the Isle of Wight participated. PRACTICE DESCRIPTION The pharmacists were experienced in providing New Medicine Services to patients in their communities. PRACTICE INNOVATION The pharmacists utilized a commercially available DHFS. The DHFS utilized FDA-cleared and CE-marked class 2 medical devices passively captured and shared information about medication-taking using an ingestible sensor, and daily patterns of rest, activity, and exercise using a wearable patch that incorporates an accelerometer. INTERVENTIONS Pharmacists provided targeted counselling for BP management as guided by the digital information. EVALUATION Blood pressure was measured serially, and patient and provider experiences with DHFS use were assessed using satisfaction surveys. RESULTS The mean change in SBP over the 2-week evaluation period was -7.9 ± 22.1; mean change in DBP was -2.8 ± 12.9. A root cause for persistent hypertension was determined for all of these 34 patients: 68% had pharmaceutical resistance, and 32% had inadequate medication use. Specifically, 29% were found to be capable to achieving blood pressure control on their currently prescribed medications, 68% were found to have a need for additional pharmacological treatment, and 3% needed additional adherence support. Pharmacists found that the DHFD helped in targeting specific recommendations, and to create a collaborative experience with their patients. Patients found the experience to be positive and helpful. CONCLUSION DHFS that provides confirmation of medication taking and objective measures of lifestyle patterns can help pharmacists to identify specific factors contributing to uncontrolled hypertension, to make evidence-based prescribing and lifestyle recommendations for achieving treatment goals, and to create a collaborative experience for patients in the management of their self-care.

Patient-Centered Home Care Using Digital Medicine and Telemetric Data for Hypertension: Feasibility and Acceptability of Objective Ambulatory Assessment.

Objective information that can be passively obtained in an ambulatory setting could be potentially useful for determining appropriate care in blood pressure (BP) management. This study utilized digital medicine (DM) prototypes and telemetric data acquisition to directly confirm medication use and to assess habits of daily living in a hypertensive population. Thirty‐seven patients (23 men age 62±9 years) used the system for 6 weeks. DM prototypes consisted of valsartan 80 mg or 160 mg placed in a gelatin hemicapsule with an excipient tablet as a “stopper,” with a poppy seed–sized ingestible sensor (IS) made of foodstuff on its external surface and capable of creating a biogalvanic current on ingestion to alert a wearable sensor (WS) that was worn on the torso. Passive data collection included IS ingestion dates and times, daily step count, BP, and weight. Automatic short message service (SMS) reminders were sent whenever BP or weight values were not received. Passive detection of DM ingestion was 98% when compared with directly observed dosing. Mean taking and timing adherence rates were 90% and 83%, respectively, and the average step count at a pace of ≥60 steps per minute was 2.0±1.5 h/d. An automatic SMS was sent and 100% confirmed for 251 BP and 14 weight values that were not received. Mild and transient WS‐related skin irritation was the most common device‐related adverse event. There were no serious or unanticipated adverse events. Ninety percent of patients did not mind swallowing a DM capsule, and 75% had a positive overall experience with the system. Ambulatory evaluation of medication adherence and habits of daily living appear to be feasible and acceptable using DM and passive acquisition of telemetric data.

Analysis of Glycemic Control of a Pharmacist-Led Medication Management Program in Patients with Type 2 Diabetes.

BACKGROUND An integrated health care system with its own regional health plan located in Texas implemented a pharmacist-led diabetes medication management program (MMP) to treat type 2 diabetic patients (baseline A1c > 7.5%). The MMP formed collaborative practice agreements with the systems physicians to allow ambulatory care pharmacists to modify and adjust diabetic drug regimens when appropriate. Enrolled MMP patients received personalized visits with ambulatory care pharmacists and a copay waiver on diabetes medications. OBJECTIVE To study the outcomes of an outpatient, pharmacist-led MMP, along with a copay waiver on diabetes drugs, in treating adults with type 2 diabetes mellitus over a 2-year period compared with standard care practice. METHODS This retrospective study employed a quasi-experimental design and used medical claims, pharmacy claims, eligibility data, and electronic medical records. Patients aged 18 to 62 years, who were diagnosed with type 2 diabetes mellitus, and had at least 1 diabetes-related pharmacy claim in the year before the MMP, as well as continuous enrollment in the health plan, were included. Patients enrolled in the pharmacist-led MMP for at least 2 years (n =75) were matched to standard care patients (n =75) on age, gender, baseline A1c, insulin use, and physical comorbidity. The primary outcome was the 2-year change in A1c. Secondary outcomes included inpatient costs, outpatient costs, and pharmacy costs from the baseline period (year before enrollment) compared with the follow-up period (second year of enrollment). RESULTS After matching MMP patients (n = 75) to control patients (n = 75), the baseline A1c (9.30 and 9.26), the mean age (53.0 and 53.3, respectively), the Selim Physical Score (3.32 and 3.26, respectively), and the use of insulin (56.0% and 56.0%, respectively) were similar in both groups. MMP patients had a greater mean reduction in A1c compared with standard care patients (-1.24 vs. -0.59, P = 0.009) from baseline to after 2 years. After 2 years, the A1c for MMP patients was significantly lower compared with control patients (8.06 vs.8.67, respectively, P = 0.014). There was also a difference in A1c after 1 year for MMP patients versus control patients (8.18 and 8.69, respectively, P = 0.012). CONCLUSIONS A pharmacist-led diabetes MMP, combined with a diabetes drug copay waiver, was effective in significantly reducing A1c over a 2-year period for type 2 diabetic patients in this regional health plan.

Acceptability of Voluntary Medical Male Circumcision (VMMC) among Male Sexually Transmitted Diseases Patients (MSTDP) in China.

Voluntary Medical Male circumcision (VMMC) is an evidence-based, yet under-utilized biomedical HIV intervention in China. No study has investigated acceptability of VMMC among male sexually transmitted diseases patients (MSTDP) who are at high risk of HIV transmission. A cross-sectional survey interviewed 350 HIV negative heterosexual MSTDP in Shenzhen, China; 12.0% (n = 42) of them were circumcised at the time of survey. When the uncircumcised participants (n = 308) were informed that VMMC could reduce the risk of HIV infection via heterosexual intercourse by 50%, the prevalence of acceptability of VMMC in the next six months was 46.1%. Adjusted for significant background variables, significant factors of acceptability of VMMC included: 1) emotional variables: the Emotional Representation Subscale (adjusted odds ratios, AOR = 1.13, 95%CI: 1.06–1.18), 2) cognitive variables derived from Health Belief Model (HBM): perceived some chance of having sex with HIV positive women in the next 12 months (AOR = 2.48, 95%CI: 1.15–5.33) (perceived susceptibility), perceived severity of STD infection (AOR = 1.06, 95%CI: 1.02–1.10), perceived benefit of VMMC in risk reduction (AOR = 1.29, 95%CI: 1.16–1.42) and sexual performance (AOR = 1.45, 95%CI: 1.26–1.71), perceived barriers against taking up VMMC (AOR = 0.88, 95%CI: 0.81–0.95), and perceived cue to action (AOR = 1.41, 95%CI: 1.23–1.61) and self-efficacy (AOR = 1.38, 95%CI: 1.26–1.35) related to taking up VMMC. The association between perceived severity of STD infection and acceptability was fully mediated by emotional representation of STD infection. The relatively low prevalence of circumcision and high acceptability suggested that the situation was favorable for implementing VMMC as a means of HIV intervention among MSTDP in China. HBM is a potential suitable framework to guide the design of future VMMC promotion. Future implementation programs should be conducted in STD clinic settings, taking the important findings of this study into account.

Screening and management of viral hepatitis and hepatocellular carcinoma in Mongolia: results from a survey of Mongolian physicians from all major provinces of Mongolia

Background According to Globocan, Mongolia has the highest worldwide hepatocellular carcinoma (HCC) incidence (78.1/100 000, 3.5× higher than China). Aims and methods We conducted an anonymous survey of physicians from major provinces who attended an educational liver symposium, analysing their demography, practice, knowledge, perceptions and proposed solutions. Multivariate logistic regression was used to estimate OR relating demography and practice factors with higher provider knowledge and improvement. Results Of the 121 attendees, 44–95 (36–79%) responded to each question. Most were female (87%), young (79% age <50), subspecialists (81%), university-affiliated (74%), and practised in urban areas (61%). The mean pretest and post-test scores per physician were 60.4±20.4 and 65.6±21.3, with no observed significant predictors for baseline knowledge or improvement. Most (>80%) noted that <50% of patients who need hepatitis or HCC screening receive it. The main perceived barriers to screening were inability to pay for tests, lack of guidelines and poor patient awareness. Hepatitis treatment rates were low; 83% treated hepatitis C virus in <10 patients in the past year, and 86% treated hepatitis B virus in <10 patients/month. Treatment barriers were multifactorial, with cost as a principal barrier. Proposed solutions were universal screening policies (46%), removal of financial barriers (28%) and provider education (20%). Conclusions Physicians from major regions of Mongolia noted low screening for viral hepatitis, even lower treatment rates, financial barriers and the need for increased educational efforts. We advocate broad-based medical education tailored to local needs and based on needs assessment and outcome measurements.

Anticipated Negative Responses by Students to Possible Ebola Virus Outbreak, Guangzhou, China.

To the Editor: In 2014, a serious Ebola virus disease (EVD) outbreak occurred in West Africa (1). In a study on EVD-related perceptions, 85% of US respondents mistakenly believed that EVD could be transmitted through airborne droplets from patients’ sneezes or coughs (2). EVD-related panic was reported in the United States (3) and the United Kingdom (4). During November 15–December 20, 2014, we conducted a cross-sectional survey of 1,295 undergraduate students in Guangzhou, China, where the population of immigrants from Africa is high, who had heard of EVD (Technical Appendix). Our aim was to measure students’ anticipated negative emotional responses and avoidance activities (dependent variables) to a possible outbreak of EVD (5). We constructed scales for the dependent and independent variables to assess EVD-related perceptions: 1) misconceptions/knowledge about transmission modes, 2) scenarios of an EVD outbreak in Guangzhou (chances, severity, control), 3) efficacy of preventive measures and self-protection, and 4) public stigma toward EVD survivors. MLwiN 2.30 (Centre for Multilevel Modeling, University of Bristol, Bristol, UK) was used for multilevel regression analyses (Technical Appendix). We analyzed data from 1,155 (89.2%) students who have heard of EVD. To the example of 2–3 EVD cases detected in Guangzhou, 31.0% showed >4 types of anticipated negative emotions (e.g., fear, panic, worry); 59.5% showed >3 types of anticipated unnecessary avoidance. Most (80.0%) indicated >1 misconception regarding transmission mode (e.g., believed it was droplet or waterborne) but knew that direct contact with the corpse of an infected person (69.0%) and body fluids (81.4%) could lead to infection and perceived EVD as fatal (85.6%,) and highly infectious (81.6%). About half of respondents believed that effective treatment and a vaccine were unavailable (51.9% and 59.1%, respectively); 22.2% anticipated EVD outbreaks among Africans in Guangzhou (during the next 12 months). Many students perceived severe consequences if a small EVD outbreak occurred in Guangzhou and believed an outbreak would have a high fatality rate (70.5%), EVD is highly infectious (65.4%), an outbreak would be of long duration (47.5%), and the number of infected persons would be high (39.9%); 52.5%–79.2% of respondents lacked confidence in the government’s ability to control an outbreak (e.g., ability to provide adequate vaccines, medication, protective gear). Half or more of respondents believed that restricting travel by Africans to and from Africa and avoiding visiting African-inhabited areas were effective means of prevention. About 40% were confident that they could protect themselves or family members from EVD (Technical Appendix Tables 1, 2). Older age, female sex, longer school years, and rural origin were associated with negative emotional responses, avoidance, or both (Technical Appendix Table 3). In multivariate analyses that adjusted for significant background variables, we found positive associations between both dependent variables and the following independent variables: perceived fatality of EVD, perceived nonavailability of treatment, misconceptions regarding modes of transmission, perceived severity of a Guangzhou outbreak, perceived efficacy of restricting Africans’ travel, perceived efficacy of avoiding African-inhabited areas, and public stigma toward EVD survivors. Confidence in governmental control was negatively associated with both dependent variables. Some variables were positively associated with emotional response but not avoidance (perceived irreversible harm, perceived chance of outbreak in Guangzhou and in other parts in China, perceived self-efficacy for protection); 2 variables (perceived nonavailability of vaccine and knowledge of transmission mode) were positively associated with avoidance measures but not with emotional responses (Table). Table Factors associated with anticipated responses to EVD, adjusted for sociodemographic variables, Guangzhou, China, 2014* Because EVD causes serious physical harm, negative emotional responses and unnecessary avoidance practices were anticipated. Such negative community responses might cause individual and societal harm, as witnessed during the epidemic of severe acute respiratory syndrome (6). Misconceptions concerning transmission modes were prevalent and significantly correlated with both dependent variables. More than 80% of respondents perceived that the virus was highly infectious, another significant factor. About 20% of participants believed that an EVD outbreak would occur in Guangzhou in the next year. Among all participants, many anticipated severe outcomes but were not confident that the government was prepared for and could control such an outbreak. The concentration of immigrants from Africa in this region might have increased perceived chances of an EVD outbreak and thus lead to avoidance of this population. The high percentages of those who believed that restricting Africans’ travel was effective also might result in discrimination. Public stigmatization toward EVD survivors, another significant factor, was a prominent attitude (7,8). Fear, misconceptions, and perceived likelihood of EVD to cause death may lead to patient stigmatizing, which could hinder case detection and patients’ service seeking. The relationship between stigmatization and EVD-related perceptions should be investigated. The study’s limitations included the inability to assess real responses, inability to generalize findings to all university students and the general public, and the use of scales that had not been validated. Also, some students might have given exaggerated responses. In summary, misconceptions and perceptions regarding EVD may result in negative community responses in Guangzhou. Health education is needed to clarify that EVD is not airborne or waterborne or highly infectious and that avoidance is not an effective preventive measure. In addition, the government should start developing and publicizing its preparedness plans. Technical Appendix. Detailed methods and background variables of the study participants in Guangzhou, China, the frequency distribution of items related to Ebola virus disease (EVD), associations between sociodemographic factors and anticipated responses to an EVD outbreak, and univariate associations between independent variables and anticipated responses to EVD by participants. Click here to view.(269K, pdf)

Economic and clinical burden of viral hepatitis in California: A population-based study with longitudinal analysis

Background Economic burden of HBV and HCV infection are trending upwards. Aims Compare hepatitis B virus (HBV) and hepatitis C virus (HCV) related hospital admission rates, charges, mortality rates, causes of death in a US population-based study. Methods Retrospective cohort analysis of HBV and HCV patients from the California Office of Statewide Health Planning and Development (2006–2013) database. Results A total of 23,891 HBV and 148,229 HCV patients were identified. Across the 8-year period, the mean increase for all-cause (