Evaluating the impact of regulatory action on denosumab-induced hypocalcaemia in Japan.

WHAT IS KNOWN AND OBJECTIVE: Since its introduction in April 2012, denosumab has been administered to approximately 7,300 patients as of August 2012, and 32 cases of serious hypocalcaemia after denosumab administration, including two deaths, have been reported in Japan. A Dear Healthcare Professional Letter of Rapid Safety Communication ('Blue letter') was released to warn about the risks of hypocalcaemia associated with denosumab. The goal of this study therefore was to measure the impact of regulatory action on denosumab-induced hypocalcaemia in Japan by using an electronic medical information database (MID). METHODS: We used two different aggregated data sets based on MIDs (data sets one and two). The patients studied were those who were newly prescribed denosumab or zoledronic acid between April 2012 and September 2014. We assessed four indicators: (a) the proportion of patients with calcium supplementation at the initial denosumab treatment, (b) the proportion of patients who underwent a serum calcium test, (c) the average number of serum calcium tests performed and (d) the prevalence of hypocalcaemia. All indices were aggregated by every 3 months. To evaluate the impact of regulatory action, we used difference in difference (DID) analysis. RESULTS AND DISCUSSION: The proportion of patients with calcium supplementation at the initial denosumab treatment increased year by year in both data sets. The average number of serum calcium tests increased year by year in data set two. There was a significant difference in the prevalence of hypocalcaemia in data set two. This suggests that the estimate of impact of the regulatory action may vary according to the database. In DID analysis, however, significant influences of the regulatory action on combination use with a calcium supplement were detected in both data sets. WHAT IS NEW AND CONCLUSION: There was a significant influence on combination use of denosumab with vitamin D and/or calcium supplement in both data sets. That there was no apparent increase in the prevalence of denosumab-induced hypocalcaemia, suggests that the regulatory action had an impact in the clinical setting studied. Such regulatory actions may play an important role in the promotion of drug safety.

Analyzing intent-to-treat and per-protocol effects on safety outcomes using a medical information database: an application to the risk assessment of antibiotic-induced liver injury.

OBJECTIVE: To apply a causal analysis approach to estimate the intent-to-treat and per-protocol effects in a safety outcome study of the 30-day risk of liver injury associated with antibiotic use (macrolides, penicillin-based antibiotics, and fluoroquinolones). RESEARCH DESIGN AND METHODS: For each antibiotic class, we constructed a pooled cohort of treated episodes matched with untreated episodes using an electronic medical record database from a university hospital. High-dimensional propensity scores were calculated using baseline patient characteristics, concomitant medications and medical history as surrogate confounders. Intent-to-treat hazard ratios (HRs) were estimated using inverse probability of treatment weighted discrete hazard models that ignored subsequent treatment changes. Per-protocol HRs were calculated using inverse probability of treatment and censoring weighted models after terminating each episode's observation at the first treatment change. RESULTS: For macrolides, the intent-to-treat HR (95% confidence interval) was 1.22 (0.75-1.98) and the per-protocol HR was 1.22 (0.67-2.22). For penicillin-based antibiotics, the intent-to-treat HR was 4.01 (3.16-5.08) and the per-protocol HR was 7.25 (5.58-9.41). For fluoroquinolones, the intent-to-treat HR was 1.60 (1.27-2.03) and the per-protocol HR was 1.69 (1.23-2.30). CONCLUSION: Researchers should clearly define the target estimands, and carefully estimate and interpret both effects.

Health checkup and telemedical intervention program for preventive medicine in developing countries: verification study.

BACKGROUND: The prevalence of non-communicable diseases is increasing throughout the world, including developing countries. OBJECTIVE: The intent was to conduct a study of a preventive medical service in a developing country, combining eHealth checkups and teleconsultation as well as assess stratification rules and the short-term effects of intervention. METHODS: We developed an eHealth system that comprises a set of sensor devices in an attaché case, a data transmission system linked to a mobile network, and a data management application. We provided eHealth checkups for the populations of five villages and the employees of five factories/offices in Bangladesh. Individual health condition was automatically categorized into four grades based on international diagnostic standards: green (healthy), yellow (caution), orange (affected), and red (emergent). We provided teleconsultation for orange- and red-grade subjects and we provided teleprescription for these subjects as required. RESULTS: The first checkup was provided to 16,741 subjects. After one year, 2361 subjects participated in the second checkup and the systolic blood pressure of these subjects was significantly decreased from an average of 121 mmHg to an average of 116 mmHg (P<.001). Based on these results, we propose a cost-effective method using a machine learning technique (random forest method) using the medical interview, subject profiles, and checkup results as predictor to avoid costly measurements of blood sugar, to ensure sustainability of the program in developing countries. CONCLUSIONS: The results of this study demonstrate the benefits of an eHealth checkup and teleconsultation program as an effective health care system in developing countries.

Evaluation of "Portable Health Clinic" with BAN standard for 10K subjects in Bangladesh.

Management system of chronic diseases in developing countries and post-disaster situation has been required. Body area network (BAN, IEEE 802.15.6) is expected to be useful in medical field. To evaluate BAN standard, we are implementing BAN in our attaché case type sensor set named "Portable Health Clinic" (PHC), and conducting systematic health checkup in rural and urban areas in Bangladesh. (Methods) In the PHC, we packed weight scale, blood pressure meter, blood sugar meter, body thermometer, pulse oxymeter, as electrical devices, and tape measure (for height, waist and hip), urine test tape (for urine sugar, urine protein and urobilinogen) as no-electrical devices. We provided checkup in rural villages and urban companies in Bangladesh by PHC, and transmitted data by cellphone network to the data center in Dhaka. Individual health condition was categorized into 4 grades, green (healthy), yellow (caution), orange (affected), and red (emergent) by international diagnosis standards of diseases. We provided telemedicine for orange and red, and tele-prescription for hypertensive patients. We are making all sensor devices implemented with BAN. (Results) The health checkup was provided to 5498 subjects until the end of 2012 and categorized green 14%, yellow 66%, orange 17%, and red 3%. The result shows its potency as an effective healthcare system in developing countries and in a chronic phase after disaster. We continue to provide the e-health service for 10K-15 K people each year until March 2014.

Storing health data in JPEG: looking at exif area capacity limits.

Formats for data storage in personal computers vary according to manufacturer and models for personal health-monitoring devices such as blood-pressure and body-composition meters. In contrast, the data format of images from digital cameras is unified into a JPEG format with an Exif area and is already familiar to many users. We have devised a method that can contain health data as a JPEG file. Health data is stored in the Exif area in JPEG in a HL7 format. There is, however, a capacity limit of 64 KB for the Exif area. The aim of this study is to examine how much health data can actually be stored in the Exif area. We found that even with combined data from multiple devices, it was possible to store over a month of health data in a JPEG file, and using multiple JPEG files simply overcomes this limit. We believe that this method will help people to more easily handle health data regardless of the various device modelsthey use.

Coffee consumption, serum γ-glutamyltransferase, and glucose tolerance status in middle-aged Japanese men.

BACKGROUND: Recently, coffee consumption has been related to decreased risk of type 2 diabetes mellitus (DM) among those with high levels of serum γ-glutamyltransferase (GGT). We examined the association between coffee and glucose tolerance, determined by a 75 g oral glucose tolerance test, and the effect modification of serum GGT on the association. METHODS: The study subjects were 5320 men aged 46-60 years who received a health examination at two Self-Defense Forces hospitals from January 1997 to March 2004. Those medicated for DM were excluded. Coffee consumption was classified into <1, 1-2, 3-4, and ≥5 cups/day. Statistical adjustment was made for age, body mass index, smoking, alcohol use, leisure-time physical activity, green tea consumption, parental diabetes, hospital, and rank in the Self-Defense Forces. RESULTS: Men with normal glucose tolerance, isolated impaired fasting glucose (IFG), isolated impaired glucose tolerance (IGT), combined IFG/IGT, and type 2 DM numbered 3384, 398, 790, 348, and 400, respectively. The prevalence odds of isolated IGT, combined IFG/IGT, and type 2 DM, but not of isolated IFG, decreased with increasing consumption of coffee. An inverse association with coffee was observed for isolated IGT in both low (≤40 IU/L) and high (>40 IU/L) GGT groups, and for combined IFG/IGT and type 2 DM in the latter group. CONCLUSIONS: Coffee drinking is protective against glucose intolerance. A possible effect modification of GGT on the coffee-DM association warrants further studies.