Effectiveness of Digital Medicines to Improve Clinical Outcomes in Patients with Uncontrolled Hypertension and Type 2 Diabetes: Prospective, Open-Label, Cluster-Randomized Pilot Clinical Trial.

BACKGROUND: Hypertension and type 2 diabetes mellitus are major modifiable risk factors for cardiac, cerebrovascular, and kidney diseases. Reasons for poor disease control include nonadherence, lack of patient engagement, and therapeutic inertia. OBJECTIVE: The aim of this study was to assess the impact on clinic-measured blood pressure (BP) and glycated hemoglobin (HbA1c) using a digital medicine offering (DMO) that measures medication ingestion adherence, physical activity, and rest using digital medicines (medication taken with ingestible sensor), wearable sensor patches, and a mobile device app. METHODS: Participants with elevated systolic BP (SBP ≥140 mm Hg) and HbA1c (≥7%) failing antihypertensive (≥2 medications) and oral diabetes therapy were enrolled in this three-arm, 12-week, cluster-randomized study. Participants used DMO (includes digital medicines, the wearable sensor patch, and the mobile device app) for 4 or 12 weeks or received usual care based on site randomization. Providers in the DMO arms could review the DMO data via a Web portal. In all three arms, providers were instructed to make medical decisions (medication titration, adherence counseling, education, and lifestyle coaching) on all available clinical information at each visit. Primary outcome was change in SBP at week 4. Other outcomes included change in SBP and HbA1c at week 12, and low-density lipoprotein cholesterol (LDL-C) and diastolic blood pressure (DBP) at weeks 4 and 12, as well as proportion of patients at BP goal (<140/90 mm Hg) at weeks 4 and 12, medical decisions, and medication adherence patterns. RESULTS: Final analysis included 109 participants (12 sites; age: mean 58.7, SD years; female: 49.5%, 54/109; Hispanic: 45.9%, 50/109; income ≤ US $20,000: 56.9%, 62/109; and ≤ high school education: 52.3%, 57/109). The DMO groups had 80 participants (7 sites) and usual care had 29 participants (5 sites). At week 4, DMO resulted in a statistically greater SBP reduction than usual care (mean -21.8, SE 1.5 mm Hg vs mean -12.7, SE 2.8 mmHg; mean difference -9.1, 95% CI -14.0 to -3.3 mm Hg) and maintained a greater reduction at week 12. The DMO groups had greater reductions in HbA1c, DBP, and LDL-C, and a greater proportion of participants at BP goal at weeks 4 and 12 compared with usual care. The DMO groups also received more therapeutic interventions than usual care. Medication adherence was ≥80% while using the DMO. The most common adverse event was a self-limited rash at the wearable sensor site (12%, 10/82). CONCLUSIONS: For patients failing hypertension and diabetes oral therapy, this DMO, which provides dose-by-dose feedback on medication ingestion adherence, can help lower BP, HbA1c, and LDL-C, and promote patient engagement and provider decision making. TRIAL REGISTRATION: Clinicaltrials.gov NCT02827630; https://clinicaltrials.gov/show/NCT02827630 (Archived by WebCite at http://www.webcitation.org/6rL8dW2VF).

Osteopetrosis in a Patient of Systemic Sclerosis Sine Scleroderma: A Rare Association.

Systemic sclerosis is a connective tissue disorder of unknown etiology. Although it is a multisystemic disorder, skin thickening is considered as a hallmark of the disease. It usually involves the lungs, gastrointestinal, and musculoskeletal systems. However, a rare subset of systemic sclerosis, systemic sclerosis sine scleroderma, is characterized by internal organ involvement and positive serologic markers with the total or partial absence of cutaneous manifestations. We present a rare association of osteopetrosis in a case of systemic sclerosis sine scleroderma, in a 22-year-old male patient, who presented with pulmonary symptoms as his chief complaints, unreported so far in literature.

Usability of a novel digital medicine system in adults with schizophrenia treated with sensor-embedded tablets of aripiprazole.

OBJECTIVE: Digital medicine system (DMS) is a novel drug-device combination that objectively measures and reports medication ingestion. The DMS consists of medication embedded with an ingestible sensor (digital medicine), a wearable sensor, and software applications. This study evaluated usability of the DMS in adults with schizophrenia rated by both patients and their health care providers (HCPs) during 8-week treatment with prescribed doses of digital aripiprazole. METHODS: Six US sites enrolled outpatients into this Phase IIa, open-label study (NCT02219009). The study comprised a screening phase, a training phase (three weekly site visits), and a 5-week independent phase. Patients and HCPs independently rated usability of and satisfaction with the DMS. RESULTS: Sixty-seven patients were enrolled, and 49 (73.1%) patients completed the study. The mean age (SD) of the patients was 46.6 years (9.7 years); the majority of them were male (74.6%), black (76.1%), and rated mildly ill on the Clinical Global Impression - Severity scale (70.1%). By the end of week 8 or early termination, 82.1% (55/67) of patients had replaced the wearable sensor independently or with minimal assistance, based on HCP rating. The patients used the wearable sensor for a mean (SD) of 70.7% (24.7%) and a median of 77.8% of their time in the trial. The patients contacted a call center most frequently at week 1. At the last visit, 78% (47/60) of patients were somewhat satisfied/satisfied/extremely satisfied with the DMS. CONCLUSION: A high proportion of patients with schizophrenia were able to use the DMS and reported satisfaction with the DMS. These data support the potential utility of the DMS in clinical practice.

Philadelphia chromosome-positive acute lymphoblastic leukemia: 8 years' experience from a tertiary care center in India.

INTRODUCTION: The Philadelphia chromosome (Ph) is the most common cytogenetic abnormality associated with adult acute lymphoblastic leukemia (ALL) occurring in 20% to 40% of patients. It is also detected in 2% to 5% of children with ALL. Historically, patients with Ph-positive ALL carried a dismal prognosis, with poor response to most chemotherapy combinations, short remission durations, and long-term disease-free survival rates of 10% to 20%. The advent of tyrosine kinase inhibitors (TKIs) has revolutionized therapy of Ph-positive ALL. MATERIALS AND METHODS: This retrospective and descriptive single center study was carried out based on data retrieved of 508 patients treated for ALL from 2007 to 2014. Of these thirty patients were Ph-positive ALL and were available for analysis, and these patients were included in the study. Ph-positive ALL was defined as ALL carrying the t(9;22) translocation on standard karyotype and/or fluorescent in situ hybridization analysis and/or positivity for BCR-ABL fusion transcript detection by real-time quantitative polymerase chain reaction (RQ-PCR) analysis. Patients were treated with combination chemotherapy and oral TKIs and responses were classified as either CR defined by the absence of circulating blasts and <5% marrow blasts on a bone marrow examination done at the end of induction chemotherapy or failure, including persistent disease and early death. RESULTS: There were 30 (5.9%) cases of Ph-positive ALL out of a total of 508 cases of ALL with a median age of 27.5 years (range: 7-55). The choice of first line TKI was Imatinib in 25 (83.3 %) patients and Dasatinib in 1 (3.3 %) patient. Fourteen patients (46.6 %) had a CR, 3 (10 %) had a partial response (PR), 8 (26.6 %) had persistence of disease at the end of induction chemotherapy. The overall survival in those who received sequential chemotherapy followed by TKI (n = 4) was 28.5 months (95% CI 10.78 to 46.21 months) compared with 13.98 months (95% CI 6.04 to 21.97 months) for patients who received concurrent chemotherapy and TKI (n = 20); log rank (Mantel Cox) X2 = 8.33, P = 0.040), however limited sample precluded meaningful subgroup analysis. CONCLUSION: The results of our study showed that we still have a long way to go to match outcomes of western published series, even when the same treatment protocol is used, probably due to the underutilization of Allogeneic SCT as an option in first CR.

The association of self-monitoring of blood glucose use with medication adherence and glycemic control in patients with type 2 diabetes initiating non-insulin treatment.

BACKGROUND: The value of self-monitoring of blood glucose (SMBG) for persons with type 2 diabetes who do not use insulin remains controversial. This observational study compares the likelihood of medication adherence and change in glycated hemoglobin (A1C) for non-insulin-using patients using SMBG versus those not using SMBG. The study also assessed the association between diabetes medication adherence and SMBG use. PATIENTS AND METHODS: Data were extracted on 5,172 patients who began non-insulin diabetes medication between October 1, 2006, and March 31, 2009. The study assessed change in A1C associated with SMBG use and testing frequency at different categorical levels of baseline A1C. The likelihood of medication adherence for SMBG users was compared with that for non-SMBG users at different categorical levels of baseline A1C. The study further explored the interactions between SMBG use and medication adherence on change in A1C. RESULTS: SMBG users had greater reductions in A1C compared with nonusers when the baseline A1C was ≥ 7%. Increasing SMBG frequency was associated with greater reductions in A1C. The study also examined the associations among SMBG use, medication adherence, and change in A1C. SMBG users had greater decreases in A1C for both medication-adherent and -nonadherent patients. As expected, medication adherence was associated with greater reductions in A1C for both SMBG nonusers and users. It is interesting that medication-nonadherent SMBG users had similar reductions in A1C compared with medication-adherent non-SMBG users. CONCLUSIONS: Both SMBG use and medication adherence were associated with similar degrees of A1C reduction after controlling for baseline A1C, suggesting that both factors may be important for attaining glycemic control.

Clinical evaluation of a novel test strip technology for blood glucose monitoring: accuracy at hypoglycaemic glucose levels.

AIM: To evaluate OneTouch® Verio™ test strip performance at hypoglycaemic blood glucose (BG) levels (<3.9 mmol/L [<70 mg/dL]) at seven clinical studies. METHODS: Trained clinical staff performed duplicate capillary BG monitoring system tests on 700 individuals with type 1 and type 2 diabetes using blood from a single fingerstick lancing. BG reference values were obtained using a YSI 2300 STAT™ Glucose Analyzer. The number and percentage of BG values within ±0.83 mmol/L (±15 mg/dL) and ±0.56 mmol/L (±10 mg/dL) were calculated at BG concentrations of <3.9 mmol/L (<70 mg/dL), <3.3 mmol/L (<60 mg/dL), and <2.8 mmol/L (<50 mg/dL). RESULTS: At BG concentrations <3.9 mmol/L (<70 mg/dL), 674/674 (100%) of meter results were within ±0.83 mmol/L (±15 mg/dL) and 666/674 (98.8%) were within ±0.56 mmol/L (±10 mg/dL) of reference values. At BG concentrations <3.3 mmol/L (<60 mg/dL), and <2.8 mmol/L (<50 mg/dL), 358/358 (100%) and 270/270 (100%) were within ±0.56 mmol/L (±10 mg/dL) of reference values, respectively. CONCLUSION: In this analysis of data from seven independent studies, OneTouch Verio test strips provide highly accurate results at hypoglycaemic BG levels.