Patient adherence with a smartphone app for patient-reported outcomes in rheumatoid arthritis.

OBJECTIVES: Electronic patient-reported outcomes (ePROs) transmitted digitally allow patients to communicate with their clinicians and track the activity of chronic diseases, such as RA. Several ePRO smartphone apps have been developed in rheumatology, yet few data have been reported regarding patient adherence. We developed a PRO app for RA and assessed adherence over 6 months. METHODS: We developed an app to deliver daily assessments to participants (RA App v.1.0). The app was tested as part of a randomized controlled trial examining potential clinical benefits. The current analyses focus on the adherence to the ePRO app for patients randomized to receive the app. We recruited RA patients from an academic rheumatology practice in the USA. Patients randomized to receive the app received daily notifications regarding ePROs. We examined adherence to the PRO questionnaires over the 6-month study and examined factors related to adherence. RESULTS: Seventy-eight patients received the app and have data included in these analyses: 63 (80.7%) were female, mean age was 55.2 years, 71% had attended college or beyond, and the mean Clinical Disease Activity Index at baseline was 9.7 (low disease activity). Median adherence to the daily questions was 79% (interquartile range 48-90%). Significant predictors of increased adherence were age ≥65 (P = 0.03) and low baseline Clinical Disease Activity Index (P = 0.02). CONCLUSION: We developed and tested an ePRO app for RA over a 6-month study. Adherence to the app was strong. There was correlation between older age and better disease control and increased adherence. TRIAL REGISTRATION: ClinicalTrials.gov, https://clinicaltrials.gov/, NCT02822521.

Adverse Effects of Low-Dose Methotrexate: A Randomized Trial.

Background: Low-dose methotrexate (LD-MTX) is the most commonly used drug for systemic rheumatic diseases worldwide and is the recommended first-line agent for rheumatoid arthritis. Despite extensive clinical use for more than 30 years, few data on adverse event (AE) rates derive from randomized, placebo-controlled trials, where both causality and magnitude of risk can be inferred. Objective: To investigate AE rates, risk, and risk differences comparing LD-MTX versus placebo. Design: Prespecified secondary analyses of a double-blind, placebo-controlled, randomized trial. (ClinicalTrials.gov: NCT01594333). Setting: North America. Participants: Adults with known cardiovascular disease and diabetes or metabolic syndrome. Intervention: Random allocation to LD-MTX (≤20 mg/wk) or placebo. All participants received folic acid, 1 mg/d, 6 days per week. Measurements: Risks for specific AEs of interest, as well as for all AEs, were compared across treatment groups after blinded adjudication. Results: After an active run-in period, 6158 patients were enrolled and 4786 randomly assigned to a group; median follow-up was 23 months and median dosage 15 mg/wk. Among the randomly assigned participants, 81.2% were male, median age was 65.7 years, and median body mass index was 31.5 kg/m2. Of 2391 participants assigned to LD-MTX, 2080 (87.0%) had an AE of interest, compared with 1951 of 2395 (81.5%) assigned to placebo (hazard ratio [HR], 1.17 [95% CI, 1.10 to 1.25]). The relative hazards of gastrointestinal (HR, 1.91 [CI, 1.75 to 2.10]), pulmonary (HR, 1.52 [CI, 1.16 to 1.98]), infectious (HR, 1.15 [CI, 1.01 to 1.30]), and hematologic (HR, 1.15 [CI, 1.07 to 1.23]) AEs were elevated for LD-MTX versus placebo. With the exception of increased risk for skin cancer (HR, 2.05 [CI, 1.28 to 3.28]), the treatment groups did not differ in risk for other cancer or mucocutaneous, neuropsychiatric, or musculoskeletal AEs. Renal AEs were reduced in the LD-MTX group (HR, 0.85 [CI, 0.78 to 0.93]). Limitation: The trial was done in patients without rheumatic disease who tolerated LD-MTX during an active run-in period. Conclusion: Use of LD-MTX was associated with small to moderate elevations in risks for skin cancer and gastrointestinal, infectious, pulmonary, and hematologic AEs, whereas renal AEs were decreased. Primary Funding Source: National Institutes of Health.

Factors affecting pain during outpatient clinic based surgical procedures in gynecologic oncology.

Colposcopy-directed punch biopsy (punch biopsy) and endocervical curettage (ECC) are accompanied by considerable pain. However, many physicians perform these procedures without adequate pain management. Therefore, identification of factors affecting pain experienced during the procedures may encourage physician effort in selective pain management. This study investigated factors affecting the severity of pain experienced during punch biopsy and ECC in an outpatient clinic of gynecologic oncology department.In this retrospective, exploratory study, a total of 101 Korean patients with abnormal cervical cytology underwent punch biopsy and ECC under a paracervical block performed for pain relief. Residents under training performed these procedures and recorded patient-reporting maximum Numeric Rating Scale (NRS) scores experienced during the procedures. Residents were classified into four outpatient clinic training groups (1st-4th); the group designators correspond to the resident's experience in performing these procedures. A linear mixed model adjusted for physician factors such as either residents or outpatient clinic training groups was used to analyze the association between each variable and maximum NRS score.Among the outpatient clinic training groups, maximum NRS scores significantly decreased in the 4th group, compared with those in the 1st group although those were not different among groups when adjusted for residents. Some of cervical cytology findings and discrepancies between the severity of cervical cytology results and those of punch biopsy or ECC showed significant associations with maximum NRS scores. However, when adjusted for either residents or outpatient clinic training groups, maximum NRS scores were not different by age, body mass index, presence of menopause, cervical cytology findings, discrepancies between the severity of cervical cytology results and those of punch biopsy or ECC, and tissue volume.There are no significant factors affecting the severity of pain experienced during punch biopsy and ECC.

Mitochondrial permeability transition pore as a selective target for anti-cancer therapy.

Mitochondrial outer membrane permeabilization (MOMP) is the ultimate step in dozens of lethal apoptotic signal transduction pathways which converge on mitochondria. One of the representative systems proposed to be responsible for the MOMP is the mitochondrial permeability transition pore (MPTP). Although the molecular composition of the MPTP is not clearly understood, the MPTP attracts much interest as a promising target for resolving two conundrums regarding cancer treatment: tumor selectivity and resistance to treatment. The regulation of the MPTP is closely related to metabolic reprogramming in cancer cells including mitochondrial alterations. Restoration of deregulated apoptotic machinery in cancer cells by tumor-specific modulation of the MPTP could therefore be a promising anti-cancer strategy. Currently, a number of MPTP-targeting agents are under pre-clinical and clinical studies. Here, we reviewed the structure and regulation of the MPTP as well as the current status of the development of promising MPTP-targeting drugs.