Impact of Lactate Dehydrogenase and Hemoglobin Levels on Clinical Outcomes in Patients With Paroxysmal Nocturnal Hemoglobinuria: Results From the National Korean PNH Registry.

BACKGROUND: Paroxysmal nocturnal hemoglobinuria (PNH) is a rare hematologic disorder caused by uncontrolled terminal complement activation, which leads to intravascular hemolysis (IVH), thromboembolism (TE), renal failure, and premature mortality. METHODS: We performed a secondary analysis of data collected from patients enrolled in the Korean National PNH Registry to assess the relative importance of risk factors, specifically lactate dehydrogenase (LDH) and hemoglobin (Hb), in predicting the incidence of TE, impaired renal function, and death in complement inhibitor-naïve patients with PNH. RESULTS: Multivariate regression modeling indicated that LDH ≥ 1.5 × upper limit of normal (ULN), male sex, and pain were associated with increased risk of TE (P = 0.016, 0.045, and 0.033, respectively), hemoglobinuria and pain were associated with an increased risk of impaired renal function (P = 0.034 and 0.022, respectively), and TE was associated with an increased incidence of death (P < 0.001). Hb < 8 g/dL was not a predictor of TE, impaired renal function, or death in multivariate regression analyses. Standardized mortality ratio analysis indicated that LDH ≥ 1.5 × ULN (P < 0.001), Hb < 8 g/dL (P < 0.001), and Hb ≥ 8 g/dL (P = 0.004) were all risk factors for death; in contrast, patients with LDH < 1.5 × ULN had similar mortality to the general population. CONCLUSION: In complement inhibitor-naïve patients with PNH, LDH ≥ 1.5 × ULN was a significant predictor of TE, and TE was a significant predictor of death. Hb was not a significant predictor of TE, impaired renal function, or death. Therefore, controlling IVH will improve clinical outcomes for patients with PNH.

Amivantamab compared with real-world therapies in patients with advanced non-small cell lung cancer EGFR Exon 20 insertion mutations after platinum-based chemotherapy.

BACKGROUND: In the single-arm CHRYSALIS trial, advanced non-small cell lung cancer patients harboring epidermal growth factor receptor (EGFR) exon 20 insertion (Exon 20ins) showed durable responses to amivantamab, an EGFR-MET bispecific antibody targeting tumors with EGFR Exon 20ins. This study compared the effectiveness of amivantamab to real-world systemic anti-cancer therapies in Japan. PATIENTS AND METHODS: External control patients were selected by applying CHRYSALIS eligibility to Japanese patients from LC-SCRUM-Asia. External control patients were included for every qualifying line of therapy after platinum-based chemotherapy. Propensity score weighting was applied to external control patients to adjust for differences in baseline characteristics. Outcomes were compared between external control patients, and all and Asian-only CHRYSALIS patients using weighted Cox proportional hazards regression models for progression-free survival (PFS), time to next therapy (TTNT), and overall survival (OS), and generalized estimating equations with repeated measurements for overall response rate (ORR). RESULTS: One hundred fifteen CHRYSALIS and 94 external control patients were identified. Compared to external control patients, amivantamab-treated patients had significantly longer OS (median OS 19.88 vs 14.09 months, HR [95% CI] 0.59 [0.40-0.88]), PFS (median PFS 6.74 vs 4.73 months, HR 0.59 [0.45-0.78]), TTNT (median TTNT 12.16 vs 5.09 months, HR 0.39 [0.29-0.53]), and significantly higher ORR (41.7% vs 14.1%). Analyses of amivantamab-treated Asian patients (n = 61) showed similar clinical benefits. CONCLUSION: In the absence of clinical evidence from randomized clinical trials, this study reflects the benefit of amivantamab after platinum-based chemotherapy for advanced non-small cell lung cancer patients harboring EGFR Exon 20ins, compared to current real-world therapies.

Comparative Treatment Persistence with Bone-Targeting Agents Among Asian Patients with Bone Metastases from Solid Tumors: A Multinational Retrospective Cohort Study.

BACKGROUND: The efficacy of bone-targeting agents has been confirmed, but the generalizability of results to Asia is in question. OBJECTIVE: We aimed to evaluate and compare treatment persistence and re-initiation with different bone-targeting agents among patients with bone metastases from solid tumors. METHODS: This population-based cohort study included patients with bone metastasis with breast, lung, or prostate cancer who initiated bone-targeting agents, including denosumab, zoledronic acid, and pamidronate in Taiwan (2013-17), Hong Kong (2013-17), and Korea (2012-16). We described the patients' persistence with bone-targeting agents, by evaluating the interruption probability, and compared risks of treatment interruption. The rates of re-initiation with index bone-targeting agents were evaluated. RESULTS: We included 5127 patients (denosumab: 3440, zoledronic acid: 1210, pamidronate: 477) from Taiwan, 883 patients (denosumab: 458, zoledronic acid: 357, pamidronate: 68) from Hong Kong, and 4800 patients (zoledronic acid: 4068, pamidronate: 732) from Korea. Compared with zoledronic acid, denosumab had a lower risk of interruption in Taiwan (adjusted hazard ratio: 0.44; 95% confidence interval 0.40-0.48) and Hong Kong (0.36; 0.28-0.45). However, pamidronate was more likely to be interrupted than zoledronic acid in Taiwan (1.31; 1.11-1.54) and Korea (2.06; 1.83-2.32), but not in Hong Kong (1.13; 0.71-1.78). After discontinuation, original treatments with denosumab in Taiwan and zoledronic acid in Hong Kong were more likely to be resumed, while in Korea, the rates were similar among the bisphosphonates. CONCLUSIONS: Denosumab was associated with a lower risk of interruption than bisphosphonates in patients with bone metastases in Taiwan and Hong Kong. Further investigations may be required to verify patients' actual reasons for discontinuation.

Sexual function after voluntary medical male circumcision for human immunodeficiency virus prevention: Results from a programmatic delivery setting in Botswana.

BACKGROUND: Uptake of voluntary medical male circumcision (VMMC) remains modest in Botswana in spite of the government's commitment and service provision availability. Data on sexual function post-VMMC in programmatic settings could help guide messaging tailored to Botswana. OBJECTIVES: At 3-month post-VMMC, we evaluated changes in sexual function and satisfaction with the VMMC procedure amongst a cohort of HIV-negative, sexually active men aged 18-49 years who underwent VMMC in a public-sector clinic in Botswana. METHODS: We assessed whether each of the following domains of sexual function had improved, stayed the same or worsened since VMMC: sexual desire, ability to use condoms, ease of vaginal penetration, ease of ejaculation, ability to achieve and maintain an erection and hygiene or cleanliness. RESULTS: Data on sexual function were available for 378 men at 3-month post-VMMC. Median age was 27 years - 54% had a higher than secondary education, 72% were employed and 27% were married. Nearly all (96%) the men reported improvement in at least one domain of sexual function, while 19% reported improvement in all six domains. One-fourth (91/378, 24%) of the men reported that at least one domain of sexual function worsened post-VMMC. The most frequently reported domain that worsened was sexual desire (11%); in all other domains, < 10% of the men reported worsening. Men who reported any worsening sexual function were 2.3-fold as likely to be less than 'very satisfied' with the VMMC procedure (risk ratio 2.36, 95% confidence interval [CI] 1.66-3.34, p < 0.001). CONCLUSION: Emphasising improved sexual function experienced after VMMC in demand-creation efforts could potentially increase VMMC uptake in Botswana.

Voluntary Medical Male Circumcision and Perceived Sexual Functioning, Satisfaction, and Risk Behavior: A Qualitative Study in Botswana.

This article examines perceptions of sexual functioning, satisfaction, and risk-taking related to voluntary medical male circumcision (VMMC) in Botswana. Twenty-seven focus group discussions were conducted in four purposively selected communities with community leaders, men, and women. Discussions were analyzed using an inductive content analytic approach. Perceptions of VMMC's impact on sexual functioning and satisfaction varied. Increased satisfaction was attributed to improved penile health and increased ejaculatory latency time, whereas decreased satisfaction was attributed to erectile dysfunction and increased vaginal irritation during sex. Most participants thought sexual disinhibition occurred after circumcision; nevertheless, some women said they used male circumcision status as a marker of HIV status, thereby influencing sexual decision-making and partner selection. Messaging should emphasize that VMMC does not afford complete HIV protection. Optimizing VMMC's impact requires increasing uptake while minimizing behavioral disinhibition, with a balance between potential messaging of improved sexual functioning and satisfaction and the potential impact on sexual disinhibition.

Immediate Motivators to Seeking Voluntary Medical Male Circumcision Among HIV-Negative Adult Men in an Urban Setting in Botswana.

Randomized trials have shown that voluntary medical male circumcision (VMMC) significantly reduces HIV acquisition risk in men. We sought to identify subpopulations of Botswanan men with high levels of VMMC uptake by comparing an observational cohort of men presenting for circumcision services at two high-volume clinics in Botswana's capital city, Gabo-rone, with a matched, population-based random sample of uncircumcised men. Among these high uptake VMMC subpopulations, we then examined the immediate factors that play a role in men's decision to seek VMMC services. As compared to their population-based controls, men choosing to undergo circumcision were more likely to be ages 24-34, more highly educated, to have a religious affiliation, and in a serious relationship. Our results suggest that married men and highly educated men were more likely to pursue circumcision for personal hygiene reasons. These findings have direct implications for targeted demand creation and mobilization activities to increase VMMC uptake in Botswana.

We Can Work (It) Out Together: Type 1 Diabetes Boot Camp for Adult Patients and Providers Improves Exercise Self-Efficacy.

OBJECTIVES: This project aimed to use education sessions and exercise classes to improve exercise self-efficacy in individuals with type 1 diabetes and in diabetes care providers (DCPs). METHODS: We recruited 12 adults with type 1 diabetes and 12 DCPs who participated in 4 weekly group sessions to learn about exercise physiology and to experience various exercise types. We provided participants who had type 1 diabetes with real-time continuous glucose monitors and heart rate monitors to enhance experiential learning. Both groups completed questionnaires before and after the study to assess confidence concerning exercise. Following the study, focus groups assessed the impact of the study on knowledge and self-efficacy. RESULTS: There was an improvement in DCPs' attitudes toward exercise (p=0.004). DCPs' confidence in providing clients with advice regarding the time, type and intensity of exercise (p=0.005) and strategies for overcoming barriers to exercise (p=0.016) improved significantly. We found no significant changes in results in the questionnaires of participants with type 1 diabetes. Focus group analysis suggested that the study improved awareness of the importance of exercise as well as knowledge about the effects of exercise in type 1 diabetes by both DCPs and participants. Continuous glucose monitor use alleviated fear of hypoglycemia by participants with type 1 diabetes. CONCLUSIONS: These findings suggest that a 4-week education- and exercise-focused program improves DCPs' self-efficacy in providing exercise advice to patients. People with type 1 diabetes did not experience an improvement in exercise self-efficacy; however, the study supports the use of continuous glucose monitoring and the grouping of DCPs and individuals with type 1 diabetes to facilitate experiential learning.

Modifying the health system to maximize voluntary medical male circumcision uptake: a qualitative study in Botswana.

BACKGROUND: In 2007, the World Health Organization and the Joint United Nations Programme on HIV/AIDS endorsed voluntary medical male circumcision (VMMC) as an add-on HIV-prevention strategy. Similar to many other sub-Saharan countries, VMMC uptake in Botswana has been low; as of February 2016, only 42.7% of the program target had been achieved. Previous work has examined how individual-level factors, such as knowledge and attitudes, influence the update of VMMC. This paper examines how factors related to the health system can be leveraged to maximize uptake of circumcision services, with a focus on demand creation, access to services, and service delivery. METHODS: Twenty-seven focus group discussions with 238 participants were conducted in four communities in Botswana among men (stratified by circumcision status and age), women (stratified by age), and community leaders. A semi-structured guide was used by a trained same-gender interviewer to facilitate discussions, which were audio recorded, transcribed, translated to English, and analyzed using an inductive analytic approach. RESULTS: Participants felt demand creation activities utilizing age- and gender-appropriate mobilizers and community leaders were more effective than mass media campaigns. Participants felt improved access to VMMC clinics would facilitate service uptake, as would designated men's clinics with male-friendly providers for VMMC service delivery. Additionally, providing comprehensive pre-procedure counseling and education, outlining the benefits and disadvantages of the surgical procedure, and explaining the differences between the surgical and non-surgical procedures, were suggested by participants to increase understanding and uptake of VMMC. CONCLUSION: Cultural acceptability of circumcision services can be improved by engaging age- and gender-appropriate community mobilizers. Involving influential community leaders, providing a forum for men to discuss health issues, and bringing services closer to people can increase VMMC utilization. Service delivery can be improved by communicating the pros and cons of the procedure to the clients for informed decision-making.

Improved Medication Adherence and Frequency of Blood Glucose Self-Testing Using an m-Health Platform Versus Usual Care in a Multisite Randomized Clinical Trial Among People with Type 2 Diabetes in India.

BACKGROUND: In 2015, India had an estimated 69.2 million people with diabetes and a national prevalence of 8.7%. Evidence is mounting for the benefits of telemedicine in diabetes care, but remains limited on mobile-health (m-Health) interventions. INTRODUCTION: This study assessed the impact of an m-Health diabetes platform on clinical outcomes, patient-reported outcomes, patient and provider satisfaction, and app usage. MATERIALS AND METHODS: This open-label, two-arm parallel study enrolled 91 people at 3 sites in India, aged 18-65, with type 2 diabetes, and an A1c between 7.5% and 12.5% (58-113 mmol/mol). Participants were randomly assigned 1:1 to m-Health or usual care and observed for 6 months. All received free visits, laboratory tests, transportation fees, and strips and lancets. Intervention participants received the m-Health app and a mobile phone data stipend. RESULTS: A1c change was previously reported as statistically significant. Significantly more participants in intervention than control had improved medication adherence (39.0% vs. 12.8%; p = 0.03) and increased frequency of blood glucose (BG) self-testing (39.0% vs. 10.3%; p = 0.01) at 6 months from baseline. No other outcomes were significantly different. Among m-Health users, 75% of participants actively used the app at week 24. Participants entered 29,668 medications and 2,575 BG readings, sent 497 messages, and received 890 messages. Most participants (80%) were satisfied with all aspects of the app and all seven providers rated the software very acceptable. DISCUSSION: Participants assigned to m-Health had increased medication adherence and frequency of BG testing compared with usual care participants. CONCLUSIONS: This tool could be an effective way to expand access to quality chronic disease care and improve outcomes.

Antiretroviral therapy adherence measurement in non-clinical settings in South India.

Optimal adherence to antiretroviral therapy (ART) is key to viral suppression, but may be impeded by psychosocial consequences of HIV-infection such as stigma and depression. Measures of adherence in India have been examined in clinic populations, but little is known about the performance of these measures outside clinical settings. We conducted a cross-sectional study of 151 Tamil-speaking people living with HIV/AIDS (PLHA) in India recruited through HIV support networks and compared single item measures from the Adult AIDS Clinical Trial Group (AACTG) scale, a visual analog scale (VAS), and a question on timing of last missed dose. Depression was measured using the Major Depression Inventory (MDI) and HIV-related stigma was measured using an adaptation of the Berger Stigma Scale. Mean age was 35.6 years (SD ± 5.9); 55.6% were male; mean MDI score was 11.9 (SD ± 9.1); and mean stigma score was 67.3 (SD ± 12.0). Self-reported perfect adherence (no missed doses) was 93.3% using the AACTG item, 87.1% using last missed dose, and 83.8% using the VAS. The measures had moderate agreement with each other (kappa 0.45-0.57). Depression was associated with lower adherence irrespective of adherence measure used, and remained significantly associated in multivariable analyses adjusting for age and marital status. Stigma was not associated with adherence irrespective of the measure used. The VAS captured the greatest number of potentially non-adherent individuals and may be useful for identifying PLHA in need of adherence support. Given the consistent and strong association between poorer adherence and depression, programs that jointly address adherence and mental health for PLHA in India may be more effective than programs targeting only one.