OBJECTIVE: We sought to investigate the incidence of gene mosaicism in patients with PIDs.
METHODS: The amplicon-based deep sequencing method was used in the 3 parts of the study that establish (1) the allele frequency of germline variants (n = 100), (2) the incidence of parental gonosomal mosaicism in families with PIDs with de novo mutations (n = 92), and (3) the incidence of mosaicism in families with PIDs with moderate-to-high suspicion of gene mosaicism (n = 36). Additional investigations evaluated body distribution of postzygotic mutations, their stability over time, and their characteristics.
RESULTS: The range of allele frequency (44.1% to 55.6%) was established for germline variants. Those with minor allele frequencies of less than 44.1% were assumed to be postzygotic. Mosaicism was detected in 30 (23.4%) of 128 families with PIDs, with a variable minor allele frequency (0.8% to 40.5%). Parental gonosomal mosaicism was detected in 6 (6.5%) of 92 families with de novo mutations, and a high incidence of mosaicism (63.9%) was detected among families with moderate-to-high suspicion of gene mosaicism. In most analyzed cases mosaicism was found to be both uniformly distributed and stable over time.
CONCLUSION: This study represents the largest performed to date to investigate mosaicism in patients with PIDs, revealing that it affects approximately 25% of enrolled families. Our results might have serious consequences regarding treatment and genetic counseling and reinforce the use of next-generation sequencing-based methods in the routine analyses of PIDs.
OBJECTIVE: This study aims to describe the protocol used in developing and testing a web-based platform (ie, CINTAI) providing an HIVST kit and real-time e-counseling to support online-to-offline linkage to HIV care services for MSM in Malaysia.
METHODS: The methods are reported according to the SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) 2013 guidelines. In phase I, we will adapt existing HIVST web-based platforms to create a new online-to-offline HIVST and counseling platform called "CINTAI" for Malaysian MSM. In phase II, we will use a type 1 hybrid implementation trial design to determine the feasibility, acceptability, and preliminary efficacy of "CINTAI" compared with treatment as usual among Malaysian MSM, with assessments conducted over 6 months. Multilevel implementation factors will also be collected to guide future adoption and scale-up. We will enroll 78 MSM in the pilot randomized controlled trial. Baseline characteristics will be tested for homogeneity between groups using appropriate statistical tests. A generalized linear mixed model with random subject effects will account for within-subject correlation. Treatment assignment, time, interaction, and confounders will be included. The proportion of MSM tested for HIV over 6 months and other outcomes (pre-exposure prophylaxis for HIV or antiretroviral therapy linkage, HIV risk behaviors, and chemsex harm reduction) will be compared using linear contrasts.
RESULTS: We completed phase I of the proposed study in April 2024 and started phase II in May 2024, with 15 participants recruited (7 in the CINTAI and 8 in the treatment-as-usual groups). On the basis of a series of formative works completed during phase I, we developed a fully functional, web-based platform that provides a digital platform for MSM in Malaysia to order HIVST kits for free and to receive HIV counseling, followed by offline linkage to HIV prevention services (if HIV negative) or HIV treatment services (if HIV positive).
CONCLUSIONS: Despite being at high risk for HIV transmission, MSM in Malaysia have alarmingly low testing and linkage to HIV care services, prompting the need for innovative approaches to support HIV prevention efforts. If found to be feasible and acceptable, CINTAI can be easily adapted for a range of health outcomes and health care delivery services for MSM, including adaptation to other low- and middle-income countries.
INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/60962.
MATERIALS AND METHODS: This prospective randomised control trial was conducted on smokers in a factory. A total of 163 participants were recruited and randomised into control and intervention groups using a table of random numbers. The intervention group received a ten-minute brief physician counselling session to quit smoking. Stages of smoking behaviour were measured in both groups using a translated and validated questionnaire at baseline, one month and three months post intervention.
RESULTS: There was a significant improvement in smoking behaviour at one-month post intervention (p=0.024, intention to treat analysis; OR=2.525; CI=1.109-5.747). This was not significant at three-month post intervention (p=0.946, intention to treat analysis; OR=1.026; 95% CI=0.486-2.168).
CONCLUSIONS: A session of brief physician counselling was effective in improving smokers' behaviour at workplace, but the effect was not sustained.
METHODS: A total of 1113 patient dispenser interactions were observed from a randomly selected sample of 371 pharmacies by using convenient sampling technique in the three respective cities namely Islamabad (118), Peshawar (120) and Lahore (133). The data collection tool was adapted from WHO structure observation form and was modified according to the objectives of the study.
MAIN OUTCOME MEASURES: The process of prescription handling at community pharmacies in terms of patient dispenser interaction, prescription validation and medication counseling was assessed. The data was coded, entered and analyzed by using SPSS Version 16.
RESULTS: A total of 1113 patient dispenser interactions were observed at the community pharmacies in the three respective cities namely Islamabad (n = 354), Peshawar (n = 360) and Lahore (n = 399). Out of 1113 patient/dispenser interactions the providers present at the community pharmacies were; pharmacist (degree of B-pharm/pharm D) 1.6% (n = 18), pharmacy assistant (diploma in pharmacy) 7% (n = 78), diploma holder (certified course of drug dispensing) 5.6% (n = 62) and salesmen (no medicine related education) 85.8% (n = 955).There was no significant difference in the practice between pharmacists, pharmacy assistants, diploma holders and salesmen. Prescription validation was carried out in 18% (n = 206) of the cases, drugs verification in 32% (n = 360) of the cases while labelling of drugs was performed in only 6% (n = 76) of the cases. Completely counselling about medication was provided in 3.1% (n = 35) of the cases while no counselling at all was given in 52.7% (n = 582) of the cases.
CONCLUSION: The process of medication counselling and dispensing practices at community pharmacies in Pakistan is not satisfactory. The patients are largely handled by unqualified salesmen. Thus there is a strong need to improve medication counselling and dispensing practices at community pharmacies by improving the skills of the dispensers through a mix of interventions, and law should be implemented to ensure presence of qualified person which in turn will result in the provision of better patient oriented services at community pharmacies.
METHOD: A mixed methods approach will be used. Qualitative part: Design: focus group discussions (FGDs) will be conducted.
SETTING: Hospital/NGOs in Terengganu, Malaysia.
PARTICIPANTS: Three FGDs will be conducted with male and female HIV/AIDS patients, and one group of local community leaders. One FGD will be conducted for each group. Three in-depth interviews (IDIs) will be conducted with patients who had HIV/AIDS, of which one will be female. Quantitative part: Design: a cluster randomized clinical trial with 384 HIV/AIDS patients in Terengganu, Malaysia.
INTERVENTION: Mobile SMS counselling intervention for patients concerning the prevention of HIV/AIDS.
RESULTS: The main outcomes of this study will be the differences in knowledge, attitude, and practices of patients concerning the prevention of HIV/AIDS between the baseline and immediate follow-up after the intervention, and after 3 months.
CONCLUSIONS: The mobile based SMS counselling intervention developed will be effective in improving the knowledge, attitude, and practices of patients concerning HIV/AIDS prevention in Terengganu, Malaysia.
TRIAL REGISTRATION: Thai Clinical Trials Registry, TCTR20200212001; 7/02/2020.