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Journal of Medical Internet Research Feb 2022Nonadherence to medication in tuberculosis (TB) hampers optimal treatment outcomes. Digital health technology (DHT) seems to be a promising approach to managing problems... (Review)
Review
BACKGROUND
Nonadherence to medication in tuberculosis (TB) hampers optimal treatment outcomes. Digital health technology (DHT) seems to be a promising approach to managing problems of nonadherence to medication and improving treatment outcomes.
OBJECTIVE
This paper systematically reviews the effect of DHT in improving medication adherence and treatment outcomes in patients with TB.
METHODS
A literature search in PubMed and Cochrane databases was conducted. Randomized controlled trials (RCTs) that analyzed the effect of DHT interventions on medication adherence outcomes (treatment completion, treatment adherence, missed doses, and noncompleted rate) and treatment outcomes (cure rate and smear conversion) were included. Adult patients with either active or latent TB infection were included. The Jadad score was used for evaluating the study quality. The PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guideline was followed to report study findings.
RESULTS
In all, 16 RCTs were selected from 552 studies found, and 6 types of DHT interventions for TB were identified: 3 RCTs examined video directly observed therapy (VDOT), 1 examined video-observed therapy (VOT), 1 examined an ingestible sensor, 1 examined phone call reminders, 2 examined medication monitor boxes, and 8 examined SMS text message reminders. The outcomes used were treatment adherence, including treatment completion, treatment adherence, missed dose, and noncompleted rate, as well as clinical outcomes, including cure rate and smear conversion. In treatment completion, 4 RCTs (VDOT, VOT, ingestible sensor, SMS reminder) found significant effects, with odds ratios and relative risks (RRs) ranging from 1.10 to 7.69. Treatment adherence was increased in 1 study by SMS reminders (RR 1.05; 95% CI 1.04-1.06), and missed dose was reduced in 1 study by a medication monitor box (mean ratio 0.58; 95% CI 0.42-0.79). In contrast, 3 RCTs of VDOT and 3 RCTs of SMS reminders did not find significant effects for treatment completion. Moreover, no improvement was found in treatment adherence in 1 RCT of VDOT, missed dose in 1 RCT of SMS reminder, and noncompleted rate in 1 RCT of a monitor box, and 2 RCTs of SMS reminders. For clinical outcomes such as cure rate, 2 RCTs reported that phone calls (RR 1.30; 95% CI 1.07-1.59) and SMS reminders (OR 2.47; 95% CI 1.13-5.43) significantly affected cure rates. However, 3 RCTs found that SMS reminders did not have a significant impact on cure rate or smear conversion.
CONCLUSIONS
It was found that DHT interventions can be a promising approach. However, the interventions exhibited variable effects regarding effect direction and the extent of improving TB medication adherence and clinical outcomes. Developing DHT interventions with personalized feedback is required to have a consistent and beneficial effect on medication adherence and outcomes among patients with TB.
Topics: Adult; Biomedical Technology; Cell Phone; Humans; Medication Adherence; Randomized Controlled Trials as Topic; Reminder Systems; Text Messaging; Treatment Outcome; Tuberculosis
PubMed: 35195534
DOI: 10.2196/33062 -
Lancet (London, England) Sep 2020The anti-progesterone drug mifepristone and the prostaglandin misoprostol can be used to treat missed miscarriage. However, it is unclear whether a combination of... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
The anti-progesterone drug mifepristone and the prostaglandin misoprostol can be used to treat missed miscarriage. However, it is unclear whether a combination of mifepristone and misoprostol is more effective than administering misoprostol alone. We investigated whether treatment with mifepristone plus misoprostol would result in a higher rate of completion of missed miscarriage compared with misoprostol alone.
METHODS
MifeMiso was a multicentre, double-blind, placebo-controlled, randomised trial in 28 UK hospitals. Women were eligible for enrolment if they were aged 16 years and older, diagnosed with a missed miscarriage by pelvic ultrasound scan in the first 14 weeks of pregnancy, chose to have medical management of miscarriage, and were willing and able to give informed consent. Participants were randomly assigned (1:1) to a single dose of oral mifepristone 200 mg or an oral placebo tablet, both followed by a single dose of vaginal, oral, or sublingual misoprostol 800 μg 2 days later. Randomisation was managed via a secure web-based randomisation program, with minimisation to balance study group assignments according to maternal age (<30 years vs ≥30 years), body-mass index (<35 kg/mvs ≥35 kg/m), previous parity (nulliparous women vs parous women), gestational age (<70 days vs ≥70 days), amount of bleeding (Pictorial Blood Assessment Chart score; ≤2 vs ≥3), and randomising centre. Participants, clinicians, pharmacists, trial nurses, and midwives were masked to study group assignment throughout the trial. The primary outcome was failure to spontaneously pass the gestational sac within 7 days after random assignment. Primary analyses were done according to intention-to-treat principles. The trial is registered with the ISRCTN registry, ISRCTN17405024.
FINDINGS
Between Oct 3, 2017, and July 22, 2019, 2595 women were identified as being eligible for the MifeMiso trial. 711 women were randomly assigned to receive either mifepristone and misoprostol (357 women) or placebo and misoprostol (354 women). 696 (98%) of 711 women had available data for the primary outcome. 59 (17%) of 348 women in the mifepristone plus misoprostol group did not pass the gestational sac spontaneously within 7 days versus 82 (24%) of 348 women in the placebo plus misoprostol group (risk ratio [RR] 0·73, 95% CI 0·54-0·99; p=0·043). 62 (17%) of 355 women in the mifepristone plus misoprostol group required surgical intervention to complete the miscarriage versus 87 (25%) of 353 women in the placebo plus misoprostol group (0·71, 0·53-0·95; p=0·021). We found no difference in incidence of adverse events between the study groups.
INTERPRETATION
Treatment with mifepristone plus misoprostol was more effective than misoprostol alone in the management of missed miscarriage. Women with missed miscarriage should be offered mifepristone pretreatment before misoprostol to increase the chance of successful miscarriage management, while reducing the need for miscarriage surgery.
FUNDING
UK National Institute for Health Research Health Technology Assessment Programme.
Topics: Abortion, Missed; Adult; Double-Blind Method; Drug Therapy, Combination; Humans; Mifepristone; Misoprostol; Oxytocics; Treatment Outcome
PubMed: 32853559
DOI: 10.1016/S0140-6736(20)31788-8 -
Journal of Clinical Hypertension... May 2019In a multicenter, randomized trial, we investigated whether the long half-time dihydropyridine calcium channel blocker amlodipine was more efficacious than the... (Randomized Controlled Trial)
Randomized Controlled Trial
In a multicenter, randomized trial, we investigated whether the long half-time dihydropyridine calcium channel blocker amlodipine was more efficacious than the gastrointestinal therapeutic system (GITS) formulation of nifedipine in lowering ambulatory blood pressure (BP) in sustained hypertension (clinic systolic/diastolic BP 140-179/90-109 mm Hg and 24-hour systolic/diastolic BP ≥ 130/80 mm Hg). Eligible patients were randomly assigned to amlodipine 5-10 mg/day or nifedipine-GITS 30-60 mg/day. Ambulatory BP monitoring was performed for 24 hours at baseline and 4-week treatment and for 48 hours at 8-week treatment with a dose of medication missed on the second day. After 8-week treatment, BP was similarly reduced in the amlodipine (n = 257) and nifedipine-GITS groups (n = 248) for both clinic and ambulatory (24-hour systolic/diastolic BP 10.3/6.5 vs 10.9/6.3 mm Hg, P ≥ 0.24) measurements. However, after missing a dose of medication, ambulatory BP reductions were greater in the amlodipine than nifedipine-GITS group, with a significant (P ≤ 0.04) between-group difference in 24-hour (-1.2 mm Hg) and daytime diastolic BP (-1.5 mm Hg). In conclusion, amlodipine and nifedipine-GITS were efficacious in reducing 24-hour BP. When a dose of medication was missed, amlodipine became more efficacious than nifedipine-GITS.
Topics: Amlodipine; Blood Pressure; Blood Pressure Monitoring, Ambulatory; Calcium Channel Blockers; Case-Control Studies; China; Circadian Rhythm; Female; Humans; Hypertension; Male; Middle Aged; Nifedipine; Safety; Treatment Outcome
PubMed: 30973207
DOI: 10.1111/jch.13543 -
Vaccine Sep 2022'Zero-dose' refers to a person who does not receive a single dose of any vaccine in the routine national immunization schedule, while 'missed dose' refers to a person... (Review)
Review
'Zero-dose' refers to a person who does not receive a single dose of any vaccine in the routine national immunization schedule, while 'missed dose' refers to a person who does not complete the schedule. These peopleremain vulnerable to vaccine-preventable diseases, and are often already disadvantaged due to poverty, conflict, and lack of access to basic health services. Globally, more 22.7 million children are estimated to be zero- or missed-dose, of which an estimated 3.1 million (∼14 %) reside in Nigeria.We conducted a scoping review tosynthesize recent literature on risk factors and interventions for zero- and missed-dosechildren in Nigeria. Our search identified 127 papers, including research into risk factors only (n = 66); interventions only (n = 34); both risk factors and interventions (n = 18); and publications that made recommendations only (n = 9). The most frequently reported factors influencing childhood vaccine uptake were maternal factors (n = 77), particularly maternal education (n = 22) and access to ante- and perinatal care (n = 19); heterogeneity between different types of communities - including location, region, wealth, religion, population composition, and other challenges (n = 50); access to vaccination, i.e., proximity of facilities with vaccines and vaccinators (n = 37); and awareness about immunization - including safety, efficacy, importance, and schedules (n = 18).Literature assessing implementation of interventions was more scattered, and heavily skewed towards vaccination campaigns and polio eradication efforts. Major evidence gaps exist in how to deliver effective and sustainable routine childhood immunization. Overall, further work is needed to operationalise the learnings from these studies, e.g. through applying findings to Nigeria's next review of vaccination plans, and using this summary as a basis for further investigation and specific recommendations on effective interventions.
Topics: Child; Female; Humans; Immunization; Immunization Programs; Infant; Nigeria; Poliomyelitis; Pregnancy; Vaccination; Vaccines
PubMed: 35973864
DOI: 10.1016/j.vaccine.2022.07.058 -
Frontiers in Oncology 2022Dose painting (DP) is a radiation therapy (RT) strategy for patients with heterogeneous tumors delivering higher dose to radiation resistant regions and less to...
PURPOSE
Dose painting (DP) is a radiation therapy (RT) strategy for patients with heterogeneous tumors delivering higher dose to radiation resistant regions and less to sensitive ones, thus aiming to maximize tumor control with limited side effects. The success of DP treatments is influenced by the spatial accuracy in dose delivery. Adaptive RT (ART) workflows can reduce the overall geometric dose delivery uncertainty. The purpose of this study is to dosimetrically compare ART and non-adaptive conventional RT workflows for delivery of DP prescriptions in the treatment of prostate cancer (PCa).
MATERIALS AND METHODS
We performed a planning and treatment simulation study of four study arms. Adaptive and conventional workflows were tested in combination with DP and Homogeneous dose. We used image data from 5 PCa patients that had been treated on the Elekta Unity MR linac; the patients had been imaged in treatment position before each treatment fraction (7 in total). The local radiation sensitivity from apparent diffusion coefficient maps of 15 high-risk PCa patients was modelled in a previous study. these maps were used as input for optimization of DP plans aiming for maximization of tumor control probability (TCP) under rectum dose constraints. A range of prostate doses were planned for the homogeneous arms. Adaptive plans were replanned based on the anatomy-of-the-day, whereas conventional plans were planned using a pre-treatment image and subsequently recalculated on the anatomy-of-the-day. The dose from 7 fractions was accumulated using dose mapping. The endpoints studied were the TCP and dose-volume histogram metrics for organs at risk.
RESULTS
Accumulated DP doses (adaptive and conventional) resulted in high TCP, between 96-99%. The largest difference between adaptive and conventional DP was 2.6 percentage points (in favor of adaptive DP). An analysis of the dose per fraction revealed substantial target misses for one patient in the conventional workflow that-if systematic-could jeopardize the TCP. Compared to homogeneous prescriptions with equal mean prostate dose, DP resulted in slightly higher TCP.
CONCLUSION
Compared to homogeneous dose, DP maintains or marginally increases the TCP. Adaptive DP workflows could avoid target misses compared to conventional workflows.
PubMed: 36237318
DOI: 10.3389/fonc.2022.973067 -
International Journal of Pharmaceutics Jul 2022Cocrystals have been extensively used to improve the physicochemical properties and bioavailability of active pharmaceutical ingredients. Cocrystals of anti-tuberculosis... (Review)
Review
Cocrystals have been extensively used to improve the physicochemical properties and bioavailability of active pharmaceutical ingredients. Cocrystals of anti-tuberculosis medications are among those commonly reported. This review provides a summary of the tuberculosis antibiotic cocrystals reported in the literature, providing the main results on current tuberculosis medications utilized in cocrystals. Moreover, anti-tuberculosis cocrystals limitations and advantages are described, including evidence for enhanced solubility, stability and effect. Opportunities to enhance anti-tuberculosis medications and fixed dose combinations using cocrystals are given. Several cocrystal pairs are suggested to enhance the effectiveness of anti-tuberculosis drugs.
Topics: Anti-Bacterial Agents; Biological Availability; Crystallization; Solubility
PubMed: 35738333
DOI: 10.1016/j.ijpharm.2022.121924 -
CPT: Pharmacometrics & Systems... Dec 2022Response-based dose individualization or dose titration is a powerful approach to achieve precision dosing. Yet, titration as an individualization strategy is underused...
Response-based dose individualization or dose titration is a powerful approach to achieve precision dosing. Yet, titration as an individualization strategy is underused in drug development and therefore not reflected in labeling, possibly partly because of the data analysis challenges associated with assessing dose/exposure-response under dose titration, where there is an inherent risk of selection bias because poor responders would get high doses, whereas good responders would get low doses. In a recent article, this issue of selection bias was termed the "titration paradox." In this study, we demonstrate by means of simulation that the titration paradox may be overcome if longitudinal data from dose titration trials is analyzed using a population approach that accounts for the fact that dose/exposure-response relationships differ between individuals. We show that with an appropriate sample size and missing data missing at random, stepwise dose/exposure-response modeling based on data obtained under dose titration is not by definition subject to model selection bias or bias in parameter estimates. We also illustrate the challenges of graphical exploration of data obtained under dose titration and discuss the use of model diagnostic tools with such data. Our study shows that if, at every timepoint in the course of a trial, there is a clear causal relationship between the response and the dose/exposure level, and a population approach is used, it will in many cases be possible to develop, estimate, and appropriately qualify a dose/exposure-response model also for data obtained under dose titration, thus overcoming the titration paradox.
Topics: Humans; Computer Simulation; Dose-Response Relationship, Drug
PubMed: 36125910
DOI: 10.1002/psp4.12863 -
Journal of Family Medicine and Primary... Oct 2021The aging population is of growing concern all across the globe as well as in India. Polypharmacy has been defined as the simultaneous use of multiple medications by an... (Review)
Review
The aging population is of growing concern all across the globe as well as in India. Polypharmacy has been defined as the simultaneous use of multiple medications by an individual and the clinical suitability of such use. Polypharmacy is found more frequently in the geriatric population. Researches in India have also reiterated the fact. Polypharmacy in the geriatric population leads to many negative consequences such as increased adverse drug reactions, falls, frailty, and even increased mortality. Moreover, it leads to increased out-of-pocket expenditure. Polypharmacy also poses risk of poor treatment adherence and missed dose in the geriatric population. Mitigation measures in this regard may include increased awareness among physicians, improved medication management and adherence, efforts to reduce self-medication, and improper crosspathy.
PubMed: 34934644
DOI: 10.4103/jfmpc.jfmpc_2581_20 -
PLOS Global Public Health 2022Initiating with a birth dose and a full immunization against hepatitis-B is crucial during early childhood in a country like India where maternal screening of...
Initiating with a birth dose and a full immunization against hepatitis-B is crucial during early childhood in a country like India where maternal screening of hepatitis-B surface antigen is almost negligible and there is a considerable risk of vertical transmission among children. It is also evident that coverage of hepatitis-B is lowest among all other vaccine doses included in the universal immunization program. In addition, the major challenge is posed by the missed and drop-out of different doses of hepatitis-B among Indian children. In this context, this study examined the population and sub-national level diversity in missed and dropout of different doses of hepatitis-B vaccine in India. We analysed a large dataset of 196,654 children aged 12-59 months from a nationally representative cross-sectional survey, the National Family Health Survey (NFHS), 2015-16. Bivariate cross tabulation was used to estimate the prevalence and the dropout rates. Multivariable-adjusted logistic regression was applied to assess the likelihood of the study events. Within a Bayesian framework, a district-level spatial analysis was conducted employing the Besag-York-Mollie (BYM) Model and the Leroux Model. During 2016, 38% of the children missed the birth dose nationally and 45% of the children did not complete full immunization of hepatitis-B. Findings suggest, presence of socio-economic and demographic gradients in missed and drop-out of different doses of hepatitis-B at national level. The sub-national level spatial analysis identifies more than 280 (out of 640) districts with substantially higher risk (Posterior Median Risk>1) in terms of missed and drop-out of different doses. Most of these districts are scattered across the North-Eastern and Northern part of India. The findings hint the existence of a population and sub-national level diversity in India's missed out and dropout of hepatitis-B doses. Identifying high risk population sub-groups and the districts with children at higher risk of missing the birth and consecutive doses informs the existing knowledge base and helps in formulating community-oriented policies and programs.
PubMed: 36962208
DOI: 10.1371/journal.pgph.0000243