-
Vaccine Sep 2019The majority of countries with the highest rotavirus-associated death rates are in sub-Saharan Africa. In 2009, the World Health Organization (WHO) recommended routine...
BACKGROUND
The majority of countries with the highest rotavirus-associated death rates are in sub-Saharan Africa. In 2009, the World Health Organization (WHO) recommended routine vaccination against rotavirus worldwide, with unique age recommendations to administer the first dose before 15 weeks of age and last dose by 32 weeks of age. These age restrictions were relaxed in January 2013, but they may still lead to lower rotavirus vaccine coverage.
METHODS
Children age-eligible to have received rotavirus vaccine that were enrolled in Ghana, Zimbabwe, Rwanda or Burkina Faso's active rotavirus surveillance platforms from 2013 to 2017 and had a stool specimen that tested rotavirus-negative were included in the analysis. Proportion vaccinated and timeliness of rotavirus vaccine versus DTPw-HepB-Hib (pentavalent) first dose and last dose were compared at weeks 15 and 32, respectively, using Chi-square analyses. Odds ratios were calculated using logistic regression.
RESULTS
Among children who received rotavirus vaccine dose 1, 96-99% received this dose by 15 weeks of age and among children who received the last dose, 98-99% received it by 32 weeks of age. In all four countries, there was no significant difference in the proportion of children who received first dose rotavirus versus pentavalent vaccine by week 15, or last dose rotavirus versus concordant pentavalent vaccine by week 32. Delayed administration of first dose pentavalent vaccine was significantly associated with missing first dose of rotavirus vaccine in 3 of the 4 countries studied, although delays in administration were rare (1-4%).
CONCLUSIONS
Rotavirus vaccination was timely among sentinel sites in these four early rotavirus vaccine-introducing countries in Africa. Late presentation for vaccination may have resulted in some children with access to care missing first dose of rotavirus vaccine; however, vaccination delays were infrequent and therefore the potential impact of the age restrictions on overall proportion vaccinated was minimal.
Topics: Adult; Africa; Aged; Female; Hospitalization; Humans; Immunization Programs; Immunization Schedule; Male; Middle Aged; Rotavirus; Rotavirus Infections; Rotavirus Vaccines; Vaccination
PubMed: 31455587
DOI: 10.1016/j.vaccine.2019.08.008 -
Indian Journal of Nuclear Medicine :... 2020Radioiodine (I) therapy is approved and well-accepted modality for the treatment of hyperthyroidism. The dosage of I for successful treatment is based on many factors;...
PURPOSE OF THE STUDY
Radioiodine (I) therapy is approved and well-accepted modality for the treatment of hyperthyroidism. The dosage of I for successful treatment is based on many factors; however, an objective tool to determine the dose was missing. In a retrospective study, we found that high I uptake values required more dose to achieve desirable results contrary to the belief.
MATERIALS AND METHODS
Clinically and scintigraphically proven Graves' disease patients with high I uptake (>50%) were accrued for this study and block randomized into low-dose (Group I) and high-dose (Group II) groups. Low activity (5 mCi) was administered in Group I and higher activity (10 mCi) in Group II. The patients were followed up after 3 months with thyroid function tests to determine the outcome.
RESULTS
A total of 344 patients were analyzed at the end of 3 months, with 174 in low-dose group and 170 in high-dose group. Euthyroidism/hypothyroidism was achieved in significantly higher number of patients as compared to the low-dose group.
CONCLUSION
The higher dose of I is required to achieve euthyroidism/hypothyroidism in patients with high I uptake.
PubMed: 31949364
DOI: 10.4103/ijnm.IJNM_158_19 -
Vaccines Jul 2023As the world continues to urbanize, particularly in low- and middle-income countries, understanding the barriers and effective interventions to improve urban... (Review)
Review
INTRODUCTION
As the world continues to urbanize, particularly in low- and middle-income countries, understanding the barriers and effective interventions to improve urban immunization equity is critical to achieving both Immunization Agenda 2030 targets and the Sustainable Development Goals. Approximately 25 million children missed one or more doses of the diphtheria, tetanus and pertussis (DTP3) vaccine in 2021 and it is estimated that close to 30% of the world's children missing the first dose of DTP, known as zero-dose, live in urban and peri-urban settings.
METHODS
The aim of this research is to improve understanding of urban immunization equity through a qualitative review of mixed method studies, urban immunization strategies and funding proposals across more than 70 urban areas developed between 2016 and 2020, supported by Gavi, the Vaccine Alliance. These research studies and strategies created a body of evidence regarding the barriers to vaccination in urban settings and potential interventions relevant to low- and middle-income countries (LMICs) with a focus on the vaccination of urban poor, populations of concern and residents of informal settlements. Through the document review we identified common challenges to achieving equitable coverage in urban areas and mapped proposed interventions.
RESULTS
We identified 70 documents as part of the review and categorized results across (1) social determinants of health, (2) immunization service-delivery barriers and (3) quality of services. Barriers and solutions identified in the documents were categorized in these thematic areas, drawing information from results in more than 21 countries.
CONCLUSION
Populations of concern such as migrants, refugees, residents of informal settlements and the urban poor face barriers to accessing care which include poor availability and quality of service. Example solutions proposed to these challenges include tailored delivery strategies, improved use of digital data collection and child-friendly services. More research is required on the efficacy of the proposed interventions identified and on gender-specific dynamics in urban poor areas affecting equitable immunization coverage.
PubMed: 37515016
DOI: 10.3390/vaccines11071200 -
Diabetes Therapy : Research, Treatment... Sep 2021Controlling insulin-treated diabetes is challenging in low-resource settings where only Neutral Protamine Hagedorn (NPH), regular (R) and premixed insulin formulations...
INTRODUCTION
Controlling insulin-treated diabetes is challenging in low-resource settings where only Neutral Protamine Hagedorn (NPH), regular (R) and premixed insulin formulations are available, self-monitoring of blood glucose (SMBG) supplies are scarce and food insecurity is common. We examined the impact of a treatment protocol that includes sliding scale-based 70/30 insulin adjustments in Haiti.
METHODS
Thirty young patients aged 11-28 years with diabetes treated with premixed 70/30 insulin twice daily were included in the study. The participants performed one or two daily self-monitoring of blood glucose (SMBG) tests and attended our diabetes clinic monthly. They were randomized to two treatment groups, with one group remaining on the 70/30 insulin formulation (group 70 [G70]) and the other group switching to self-mixed NPH + R (group NR [GNR]). Sliding scales for insulin correction doses and meal insulin doses were designed based on the total daily insulin dose (TDD), carbohydrate ratio and insulin sensitivity factor. SMBG tests and insulin were administered before the morning and evening meals. The frequency of visits to the diabetes clinic was increased to biweekly during a 14-week follow-up.
RESULTS
Fifteen patients of each group were included in the analysis. Baseline characteristics, increase in total daily dose and number of missed SMBG tests and skipped meals at 14 weeks did not differ between the two groups. Hemoglobin A1c (HbA1c) decreased from 9.5% (interquartile range [IQR] 8.8, 10.5) (80.3 mmol/mol) to 8.0% (IQR 7.1%, 9.0%) (63.9 mmol/mol) in G70 (p = 0.01), and from 10.6% (IQR 8.1,% 13.1)% (92.4 mmol/mol) to 9.0% (IQR 7.6%, 9.6%) (74.9 mmol/mol) in GNR (p = 0.10), with no significant between-group difference in reductions (p = 0.12). No serious acute complications were reported. Stopping the use of sliding scales and resuming monthly visits increased HbA1c to values not significantly different from baseline in both groups after 15 weeks.
CONCLUSION
The use of sliding scales adjusted for missed SMBG tests and skipped meals, and frequent clinic visits that focus on patient self-management education significantly improved glycemic control in the patients with youth-onset diabetes in our study treated with premixed 70/30 human insulin in a low-resource setting.
PubMed: 34382158
DOI: 10.1007/s13300-021-01130-x -
Antimicrobial Agents and Chemotherapy May 2022The integrase strand transfer inhibitor (INSTI)-based regimens bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF), dolutegravir (DTG)+FTC/TAF, DTG/lamivudine...
The integrase strand transfer inhibitor (INSTI)-based regimens bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF), dolutegravir (DTG)+FTC/TAF, DTG/lamivudine (3TC), and DTG/rilpivirine (RPV) are all approved for treatment of HIV-infected patients, with various limitations. Here, time to viral breakthrough (VB) and resistance barrier using simulated human drug exposures at either full or suboptimal treatment adherence to each regimen were compared. At drug concentrations corresponding to full adherence and 1 missed dose ( and -1), no VB occurred with any regimen. At -2, VB occurred only with DTG+3TC, with emergent resistance to both drugs. At -3, VB occurred with all regimens: 100% of DTG+3TC cultures had VB by day 12, and <15% of BIC+FTC+TAF, DTG+FTC+TAF, and DTG+RPV cultures had VB. Emergent reverse transcriptase (RT) or integrase (IN) resistance was seen with DTG+RPV and DTG+3TC but not with BIC+FTC+TAF or DTG+FTC+TAF. At -4, 100% VB occurred with DTG+3TC and DTG+FTC+TAF by day 12, while 94% VB occurred with DTG+RPV by day 25 and only 50% VB occurred with BIC+FTC+TAF by day 35. Emergent -4 drug resistance was seen with all regimens but at differing frequencies; DTG+RPV had the most cultures with resistance. Emergent resistance was consistent with clinical observations. Overall, under high adherence conditions, no VB or resistance development occurred with these INSTI-based regimens. However, when multiple missed doses were simulated , BIC+FTC+TAF had the highest forgiveness and barrier to resistance of all tested regimens. Compared to DTG+3TC and DTG+FTC+TAF, DTG+RPV had higher forgiveness but lower resistance barrier after several simulated missed doses.
Topics: Anti-HIV Agents; Emtricitabine; Forgiveness; HIV Infections; Heterocyclic Compounds, 3-Ring; Humans; Integrases; Lamivudine; Pyridones
PubMed: 35389236
DOI: 10.1128/aac.02038-21 -
International Journal of Cardiology Jul 2016PEGASUS trial reported reduction of composite primary endpoint after conventional 180mg/daily ticagrelor (CT), and lower 120mg/daily dose ticagrelor (LT) at expense of...
PEGASUS trial reported reduction of composite primary endpoint after conventional 180mg/daily ticagrelor (CT), and lower 120mg/daily dose ticagrelor (LT) at expense of extra bleeding. Following approval of CT and LT for long-term secondary prevention indication, recent FDA review verified some bleeding outcomes in PEGASUS. To compare the risks after CT and LT against placebo by seven TIMI scale variables, and 9 bleeding categories considered as serious adverse events (SAE) in light of PEGASUS drug discontinuation rates (DDR). The DDR in all PEGASUS arms was high reaching astronomical 32% for CT. The distribution of some outcomes (TIMI major, trauma, epistaxis, iron deficiency, hemoptysis, and anemia) was reasonable. However, the TIMI minor events were heavily underreported when compared to similar trials. Other bleedings (intracranial, spontaneous, hematuria, and gastrointestinal) appear sporadic, lacking expected dose-dependent impact of CT and LT. Few SAE outcomes (fatal, ecchymosis, hematoma, bruises, bleeding) paradoxically reported more bleeding after LT than after CT. Many bleeding outcomes were probably missed in PEGASUS potentially due to massive non-compliance, information censoring, or both. The FDA must improve reporting of trial outcomes especially in the sponsor-controlled environment when DDR and incomplete follow-up rates are high.
Topics: Adenosine; Censorship, Research; Drug Administration Schedule; Hemorrhage; Humans; Myocardial Infarction; Randomized Controlled Trials as Topic; Ticagrelor
PubMed: 27128533
DOI: 10.1016/j.ijcard.2016.04.114 -
Drug Metabolism and Personalized Therapy Dec 2022To determine the impacts of missed phenobarbital (PB) doses on its pharmacokinetics and to investigate the appropriate replacement dosing scheme for various PB missed...
OBJECTIVES
To determine the impacts of missed phenobarbital (PB) doses on its pharmacokinetics and to investigate the appropriate replacement dosing scheme for various PB missed dose scenarios.
METHODS
Monte Carlo simulations were performed using parameters from the selected population pharmacokinetic study. The impacts of missed PB dose and the proper replacement dosing scheme were assessed based on the percent deviation of simulated concentrations outside the reference range from the full adherence scenario.
RESULTS
The impact of missed PB dose on its concentrations depended on the daily dose. The replacement with a respective regular dose and one and a half regular dose was appropriate for the one and two missed doses scenarios for patients receiving PB monotherapy. For patients receiving PB with valproic acid or phenytoin, the same replacement scheme was still appropriate. The results also indicated that weight did not influence the proper replacement dosing scheme.
CONCLUSIONS
The impacts of missed PB doses on its pharmacokinetics were identified and the proper replacement dosing schemes for different missed dose scenarios were proposed. These schemes should be implemented based on the clinician's justification of the patient's seizure control.
PubMed: 36476276
DOI: 10.1515/dmpt-2022-0104 -
Drug Metabolism and Personalized Therapy Jun 2022To determine the impacts of missed phenobarbital (PB) doses on its pharmacokinetics and to investigate the appropriate replacement dosing scheme for various PB missed...
OBJECTIVES
To determine the impacts of missed phenobarbital (PB) doses on its pharmacokinetics and to investigate the appropriate replacement dosing scheme for various PB missed dose scenarios.
METHODS
Monte Carlo simulations were performed using parameters from the selected population pharmacokinetic study. The impacts of missed PB dose and the proper replacement dosing scheme were assessed based on the percent deviation of simulated concentrations outside the reference range from the full adherence scenario.
RESULTS
The impact of missed PB dose on its concentrations depended on the daily dose. The replacement with a respective regular dose and one and a half regular dose was appropriate for the one and two missed doses scenarios for patients receiving PB monotherapy. For patients receiving PB with valproic acid or phenytoin, the same replacement scheme was still appropriate. The results also indicated that weight did not influence the proper replacement dosing scheme.
CONCLUSIONS
The impacts of missed PB doses on its pharmacokinetics were identified and the proper replacement dosing schemes for different missed dose scenarios were proposed. These schemes should be implemented based on the clinician's justification of the patient's seizure control.
PubMed: 35708353
DOI: 10.1515/dmdi-2022-0104 -
Frontiers in Toxicology 2023While targeted investigation of key toxicity pathways has been instrumental for biomarker discovery, unbiased and holistic analysis of transcriptomic data provides a...
While targeted investigation of key toxicity pathways has been instrumental for biomarker discovery, unbiased and holistic analysis of transcriptomic data provides a complementary systems-level perspective. However, in a systematic context, this approach has yet to receive comprehensive and methodical implementation. Here, we took an integrated bioinformatic approach by re-analyzing publicly available MCF7 cell TempO-seq data for 44 ToxCast chemicals using an alternative pipeline to demonstrate the power of this approach. The original study has focused on analyzing the gene signature approach and comparing them to biological pathway altering concentrations determined from ToxCast HTS assays. Our workflow, in comparison, involves sequential differential expression, gene set enrichment, benchmark dose modeling, and identification of commonly perturbed pathways by network visualization. Using this approach, we identified dose-responsive molecular changes, biological pathways, and points of departure in an untargeted manner. Critically, benchmark dose modeling based on pathways recapitulated points of departure for apical endpoints, while also revealing additional perturbed mechanisms missed by single endpoint analyses. This systems-toxicology approach provides multifaceted insights into the complex effects of chemical exposures. Our work highlights the importance of unbiased data-driven techniques, alongside targeted methods, for comprehensively evaluating molecular initiating events, dose-response relationships, and toxicity pathways. Overall, integrating omics assays with robust bioinformatics holds promise for improving chemical risk assessment and advancing new approach methodologies (NAMs).
PubMed: 38046401
DOI: 10.3389/ftox.2023.1272364