COHESION: a core outcome set for the treatment of neonatal encephalopathy.

BACKGROUND: Heterogeneity in outcomes reported in trials of interventions for the treatment of neonatal encephalopathy (NE) makes evaluating the effectiveness of treatments difficult. Developing a core outcome set for NE treatment would enable researchers to measure and report the same outcomes in future trials. This would minimise waste, ensure relevant outcomes are measured and enable evidence synthesis. Therefore, we aimed to develop a core outcome set for treating NE. METHODS: Outcomes identified from a systematic review of the literature and interviews with parents were prioritised by stakeholders (n = 99 parents/caregivers, n = 101 healthcare providers, and n = 22 researchers/ academics) in online Delphi surveys. Agreement on the outcomes was achieved at online consensus meetings attended by n = 10 parents, n = 18 healthcare providers, and n = 13 researchers/ academics. RESULTS: Seven outcomes were included in the final core outcome set: survival; brain injury on imaging; neurological status at discharge; cerebral palsy; general cognitive ability; quality of life of the child, and adverse events related to treatment. CONCLUSION: We developed a core outcome set for the treatment of NE. This will allow future trials to measure and report the same outcomes and ensure results can be compared. Future work should identify how best to measure the COS. IMPACT: We have identified seven outcomes that should be measured and reported in all studies for the treatment of neonatal encephalopathy. Previously, a core outcome set for neonatal encephalopathy treatments did not exist. This will help to reduce heterogeneity in outcomes reported in clinical trials and other studies, and help researchers identify the best treatments for neonatal encephalopathy.

Prevention of CCl4 induced hypogonadism with Raphanus sativus seeds in rat.

Raphanus sativus seeds are used as condiment and to treat hypogonadism, various ailments of liver and kidneys. The aim of this study was to evaluate the potential protective effects of methanol extract of R. sativus seeds (RSME) against hypogonadism induced with carbon tetrachloride (CCl4) in Sprague-Dawley male rats. Thirty six rats were divided in to six groups with six animals in each. Animals of Group I were control and treated with saline, Group II, III and IV were given orally CCl4 (1 ml/kg bw; 10% in corn oil). Rats of Group III and IV were also simultaneously given RSME at 100 mg/kg bw and 200 mg/kg bw respectively. However, Group V and VI received RSME (100; 200 mg/kg bw, respectively) alone. All treatments were given at alternate days for 15 days. Treatment of CCl4 to rats decreased (P < 0.001) the level of CAT, POD, SOD, GST, GSH-Px and GSR antioxidant enzymes in testes of rat. Concentration of lipid peroxides (TBARS) was increased (P < 0.001) whereas concentration of GSH was decreased (P < 0.001) in testes of CCl4 treated animals. Concentration of testosterone, FSH and LH in serum was decreased (P < 0.001) while the level of estradiol and prolactin was increased (P < 0.001) in CCl4 treated rats. Injuries in seminiferous tubules were determined in histopathology of testes. Administration of RSME, dose dependently, markedly ameliorated the oxidative stress of CCl4 thereby restoring the level of antioxidant enzymes, lipid peroxides, reduced glutathione, male hormones and alterations in histopathology.

Absorbed zinc and exchangeable zinc pool size are greater in Pakistani infants receiving traditional complementary foods with zinc-fortified micronutrient powder.

Adequacy of zinc intake from breast milk alone becomes marginal in relation to infant requirements by around 6 mo of age. Simple and cost-effective strategies are needed at the population level to ensure adequate intakes of zinc in infants and toddlers in populations at risk of zinc deficiency. We determined the amount of absorbed zinc (AZ) from a micronutrient powder (MNP) without and with 10 mg of zinc (MNP+Zn) added to local complementary foods used in Pakistan and the impact on the exchangeable zinc pool (EZP) size. As a nested study within a large, prospective, cluster randomized trial, 6-mo-old infants were randomly assigned to receive MNP or MNP+Zn. Stable isotope methodology was applied after ∼3 and 9 mo of use to measure AZ from MNP-fortified test meals of rice-lentils (khitchri) and EZP. Nineteen infants per group completed the first metabolic studies and 14 and 17 infants in the MNP and MNP+Zn groups, respectively, completed the follow-up studies. AZs were (mean ± SD) 0.1 ± 0.1 and 1.2 ± 0.5 mg at the first point for the MNP and MNP+Zn groups, respectively (P < 0.001); results were nearly identical at the follow-up measurement. EZP did not differ between groups at the first measurement but was less in the MNP group (3.7 ± 0.6 mg/kg) than in the MNP+Zn group (4.5 ± 1.0 mg/kg) at the second measurement (P = 0.01). These data confirm that the MNP+Zn in khitchri were well absorbed and after 1 y of home fortification, zinc status assessed by EZP was significantly better for the MNP+Zn group. Additional field studies may be necessary to ascertain the adequacy of this dose for infants at high risk of deficiency. This trial was registered at ClinicalTrials.gov as NCT00705445.

Exploring Knowledge and Perceptions of Polio Disease and Its Immunization in Polio High-Risk Areas of Pakistan.

Pakistan is one of the few countries where poliovirus transmission still persists, despite intensive efforts to eradicate the disease. Adequate vaccination coverage is essential to achieve polio eradication, but misconceptions about polio vaccines have hindered vaccination efforts. To address this issue, we conducted a mixed-methods study to explore knowledge and perceptions regarding polio disease and immunization in high-risk areas of Pakistan. We collected quantitative data from 3780, 1258, and 2100 households in Karachi, Bajaur, and Pishin, respectively, and supplemented this with qualitative data from focus group discussions and in-depth interviews. Our findings reveal a high level of awareness about polio and its immunization; however, misperceptions about the polio vaccine persist, leading to refusal for both polio vaccines and routine immunizations. Our study provides up-to-date data on knowledge and perceptions of polio and its immunization and identifies critical gaps. These findings can inform the development of future strategies and innovative approaches to improve the success of the polio program in Pakistan.

Factors Associated with Vaccine Refusal (Polio and Routine Immunization) in High-Risk Areas of Pakistan: A Matched Case-Control Study.

BACKGROUND: Pakistan has subpar childhood immunization rates and immunization activities have faced several challenges over the past years. We evaluated the social-behavioral and cultural barriers and risk factors for refusal of polio, Routine Immunization (RI), or both in high-risk areas of poliovirus circulation. METHODS: A matched case-control study was conducted from April to July 2017 in eight super high-risk Union Councils of five towns in Karachi, Pakistan. A total of 3 groups, each with 250 cases, including refusals for the Oral Polio Vaccine (OPV) in campaigns (national immunization days and supplementary immunization activities), RI, and both, were matched with 500 controls and identified using surveillance records. Sociodemographic characteristics, household information, and immunization history were assessed. Study outcomes included social-behavioral and cultural barriers and reasons for vaccine refusal. Data were analyzed in STATA using conditional logistic regression. RESULTS: RI refusal was associated with illiteracy and fear of the vaccine's adverse effects, while OPV refusals were linked to the mother's decision authority and the assumption that the OPV caused infertility. Conversely, higher socioeconomic status (SES) and knowledge of and willingness to vaccinate with Inactivated Polio Vaccine (IPV) were inversely associated with RI; and lower SES, walking to the vaccination point, knowledge of IPV, and an understanding of contracting polio were inversely associated with OPV refusals, with the latter two also inversely associated with complete vaccine refusal. CONCLUSION: Education, knowledge and understanding of vaccines, and socioeconomic determinants influenced OPV and RI refusals among children. Effective interventions are needed to address knowledge gaps and misconceptions among parents.

The Last Mile-Community Engagement and Conditional Incentives to Accelerate Polio Eradication in Pakistan: Study Protocol for a Quasi-Experimental Trial.

Poliomyelitis is a condition of great concern and is endemic in only two countries of the world: Pakistan and Afghanistan. Community mobilization plays a vital role in raising awareness and can help reduce polio vaccine refusals. The objective of this study will be to decrease polio vaccine refusals and zero-dose vaccines by motivating behavior change through the provision of conditional-collective-community-based incentives (C3Is) based on a reduction in polio vaccine refusals. The project will adopt a pretest/post-test quasi-experimental design with two intervention high-risk union councils (HRUCs) and two control union councils (UCs) of peri-urban (Karachi) and rural (Bannu) settings in Pakistan. A participatory community engagement and demand creation strategy with trust-building community mobilization with C3Is, to reduce vaccine refusals and improve polio immunization coverage in two HRUCs, will be used. These UCs will be divided into clusters based on the polio program framework and community groups will be formed in each cluster. These community groups will carry out awareness activities and will be given serial targets to reduce vaccine refusals and those who qualify will be provided C3Is. The project intends to create a replicable model that the government can integrate within health systems for long-term sustainability until the goal of eradication of poliovirus is achieved. The evaluation will be carried out by an independent data collection and analysis team at baseline and endline (after 12 months of intervention). The trial is registered with linicalTrials.gov with number NCT05721274.

Multi-Round versus Real-Time Delphi survey approach for achieving consensus in the COHESION core outcome set: a randomised trial.

BACKGROUND: Delphi surveys are commonly used to prioritise critical outcomes in core outcome set (COS) development. This trial aims to compare a three-round (Multi-Round) Delphi (MRD) with a Real-Time Delphi (RTD) in the prioritisation of outcomes for inclusion in a COS for neonatal encephalopathy treatments and explore whether 'feedback', 'iteration', and 'initial condition' effects may occur in the two survey methods. METHODS: We recruited 269 participants (parents/caregivers, healthcare providers and researchers/academics) of which 222 were randomised to either the MRD or the RTD. We investigated the outcomes prioritised in each survey and the 'feedback', 'iteration', and 'initial condition' effects to identify differences between the two survey methods. RESULTS: In the RTD, n = 92 participants (83%) fully completed the survey. In the MRD, n = 60 participants (54%) completed all three rounds. Of the 92 outcomes presented, 26 (28%) were prioritised differently between the RTD and MRD. Significantly fewer participants amended their scores when shown stakeholder responses in the RTD compared to the MRD ('feedback effect'). The 'iteration effect' analysis found most experts appeared satisfied with their initial ratings in the RTD and did not amend their scores following stakeholder response feedback. Where they did amend their scores, ratings were amended substantially, suggesting greater convergence. Variance in scores reduced with subsequent rounds of the MRD ('iteration effect'). Whilst most participants did not change their initial scores in the RTD, of those that did, later recruits tended to align their final score more closely to the group mean final score than earlier recruits (an 'initial condition' effect). CONCLUSION: The feedback effect differed between the two Delphi methods but the magnitude of this difference was small and likely due to the large number of observations rather than because of a meaningfully large difference. It did not appear to be advantageous to require participants to engage in three rounds of a survey due to the low change in scores. Larger drop-out through successive rounds in the MRD, together with a lesser convergence of scores and longer time to completion, indicate considerable benefits of the RTD approach. TRIAL REGISTRATION: NCT04471103. Registered on 14 July 2020.

Core outcomes in neonatal encephalopathy: a qualitative study with parents.

OBJECTIVE: To identify the outcomes considered important to parents or caregivers of infants diagnosed with neonatal encephalopathy, hypoxic ischaemic encephalopathy or birth asphyxia in high-income and low- to middle-income countries (LMiCs), as part of the outcome-identification process in developing a core outcome set (COS) for the treatment of neonatal encephalopathy. DESIGN: A qualitative study involving 25 semistructured interviews with parents or other family members (caregivers) of infants who were diagnosed with, and treated for, neonatal encephalopathy, hypoxic ischaemic encephalopathy or birth asphyxia. SETTING: Interviews were conducted in high-income countries (HiCs) (n=11) by Zoom video conferencing software and in LMiCs (n=14) by phone or face to face. FINDINGS: Parents identified 54 outcomes overall, which mapped to 16 outcome domains. The domains identified were neurological outcomes, respiratory outcomes, gastrointestinal outcomes, cardiovascular outcomes, motor development, cognitive development, development (psychosocial), development (special senses), cognitive development, development (speech and social), other organ outcomes, survival/living outcomes, long-term disability, hospitalisation, parent-reported outcomes and adverse events. CONCLUSIONS: This study provides insight into the outcomes that parents of infants diagnosed with neonatal encephalopathy have identified as the most important, to be considered in the process of developing a COS for the treatment of neonatal encephalopathy. We also provide description of the processes employed to ensure the inclusion of participants from LMiCs as well as HiCs.

Knowledge and perceptions of polio and polio immunization in polio high-risk areas of Pakistan.

Pakistan and Afghanistan remain the only countries where polio is endemic, and Pakistan reports the most cases in the world. Although the rate is lower than in previous years, the situation remains alarming. We conducted a mixed methods study in high-risk areas of Pakistan to identify knowledge, attitudes, and practices of target populations about polio vaccine and its eradication, and to estimate coverage of routine immunization and oral polio vaccine. We surveyed 10,685 households in Karachi, 2522 in Pishin, and 2005 in Bajaur. Some knowledge of polio is universal, but important misconceptions persist. The findings of this study carry strategic importance for program direction and implementation.