Report from the World Health Organization's immunization and vaccines-related implementation research advisory committee (IVIR-AC) meeting, virtual gathering, 26 February-1 March 2024.

The Immunization and Vaccine-related Implementation Research Advisory Committee (IVIR-AC) is the World Health Organization's key standing advisory body to conduct an independent review of research, particularly of transmission and economic modeling analyses that estimate the impact and value of vaccines. From 26th February-1st March 2024, at its first of two semi-annual meetings, IVIR-AC provided feedback and recommendations across four sessions; this report summarizes the proceedings and recommendations from that meeting. Session topics included modeling of the impact and cost-effectiveness of the R21/Matrix-M malaria vaccine, meta-analysis of economic evaluations of vaccines, a global analysis estimating the impact of vaccination over the last 50 years, and modeling the impact of different RTS,S malaria vaccine dose schedules in seasonal settings.

VTE1 and VTE3 Gene Expression During Vitamin E Production in Sunflower (Helianthus annuus L.) Treated with Different Fertilization.

<b>Background and Objective:</b> Sunflower is one of the important commodities in agriculture. The oil content in sunflower seeds has been widely used as cooking oil, but in Indonesia, the utilization of this oil is still relatively low. In addition, sunflowers also contain vitamin E which is useful as an antioxidant, so it can be used to reduce the risk of cardiovascular disease. This study aims to determine gene expression at the RNA level towards vitamin E biosynthesis using different fertilization treatments. <b>Materials and Methods:</b> Sunflowers that had been given different fertilizers were taken in three flowering phases, R3, R5 and R8. Flower samples were isolated until RNA was obtained. The isolation results were tested using real-time PCR to determine the relative gene expression of the <i>VTE1</i> and <i>VTE3</i> genes. After the sunflower seeds were fully ripe, vitamin E content was tested in each treatment and the results were compared with the relative gene expression obtained. <b>Results:</b> The results obtained were fluctuating, but in general, the relative gene expression obtained in the <i>VTE1</i> gene increased in the R3 phase and then decreased in the R5 and R8 phases. Whereas, in the <i>VTE3</i> gene, the relative gene expression obtained experienced an increase in the R3 and R5 phases and then decreased in the R8 phase. The highest vitamin E content was obtained by sample P3 (4218 µg mL¹) and the lowest was obtained by sample P2 (1798 µg mL¹). <b>Conclusion:</b> A balanced ratio of 92:46:30 kg ha¹ of major nutrient fertilizer involving N, P and K could increase vitamin E content in sunflowers. Such a combination exhibited stable expression of the <i>VTE1</i> and <i>VTE3</i> genes in all phases of flowering.

Regulatory enforcement of the marketing of fixed-dose combinations in India: a case study of systemic antibiotics.

BACKGROUND: In India, states have licensed the manufacture of large numbers of fixed-dose combination (FDC) drugs without the required prior approval of the central regulator. This paper describes two major regulatory initiatives to address the problem, which began in 2007 and 2013, and examines whether they have been sufficient to remove centrally unapproved systemic antibiotic FDCs from the market. METHODS: Information was extracted from documents published by the central regulator and the ministry of health, including the National List of Essential Medicines (NLEM), and court judgments, and analysed alongside sales volume data for 2008-2020 using PharmaTrac market dataset. RESULTS: The regulatory initiatives permitted 68 formulations to be given de facto approvals ('No Objection Certificates') outside the statutory regime, banned 46 FDCs and restricted one FDC. Market data show that FDCs as a proportion of total antibiotic sales increased from 32.9 in 2008 to 37.3% in 2020. The total number of antibiotic FDC formulations on the market fell from 574 (2008) to 395 (2020). Formulations with a record of prior central approval increased from 86 (2008) to 94 (2020) and their share of the antibiotic FDC sales increased from 32.0 to 55.3%. In 2020, an additional 23 formulations had been permitted de facto approval, accounting for 10.6% of the antibiotic FDC sales. Even in 2020, most marketed formulations (70.4%, 278/395) were unapproved or banned, and comprised a 15.9% share of the antibiotic FDC sales. The share of NLEM-listed antibiotic FDC sales increased from 21.2 (2008) to 26.7% (2020). CONCLUSION: The initiatives had limited impact. Regulatory enforcement has been slow and weak, with many unapproved, and even banned, FDCs remaining on the market.

Antibiotics Prescriptions Pattern among Patients Visiting Primary Health Care Centers (PHCC) before and during COVID-19 Pandemic: A Cross-Sectional Population-Based Study from Qatar.

BACKGROUND: The COVID-19 pandemic, caused by the novel coronavirus 2 (SARS-CoV-2), has been associated with an increased risk of secondary bacterial infections. Numerous studies have reported a surge in antibiotic usage during the COVID-19 pandemic. This study aims to examine the impact of the COVID-19 pandemic on the frequency and patterns of antibiotic prescriptions at Primary Health Care Centers (PHCC) in Qatar, comparing the period before and during the pandemic. METHODS: This population-based, cross-sectional study analyzed all antibiotic prescriptions issued in two-month intervals before COVID-19 (November and December 2019) and during the initial wave (June and July 2020) of COVID-19. The study included 27 PHCCs in Qatar. RESULTS: Prior to the COVID-19 outbreak, the PHCCs dispensed a total of 74,909 antibiotic prescriptions in November and December. During the first wave of COVID-19, the number decreased to 29,273 prescriptions in June and July 2020. Antibiotics were most commonly prescribed for adults and least commonly for the elderly, both before and during the COVID-19 period. In the pre-COVID-19 period, Betalactams and macrolides accounted for the majority (73%) of all antibiotic prescriptions across all age groups. However, during the COVID-19 period, Betalactams and other antibiotics such as Nitrofurantoin and Metronidazole (73%) were the most frequently prescribed. CONCLUSION: The rate of antibiotic prescriptions during the first wave of COVID-19 was lower compared to the two months preceding the pandemic at the PHCC in Qatar.

Dynamics of Anti-S IgG Antibodies Titers after the Second Dose of COVID-19 Vaccines in the Manual and Craft Worker Population of Qatar.

There is limited seroepidemiological evidence on the magnitude and long-term durability of antibody titers of mRNA and non-mRNA vaccines in the Qatari population. This study was conducted to generate evidence on long-term anti-S IgG antibody titers and their dynamics in individuals who have completed a primary COVID-19 vaccination schedule. A total of 300 male participants who received any of the following vaccines BNT162b2/Comirnaty, mRNA-1273, ChAdOx1-S/Covishield, COVID-19 Vaccine Janssen/Johnson, or BBIBP-CorV or Covaxin were enrolled in our study. All sera samples were tested by chemiluminescent microparticle immunoassay (CMIA) for the quantitative determination of IgG antibodies to SARS-CoV-2, receptor-binding domain (RBD) of the S1 subunit of the spike protein of SARS-CoV-2. Antibodies against SARS-CoV-2 nucleocapsid (SARS-CoV-2 N-protein IgG) were also determined. Kaplan-Meier survival curves were used to compare the time from the last dose of the primary vaccination schedule to the time by which anti-S IgG antibody titers fell into the lowest quartile (range of values collected) for the mRNA and non-mRNA vaccines. Participants vaccinated with mRNA vaccines had higher median anti-S IgG antibody titers. Participants vaccinated with the mRNA-1273 vaccine had the highest median anti-S-antibody level of 13,720.9 AU/mL (IQR 6426.5 to 30,185.6 AU/mL) followed by BNT162b2 (median, 7570.9 AU/mL; IQR, 3757.9 to 16,577.4 AU/mL); while the median anti-S antibody titer for non-mRNA vaccinated participants was 3759.7 AU/mL (IQR, 2059.7-5693.5 AU/mL). The median time to reach the lowest quartile was 3.53 months (IQR, 2.2-4.5 months) and 7.63 months (IQR, 6.3-8.4 months) for the non-mRNA vaccine recipients and Pfizer vaccine recipients, respectively. However, more than 50% of the Moderna vaccine recipients did not reach the lowest quartile by the end of the follow-up period. This evidence on anti-S IgG antibody titers should be considered for informing decisions on the durability of the neutralizing activity and thus protection against infection after the full course of primary vaccination in individuals receiving different type (mRNA verus non-mRNA) vaccines and those with natural infection.

Antibiotic prescriptions for oral diseases in India: evidence from national prescription data.

INTRODUCTION: The key objective of this research was to describe the prescription rate of various antibiotics for dental problems in India and to study the relevance of the prescriptions by analysing antibiotic types associated with different dental diagnoses, using a large-scale nationally representative dataset. METHODS: We used a 12-month period (May 2015 to April 2016) medical audit dataset from IQVIA (formerly IMS Health). We coded the dental diagnosis provided in the medical audit data to the International Statistical Classification of Diseases and Related Health Problems (ICD-11) and the prescribed antibiotics for the diagnosis to the Anatomic Therapeutic Chemical (ATC) -2020 classification of the World Health Organization. The primary outcome measure was the medicine prescription rate per 1,000 persons per year (PRPY1000). RESULTS: Our main findings were-403 prescriptions per 1,000 persons per year in the year 2015 -2016 for all dental ailments. Across all ATC level 1 classification, 'Diseases of hard tissues' made up the majority of the prescriptions. 'Beta-lactam', 'Penicillin,' and 'Cephalosporins' were the most commonly prescribed antibiotics for dental diagnoses followed by 'Macrolides' and 'Quinolones'. 'Dental caries', 'Discoloration of tooth', and 'Toothache' were the most common reasons for 'Beta-Lactams' and 'Penicillin' prescriptions. CONCLUSION: To conclude our study reports first ever country (India) level estimates of antibiotic prescription by antibiotic classes, age groups, and ICD-11 classification for dental ailments.

Out-of-pocket expenditure on childhood infections and its financial burden on Indian households: Evidence from nationally representative household survey (2017-18).

The key objective of this research was to estimate out of pocket expenditure (OOPE) incurred by the Indian households for the treatment of childhood infections. We estimated OOPE estimates on outpatient care and hospitalization by disease conditions and type of health facilities. In addition, we also estimated OOPE as a share of households' total consumption expenditure (TCE) by MPCE quintile groups to assess the quantum of the financial burden on the households. We analyzed the Social Consumption: Health (SCH) data from National Sample Survey Organization (NSSO) 75th round (2017-18). Outcome indicators were prevalence of selected infectious diseases in children aged less than 5 years, per episode of OOPE on outpatient care in the preceding 15 days, hospitalization in the preceding year and OOPE as a share of households' total consumption expenditure. Our analysis suggests that the most common childhood infection was 'fever with rash' followed by 'acute upper respiratory infection' and 'acute meningitis'. However, the highest OOPE for outpatient care and hospitalization was reported for 'viral hepatitis' and 'tuberculosis' episodes. Among the households reporting childhood infections, OOPE was 4.8% and 6.7% of households' total consumption expenditure (TCE) for outpatient care and hospitalization, respectively. Furthermore, OOPE as a share of TCE was disproportionately higher for the poorest MPCE quintiles (outpatient, 7.9%; hospitalization, 8.2%) in comparison to the richest MPCE quintiles (outpatient, 4.8%; hospitalization, 6.7%). This treatment and care-related OOPE has equity implications for Indian households as the poorest households bear a disproportionately higher burden of OOPE as a share of TCE. Ensuring financial risk protection and universal access to care for childhood illnesses is critical to addressing inequity in care.

Evaluating the impact of price regulation (Drug Price Control Order 2013) on antibiotic sales in India: a quasi-experimental analysis, 2008-2018.

BACKGROUND: In India, due to a lack of population-level financial risk protection mechanisms, the expenditure on healthcare is primarily out-of-pocket in nature. Through Drug Price Control Orders (DPCOs), the Indian Government attempts to keep medicine prices under check. The aim of this study was to measure the potential impact of DPCO 2013 on the utilization of antibiotics under price regulation in India using large nationally representative pharmaceutical sales data. METHODS: We used interrupted time series analysis, a quasi-experimental research design to estimate the impact of DPCO 2013 on the utilization of antibiotics in the private sector in India. Indian pharmaceutical sales data set, PharmaTrac from a market research company-All Indian Origin Chemists and Distributors Limited-was used for the study. The data are collected from a panel of around 18,000 stockists across 23 different regions of the country. The primary outcome measure is the percentage change (increase or decrease) in the sales volume of the antibiotics under DPCO 2013, measured in standard units (SUs). RESULTS: Our estimates suggest that post-intervention (after notification of DPCO 2013) there was an immediate reduction (level change) in the sales of antibiotics under DPCO 2013 by 3.7% (P > 0.05), followed by a sustained decline (trend change) of 0.3% (P > 0.05) as compared to the pre-intervention trend at the molecule level, but both changes were statistically insignificant. However, in terms of 'average monthly market share,' the DPCO 2013 notification resulted in a sharp reduction of 579% (P < 0.05) (level change) followed by a sustained increase of 9.5% (P > 0.05) (trend change) in the 'market share of antibiotics under DPCO' as compared to pre-intervention trend. CONCLUSIONS: The impact of DPCO 2013 in terms of the overall increase in the utilization of antibiotics under price regulation was limited but there was a switch from non-price controlled antibiotics to price regulated antibiotics (notified under DPCO 2013). We argue that policies on price control need to be complemented with continuous monitoring of market behavior to have a measurable and long-term impact.

Systemic antibiotic sales and WHO recommendations, India.

Objective: To analyse sales of fixed-dose combination and single antibiotics in India in relation to World Health Organization (WHO) recommendations and national regulatory efforts to control antibiotic sales. Methods: We extracted data on sales volumes of systemic antibiotics in India from a market research company sales database. We compared the market share of antibiotic sales in 2020 by WHO AWaRe (Access, Watch and Reserve) category and for those under additional national regulatory controls. We also analysed sales of fixed-dose combinations that were: formally approved for marketing or had a no-objection certificate; on the national essential medicines list; and on the WHO list of not-recommended antibiotics. Findings: There were 78 single and 112 fixed-dose combination antibiotics marketed in India, accounting for 7.6 and 4.5 billion standard units of total sales, respectively. Access, Watch and Reserve antibiotics comprised 5.8, 5.6 and 0.1 billion standard units of total market sales, respectively. All additionally controlled antibiotics were Watch and Reserve antibiotics (23.6%; 2.9 billion standard units of total sales). Fixed-dose combinations on the WHO not-recommended list were marketed in 229 formulations, with 114 formulations (49.8%) having no record of formal approval or no-objection certificate. While there were no not-recommended fixed-dose combinations on the national list of essential medicines, 13 of the top-20 selling antibiotic fixed-dose combinations were WHO not-recommended. Conclusion: The sale of Watch group drugs, and antibiotics banned or not approved, needs active investigation and enforcement in India. The evidence base underpinning formal approvals and no-objection certificates for not-recommended fixed-dose combinations should be audited.

Multimorbidity, healthcare use and catastrophic health expenditure by households in India: a cross-section analysis of self-reported morbidity from national sample survey data 2017-18.

BACKGROUND: The purpose of this research is to generate new evidence on the economic consequences of multimorbidity on households in terms of out-of-pocket (OOP) expenditures and their implications for catastrophic OOP expenditure. METHODS: We analyzed Social Consumption Health data from National Sample Survey Organization (NSSO) 75th round conducted in the year 2017-2018 in India. The sample included 1,13,823 households (64,552 rural and 49,271 urban) through a multistage stratified random sampling process. Prevalence of multimorbidity and related OOP expenditure were estimated. Using Coarsened Exact Matching (CEM) we estimated the mean OOP expenditure for individuals reporting multimorbidity and single morbidity for each episode of outpatient visits and hospital admission. We also estimated implications in terms of catastrophic OOP expenditure for households. RESULTS: Results suggest that outpatient OOP expenditure is invariably lower in the presence of multimorbidity as compared with single conditions of the selected Non-Communicable Diseases(NCDs) (overall, INR 720 [USD 11.3] for multimorbidity vs. INR 880 [USD 14.8] for single). In the case of hospitalization, the OOP expenditures were mostly higher for the same NCD conditions in the presence of multimorbidity as compared with single conditions, except for cancers and cardiovascular diseases. For cancers and cardiovascular, OOP expenditures in the presence of multimorbidity were lower by 39% and 14% respectively). Furthermore, around 46.7% (46.674-46.676) households reported incurring catastrophic spending (10% threshold) because of any NCD in the standalone disease scenario which rose to 63.3% (63.359-63.361) under the multimorbidity scenario. The catastrophic implications of cancer among individual diseases was the highest. CONCLUSIONS: Multimorbidity leads to high and catastrophic OOP payments by households and treatment of high expenditure diseases like cancers and cardiovascular are under-financed by households in the presence of competing multimorbidity conditions. Multimorbidity should be considered as an integrated treatment strategy under the existing financial risk protection measures (Ayushman Bharat) to reduce the burden of household OOP expenditure at the country level.

Dynamics of anti-S IgG antibodies titers after the second dose of COVID 19 mRNA and non-mRNA vaccines in the manual and craft worker population of Qatar

BackgroundThere is limited seroepidemiological evidence on the magnitude and long-term durability of antibody titers of mRNA and non-mRNA vaccines in the Qatari population. This study was conducted to generate evidence on long-term anti-S IgG antibodies titers and their dynamics in individuals who have completed a primary COVID-19 vaccination schedule. MethodsA total of 300 participants who received any of the following vaccines BNT162b2/Comirnaty or mRNA-1273 or ChAdOx1-S/Covishield or COVID-19 Vaccine Janssen/Johnson or BBIBP-CorV or Covaxin were enrolled in our study. All sera samples were tested by chemiluminescent microparticle immunoassay (CMIA) for the quantitative determination of IgG antibodies to SARS-CoV-2, receptor-binding domain (RBD) of the S1 subunit of the spike protein of SARS-CoV-2. Antibodies against SARS-CoV-2 nucleocapsid (SARS-CoV-2 N-protein IgG) were also determined. Kaplan-Meier survival curves were used to compare the time from the last dose of the primary vaccination schedule to the time by which anti-S IgG antibodies titers fell into the lowest quartile (range of values collected) for the mRNA and non-mRNA vaccines. ResultsParticipants vaccinated with mRNA vaccines had higher median anti-S IgG antibody titers. Participants vaccinated with the mRNA-1273 vaccine had the highest median anti-S-antibody level of 13720.9 AU/mL (IQR 6426.5 to 30185.6 AU/mL) followed by BNT162b2 (median, 7570.9 AU/ml; IQR, 3757.9 to 16577.4 AU/mL); while the median anti-S antibody titer for non-mRNA vaccinated participants was 3759.7 AU/mL (IQR, 2059.7-5693.5 AU/mL). The median time to reach the lowest quartile was 3.53 months (IQR, 2.2-4.5 months) and 7.63 months (IQR, 6.3-8.4 months) for the non-mRNA vaccine recipients and Pfizer vaccine recipients, respectively. However, more than 50% of the Moderna vaccine recipients did not reach the lowest quartile by the end of the follow-up period. ConclusionsThis evidence on anti-S IgG antibody titers, their durability and decay over time should be considered for the utility of these assays in transmission dynamics after the full course of primary vaccination.

Hybrid CT-angiography (Angio-CT) for combined CT and fluoroscopic procedures in interventional radiology enhances utilization.

PURPOSE: To investigate the utilization of an angiography-CT (Angio-CT) system and its advantages for single patient encounters. METHODS: Interventions utilizing both CT and fluoroscopy to perform multiple procedures in a single encounter or single interventions using both were identified. Cases were stratified by complexity (defined by RVUs). Comparative analyses of room (TRoom) and total encounter (TEncounter) times were performed between non-complex bundled cases and controls. RESULTS: Between June 2018 and August 2019, 1108 procedures were performed via the Angio-CT system; 10% (114/1108) used both fluoroscopy and CT. 21% (24/114) Involved more than one procedure in a single encounter that required a CT-only and fluoroscopy-only bundled procedure. 59% (67/114) were non-complex, and 70% (80/114) were non-oncologic. 82.5% (14/17) of non-complex bundled procedures demonstrated TRoom below the mean of their respective controls; 52.8% (9/17) were 2 standard deviations below the control means. Pleural catheter placement following post-lung biopsy pneumothorax was the most common non-complex bundled case with a significant reduction in TRoom when performed via Angio-CT compared to control (99 vs. 163 min, p < 0.0001). There was a significant reduction in TEncounter for abdominopelvic drain placement procedures bundled with either (1) percutaneous nephrostomy tube evaluation with or without replacement, or (2) central venous catheter placement (211 min vs. 344 min, p < 0.001 and 231 min vs. 347 min, p < 0.05, respectively). CONCLUSION: The primary use for the hybrid Angio-CT system was to perform non-oncologic and non-complex cases with potential reduction in TRoom and TEncounter for specific non-complex bundled cases.

CHCHD4 (MIA40) and the mitochondrial disulfide relay system.

Mitochondria are pivotal for normal cellular physiology, as they perform a crucial role in diverse cellular functions and processes, including respiration and the regulation of bioenergetic and biosynthetic pathways, as well as regulating cellular signalling and transcriptional networks. In this way, mitochondria are central to the cell's homeostatic machinery, and as such mitochondrial dysfunction underlies the pathology of a diverse range of diseases including mitochondrial disease and cancer. Mitochondrial import pathways and targeting mechanisms provide the means to transport into mitochondria the hundreds of nuclear-encoded mitochondrial proteins that are critical for the organelle's many functions. One such import pathway is the highly evolutionarily conserved disulfide relay system (DRS) within the mitochondrial intermembrane space (IMS), whereby proteins undergo a form of oxidation-dependent protein import. A central component of the DRS is the oxidoreductase coiled-coil-helix-coiled-coil-helix (CHCH) domain-containing protein 4 (CHCHD4, also known as MIA40), the human homologue of yeast Mia40. Here, we summarise the recent advances made to our understanding of the role of CHCHD4 and the DRS in physiology and disease, with a specific focus on the emerging importance of CHCHD4 in regulating the cellular response to low oxygen (hypoxia) and metabolism in cancer.

Quality of life assessment & out-of-pocket expenditure in multiple myeloma: An observational study.

Background & objectives: Prognosis of patients with multiple myeloma (MM) has improved significantly in the past two decades. However, the symptoms burden is high at onset and treatment is generally prolonged with significant financial burden. This study was undertaken to assess the quality of life (QoL) and to analyse out-of-pocket expenditure (OOPE) incurred on MM patients being treated at a tertiary care cancer centre in north India. Methods: This observational, cross-sectional study included 116 patients (aged >18 yr) of MM (both newly diagnosed and those with recurrent disease). For QoL assessment, European Organisation for Research and Treatment of Cancer (EORTC)-validated questionnaire (EORTC QLQ C 30 version 3.0) and disease-specific QLQ MY20 were used. For assessing OOPE incurred on treatment, the National Sample Survey Organisation (NSSO) questionnaire was used. Results: Bone pains (68.1%), fatigue (59.7%) and dyspnoea (54.6%) were common symptoms. The mean global health status/QoL score was 59.62±19.21. International Staging System (ISS) score correlated with global health status score, and gastritis was the main adverse effect. QoL score showed negative correlation to side effects of treatment (-0.53) of MY20 domain. On multivariate analysis, ISS stage (P<0.001) and adverse effects of treatment (P=0.02) were predictive factors. The median OOPE was ₹ 7900 (IQR, ₹ 4950-13,550) towards medical and ₹ 1150 (IQR, ₹ 500-3100) for non-medical expenses for the past one month. Interpretation & conclusions: Regular assessment of QoL in the clinical management of multiple myeloma patients has the potential of improving treatment outcomes. Measures to reduce out-of-pocket expenditure may improve treatment compliance.

Old drugs, new uses: Drug repurposing in hematological malignancies.

Discovery and development of novel anti-cancer drugs are expensive and time consuming. Systems biology approaches have revealed that a drug being developed for a non-cancer indication can hit other targets as well, which play critical roles in cancer progression. Since drugs for non-cancer indications would have already gone through the preclinical and partial or full clinical development, repurposing such drugs for hematological malignancies would cost much less, and drastically reduce the development time, which is evident in case of thalidomide. Here, we have reviewed some of the drugs for their potential to repurpose for treating the hematological malignancies. We have also enlisted resources that can be helpful in drug repurposing.

Early intervention physical therapy using "Parent Empowerment Program" for children with Down syndrome in Pakistan: A feasibility study.

PURPOSE: The aim of this study was to evaluate the feasibility and effectiveness of the Parent Empowerment Program (PEP) to help caretakers deliver a home program to promote developmental activities and gross motor function in their children with Down syndrome. METHODS: Parents attended a 14-month program with training sessions 1-4 times a month. Outcomes were measured using a change in the Gross Motor Function Measure (GMFM-88) at baseline and assessment one. RESULTS: Forty-eight families participated in the PEP. Children's mean age was 16.2 ± 10.8 months. There were significant changes in GMFM-88 scores between baseline and assessment one; t (30) =-9.158, p< 0.001; 95% CI -14.6 - -22.9. Previous hospitalization significantly affected GMFM scores. CONCLUSION: This study describes a clinically applied research that focuses on program design, development and evaluation. Findings indicate that the PEP is effective in improving gross motor function in children with Down's syndrome in Pakistan. Parents were satisfied with the program outcomes and were able to cope with the requirements at home. The PEP had favorable outcomes and may be an effective method to support PT services in resource poor countries.

Private sector vaccine share in overall immunization coverage in India: Evidence from private sector vaccine utilization data (2012-2015).

The objective of this research was to generate the evidence on the private sector's contribution to overall immunization coverage for selected pediatric vaccines in India. Using IMS Health's (now IQVIA) vaccine sales audit data and innovative methodological approach we estimated private-sector vaccine share in the total immunization coverage across selected pediatric vaccines in India. Our estimates suggest that private sector remains an important contributor to immunization services in India not only for Universal Immunization Program vaccines (Bacillus Calmette-Guérin [19.23%], HiB pentavalent [11.09%], hepatitis B [5.75%], oral poliovirus vaccine [5.48%], Diphtheria-Pertussis-Tetanus [2.66%], and measles [2.17%]) but also for newer vaccines (hepatitis A [4.2%], rotavirus [3.4%], typhoid [3.3%], and pneumococcal conjugate vaccine [2.5%]). As the private sector continues to remain an important access point for immunization services in the country, avenues for potential synergy between public and private sectors should be explored to improve the coverage and quality of immunization services.

The impact of stringent prescription-only antimicrobial sale regulation (Schedule H1) in India: an interrupted time series analysis, 2008-18.

OBJECTIVES: To assess the impact of Schedule H1 regulation notified and implemented in 2014 under the amended rules of the Drugs and Cosmetics Act (DCA), 1940 on the sale of antimicrobials in the private sector in India. METHODS: The dataset was obtained from the Indian pharmaceutical sales database, PharmaTrac. The outcome measure was the sales volume of antimicrobials in standard units (SUs). A quasi-experimental research design-interrupted time series analysis-was used to detect the impact of the intervention. RESULTS: We observed a substantial rise in antimicrobial consumption during 2008-18 in the private sector in India, both for antimicrobials regulated under Schedule H1 as well as outside the regulation. Key results suggested that post-intervention there was an immediate reduction (level change) in use of Schedule H1 antimicrobials by 10% (P = 0.007), followed by a sustained decline (trend change) in utilization by 9% (P > 0.000) compared with the pre-intervention trend. Segregated analysis on different antimicrobial classes suggests a sharp drop (level changes) and sustained decline (trend changes) in utilization post-intervention compared with the pre-intervention trend. Our findings remained robust on carrying out sensitivity analysis with the oral anti-diabetics market as a control. Post-intervention, the average monthly difference between antimicrobials under Schedule H1 and the control group witnessed an immediate increase of 16.3% (P = 0.10) followed by a sustained reduction of 0.5% (P = 0.13) compared with the pre-intervention scenario. CONCLUSIONS: Though the regulation had a positive impact in terms of reducing sales of antimicrobials notified under the regulation, optimizing the effectiveness of such stand-alone policies will be limited unless accompanied by a broader set of interventions.