An observation-based, reduced-form model for oxidation in the remote marine troposphere.

The hydroxyl radical (OH) fuels atmospheric chemical cycling as the main sink for methane and a driver of the formation and loss of many air pollutants, but direct OH observations are sparse. We develop and evaluate an observation-based proxy for short-term, spatial variations in OH (ProxyOH) in the remote marine troposphere using comprehensive measurements from the NASA Atmospheric Tomography (ATom) airborne campaign. ProxyOH is a reduced form of the OH steady-state equation representing the dominant OH production and loss pathways in the remote marine troposphere, according to box model simulations of OH constrained with ATom observations. ProxyOH comprises only eight variables that are generally observed by routine ground- or satellite-based instruments. ProxyOH scales linearly with in situ [OH] spatial variations along the ATom flight tracks (median r2 = 0.90, interquartile range = 0.80 to 0.94 across 2-km altitude by 20° latitudinal regions). We deconstruct spatial variations in ProxyOH as a first-order approximation of the sensitivity of OH variations to individual terms. Two terms modulate within-region ProxyOH variations-water vapor (H2O) and, to a lesser extent, nitric oxide (NO). This implies that a limited set of observations could offer an avenue for observation-based mapping of OH spatial variations over much of the remote marine troposphere. Both H2O and NO are expected to change with climate, while NO also varies strongly with human activities. We also illustrate the utility of ProxyOH as a process-based approach for evaluating intermodel differences in remote marine tropospheric OH.

Anthropogenic Fingerprint Detectable in Upper Tropospheric Ozone Trends Retrieved from Satellite.

Tropospheric ozone (O3) is a strong greenhouse gas, particularly in the upper troposphere (UT). Limited observations point to a continuous increase in UT O3 in recent decades, but the attribution of UT O3 changes is complicated by large internal climate variability. We show that the anthropogenic signal ("fingerprint") in the patterns of UT O3 increases is distinguishable from the background noise of internal variability. The time-invariant fingerprint of human-caused UT O3 changes is derived from a 16-member initial-condition ensemble performed with a chemistry-climate model (CESM2-WACCM6). The fingerprint is largest between 30°S and 40°N, especially near 30°N. In contrast, the noise pattern in UT O3 is mainly associated with the El Niño-Southern Oscillation (ENSO). The UT O3 fingerprint pattern can be discerned with high confidence within only 13 years of the 2005 start of the OMI/MLS satellite record. Unlike the UT O3 fingerprint, the lower tropospheric (LT) O3 fingerprint varies significantly over time and space in response to large-scale changes in anthropogenic precursor emissions, with the highest signal-to-noise ratios near 40°N in Asia and Europe. Our analysis reveals a significant human effect on Earth's atmospheric chemistry in the UT and indicates promise for identifying fingerprints of specific sources of ozone precursors.

Endoscopic scoring system utilization for inflammatory bowel disease activity assessment: A multicenter real-world study from Argentina.

BACKGROUND: The frequency and patterns of use of scores for the assessment of endoscopic activity in inflammatory bowel disease patients are not known. AIM: To describe the prevalence of adequate use of endoscopic scores in IBD patients who underwent colonoscopy in a real-life setting. MATERIALS AND METHODS: A multicenter observational study comprising six community hospitals in Argentina was undertaken. Patients with a diagnosis of Crohn's disease or ulcerative colitis who underwent colonoscopy for endoscopic activity assessment between 2018 and 2022 were included. Colonoscopy reports of included subjects were manually reviewed to determine the proportion of colonoscopies that included an endoscopic score report. We determined the proportion of colonoscopy reports that included all of the IBD colonoscopy report quality elements proposed by BRIDGe group. Endoscopist's specialty, years of experience as well as expertise in IBD were assessed. RESULTS: A total of 1556 patients were included for analysis (31.94% patients with Crohn's disease). Mean age was 45.94±15.46. Endoscopic score reporting was found in 58.41% of colonoscopies. Most frequently used scores were Mayo endoscopic score (90.56%) and SES-CD (56.03%) for ulcerative colitis and Crohn's disease, respectively. In addition, 79.11% of endoscopic reports failed to comply with all recommendations on endoscopic reporting for inflammatory bowel disease. CONCLUSIONS: A significant proportion of endoscopic reports of inflammatory bowel disease patients do not include the description of an endoscopic score to assess mucosal inflammatory activity in a real-world setting. This is also associated with a lack of compliance in recommended criteria for proper endoscopic reporting.

Ouabain-Na+/K+-ATPase Signaling Regulates Retinal Neuroinflammation and ROS Production Preventing Neuronal Death by an Autophagy-Dependent Mechanism Following Optic Nerve Axotomy In Vitro.

Ouabain is a classic Na+K+ATPase ligand and it has been described to have neuroprotective effects on neurons and glial cells at nanomolar concentrations. In the present work, the neuroprotective and immunomodulatory potential of ouabain was evaluated in neonatal rat retinal cells using an optic nerve axotomy model in vitro. After axotomy, cultured retinal cells were treated with ouabain (3 nM) at different periods. The levels of important inflammatory receptors in the retina such as TNFR1/2, TLR4, and CD14 were analyzed. We observed that TNFR1, TLR4, and CD14 were decreased in all tested periods (15 min, 45 min, 24 h, and 48 h). On the other hand, TNFR2 was increased after 24 h, suggesting an anti-inflammatory potential for ouabain. Moreover, we showed that ouabain also decreased Iba-1 (microglial marker) density. Subsequently, analyses of retrograde labeling of retinal ganglion cells (RGC) were performed after 48 h and showed that ouabain-induced RGC survival depends on autophagy. Using an autophagy inhibitor (3-methyladenine), we observed a complete blockage of the ouabain effect. Western blot analyses showed that ouabain increases the levels of autophagy proteins (LC3 and Beclin-1) coupled to p-CREB transcription factor and leads to autophagosome formation. Additionally, we found that the ratio of cleaved/pro-caspase-3 did not change after ouabain treatment; however, p-JNK density was enhanced. Also, ouabain decreased reactive oxygen species production immediately after axotomy. Taken together, our results suggest that ouabain controls neuroinflammation in the retina following optic nerve axotomy and promotes RGC neuroprotection through activation of the autophagy pathway.

Treatment of asymptomatic bacteriuria in the first 2 months after kidney transplant: A controlled clinical trial.

BACKGROUND: The incidence of urinary tract infections (UTIs) in the first 2 months postrenal transplantation (pRT) is very high. We evaluate the efficacy of asymptomatic bacteriuria (AB) screening and treatment on the incidence of UTI in the first 2 months pRT METHODS: We conducted a randomized controlled clinical trial. A urine culture was obtained in all patients on the day of the bladder catheter removal, on week three, and before removal of the ureteral catheter. The intervention group received treatment for AB. The control group did not receive treatment. The primary outcomes were the cumulative incidence of UTI and/or graft pyelonephritis and the time to the first episode of UTI and/or graft pyelonephritis RESULTS: Eighty patients were randomized, 40 in each group, and the median follow-up was 63 days (IQR 54-70). The average age was 29.8 years and 33.7% (n = 27) were women. The incidences of UTI (n = 10, 25 % vs. n = 4, 10%, p = .07) and pyelonephritis (n = 6, 15% vs. n = 1, 2.5%, p = .04) were greater in the intervention group, as also shown in the survival analysis: UTI (HR2.8, 95% CI 0.8-9.1, p = .07) and pyelonephritis (HR 6.5, 95% CI 0.8-54.7, p = .08), respectively. The most commonly isolated bacterium was Escherichia coli (n = 28, 59.5%), and over half were E. coli with extended-spectrum beta-lactamases (n = 15). A major limitation was not obtaining the calculated sample size due to a delay in patient recruitment resulting from the COVID-19 pandemic CONCLUSION: Treatment of AB in the first 2 months pRT does not decrease the incidence of UTI or graft pyelonephritis and may actually increase their frequency. Routine treatment of AB during the first months after renal transplantation should not be a standard procedure.

Spatiotemporal regulation of galectin-1-induced T-cell death in lamina propria from Crohn's disease and ulcerative colitis patients.

Inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), is characterized by chronic, relapsing intestinal inflammation. Galectin-1 (Gal-1) is an endogenous lectin with key pro-resolving roles, including induction of T-cell apoptosis and secretion of immunosuppressive cytokines. Despite considerable progress, the relevance of Gal-1-induced T-cell death in inflamed tissue from human IBD patients has not been ascertained. Intestinal biopsies and surgical specimens from control patients (n = 52) and patients with active or inactive IBD (n = 97) were studied. Gal-1 expression was studied by RT-qPCR, immunoblotting, ELISA and immunohistochemistry. Gal-1-specific ligands and Gal-1-induced apoptosis of lamina propria (LP) T-cells were determined by TUNEL and flow cytometry. We found a transient expression of asialo core 1-O-glycans in LP T-cells from inflamed areas (p < 0.05) as revealed by flow cytometry using peanut agglutinin (PNA) binding and assessing dysregulation of the core-2 ß 1-6-N-acetylglucosaminyltransferase 1 (C2GNT1), an enzyme responsible for elongation of core 2 O-glycans. Consequently, Gal-1 binding was attenuated in CD3+CD4+ and CD3+CD8+ LP T-cells isolated from inflamed sites (p < 0.05). Incubation with recombinant Gal-1 induced apoptosis of LP CD3+ T-cells isolated from control subjects and non-inflamed areas of IBD patients (p < 0.05), but not from inflamed areas. In conclusion, our findings showed that transient regulation of the O-glycan profile during inflammation modulates Gal-1 binding and LP T-cell survival in IBD patients.

Prevalence of pyoderma gangrenosum and Sweet´s syndrome in inflammatory bowel disease at a tertiary healthcare center.

BACKGROUND AND AIM: dermatological manifestations are normally found in one third of patients with inflammatory bowel disease. In this study, the prevalence, clinical characteristics, intestinal disease activity, and treatment response of neutrophilic dermatoses (pyoderma gangrenosum and Sweet´s syndrome) were determined in patients with inflammatory bowel disease. METHODS: a retrospective, observational study was performed in patients with inflammatory bowel disease and neutrophilic dermatoses between March 2012 and March 2018. RESULTS: of 444 patients analyzed, 10 complied with the inclusion criteria. Seven had pyoderma gangrenosum and three presented Sweet's syndrome; and one patient developed both pathologies. The prevalence of neutrophilic dermatoses was 2.3 % (10/444), comprising 1.6 % with pyoderma gangrenosum and 0.7 % with Sweet's syndrome. Six out of seven patients with pyoderma gangrenosum were female and had ulcerative colitis. The most frequent clinical presentation of pyoderma gangrenosum was the ulcerative subtype. Active moderate-to-severe intestinal disease was found in 71.4 % of patients. Biological therapy was prescribed to three patients with partial response to corticosteroids and persistent intestinal disease activity. This therapy was not indicated for cutaneous manifestations only. Three patients with moderate-to-severe Crohn´s disease presented classical (n = 2) and pustular (n = 1) Sweet's syndrome. A complete response was achieved in all Sweet's syndrome cases treated with corticosteroids. Biological therapy was prescribed to control intestinal disease activity. CONCLUSIONS: pyoderma gangrenosum was the most frequent cutaneous manifestation of neutrophilic dermatoses, predominantly in females with ulcerative colitis, and highly associated with intestinal disease activity. Anti-tumor necrosis factor was effective in patients with partial cutaneous and intestinal disease response.

[Flexible endoscopic treatment for Zenker's diverticulum: preliminary results in a single center experience in a public hospital in Argentina.] / Tratamiento del divertículo de Zenker con endoscopio flexible: experiencia en us hospital público de la Arfgentina.

Zenker's diverticulum (ZD) is an acquired protrusion of the esophageal wall. Treatment is reservedfor symptomatic cases. In Argentina, ZD has historically managed exclusively by surgical intervention. In 1995, Ishioka, et al and Mulder, et a1published their experience using flexible endoscopes for diverticulotomy. Since then, a wide variety ofdifferent techniques have been published. Objetive. To present technique modifications and results ofour center. MATERIAL AND METHODS: We reviewed the database of57patients (36 men), with a mean age of 71.9 years (range 37-98), with symptomatic Zenker ' diverticulum, who underwent endoscopic myotomy, from December 1997 to April 2015. All procedures were performed in our center, by the same endoscopist (HM). The most common symptom was dysphagia (94.7%), which was recorded by a 0-4 score (0=no dysphagia, 1 =solids, 2=semisolids, 3=liquids, 4=saliva). The first nine cases were done exposing the septum with a nasogastric tube, and the others with a soft diverticuloscope. Allprocedures were carried out with the patient under deep sedation, adminis- tered by an anesthesiologist. A myotomy was done in all cases with a needle-knife, using a coagulation current, to prevent bleeding. Clips were placed to close mucosalilaps, decrease the risk of unsuspected perforation and postprocedure bleeding. RESULTS: Seventy procedures were performed, in 56 patients. One patient was excluded because of incomplete myotomy due to a severe adverse event. Ninety-eight percent ofpatients had resolution or improvement of the dysphagia score, at 30 days. Three patients with regurgitation as their sole complaint completely resolved their symptom. Median follow-up was 25 months (1-99). Thirty-seven patients were followed for at least 1 year and 97.3% showed a favorable outcome. In 13 cases (22.8%) a reintervention was needed, with positive results in all cases. Bleeding occurred in one patient (1.4%), who required surgery. Another patient required surgical intervention due to technical issues. There were no perforations or infections. CONCLUSION: Treatment of ZD with flexible endoscope is a safe and effective option, with good long-term results. We need randomized clinical trials comparing different therapeutic options to be able to recommend a definitive strategy. Until then, we suggest using the technique with which each center has the most experience and feels most comfortable performing.

Ouabain and BDNF Crosstalk on Ganglion Cell Survival in Mixed Retinal Cell Cultures.

Brain-derived neurotrophic factor (BDNF) is a well-known and well-studied neurotrophin. Most biological effects of BDNF are mediated by the activation of TrkB receptors. This neurotrophin regulates several neuronal functions as cell proliferation, viability, and differentiation. Ouabain is a steroid that binds to the Na(+)/K(+) ATPase, inducing the activation of several intracellular signaling pathways. Previous data from our group described that ouabain treatment increases retinal ganglion cells survival (RGC). The aim of the present study was to evaluate, if this cardiac glycoside can have a synergistic effect with BDNF, the classical trophic factor for retinal ganglion cells, as well as investigate the intracellular signaling pathways involved. Our work demonstrated that the activation of Src, PLC, and PKCδ participates in the signaling cascade mediated by 50 ng/mL BDNF, since their selective inhibitors completely blocked the trophic effect of BDNF. We also demonstrated a synergistic effect on RGC survival when we concomitantly used ouabain (0.75 nM) and BDNF (10 ng/mL). Moreover, the signaling pathways involved in this synergistic effect include Src, PLC, PKCδ, and JNK. Our results suggest that the synergism between ouabain and BDNF occurs through the activation of the Src pathway, JNK, PLC, and PKCδ.

[Intraparenchymal hepatic haematoma after endoscopic retrograde cholangiopancreotography overinfected by Citrobacter freundii and Klebsiella pneumoniae BLEE]. / Hematoma intraparenquimatoso hepático post- colangiopancreatografía retrógrada endoscópica sobreinfectado por Citrobacter freundii y Klebsiella pneumoniae BLEE.

This case report describes a 37-year-old woman who develops an intraparenchymal hepatic haematoma after an endoscopic retrograde cholangiopancreatography with papillotomy and stone extraction. The procedure requires the passage of a guidewire. The patient develops acute abdominal pain 72 hours later and a magnetic resonance shows a hematoma of 124 x 93 mm. She remains under observation. Twenty one days later she complains of upper right abdominal pain and fever. Consequently, a percutaneous drainage is performed isolating Citrobacter freundii and Klebsiella pneumoniae BLEE. The patient has a good evolution.

Granulomatous Salpingo-oophoritis Secondary to Crohn's Disease.

Crohn's disease (CD) represents a subtype of inflammatory bowel disease and can affect any portion of the gastrointestinal tract, from the mouth to the anus, with the capacity to affect extraintestinal organs. Salpingo-oophoritis is an uncommon manifestation of CD. There is only a limited number of documented case reports. We present the case of a patient with ileocolonic CD and secondary granulomatous salpingo-oophoritis. We emphasize the significance of clinical suspicion and an interdisciplinary approach as crucial factors in ensuring the effective management of the case.

Prevalence of and factors associated with zero-dose and under-immunized children in selected areas of Bangladesh: Findings from Lot Quality Assurance Sampling Survey.

BACKGROUND: In the era of Gavi's 5.0 vision of "leaving no one behind with immunization", childhood routine vaccination in missed communities is considered as a priority concern. Despite having a success story at the national level, low uptake of immunization is still persistent in selected pocket areas of Bangladesh. However, prevalence and the associated factors of zero-dose (ZD) and under-immunization (UI) are still unknown at those geo-pockets of Bangladesh. Thus, the study aims to report and identify the factors associated with ZD and UI in selected geographical locations. METHODS: This study used data from a Lot Quality Assurance Sampling (LQAS) survey where 504 households from 18 clusters of four hard to reach (HTR) and one urban slum were included. Caregivers of children aged 4.5 to 23 months were interviewed. Three outcome variables- ZD, UI and ZD/UI were considered and several related attributes were considered as independent variables. Data were analyzed through bivariate analysis, binary logistic regression and dominance analysis. RESULTS: Overall, 32% of the children were either ZD (8%) or UI (26%) in the selected areas. The adjusted odds of ZD/UI for urban slum and haor (wetlands) areas were 5.62 and 3.61 respectively considering coastal areas as reference. However, distance of nearest EPI center, availability of EPI card, age of caregivers, education and occupation of mother and number of earning members in household were influential factors for ZD/UI. According to dominance analysis, availability of EPI card can explain the most of the variation of ZD/UI in this study. CONCLUSION: The study findings highlight the high prevalence ZD/UI in certain geo-pockets of the country. It provided a powerful insight of current situation and associated factors in regards to ZD/UI in the country which will help policy-makers and programme managers in designing programmes to reduce missed communities in Bangladesh.

Measuring Zero-Dose Children: Reflections on Age Cohort Flexibilities for Targeted Immunization Surveys at the Local Level.

Zero-dose (ZD) children is a critical objective in global health, and it is at the heart of the Immunization Agenda 2030 (IA2030) strategy. Coverage for the first dose of diphtheria-tetanus-pertussis (DTP1)-containing vaccine is the global operational indicator used to estimate ZD children. When surveys are used, DTP1 coverage estimates usually rely on information reported from caregivers of children aged 12-23 months. It is important to have a global definition of ZD children, but learning and operational needs at a country level may require different ZD measurement approaches. This article summarizes a recent workshop discussion on ZD measurement for targeted surveys at local levels related to flexibilities in age cohorts of inclusion from the ZD learning Hub (ZDLH) initiative-a learning initiative involving 5 consortia of 14 different organizations across 4 countries-Bangladesh, Mali, Nigeria, and Uganda-and a global learning partner. Those considerations may include the need to generate insights on immunization timeliness and on catch-up activities, made particularly relevant in the post-pandemic context; the need to compare results across different age cohort years to better identify systematically missed communities and validate programmatic priorities, and also generate insights on changes under dynamic contexts such as the introduction of a new ZD intervention or for recovering from the impact of health system shocks. Some practical considerations such as the potential need for a larger sample size when including comparisons across multiple cohort years but a potential reduction in the need for household visits to find eligible children, an increase in recall bias when older age groups are included and a reduction in recall bias for the first year of life, and a potential reduction in sample size needs and time needed to detect impact when the first year of life is included. Finally, the inclusion of the first year of life cohort in the survey may be particularly relevant and improve the utility of evidence for decision-making and enable its use in rapid learning cycles, as insights will be generated for the population being currently targeted by the program. For some of those reasons, the ZDLH initiative decided to align on a recommendation to include the age cohort from 18 weeks to 23 months, with enough power to enable disaggregation of key results across the two different cohort years. We argue that flexibilities with the age cohort for inclusion in targeted surveys at the local level may be an important principle to be considered. More research is needed to better understand in which contexts improvements in timeliness of DTP1 in the first year of life will translate to improvements in ZD results in the age cohort of 12-23 months as defined by the global DTP1 indicator.

Exploring the landscape of routine immunization in Nigeria: A scoping review of barriers and facilitators.

Background: Despite global efforts to improve vaccination coverage, the number of zero-dose and under-immunized children has increased in Africa, particularly in Nigeria, which has over 2.1 million unvaccinated (zero dose) children, the highest in the continent. This scoping review systematically maps and summarizes existing literature on the barriers and facilitators of immunization in Nigeria, focusing on regional inequalities. Methods: A comprehensive search of electronic databases was conducted, encompassing all data from their inception to October 2023, to identify articles on the determinants of routine immunization uptake in Nigeria. Eligible studies were evaluated using predefined criteria, and the data were analyzed and visualized. Results: The results revealed distinct regional variations in factors influencing immunization practices across Nigeria's six geopolitical zones. Identified barriers include logistical issues, socio-economic factors, cultural influences, and systemic healthcare deficiencies. Key facilitators across multiple zones are health literacy, maternal education, and community leader influence. However, unique regional differences were also identified. In the North-East, significant factors included peer influence, robust reminder systems, provision of additional security, and financial incentives for health facilities. In the North-West, perceived vaccine benefits, fear of non-immunization consequences, urban residence, health literacy, and antenatal care visits were reported as crucial. Perceived benefits of vaccines and trust in healthcare providers were identified as predominant factors in the North-Central zone In the South-East, maternal autonomy, health literacy, and fear of non-immunization consequences were important. In the South-South, peer influence and reminder systems like WhatsApp and SMS were notable, alongside higher maternal education levels. The South-West highlighted maternal autonomy, peer influence, health card usage, high maternal education, and supportive government policies as critical factors. Conclusion: Our findings underscore the need for region-specific interventions that address these unique barriers to improve immunization coverage across Nigeria. Tailored approaches that consider the socio-economic, cultural, and logistical challenges specific to each region are essential to bridge the immunization gap.

Identifying the zero-dose and under-immunized children in Bangladesh: Approaches and experiences.

This paper presents and elaborates on empirical methods and approaches used to identify Zero-Dose (ZD) and Under-immunized (UI) children as well as the communities that these children reside in within Bangladesh. This paper also describes demand- and supply side-barriers that lead to children being ZD and UI in the country. Time period for the study was December 2022-May 2023. The study methodology encompassed secondary data analysis using data from national surveys, primary data collection and analysis via a lot quality assurance sampling (LQAS) survey and also, qualitative data collection and analysis. Study population included caregivers of children aged 4.5 months (4 months 15 days) to 23 months for the LQAS survey. The qualitative component included policymakers, program managers and service providers working in immunization as well as mothers in the selected study areas who had a living child aged less than 2 years as the study population. Our data analysis confirms existence of ZD and UI children in areas which were categorized into haor (wetlands), hilly, char (sandy/silty land surrounded by water), coastal, plain land and urban slums. Determinant analysis showed that the mother's level of education, antenatal visits made, and access to media were significantly associated with children being ZD or UI. Reproductive autonomy emerged as a key factor that had prominent impact on a child being ZD. The qualitative analysis indicated the importance of population migration, health workforce shortages and lack of access to transportation as prominent barriers to immunization. Notably, the methods and approaches used in this study are both effective and easily replicable to identify ZD and UI children. The drivers of ZD and UI along with the barriers to immunization provide potential areas for intervention by policy-makers and can apprise about interventions to be tested in future implementation research.

A new sphenodontian (Lepidosauria: Rhynchocephalia) from the Late Triassic of Argentina and the early origin of the herbivore opisthodontians.

Sphenodontians were a successful group of rhynchocephalian reptiles that dominated the fossil record of Lepidosauria during the Triassic and Jurassic. Although evidence of extinction is seen at the end of the Laurasian Early Cretaceous, they appeared to remain numerically abundant in South America until the end of the period. Most of the known Late Cretaceous record in South America is composed of opisthodontians, the herbivorous branch of Sphenodontia, whose oldest members were until recently reported to be from the Kimmeridgian-Tithonian (Late Jurassic). Here, we report a new sphenodontian, Sphenotitan leyesi gen. et sp. nov., collected from the Upper Triassic Quebrada del Barro Formation of northwestern Argentina. Phylogenetic analysis identifies Sphenotitan as a basal member of Opisthodontia, extending the known record of opisthodontians and the origin of herbivory in this group by 50 Myr.

Assessing Potential Exemplars in Reducing Zero-Dose Children: A Novel Approach for Identifying Positive Outliers in Decreasing National Levels and Geographic Inequalities in Unvaccinated Children.

BACKGROUND: Understanding past successes in reaching unvaccinated or "zero-dose" children can help inform strategies for improving childhood immunization in other settings. Drawing from positive outlier methods, we developed a novel approach for identifying potential exemplars in reducing zero-dose children. METHODS: Focusing on 2000-2019, we assessed changes in the percentage of under-one children with no doses of the diphtheria-tetanus-pertussis vaccine (no-DTP) across two geographic dimensions in 56 low- or lower-middle-income countries: (1) national levels; (2) subnational gaps, as defined as the difference between the 5th and 95th percentiles of no-DTP prevalence across second administrative units. Countries with the largest reductions for both metrics were considered positive outliers or potential 'exemplars', demonstrating exception progress in reducing national no-DTP prevalence and subnational inequalities. Last, so-called "neighborhood analyses" were conducted for the Gavi Learning Hub countries (Nigeria, Mali, Uganda, and Bangladesh), comparing them with countries that had similar no-DTP measures in 2000 but different trajectories through 2019. RESULTS: From 2000 to 2019, the Democratic Republic of the Congo, Ethiopia, and India had the largest absolute decreases for the two no-DTP dimensions-national prevalence and subnational gaps-while Bangladesh and Burundi registered the largest relative reductions for each no-DTP metric. Neighborhood analyses highlighted possible opportunities for cross-country learning among Gavi Learning Hub countries and potential exemplars in reducing zero-dose children. CONCLUSIONS: Identifying where exceptional progress has occurred is the first step toward better understanding how such gains could be achieved elsewhere. Further examination of how countries have successfully reduced levels of zero-dose children-especially across variable contexts and different drivers of inequality-could support faster, sustainable advances toward greater vaccination equity worldwide.

Mapping of Pro-Equity Interventions Proposed by Immunisation Programs in Gavi Health Systems Strengthening Grants.

Reaching zero-dose (ZD) children, operationally defined as children who have not received a first dose of the diphtheria, tetanus, and pertussis (DTP1) vaccine, is crucial to increase equitable immunisation coverage and access to primary health care. However, little is known about the approaches already taken by countries to improve immunisation equity. We reviewed all Health System Strengthening (HSS) proposals submitted by Gavi-supported countries from 2014 to 2021 inclusively and extracted information on interventions favouring equity. Pro-equity interventions were mapped to an analytical framework representing Gavi 5.0 programmatic guidance on reaching ZD children and missed communities. Data from keyword searches and manual screening were extracted into an Excel database. Open format responses were analysed using inductive and deductive thematic coding. Data analysis was conducted using Excel and R. Of the 56 proposals included, 51 (91%) included at least one pro-equity intervention. The most common interventions were conducting outreach sessions, tailoring the location of service delivery, and partnerships. Many proposals had "bundles" of interventions, most often involving outreach, microplanning and community-level education activities. Nearly half prioritised remote-rural areas and only 30% addressed gender-related barriers to immunisation. The findings can help identify specific interventions on which to focus future evidence syntheses, case studies and implementation research and inform discussions on what may or may not need to change to better reach ZD children and missed communities moving forward.

Vaccine wastage in Ghana, Mozambique, and Pakistan: An assessment of wastage rates for four vaccines and the context, causes, drivers, and knowledge, attitudes and practices for vaccine wastage.

Vaccine procurement costs comprise a significant share of immunization program costs in low- and middle-income countries, yet not all procured vaccines are administered. Vaccine wastage occurs due to vial breakage, excessive heat or freezing, expiration, or when not all doses in a multidose vial are used. Better estimates of vaccine wastage rates and their causes could support improved management of vaccine stocks and reduce procurement costs. This study examined aspects of wastage for four vaccines at service delivery points in Ghana (n = 48), Mozambique (n = 36), and Pakistan (n = 46). We used prospective data from daily and monthly vaccine usage data entry forms, along with cross-sectional surveys, and in-depth interviews. The analysis found that estimated monthly proportional open-vial wastage rates for vaccines in single-dose vials (SDV) or in multi-dose vials (MDV) that can be kept refrigerated up to four weeks after opening ranged from 0.08 % to 3 %. For MDV where remaining doses are discarded within six hours after opening, the mean wastage rates ranged from 5 % to 33 %, with rates being highest for measles containing vaccine. Despite national-level guidance to open a vaccine vial even when only one child is present, vaccines in MDV that are discarded within six hours of opening are sometimes offered less frequently than vaccines in SDV or in MDV where remaining doses can be used for up to 4 weeks. This practice can lead to missed opportunities for vaccination. While closed-vial wastage at service delivery points (SDPs) was relatively rare, individual instances can result in large losses, suggesting that monitoring closed-vial wastage should not be neglected. Health workers reported insufficient knowledge of vaccine wastage tracking and reporting methods. Improving reporting forms would facilitate more accurate reporting of all causes of wastage, as would additional training and supportive supervision. Globally, decreasing doses per vial could reduce open-vial wastage.