IMPORTANCE: The protocol of a randomized trial is the foundation for study planning, conduct, reporting, and external review. However, trial protocols vary in their completeness and often do not address key elements of design and conduct. The SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) statement was first published in 2013 as guidance to improve the completeness of trial protocols. Periodic updates incorporating the latest evidence and best practices are needed to ensure that the guidance remains relevant to users. Herein, we systematically update the SPIRIT recommendations for minimum items to address in the protocol of a randomized trial. OBSERVATIONS: We completed a scoping review and developed a project specific database of empirical and theoretical evidence to generate a list of potential changes to the SPIRIT 2013 checklist. The list was enriched with recommendations provided by lead authors of existing SPIRIT/CONSORT (Consolidated Standards of Reporting Trials) extensions (harms, outcomes, nonpharmacological treatment) and other reporting guidelines (Template for Intervention Description and Replication [TIDieR]). The potential modifications were rated in a 3-round Delphi survey followed by a consensus meeting. Overall, 317 individuals participated in the Delphi consensus process and 30 experts attended the consensus meeting. The process led to the addition of 2 new protocol items, revision to 5 items, deletion/merger of 5 items, and integration of key items from other relevant reporting guidelines. Notable changes include a new open-science section, additional emphasis on the assessment of harms and description of interventions and comparators, and a new item on how patients and the public will be involved in trial design, conduct, and reporting. The updated SPIRIT 2025 statement consists of an evidence based checklist of 34 minimum items to address in a trial protocol, along with a diagram illustrating the schedule of enrollment, interventions, and assessments for trial participants. To facilitate implementation, we also developed an expanded version of the SPIRIT 2025 checklist and an accompanying explanation and elaboration document. CONCLUSIONS AND RELEVANCE: Widespread endorsement and adherence to the updated SPIRIT 2025 statement have the potential to enhance the transparency and completeness of trial protocols for the benefit of investigators, trial participants, patients, funders, research ethics committees, journals, trial registries, policy makers, regulators, and other reviewers.

IMPORTANCE: The protocol of a randomised trial is the foundation for study planning, conduct, reporting, and external review. However, trial protocols vary in their completeness and often do not address key elements of design and conduct. The SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) statement was first published in 2013 as guidance to improve the completeness of trial protocols. Periodic updates incorporating the latest evidence and best practices are needed to ensure that the guidance remains relevant to users. OBJECTIVE: To systematically update the SPIRIT recommendations for minimum items to address in the protocol of a randomised trial. DESIGN: We completed a scoping review and developed a project specific database of empirical and theoretical evidence to generate a list of potential changes to the SPIRIT 2013 checklist. The list was enriched with recommendations provided by lead authors of existing SPIRIT/CONSORT (Consolidated Standards of Reporting Trials) extensions (Harms, Outcomes, Non-pharmacological Treatment) and other reporting guidelines (TIDieR). The potential modifications were rated in a three-round Delphi survey followed by a consensus meeting. FINDINGS: Overall, 317 individuals participated in the Delphi consensus process and 30 experts attended the consensus meeting. The process led to the addition of two new protocol items, revision to five items, deletion/merger of five items, and integration of key items from other relevant reporting guidelines. Notable changes include a new open science section, additional emphasis on the assessment of harms and description of interventions and comparators, and a new item on how patients and the public will be involved in trial design, conduct, and reporting. The updated SPIRIT 2025 statement consists of an evidence-based checklist of 34 minimum items to address in a trial protocol, along with a diagram illustrating the schedule of enrolment, interventions, and assessments for trial participants. To facilitate implementation, we also developed an expanded version of the SPIRIT 2025 checklist and an accompanying explanation and elaboration document. CONCLUSIONS AND RELEVANCE: Widespread endorsement and adherence to the updated SPIRIT 2025 statement have the potential to enhance the transparency and completeness of trial protocols for the benefit of investigators, trial participants, patients, funders, research ethics committees, journals, trial registries, policymakers, regulators, and other reviewers.

BACKGROUND: Well designed and properly executed randomised trials are considered the most reliable evidence on the benefits of healthcare interventions. However, there is overwhelming evidence that the quality of reporting is not optimal. The CONSORT (Consolidated Standards of Reporting Trials) statement was designed to improve the quality of reporting and provides a minimum set of items to be included in a report of a randomised trial. CONSORT was first published in 1996, then updated in 2001 and 2010. Here, we present the updated CONSORT 2025 statement, which aims to account for recent methodological advancements and feedback from end users. METHODS: We conducted a scoping review of the literature and developed a project-specific database of empirical and theoretical evidence related to CONSORT, to generate a list of potential changes to the checklist. The list was enriched with recommendations provided by the lead authors of existing CONSORT extensions (Harms, Outcomes, Non-pharmacological Treatment), other related reporting guidelines (TIDieR) and recommendations from other sources (e.g., personal communications). The list of potential changes to the checklist was assessed in a large, international, online, three-round Delphi survey involving 317 participants and discussed at a two-day online expert consensus meeting of 30 invited international experts. RESULTS: We have made substantive changes to the CONSORT checklist. We added seven new checklist items, revised three items, deleted one item, and integrated several items from key CONSORT extensions. We also restructured the CONSORT checklist, with a new section on open science. The CONSORT 2025 statement consists of a 30-item checklist of essential items that should be included when reporting the results of a randomised trial and a diagram for documenting the flow of participants through the trial. To facilitate implementation of CONSORT 2025, we have also developed an expanded version of the CONSORT 2025 checklist, with bullet points eliciting critical elements of each item. CONCLUSIONS: Authors, editors, reviewers, and other potential users should use CONSORT 2025 when writing and evaluating manuscripts of randomised trials to ensure that trial reports are clear and transparent.

The protocol of a randomized trial is the foundation for study planning, conduct, reporting and external review. However, trial protocols vary in their completeness and often do not address key elements of design and conduct. The SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) statement was first published in 2013 as guidance to improve the completeness of trial protocols. Periodic updates incorporating the latest evidence and best practices are needed to ensure that the guidance remains relevant to users. Here, we aimed to systematically update the SPIRIT recommendations for minimum items to address in the protocol of a randomized trial. We completed a scoping review and developed a project-specific database of empirical and theoretical evidence to generate a list of potential changes to the SPIRIT 2013 checklist. The list was enriched with recommendations provided by lead authors of existing SPIRIT/CONSORT (Consolidated Standards of Reporting Trials) extensions (Harms, Outcomes, Non-pharmacological Treatment) and other reporting guidelines (TIDieR). The potential modifications were rated in a three-round Delphi survey followed by a consensus meeting. Overall, 317 individuals participated in the Delphi consensus process and 30 experts attended the consensus meeting. The process led to the addition of two new protocol items, revision to five items, deletion/merger of five items, and integration of key items from other relevant reporting guidelines. Notable changes include a new open science section, additional emphasis on the assessment of harms and description of interventions and comparators, and a new item on how patients and the public will be involved in trial design, conduct and reporting. The updated SPIRIT 2025 statement consists of an evidence-based checklist of 34 minimum items to address in a trial protocol, along with a diagram illustrating the schedule of enrollment, interventions and assessments for trial participants. To facilitate implementation, we also developed an expanded version of the SPIRIT 2025 checklist and an accompanying explanation and elaboration document. Widespread endorsement and adherence to the updated SPIRIT 2025 statement have the potential to enhance the transparency and completeness of trial protocols for the benefit of investigators, trial participants, patients, funders, research ethics committees, journals, trial registries, policymakers, regulators and other reviewers.

IMPORTANCE: The protocol of a randomised trial is the foundation for study planning, conduct, reporting, and external review. However, trial protocols vary in their completeness and often do not address key elements of design and conduct. The SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) statement was first published in 2013 as guidance to improve the completeness of trial protocols. Periodic updates incorporating the latest evidence and best practices are needed to ensure that the guidance remains relevant to users. OBJECTIVE: To systematically update the SPIRIT recommendations for minimum items to address in the protocol of a randomised trial. DESIGN: We completed a scoping review and developed a project specific database of empirical and theoretical evidence to generate a list of potential changes to the SPIRIT 2013 checklist. The list was enriched with recommendations provided by lead authors of existing SPIRIT/CONSORT (Consolidated Standards of Reporting Trials) extensions (Harms, Outcomes, Non-pharmacological Treatment) and other reporting guidelines (TIDieR). The potential modifications were rated in a three-round Delphi survey followed by a consensus meeting. FINDINGS: Overall, 317 individuals participated in the Delphi consensus process and 30 experts attended the consensus meeting. The process led to the addition of two new protocol items, revision to five items, deletion/merger of five items, and integration of key items from other relevant reporting guidelines. Notable changes include a new open science section, additional emphasis on the assessment of harms and description of interventions and comparators, and a new item on how patients and the public will be involved in trial design, conduct, and reporting. The updated SPIRIT 2025 statement consists of an evidence based checklist of 34 minimum items to address in a trial protocol, along with a diagram illustrating the schedule of enrolment, interventions, and assessments for trial participants. To facilitate implementation, we also developed an expanded version of the SPIRIT 2025 checklist and an accompanying explanation and elaboration document. CONCLUSIONS AND RELEVANCE: Widespread endorsement and adherence to the updated SPIRIT 2025 statement have the potential to enhance the transparency and completeness of trial protocols for the benefit of investigators, trial participants, patients, funders, research ethics committees, journals, trial registries, policymakers, regulators, and other reviewers.

Critical appraisal of the quality of randomised trials is possible only if their design, conduct, analysis, and results are completely and accurately reported. Without transparent reporting of the methods and results, readers will not be able to fully evaluate the reliability and validity of trial findings. The CONSORT (Consolidated Standards of Reporting Trials) statement aims to improve the quality of reporting and provides a minimum set of items to be included in a report of a randomised trial. CONSORT was first published in 1996 and was updated in 2001 and 2010. CONSORT comprises a checklist of essential items that should be included in reports of randomised trials and a diagram for documenting the flow of participants through a trial. The CONSORT statement has been updated (CONSORT 2025) to reflect recent methodological advancements and feedback from end users, ensuring that it remains fit for purpose. Here, we present the updated CONSORT explanation and elaboration document, which has been extensively revised and describes the rationale and scientific background for each CONSORT 2025 checklist item and provides published examples of good reporting. The objective is to enhance the use, understanding, and dissemination of CONSORT 2025 and provide guidance to authors about how to improve the reporting of their trials and ensure trial reports are complete, and transparent.

IMPORTANCE: Well-designed and properly executed randomized trials are considered the most reliable evidence on the benefits of health care interventions. However, there is overwhelming evidence that the quality of reporting is not optimal. The CONSORT (Consolidated Standards of Reporting Trials) statement was designed to improve the quality of reporting and provides a minimum set of items to be included in a report of a randomized trial. CONSORT was first published in 1996, then updated in 2001 and 2010. Herein, we present the updated CONSORT 2025 statement, which aims to account for recent methodological advancements and feedback from end users. OBSERVATIONS: We conducted a scoping review of the literature and developed a project-specific database of empirical and theoretical evidence related to CONSORT to generate a list of potential changes to the checklist. The list was enriched with recommendations provided by the lead authors of existing CONSORT extensions (harms, outcomes, nonpharmacological treatment), other related reporting guidelines (Template for Intervention Description and Replication [TIDieR]), and recommendations from other sources (eg, personal communications). The list of potential changes to the checklist was assessed in a large, international, online, 3-round Delphi survey involving 317 participants and discussed at a 2-day online expert consensus meeting of 30 invited international experts. We have made substantive changes to the CONSORT checklist. We added 7 new checklist items, revised 3 items, deleted 1 item, and integrated several items from key CONSORT extensions. We also restructured the CONSORT checklist, with a new section on open science. The CONSORT 2025 statement consists of a 30-item checklist of essential items that should be included when reporting the results of a randomized trial and a diagram for documenting the flow of participants through the trial. To facilitate implementation of CONSORT 2025, we have also developed an expanded version of the CONSORT 2025 checklist, with bullet points eliciting critical elements of each item. CONCLUSIONS AND RELEVANCE: Authors, editors, reviewers, and other potential users should use CONSORT 2025 when writing and evaluating manuscripts of randomized trials to ensure that trial reports are clear and transparent.

IMPORTANCE: During the 2023-2024 respiratory syncytial virus (RSV) season in the United States, 2 new RSV prevention products were recommended to protect infants in their first RSV season: nirsevimab and Pfizer's maternal RSV vaccine. Postlicensure studies are needed to assess prevention product impact and effectiveness. OBJECTIVE: To compare the epidemiology and disease burden of medically attended RSV-associated acute respiratory illness (ARI) among children younger than 5 years during the 2023-2024 RSV season with 3 prepandemic RSV seasons (2017-2020), estimate nirsevimab effectiveness against medically attended RSV-associated ARI, and compare nirsevimab binding site mutations among circulating RSV in infants with and without nirsevimab receipt. DESIGN, SETTING, AND PARTICIPANTS: This study included a prospective population-based surveillance for medically attended ARI with systematic molecular testing for RSV and whole-genome sequencing of RSV positive samples, as well as a test-negative case-control design to estimate nirsevimab effectiveness. The study was conducted in 7 academic pediatric medical centers in the United States with data from RSV seasons (September 1 through April 30) in 2017 through 2024. Participants were children younger than 5 years with medically attended ARI. EXPOSURE: For the nirsevimab effectiveness analyses, nirsevimab receipt among infants younger than 8 months as of or born after October 1, 2023. MAIN OUTCOME AND MEASURE: Medically attended RSV-associated ARI. RESULTS: Overall, 28 689 children younger than 5 years with medically attended ARI were enrolled, including 9536 during September 1, 2023, through April 30, 2024, and 19 153 during the same calendar period of 2017-2020. Of these children, 16 196 (57%) were male, and 12 444 (43.4) were female; the median (IQR) age was 15 (6-29) months. During 2023-2024, the proportion of children with RSV was 23% (2199/9490) among all medically attended episodes, similar to 2017-2020. RSV-associated hospitalization rates in 2023-2024 were similar to average 2017-2020 seasonal rates with 5.0 (95% CI, 4.6-5.3) per 1000 among children younger than 5 years; the highest rates were among children aged 0 to 2 months (26.6; 95% CI, 23.0-30.2). Low maternal RSV vaccine uptake precluded assessment of effectiveness. Overall, 10 of 765 case patients (1%) who were RSV positive and 126 of 851 control patients (15%) who were RSV negative received nirsevimab. Nirsevimab effectiveness was 89% (95% CI, 79%-94%) against medically attended RSV-associated ARI and 93% (95% CI, 82%-97%) against RSV-associated hospitalization. Among 229 sequenced specimens, there were no differences in nirsevimab binding site mutations by infant nirsevimab receipt status. CONCLUSIONS AND RELEVANCE: This analysis documented the continued high burden of medically attended RSV-associated ARI among young children in the US. There is a potential for substantial public health impact with increased and equitable prevention product coverage in future seasons.

The World Health Organization's Immunization and Vaccines-related Implementation Research Advisory Committee (IVIR-AC) serves to independently review and evaluate vaccine-related research to maximize the potential impact of vaccination programs. From 28 June - 1 July 2024, IVIR-AC was convened for an ad hoc meeting to discuss new evidence on criteria for rubella vaccine introduction and the risk of congenital rubella syndrome. This report summarizes background information on rubella virus transmission and the burden of congenital rubella syndrome, meeting structure and presentations, proceedings, and recommendations.

This article summarizes what is currently known about the 2019 novel coronavirus and offers interim guidance.

BACKGROUND: Critical congenital heart defects (CCHDs) are one of the most common types of birth defects and can lead to significant morbidity and mortality along with surgical or catheter interventions within the first year of life. This report updates previously published estimates of CCHD prevalence with the latest population-based surveillance data from 19 birth defect surveillance programs. METHODS: The U.S. population-based surveillance programs submitted data on identified cases of 12 CCHDs and co-occurring cardiovascular and chromosomal birth defects from 2014 to 2018. We estimated prevalence by program type and maternal and infant characteristics. Among nine programs with active case ascertainment that collect more than live births, we estimated the percentage of co-occurring cardiovascular and chromosomal birth defects for the 12 CCHDs. RESULTS: We identified 18,587 cases of CCHD among all participating programs. Overall CCHD prevalence was 19.6 per 10,000 live births among all 19 programs and 20.2 per 10,000 live births among active programs. Among maternal racial/ethnic groups, infants/fetuses born to American Indian/Alaska Native mothers showed the highest overall prevalence for all CCHDs (28.3 per 10,000) along with eight of the 12 individual CCHDs. Among 7,726 infants/fetuses with CCHD from active case ascertainment programs, 15.8% had at least one co-occurring chromosomal birth defect. CONCLUSION: Our study provides prevalence estimates for CCHDs by maternal and infant characteristics along with co-occurrence with cardiovascular and chromosomal birth defects among infants/fetuses with CCHD using one of the largest and most recent cohorts since the implementation of widespread CCHD screening. These data can provide a basis for future research to better understand risk factors for these defects.

BACKGROUND: An association between rotavirus vaccination and intussusception has been documented in post-licensure studies in some countries. We evaluated the risk of intussusception associated with monovalent rotavirus vaccine (Rotavac) administered at 6, 10 and 14 weeks of age in India. METHODS: Active prospective surveillance for intussusception was conducted at 22 hospitals across 16 states from April 2016 through September 2017. Data on demography, clinical features and vaccination were documented. Age-adjusted relative incidence for 1-7, 8-21, and 1-21 days after rotavirus vaccination in children aged 28-364 days at intussusception onset was estimated using the self-controlled case-series (SCCS) method. Only Brighton Collaboration level 1 cases were included. RESULTS: Out of 670 children aged 2-23 months with intussusception, 311 (46.4%) children were aged 28-364 days with confirmed vaccination status. Out of these, 52 intussusception cases with confirmed receipt of RVV were included in the SCCS analysis. No intussusception case was observed within 21 days of dose 1. Only one case occurred during 8-21 days after the dose 2. Post-dose 3, two cases in 1-7 days and 7 cases during 8-21 days period were observed. There was no increased risk of intussusception during 1-7 days after the doses 1 and 2 (zero cases observed) or dose 3 (relative incidence [RI], 1.71 [95% confidence interval {CI} 0.0-5.11]). Similarly, no increased risk during 8-21 days after the dose 1 (zero cases observed), dose 2 (RI, 0.71 [95% CI, 0.0-3.28]) or dose 3 (RI, 2.52 [95% CI, 0.78-5.61]). The results were similar for 1-21 day periods after the doses separately or pooled. CONCLUSIONS: The risk of intussusception during the first 21 days after any dose of rotavirus vaccine (Rotavac) was not higher among the Indian infants than the background risk, based on limited SCCS analysis of 52 children.

The global programme for the eradication of Guinea worm disease, caused by the parasitic nematode Dracunculus medinensis, has been successful in driving down human cases, but infections in non-human animals, particularly domestic dogs (Canis familiaris), now present a major obstacle to further progress. Dog infections have mainly been found in Chad and, to a lesser extent in Mali and Ethiopia. While humans classically acquire infection by drinking water containing infected copepods, it has been hypothesised that dogs might additionally or alternatively acquire infection via a novel pathway, such as consumption of fish or frogs as possible transport or paratenic hosts. We characterised the ecology of free-ranging dogs living in three villages in Gog woreda, Gambella region, Ethiopia in April-May 2018. We analysed their exposure to potential sources of Guinea worm infection, and investigated risk factors associated with infection histories. The home ranges of 125 dogs and their activity around water sources were described using GPS tracking, and the diets of 119 dogs were described using stable isotope analysis. Unlike in Chad, where Guinea worm infection is most frequent, we found no ecological or behavioural correlates of infection history in dogs in Ethiopia. Unlike in Chad, there was no effect of variation among dogs in their consumption of aquatic vertebrates (fish or frogs) on their infection history, and we found no evidence to support hypotheses for this novel transmission pathway in Ethiopia. Dog owners had apparently increased the frequency of clean water provision to dogs in response to previous infections. Variations in dog ranging behaviour, owner behaviour and the characteristics of natural water bodies all influenced the exposure of dogs to potential sources of infection. This initial study suggests that the classical transmission pathway should be a focus of attention for Guinea worm control in non-human animals in Ethiopia.

OBJECTIVE: Resistance to colistin, a last resort antibiotic, has emerged in India. We investigated colistin-resistant Klebsiella pneumoniae(ColR-KP) in a hospital in India to describe infections, characterize resistance of isolates, compare concordance of detection methods, and identify transmission events. DESIGN: Retrospective observational study. METHODS: Case-patients were defined as individuals from whom ColR-KP was isolated from a clinical specimen between January 2016 and October 2017. Isolates resistant to colistin by Vitek 2 were confirmed by broth microdilution (BMD). Isolates underwent colistin susceptibility testing by disk diffusion and whole-genome sequencing. Medical records were reviewed. RESULTS: Of 846 K. pneumoniae isolates, 34 (4%) were colistin resistant. In total, 22 case-patients were identified. Most (90%) were male; their median age was 33 years. Half were transferred from another hospital; 45% died. Case-patients were admitted for a median of 14 days before detection of ColR-KP. Also, 7 case-patients (32%) received colistin before detection of ColR-KP. All isolates were resistant to carbapenems and susceptible to tigecycline. Isolates resistant to colistin by Vitek 2 were also resistant by BMD; 2 ColR-KP isolates were resistant by disk diffusion. Moreover, 8 multilocus sequence types were identified. Isolates were negative for mobile colistin resistance (mcr) genes. Based on sequencing analysis, in-hospital transmission may have occurred with 8 case-patients (38%). CONCLUSIONS: Multiple infections caused by highly resistant, mcr-negative ColR-KP with substantial mortality were identified. Disk diffusion correlated poorly with Vitek 2 and BMD for detection of ColR-KP. Sequencing indicated multiple importation and in-hospital transmission events. Enhanced detection for ColR-KP may be warranted in India.

BACKGROUND: Using the National Birth Defects Prevention Network (NBDPN) annual data report, U.S. national prevalence estimates for major birth defects are developed based on birth cohort 2010-2014. METHODS: Data from 39 U.S. population-based birth defects surveillance programs (16 active case-finding, 10 passive case-finding with case confirmation, and 13 passive without case confirmation) were used to calculate pooled prevalence estimates for major defects by case-finding approach. Fourteen active case-finding programs including at least live birth and stillbirth pregnancy outcomes monitoring approximately one million births annually were used to develop national prevalence estimates, adjusted for maternal race/ethnicity (for all conditions examined) and maternal age (trisomies and gastroschisis). These calculations used a similar methodology to the previous estimates to examine changes over time. RESULTS: The adjusted national birth prevalence estimates per 10,000 live births ranged from 0.62 for interrupted aortic arch to 16.87 for clubfoot, and 19.93 for the 12 critical congenital heart defects combined. While the birth prevalence of most birth defects studied remained relatively stable over 15 years, an increasing prevalence was observed for gastroschisis and Down syndrome. Additionally, the prevalence for atrioventricular septal defect, tetralogy of Fallot, omphalocele, and trisomy 18 increased in this period compared to the previous periods. Active case-finding programs generally had higher prevalence rates for most defects examined, most notably for anencephaly, anophthalmia/microphthalmia, trisomy 13, and trisomy 18. CONCLUSION: National estimates of birth defects prevalence provide data for monitoring trends and understanding the impact of these conditions. Increasing prevalence rates observed for selected conditions warrant further examination.

BACKGROUND: Globally, hepatitis E virus (HEV) is a major cause of acute viral hepatitis. Epidemiology and clinical presentation of hepatitis E vary greatly by location and are affected by the HEV genotype. Nucleic acid amplification technique (NAT)-based assays are important for the detection of acute HEV infection as well for monitoring chronic cases of hepatitis E. OBJECTIVES: The aim of the study was to evaluate a panel of samples containing different genotypes of HEV for use in nucleic NAT-based assays. STUDY DESIGN: The panel of samples comprises eleven different members including HEV genotype 1a (2 strains), 1e, 2a, 3b, 3c, 3e, 3f, 4c, 4g as well as a human isolate related to rabbit HEV. Each laboratory assayed the panel members directly against the 1(st) World Health Organization (WHO) International Standard (IS) for HEV RNA (6329/10) which is based upon a genotype 3 a strain. RESULTS: The samples for evaluation were distributed to 24 laboratories from 14 different countries and assayed on three separate days. Of these, 23 participating laboratories returned a total of 32 sets of data; 17 from quantitative assays and 15 from qualitative assays. The assays used consisted of a mixture of in-house developed and commercially available assays. The results showed that all samples were detected consistently by the majority of participants, although in some cases, some samples were detected less efficiently. CONCLUSIONS: Based on the results of the collaborative study the panel (code number 8578/13) was established as the "1st International Reference Panel (IRP) for all HEV genotypes for NAT-based assays" by the WHO Expert Committee on Biological Standardization. This IRP will be important for assay validation and ensuring adequate detection of different genotypes and clinically important sub-genotypes of HEV.

Pharmacogenetic (PGx) testing is increasingly available from clinical and research laboratories. However, only a limited number of quality control and other reference materials (RMs) are currently available for the complex rearrangements and rare variants that occur in the CYP2D6 gene. To address this need, the Division of Laboratory Systems, Centers for Disease Control and Prevention based Genetic Testing Reference Material Coordination Program (GeT-RM), in collaboration with members of the pharmacogenetic testing and research communities and the Coriell Cell Repositories, has characterized 179 DNA samples derived from Coriell cell lines. Testing included the re-characterization of 137 genomic DNAs that were genotyped in previous GeT-RM studies and 42 additional samples that had not been previously characterized. DNA samples were distributed to volunteer testing laboratories for genotyping using a variety of commercially available and laboratory developed tests. These publicly available samples will support the quality assurance and quality control programs of clinical laboratories performing CYP2D6 testing.

OBJECTIVE: We examined quality measures for screening, diagnosis and treatment of lupus nephritis (LN) among participants of the California Lupus Epidemiology Study (CLUES) across 25 different clinical sites to identify gaps in quality of care. METHODS: Data from 250 lupus participants was analyzed across three sources (medical records, physician examination, and patient interviews). Overall performance on eight quality measures was calculated separately for participants with and without LN. We used generalized estimating equations in which the outcome was performance on measures, adjusting for participant demographics, lupus disease severity and practice characteristics. RESULTS: Of 148 patients without LN, 42% had screening labs for nephritis, 38% had lupus activity serologies and 81% had blood pressure checked every 6 months. Of 102 LN patients, 67% had a timely kidney biopsy, at least 81% had appropriate treatment and 78% achieved target blood pressure within 1 year of diagnosis. Overall performance in participants across quality measures was 54% (no LN) and 80% (LN). Significantly higher overall performance for screening measures for LN was seen at academic (63.4-73%) versus community clinics (37.9-38.4%). Similarly, among those with LN, higher performance in academic (84.1-85.2%) versus community clinics (54.8-60.2%) was observed for treatment measures. CONCLUSION: In this quality of care analysis across 25 diverse clinical settings, we found relatively high performance on measures for management of LN. However, future work should focus on bridging the gaps in lupus quality of care for patients without nephritis, particularly in community settings. This article is protected by copyright. All rights reserved.

Mumps, a vaccine-preventable disease, causes inflammation of salivary glands and may cause severe complications such as encephalitis, meningitis, deafness, and orchitis/oophoritis. In India, mumps vaccine is not included in the universal immunization program and during 2009-2014, 72 outbreaks with >1500 cases were reported. In August 2016, a suspected mumps outbreak was reported in Jaisalmer block, Rajasthan. We investigated to confirm the etiology, describe epidemiology, and recommend prevention and control measures. We defined a case as swelling in the parotid region in a Jaisalmer block resident between June 23 and September 10, 2016. We searched for cases in health facilities and house-to-house in affected villages and hamlets. We tested blood samples of cases for mumps IgM ELISA. We found 162 cases (60% males) with median age of 9.4 years (range: 7 month-38 years) and 65 (40%) were females. Symptoms included fever (70%) and bilateral swelling in neck (65%). None were vaccinated against mumps. Most (84%) cases were school-going children (3-16 years old). The overall attack rate was 2%. Village A, with two hamlets, had the highest attack rate (hamlet 1=13% and hamlet 2=12%). School A of village A, hamlet 1 which accommodated 200 children in two classrooms had an attack rate of 55%. Of 18 blood samples from cases, 11 tested positive for mumps IgM ELISA. This was a confirmed mumps outbreak in Jaisalmer bl0ock that disproportionately affected school-going children. We recommended continued surveillance, five-day absence from school, and vaccination. This article is protected by copyright. All rights reserved.

Gastroschisis is a serious congenital defect in which the intestines protrude through an opening in the abdominal wall. Gastroschisis requires surgical repair soon after birth and is associated with an increased risk for medical complications and mortality during infancy. Reports from multiple surveillance systems worldwide have documented increasing prevalence of gastroschisis since the 1980s, particularly among younger mothers; however, since publication of a multistate U.S. report that included data through 2005 (1), it is not known whether prevalence has continued to increase. Data on gastroschisis from 14 population-based state surveillance programs were pooled and analyzed to assess the average annual percent change (AAPC) in prevalence and to compare the prevalence during 2006-2012 with that during 1995-2005, stratified by maternal age and race/ethnicity. The pooled data included approximately 29% of U.S. births for the period 1995-2012. During 1995-2012, gastroschisis prevalence increased in every category of maternal age and race/ethnicity, and the AAPC ranged from 3.1% in non-Hispanic white (white) mothers aged <20 years to 7.9% in non-Hispanic black (black) mothers aged <20 years. These corresponded to overall percentage increases during 1995-2012 that ranged from 68% in white mothers aged <20 years to 263% in black mothers aged <20 years. Gastroschisis prevalence increased 30% between the two periods, from 3.6 per 10,000 births during 1995-2005 to 4.9 per 10,000 births during 2006-2012 (prevalence ratio = 1.3, 95% confidence interval [CI]: 1.3-1.4), with the largest increase among black mothers aged <20 years (prevalence ratio = 2.0, 95% CI: 1.6-2.5). Public health research is urgently needed to identify factors contributing to this increase.

Pharmacogenetic testing is increasingly available from clinical laboratories. However, only a limited number of quality control and other reference materials are currently available to support clinical testing. To address this need, the Centers for Disease Control and Prevention-based Genetic Testing Reference Material Coordination Program, in collaboration with members of the pharmacogenetic testing community and the Coriell Cell Repositories, has characterized 137 genomic DNA samples for 28 genes commonly genotyped by pharmacogenetic testing assays (CYP1A1, CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2E1, CYP3A4, CYP3A5, CYP4F2, DPYD, GSTM1, GSTP1, GSTT1, NAT1, NAT2, SLC15A2, SLC22A2, SLCO1B1, SLCO2B1, TPMT, UGT1A1, UGT2B7, UGT2B15, UGT2B17, and VKORC1). One hundred thirty-seven Coriell cell lines were selected based on ethnic diversity and partial genotype characterization from earlier testing. DNA samples were coded and distributed to volunteer testing laboratories for targeted genotyping using a number of commercially available and laboratory developed tests. Through consensus verification, we confirmed the presence of at least 108 variant pharmacogenetic alleles. These samples are also being characterized by other pharmacogenetic assays, including next-generation sequencing, which will be reported separately. Genotyping results were consistent among laboratories, with most differences in allele assignments attributed to assay design and variability in reported allele nomenclature, particularly for CYP2D6, UGT1A1, and VKORC1. These publicly available samples will help ensure the accuracy of pharmacogenetic testing.

BACKGROUND: Non-fatal health outcomes from diseases and injuries are a crucial consideration in the promotion and monitoring of individual and population health. The Global Burden of Disease (GBD) studies done in 1990 and 2000 have been the only studies to quantify non-fatal health outcomes across an exhaustive set of disorders at the global and regional level. Neither effort quantified uncertainty in prevalence or years lived with disability (YLDs). METHODS: Of the 291 diseases and injuries in the GBD cause list, 289 cause disability. For 1160 sequelae of the 289 diseases and injuries, we undertook a systematic analysis of prevalence, incidence, remission, duration, and excess mortality. Sources included published studies, case notification, population-based cancer registries, other disease registries, antenatal clinic serosurveillance, hospital discharge data, ambulatory care data, household surveys, other surveys, and cohort studies. For most sequelae, we used a Bayesian meta-regression method, DisMod-MR, designed to address key limitations in descriptive epidemiological data, including missing data, inconsistency, and large methodological variation between data sources. For some disorders, we used natural history models, geospatial models, back-calculation models (models calculating incidence from population mortality rates and case fatality), or registration completeness models (models adjusting for incomplete registration with health-system access and other covariates). Disability weights for 220 unique health states were used to capture the severity of health loss. YLDs by cause at age, sex, country, and year levels were adjusted for comorbidity with simulation methods. We included uncertainty estimates at all stages of the analysis. FINDINGS: Global prevalence for all ages combined in 2010 across the 1160 sequelae ranged from fewer than one case per 1 million people to 350,000 cases per 1 million people. Prevalence and severity of health loss were weakly correlated (correlation coefficient -0.37). In 2010, there were 777 million YLDs from all causes, up from 583 million in 1990. The main contributors to global YLDs were mental and behavioural disorders, musculoskeletal disorders, and diabetes or endocrine diseases. The leading specific causes of YLDs were much the same in 2010 as they were in 1990: low back pain, major depressive disorder, iron-deficiency anaemia, neck pain, chronic obstructive pulmonary disease, anxiety disorders, migraine, diabetes, and falls. Age-specific prevalence of YLDs increased with age in all regions and has decreased slightly from 1990 to 2010. Regional patterns of the leading causes of YLDs were more similar compared with years of life lost due to premature mortality. Neglected tropical diseases, HIV/AIDS, tuberculosis, malaria, and anaemia were important causes of YLDs in sub-Saharan Africa. INTERPRETATION: Rates of YLDs per 100,000 people have remained largely constant over time but rise steadily with age. Population growth and ageing have increased YLD numbers and crude rates over the past two decades. Prevalences of the most common causes of YLDs, such as mental and behavioural disorders and musculoskeletal disorders, have not decreased. Health systems will need to address the needs of the rising numbers of individuals with a range of disorders that largely cause disability but not mortality. Quantification of the burden of non-fatal health outcomes will be crucial to understand how well health systems are responding to these challenges. Effective and affordable strategies to deal with this rising burden are an urgent priority for health systems in most parts of the world. FUNDING: Bill & Melinda Gates Foundation.

BACKGROUND: Measuring disease and injury burden in populations requires a composite metric that captures both premature mortality and the prevalence and severity of ill-health. The 1990 Global Burden of Disease study proposed disability-adjusted life years (DALYs) to measure disease burden. No comprehensive update of disease burden worldwide incorporating a systematic reassessment of disease and injury-specific epidemiology has been done since the 1990 study. We aimed to calculate disease burden worldwide and for 21 regions for 1990, 2005, and 2010 with methods to enable meaningful comparisons over time. METHODS: We calculated DALYs as the sum of years of life lost (YLLs) and years lived with disability (YLDs). DALYs were calculated for 291 causes, 20 age groups, both sexes, and for 187 countries, and aggregated to regional and global estimates of disease burden for three points in time with strictly comparable definitions and methods. YLLs were calculated from age-sex-country-time-specific estimates of mortality by cause, with death by standardised lost life expectancy at each age. YLDs were calculated as prevalence of 1160 disabling sequelae, by age, sex, and cause, and weighted by new disability weights for each health state. Neither YLLs nor YLDs were age-weighted or discounted. Uncertainty around cause-specific DALYs was calculated incorporating uncertainty in levels of all-cause mortality, cause-specific mortality, prevalence, and disability weights. FINDINGS: Global DALYs remained stable from 1990 (2.503 billion) to 2010 (2.490 billion). Crude DALYs per 1000 decreased by 23% (472 per 1000 to 361 per 1000). An important shift has occurred in DALY composition with the contribution of deaths and disability among children (younger than 5 years of age) declining from 41% of global DALYs in 1990 to 25% in 2010. YLLs typically account for about half of disease burden in more developed regions (high-income Asia Pacific, western Europe, high-income North America, and Australasia), rising to over 80% of DALYs in sub-Saharan Africa. In 1990, 47% of DALYs worldwide were from communicable, maternal, neonatal, and nutritional disorders, 43% from non-communicable diseases, and 10% from injuries. By 2010, this had shifted to 35%, 54%, and 11%, respectively. Ischaemic heart disease was the leading cause of DALYs worldwide in 2010 (up from fourth rank in 1990, increasing by 29%), followed by lower respiratory infections (top rank in 1990; 44% decline in DALYs), stroke (fifth in 1990; 19% increase), diarrhoeal diseases (second in 1990; 51% decrease), and HIV/AIDS (33rd in 1990; 351% increase). Major depressive disorder increased from 15th to 11th rank (37% increase) and road injury from 12th to 10th rank (34% increase). Substantial heterogeneity exists in rankings of leading causes of disease burden among regions. INTERPRETATION: Global disease burden has continued to shift away from communicable to non-communicable diseases and from premature death to years lived with disability. In sub-Saharan Africa, however, many communicable, maternal, neonatal, and nutritional disorders remain the dominant causes of disease burden. The rising burden from mental and behavioural disorders, musculoskeletal disorders, and diabetes will impose new challenges on health systems. Regional heterogeneity highlights the importance of understanding local burden of disease and setting goals and targets for the post-2015 agenda taking such patterns into account. Because of improved definitions, methods, and data, these results for 1990 and 2010 supersede all previously published Global Burden of Disease results. FUNDING: Bill & Melinda Gates Foundation.