Infant vaccination timing: Beyond traditional coverage metrics for maximizing impact of vaccine programs, an example from southern Nepal.

Background Immunization programs currently measure coverage by assessing the proportion of children 12–24 months who have been immunized but this does not address the important question of when the scheduled vaccines were administered. Data capturing the timing of vaccination in first 6 months, when severe disease is most likely to occur, are limited. Objective To estimate the time to Bacillus Calmette–Guérin (BCG) (recommended at birth), diphtheria-tetanus-pertussis-H, influenza b-hepatitis B (DTP-Hib-HepB), and oral polio vaccine (OPV) (recommended at 6, 10, and 14 weeks) vaccinations and risk factors for vaccination delay in infants \u3c6 months of age in a district in southern Nepal where traditional coverage metrics are high. Design/methods Infants enrolled in a randomized controlled trial of maternal influenza vaccination were visited weekly at home from birth through age 6 months to ascertain if any vaccinations had been given in the prior week. Infant, maternal, and household characteristics were recorded. BCG, DTP-Hib-HepB, and OPV vaccination coverage at 4 and 6 months was estimated. Time to vaccination was estimated through Kaplan–Meier curves; Cox-proportional hazards models were used to examine risk factors for delay for the first vaccine. Results The median age of BCG, first OPV and DTP-Hib-HepB receipt was 22, 21, and 18 weeks, respectively. Almost half of infants received no BCG by age 6 months. Only 8% and 7% of infants had received three doses of OPV and DTP-Hib-HepB, respectively, by age 6 months. Conclusion A significant delay in receipt of infant vaccines was found in a prospective, population-based, cohort in southern Nepal despite traditional coverage metrics being high. Immunization programs should consider measuring time to receipt relative to the official schedule in order to maximize benefits for disease control and child health

Pertussis Seroepidemiology in Women and Their Infants in Sarlahi District, Nepal.

Background Infants are at greatest risk for pertussis morbidity and mortality. Maternal vaccination during pregnancy has been shown to prevent pertussis in young infants in high- and middle-income countries. However, data on the levels of maternal pertussis antibodies and the efficiency of transplacental transfer in low-income South Asian settings are limited. Objective To estimate the prevalence of maternal pertussis antibodies and the efficiency of transplacental transfer in rural southern Nepal. Design/methods Paired maternal-infant blood samples were collected from a subsample of participants in a randomized, controlled trial of maternal influenza immunization (n = 291 pairs). Sera were tested by enzyme-linked immunosorbent assays for pertussis toxin, filamentous hemagglutinin, pertactin, and fimbriae. Maternal and infant pertussis antibody levels and transplacental transfer efficiency were determined and potential factors associated with both were assessed. Results Elevated maternal antibodies to pertussis toxin, suggesting recent pertussis infection, were rarely detected (4%, tested n = 305). However, paired maternal-cord sera were highly correlated across all antibodies; transplacental antibody transfer ratios for pertussis toxin were 1.14 (n = 291, 95% CI 1.07–1.20); filamentous hemagglutinin 1.10 (n = 120, 95% CI: 1.01–1.20); fimbriae 2/3 1.05 (n = 120, 95% CI: 0.96–1.15) and pertactin 0.96 (n = 289, 95% CI: 0.91–1.00). Older gestational age was associated with increased pertussis toxin and decreased fimbriae 2/3 antibody transport. Conclusions A low prevalence of maternal antibody to all four pertussis antigens was noted in Nepal, but transplacental antibody transfer was efficient. No consistent demographic factors were associated with elevated maternal antibody levels or efficiency of transplacental transfer. If an increase in infant pertussis disease burden was detected in this population, maternal immunization could be an effective intervention to prevent disease in early infancy

Population-Based Pertussis Incidence and Risk Factors in Infants Less Than 6 Months in Nepal.

Background. Pertussis is estimated to cause 2 percent of childhood deaths globally and is a growing public health problem in developed countries despite high vaccination coverage. Infants are at greatest risk of morbidity and mortality. Maternal vaccination during pregnancy may be effective to prevent pertussis in young infants, but population-based estimates of disease burden in infants are lacking, particularly in low-income countries. The objective of this study was to estimate the incidence of pertussis in infants less than 6 months of age in Sarlahi District, Nepal. Methods. Nested within a population-based randomized controlled trial of influenza vaccination during pregnancy, infants were visited weekly from birth through 6 months to assess respiratory illness in the prior week. If any respiratory symptoms had occurred, a nasal swab was collected and tested with a multitarget pertussis polymerase chain reaction (PCR) assay. The prospective cohort study includes infants observed between May 2011 and August 2014. Results. The incidence of PCR-confirmed Bordetella pertussis was 13.3 cases per 1000 infant-years (95% confidence interval, 7.7–21.3) in a cohort of 3483 infants with at least 1 day of follow-up. Conclusions. In a population-based active home surveillance for respiratory illness, a low risk for pertussis was estimated among infants in rural Nepal. Nepal’s immunization program, which includes a childhood whole cell pertussis vaccine, may be effective in controlling pertussis in infants

Viral Findings in Adult Hematological Patients with Neutropenia

BACKGROUND: Until recently, viral infections in patients with hematological malignancies were concerns primarily in allogeneic hematopoietic stem cell transplant (HSCT) recipients. During the last years, changed treatment regimens for non-transplanted patients with hematological malignancies have had potential to increase the incidence of viral infections in this group. In this study, we have prospectively investigated the prevalence of a broad range of respiratory viruses in nasopharyngeal aspirate (NPA) as well as viruses that commonly reactivate after allogeneic HSCT. METHODOLOGY/PRINCIPAL FINDINGS: Patients with hematological malignancies and therapy induced neutropenia (n = 159) were screened regarding a broad range of common respiratory viruses in the nasopharynx and for viruses commonly detected in severely immunosuppressed patients in peripheral blood. Quantitative PCR was used for detection of viruses. A viral pathogen was detected in 35% of the patients. The detection rate was rather similar in blood (22%) and NPA (18%) with polyoma BK virus and rhinovirus as dominating pathogens in blood and NPA, respectively. Patients with chronic lymphocytic leukemia (CLL) (p<0.01) and patients with fever (p<0.001) were overrepresented in the virus-positive group. Furthermore, viral findings in NPA were associated with upper respiratory symptoms (URTS) (p<0.0001). CONCLUSIONS/SIGNIFICANCE: Both respiratory viral infections and low titers of viruses in blood from patients with neutropenia were common. Patients with CLL and patients with fever were independently associated to these infections, and viral findings in NPA were associated to URTS indicating active infection. These findings motivate further studies on viruses' impact on this patient category and their potential role as causative agents of fever during neutropenia

Global Perspectives on Immunization During Pregnancy and Priorities for Future Research and Development: An International Consensus Statement.

Immunization during pregnancy has been recommended in an increasing number of countries. The aim of this strategy is to protect pregnant women and infants from severe infectious disease, morbidity and mortality and is currently limited to tetanus, inactivated influenza, and pertussis-containing vaccines. There have been recent advancements in the development of vaccines designed primarily for use in pregnant women (respiratory syncytial virus and group B Streptococcus vaccines). Although there is increasing evidence to support vaccination in pregnancy, important gaps in knowledge still exist and need to be addressed by future studies. This collaborative consensus paper provides a review of the current literature on immunization during pregnancy and highlights the gaps in knowledge and a consensus of priorities for future research initiatives, in order to optimize protection for both the mother and the infant

De novo CCND2 mutations leading to stabilization of cyclin D2 cause megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome

Activating mutations in genes encoding phosphatidylinositol 3-kinase (PI3K)-AKT pathway components cause megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome (MPPH, OMIM 603387). Here we report that individuals with MPPH lacking upstream PI3K-AKT pathway mutations carry de novo mutations in CCND2 (encoding cyclin D2) that are clustered around a residue that can be phosphorylated by glycogen synthase kinase 3β (GSK-3β). Mutant CCND2 was resistant to proteasomal degradation in vitro compared to wild-type CCND2. The PI3K-AKT pathway modulates GSK-3β activity, and cells from individuals with PIK3CA, PIK3R2 or AKT3 mutations showed similar CCND2 accumulation. CCND2 was expressed at higher levels in brains of mouse embryos expressing activated AKT3. In utero electroporation of mutant CCND2 into embryonic mouse brains produced more proliferating transfected progenitors and a smaller fraction of progenitors exiting the cell cycle compared to cells electroporated with wild-type CCND2. These observations suggest that cyclin D2 stabilization, caused by CCND2 mutation or PI3K-AKT activation, is a unifying mechanism in PI3K-AKT–related megalencephaly syndromes

2023 EULAR classification criteria for hand osteoarthritis

The objective of this study is to develop classification criteria for overall hand osteoarthritis (OA), interphalangeal OA and thumb base OA based on self-reported data and radiographic features. The classification criteria sets were developed in three phases. In phase 1, we identified criteria that discriminated hand OA from controls. In phase 2, we used a consensus-based decision analysis approach to derive a clinician-based evaluation of the relative importance of the criteria. In phase 3, we refined the scoring system, determined the cut-offs for disease classification and compared the sensitivity and specificity of the European Alliance of Associations for Rheumatology (EULAR) criteria with the 1990 American College of Rheumatology (ACR) criteria. In persons with hand symptoms and no other disease (including psoriasis) or acute injury that can explain the hand symptoms (mandatory criteria), hand OA can be classified based on age, duration of morning stiffness, number of joints with osteophytes and joint space narrowing, and concordance between symptoms and radiographic findings. Using a sum of scores based on each diagnostic element, overall hand OA can be classified if a person achieves 9 or more points on a 0-15 scale. The cut-off for interphalangeal OA and thumb base OA is 8 points. While the EULAR criteria demonstrated better sensitivity than the ACR criteria in the phase 1 data set, the performance of the two criteria sets was similar in two external cohorts. International experts developed the EULAR criteria to classify overall hand OA, interphalangeal OA and thumb base OA in clinical studies using a rigorous methodology

Klimatneutralitet 2030? : En analys av praktiska förutsättningar av klimatomställningsarbetet i Lund och Umeå

Uppdraget att hålla den globala uppvärmningen under 1,5-grader och att minska effekten av den globala uppvärmningen är ett gemensamt uppdrag där inte bara nationer utan även städer har en avgörande roll. I Sverige bor över 87% av landets invånare i stadsområden eller tätorter och siffran förväntas att stiga. Städers utformning har därför ett stort inflytande på användningen av jordens resurser och mängden utsläppta växthusgaser. För att nå målet om 1,5-grad behöver länders åtagande mer än femfaldigats och för att öka takten i omställningen har flera länder, som Sverige, förbundit sig till att nå nollutsläpp eller klimatneutralitet till mitten av århundradet eller tidigare.  Sverige antog 2017 ett klimatpolitiskt ramverk med långsiktig målsättning om att inte ha några nettoutsläpp till år 2045. Ramverket tillsammans med andra politiska klimatmål har lett till att flera kommuner i Sverige har beslutat att bli klimatneutrala 2030. Nio kommuner har valt att axla ledarrollen och gå före i omställningsarbetet. För att förstå de möjligheter den kommunala verksamheten har att bedriva klimatarbete är det viktigt att undersöka kommunernas handlingskapacitet samt vad som skapar och försvårar kapaciteten.  Intervjuer har genomförts med strategiska nyckelaktörer i framgångskommunerna Lund och Umeå för att undersöka hur de tar sig an arbetet med klimatneutralitet och hur arbetet bidrar till att komma vidare med klimatarbetet. Viable Cities är ett innovationsprogram som både Lunds och Umeås kommun är delaktiga i, vars syfte är att skynda på omställningen i städer och med hjälp av digitalisering, samverkan och innovation. Båda kommunerna utgår från en projektorganisering i sitt arbete med klimatneutralitet där de samverkar med interna och externa aktörer.  Analysen utgick från fyra teman som identifierades induktivt; definition klimatneutralitet, fokusområden, organisering och kapacitetsskapande. Resultatet visar att klimatkontraktet som båda kommunerna skrivit under om klimatneutralitet till 2030 fungerar som en kraftsamling som enar politiken och bidrar med legitimitet i klimatarbetet. Trots det kommer kommunerna troligen inte uppnå målet då det finns brister gällande åtgärderna som vidtas samt att det är frågor som inte hanteras. Försvårande faktorer som går att se är att kunskap inte alltid leder till handling, ökat politiskt stöd inte alltid resulterar i att frågan blir prioriterad samt att ambitiösa mål inte är tillräcklig utan det måste även finnas resurser.

The Effects of Early Adult Alcohol and Cannabis Disorders on Adult Health in a Prospective, Longitudinal Study

Faculty Advisor: Michelle EnglundThis research was supported by the Undergraduate Research Opportunities Program (UROP)

Why has the acceptance of laparoscopic hysterectomy been slow? Results of an anonymous survey of Australian gynecologists

Study objective: To determine whether Australian gynecologists would like to increase the proportion of hysterectomies they perform laparoscopically and the factors that might limit their acceptance of laparoscopic hysterectomy (LH). Design: Anonymous postal survey (Canadian Task Force classification III). Setting: Department of obstetrics and gynecology of a major Australian medical school. Participants: Seven hundred ninety-six certified obstetrician/gynecologists in practice in Australia. Main Results: Of 796 respondents, 654 (82%) reported that hysterectomy was part of their normal clinical practice. Of those, 206 (31%) did not perform LH. Respondents who reported performing the highest proportion of LH were those in urban, private hospital settings. Of those who performed hysterectomy, 62% (403/654) reported they did not wish to increase the proportion of LH they undertook. However, of those, 49% (197/403) already performed LH, with 20% (39/197) of that group performing 80% or more of all hysterectomies as LH. Overall, 38% (251/654) of respondents indicated a desire to perform an increased proportion of LH. The commonest factors cited as limited acceptance of LH were insufficient experience and training, lack of hospital equipment, and lack of support from colleagues. Conclusion: Many Australian gynecologists report a desire to increase their rate of LH, but those intentions are compromised by problems with training, equipment, and support