Community cohort study of rotavirus and other enteropathogens: are routine vaccinations associated with sex-differential incidence rates?

OBJECTIVE: Community studies in West Africa have demonstrated that routine vaccinations may have non-targeted effects, the female-male mortality ratio being reduced after administration of BCG and increased after diphtheria-tetanus-pertussis (DTP). We examined whether immunisation status was associated with infection with rotavirus and other enteropathogens. METHODS: We recruited 200 children shortly after birth and followed them until 2 years of age with weekly morbidity interviews and stool sampling. Vaccination status for each child was classified according to the most recent vaccination as documented by vaccination card. MAIN OUTCOME MEASURES: The female-male incidence rate ratios (IRR) of infection with an enteropathogen and of enteropathogen-associated diarrhoea were estimated for children according to whether they had received BCG or DTP as their last vaccination. RESULTS: For children who received BCG as their last vaccine, the adjusted female-male IRRs for primary rotavirus-infection and diarrhoea were 1.05 (95% CI: 0.21-5.28) and 0.0 (95% CI: 0-3.02), respectively. For children who received DTP as their last vaccine, the adjusted female-male IRRs were 1.93 (0.89-4.21) and 1.92 (0.70-5.32), respectively, for rotavirus-associated infection and diarrhoea. Restricted to the rotavirus season, the female-male IRRs for rotavirus infection and diarrhoea were 2.56 (1.17-5.63) and 2.63 (0.94-7.34), respectively. The female-male IRR for rotavirus-associated diarrhoea differed significantly among BCG and DTP recipients (p=0.02). Infections with enteropathogens not associated with diarrhoea were associated with lower female-male IRRs after BCG of 0.82 (0.55-1.23) and higher female-male IRRs after DTP vaccination of 1.32 (1.03-1.70) for primary infection (p=0.05). Though there were few infections with other diarrhoea-causing enteropathogens, these were also associated with a lower female-male IRR after BCG of 0.62 (0.26-1.52) and a higher female-male IRR after DTP vaccination of 1.51 (1.04-2.20) for all infection. CONCLUSION: Routine immunisations may affect morbidity for non-targeted infections. As in studies of infant mortality, BCG is associated with lower risk for girls, whereas, DTP is associated with higher risk for girls relative to boys

Recombinant FXIII (rFXIII-A(2)) Prophylaxis Prevents Bleeding and Allows for Surgery in Patients with Congenital FXIII A-Subunit Deficiency

Recombinant factor XIII-A(2) (rFXIII-A(2)) was developed for prophylaxis and treatment of bleeds in patients with congenital FXIII A-subunit deficiency.mentor (TM) 2 (NCT00978380), a multinational, open-label, single-arm, multiple-dosing extension to the pivotal mentor (TM) 1 trial, assessed long-term safety and efficacy of rFXIII-A(2) prophylaxis in eligible patients (patients with severe [= 6 years. Patients received 35IU/kgrFXIII-A(2) (exactdosing) every 28 +/- 2 days for >= 52 weeks. Primary endpoint was safety (adverse events including immunogenicity); secondary endpoints were rate of bleeds requiring FXIII treatment, haemostatic response after one 35 IU/kg rFXIII-A(2) dose for breakthrough bleeds and withdrawals due to lack of rFXIII-A(2) efficacy. Steady-state pharmacokinetic variables were also summarized. Elective surgery was permitted during the treatment period. Sixty patients were exposed to rFXIII-A(2); their median age was 26.0 years (range: 7.0-77.0). rFXIII-A(2) was well tolerated without any safety concerns. No non-neutralizing or neutralizing antibodies (inhibitors) against FXIII were detected. Mean annualized bleeding rate (ABR) was 0.043/patient-year. Mean spontaneous ABR was 0.011/patient-year. No patients withdrew due to lack of efficacy. Geometric mean FXIII trough levelwas 0.17 IU/mL. Geometric terminal half-life was 13.7 days. rFXIII-A(2) prophylaxis provided sufficient haemostatic coverage for 12 minor surgeries without the need for additional FXIII therapy; eight procedures were performed within 7 days of the patient's last scheduled rFXIII-A(2) dose, and four were performed 10 to 21 days after the last dose.Peer reviewe

Measles vaccination in the presence or absence of maternal measles antibody: impact on child survival.

BACKGROUND: Measles vaccine (MV) has a greater effect on child survival when administered in early infancy, when maternal antibody may still be present. METHODS: To test whether MV has a greater effect on overall survival if given in the presence of maternal measles antibody, we reanalyzed data from 2 previously published randomized trials of a 2-dose schedule with MV given at 4-6 months and at 9 months of age. In both trials antibody levels had been measured before early measles vaccination. RESULTS: In trial I (1993-1995), the mortality rate was 0.0 per 1000 person-years among children vaccinated with MV in the presence of maternal antibody and 32.3 per 1000 person-years without maternal antibody (mortality rate ratio [MRR], 0.0; 95% confidence interval [CI], 0-.52). In trial II (2003-2007), the mortality rate was 4.2 per 1000 person-years among children vaccinated in presence of maternal measles antibody and 14.5 per 1000 person-years without measles antibody (MRR, 0.29; 95% CI, .09-.91). Possible confounding factors did not explain the difference. In a combined analysis, children who had measles antibody detected when they received their first dose of MV at 4-6 months of age had lower mortality than children with no maternal antibody, the MRR being 0.22 (95% CI, .07-.64) between 4-6 months and 5 years. CONCLUSIONS: Child mortality in low-income countries may be reduced by vaccinating against measles in the presence of maternal antibody, using a 2-dose schedule with the first dose at 4-6 months (earlier than currently recommended) and a booster dose at 9-12 months of age. CLINICAL TRIALS REGISTRATION: NCT00168558

Interleukin 7 from Maternal Milk Crosses the Intestinal Barrier and Modulates T- Cell Development in Offspring

Background Breastfeeding protects against illnesses and death in hazardous environments, an effect partly mediated by improved immune function. One hypothesis suggests that factors within milk supplement the inadequate immune response of the offspring, but this has not been able to account for a series of observations showing that factors within maternally derived milk may supplement the development of the immune system through a direct effect on the primary lymphoid organs. In a previous human study we reported evidence suggesting a link between IL-7 in breast milk and the thymic output of infants. Here we report evidence in mice of direct action of maternally-derived IL-7 on T cell development in the offspring. Methods and Findings  We have used recombinant IL-7 labelled with a fluorescent dye to trace the movement in live mice of IL-7 from the stomach across the gut and into the lymphoid tissues. To validate the functional ability of maternally derived IL- 7 we cross fostered IL-7 knock-out mice onto normal wild type mothers. Subsets of thymocytes and populations of peripheral T cells were significantly higher than those found in knock-out mice receiving milk from IL-7 knock-out mothers. Conclusions/Significance Our study provides direct evidence that interleukin 7, a factor which is critical in the development of T lymphocytes, when maternally derived can transfer across the intestine of the offspring, increase T cell production in the thymus and support the survival of T cells in the peripheral secondary lymphoid tissue

A randomized trial of a standard dose of Edmonston-Zagreb measles vaccine given at 4.5 months of age: effect on total hospital admissions.

Observational studies and trials from low-income countries indicate that measles vaccine has beneficial nonspecific effects, protecting against non-measles-related mortality. It is not known whether measles vaccine protects against hospital admissions. Between 2003 and 2007, 6417 children who had received the third dose of diphtheria, tetanus, and pertussis vaccine were randomly assigned to receive measles vaccine at 4.5 months or no measles vaccine; all children were offered measles vaccine at 9 months of age. Using hospital admission data from the national pediatric ward in Bissau, Guinea-Bissau, we compared admission rates between enrollment and the 9-month vaccination in Cox models, providing admission hazard rate ratios (HRRs) for measles vaccine versus no measles vaccine. All analyses were conducted stratified by sex and reception of neonatal vitamin A supplementation (NVAS). Before enrollment the 2 groups had similar admission rates. Following enrollment, the measles vaccine group had an admission HRR of 0.70 (95% confidence interval [CI], .52-.95), with a ratio of 0.53 (95% CI, .32-.86) for girls and 0.86 (95% CI, .58-1.26) for boys. For children who had not received NVAS, the admission HRR was 0.53 (95% CI, .34-.84), with an effect of 0.30 (95% CI, .13-.70) for girls and 0.73 (95% CI, .42-1.28) for boys (P = .08, interaction test). The reduction in admissions was separately significant for measles infection (admission HRR, 0 [95% CI, 0-.24]) and respiratory infections (admission HRR, 0.37 [95% CI, .16-.89]). Early measles vaccine may have major benefits for infant morbidity patterns and healthcare costs. Clinical trials registration NCT00168558

Immunometabolic pathways in BCG-induced trained immunity

The protective effects of the tuberculosis vaccine Bacillus Calmette-Guerin (BCG) on unrelated infections are thought to be mediated by long-term metabolic changes and chromatin remodeling through histone modifications in innate immune cells such as monocytes, a process termed trained immunity. Here, we show that BCG induction of trained immunity in monocytes is accompanied by a strong increase in glycolysis and, to a lesser extent, glutamine metabolism, both in an in-vitro model and after vaccination of mice and humans. Pharmacological and genetic modulation of rate-limiting glycolysis enzymes inhibits trained immunity, changes that are reflected by the effects on the histone marks (H3K4me3 and H3K9me3) underlying BCG-induced trained immunity. These data demonstrate that a shift of the glucose metabolism toward glycolysis is crucial for the induction of the histone modifications and functional changes underlying BCG-induced trained immunity. The identification of these pathways may be a first step toward vaccines that combine immunological and metabolic stimulation.M.G.N. was supported by an ERC consolidator grant (#310372) and a Spinoza prize of the Netherlands Organization for Scientific Research. A.C., F.R., and R.S. were supported by the Northern Portugal Regional Operational Programme (NORTE 2020), under the Portugal 2020 Partnership Agreement, through the European Regional Development Fund (FEDER) (NORTE-01-0145-FEDER-000013), and by the Fundação para a Ciência e Tecnologia (FCT) (IF/00735/2014 to A.C., IF/00021/2014 to R.S., and SFRH/BPD/96176/2013 to C.C.). L.G.G. was financially supported by Project LISBOA-01-0145-FEDER-007660 (Microbiologia Molecular, Estrutural e Celular), funded by FEDER funds through COMPETE2020 - Programa Operacional Competitividade e Internacionalização (POCI) and by national funds through the FCT (SFRH/BPD/111100/2015). The NMR spectrometers are part of the National NMR Facility supported by the FCT (RECI/BBB-BQB/0230/2012). G.M. was supported by an ERC starting grant (#310496)

ASUHAN KEBIDANAN KOMPREHENSIF PADA NY “H” DI DUSUN KREBET SENDANGSARI PAJANGAN BANTUL

Latar belakang: Angka Kematian Ibu (AKI) dan Angka Kematian Bayi (AKB) di Indonesia masih cukup tinggi. Salah satu faktor penyebabnya yaitu kejadian anemia pada ibu. Anemia terjadi karena defisiensi zat besi dalam tubuh yaitu kurangnya pembentukkan sel darah merah pada tubuh yang dapat menyebabkan berat badan bayi lahir rendah (BBLR), prematuritas, cacat bawaan, perdarahan saat persalinan, ketuban pecah dini, gangguan janin dalam rahim, serta asfiksia. Tujuan: Memberikan asuhan kebidanan secara komprehensif pada ibu hamil, bersalin, nifas, dan bayi baru lahir (BBL). Metode : Metode yang digunakan dalam case report adalah deskriptif dengan pendekatan continuity of care atau peneliti melakukan survei kepada pasien dengan cara wawancara, observasi, dan pemberian penatalaksanaan asuhan. Hasil: Asuhan Kebidanan Komprehensif pada Ny. H umur 22 tahun G₁P₀A₀ diberikan sejak ibu hamil TM II, hamil TM III bersalin, nifas dan bayi baru lahir (BBL). Hasil penelitian didukung dengan pemeriksaan Haemoglobin (Hb) untuk mendeteksi komplikasi pada ibu. Sehingga bisa dilakukan pencegahan sampai proses persalinan, nifas, sampai bayi baru lahir (BBL). Kesimpulan: Setelah diberikan Asuhan Kebidanan Komprehensif didapatkan hasil yaitu ibu dapat bersalin secara normal, tidak ada tanda bahaya pada masa nifas dan bayi tidak mengalami komplikasi. Kata kunci : Asuhan Kebidanan, Continuity Of Care, Anemi

Brug af peberspray i danske fængsler og arresthuse

English title: Use of pepper spray in Danish prisons and detention centres This article discusses the use of pepper spray in Danish prisons and detention centers. Using qualitative interviews with prison officers and inmates as well as reviews of reports from prison officials about their use of pepper spray, the article examines whether the Danish rules and practices fully comply with human rights requirements and recommendations. The article offers insights into the situations in which pepper spray is typically used, where it is used and who it is used against. The article expresses concern about the use of pepper spray particularly in confined spaces and against mentally ill inmates. The authors argue that the use of pepper spray in Danish prisons should be more restrictive and more precisely regulated

Politiets brug af peberspray

English title: Police use of pepper spray This article discusses the use of pepper spray by police since its introduction to Denmark in 2008. Pepper spray contains pepper extract and has been assessed as capable of causing serious health risks by the Danish Health Authority. International human rights bodies have also expressed concerns about the use of pepper spray. Despite this, no comprehensive study or evaluation of the use of pepper spray has ever been conducted in Denmark. The article uses qualitative interviews with police officers and people exposed to pepper spray, as well as a review of reports from police officers about their use of pepper spray, in an examination of whether Danish rules and practices fully comply with human rights requirements and recommendations. The situations in which pepper spray is typically used are described with a focus on where it is used and who it is used against. The authors express concern about the use of pepper spray in a number of situations and argue that its authorization should be more restrictive and precisely regulated. Finally, the article describes a dialogue with the Danish National Police and the pending police act regulating pepper spray