Mortality, Morbidity and Related Outcomes Following Perioperative Blood Transfusion in Patients with Major Orthopaedic Surgery: A Systematic Review.

BACKGROUND: Benefits and risks of liberal and restrictive transfusion regimens are under on-going controversial discussion. This systematic review aimed at assessing both regimens in terms of pre-defined outcomes with special focus on patients undergoing major orthopaedic surgery. METHODS: We performed a literature search for mortality, morbidity and related outcomes following peri-operative blood transfusion in patients with major orthopaedic surgery in electronic databases. Combined outcome measure estimates were calculated within the scope of meta-analyses including randomised clinical trials comparing restrictive versus liberal blood transfusion regimens (e.g. MH risk ratio, Peto odds ratio). RESULTS: A total of 880 publications were identified 15 of which were finally included (8 randomised clinical trials (RCTs) with 3,693 patients and 6 observational studies with 4,244,112 patients). Regarding RCTs, no significant differences were detected between the transfusion regimes for all primary outcomes (30-day mortality, thromboembolic events, stroke/transitory ischaemic attack, myocardial infarction, wound infection and pneumonia) and a secondary outcome (length of hospital stay), whereas there was a significantly reduced risk of receiving at least one red blood concentrate under a restrictive regimen. CONCLUSION: The results of this systematic review do not suggest an increased risk associated with either a restrictive or a liberal transfusion regimen in patients undergoing major orthopaedic surgery.

Spontaneous reporting of suspected narcolepsy after vaccination against pandemic influenza A (H1N1) in Germany.

PURPOSE: We aimed at investigating whether, in Germany, the number of individual case safety reports (ICSR) of confirmed narcolepsy following Pandemrix® vaccination notified to the Paul-Ehrlich-Institut (PEI, German Federal Institute for Vaccines and Biomedicines) was higher than expected when compared with the prepandemic background incidence rates. METHODS: ICSR of narcolepsy after vaccination with Pandemrix® notified to the PEI until September 2016 were reviewed and validated according to the criteria of narcolepsy defined by the Brighton Collaboration (BC). Cases fulfilling the criteria of BC levels of diagnostic certainty 1 to 4a with symptoms onset after vaccination with Pandemrix® were eligible. Adjustment for underreporting was performed with cases of narcolepsy recruited within the scope of the German Narcolepsy Study using capture-recapture methods. An observed versus expected (OvE) analysis was conducted based on adjusted case numbers using risk windows for symptoms onset within 4 and 6 months following vaccination. RESULTS: By the end of September 2016, a total of 85 ICSR of narcolepsy after vaccination with Pandemrix® had been notified to the PEI 52 of which were eligible. The OvE estimates for the 4 and 6 months risk windows were 3.8 (95% CI: 2.6-5.4) and 2.8 (95% CI: 2.0-3.9), respectively. The number of excess cases was higher in children and adolescents (15-fold and 11.7-fold increased OvE estimate) than in adults (2.1-fold and 1.5-fold increased estimate). CONCLUSIONS: Compared with the prepandemic background incidence rate, the number of incident narcolepsy cases was 3.8-fold and 2.8-fold as high.

Retrospective multicenter matched case-control study on the risk factors for intussusception in infants less than 1 year of age with a special focus on rotavirus vaccines - the German Intussusception Study.

Studies associate rotavirus vaccination with intussusception. In Germany, a retrospective multicenter matched case-control study was performed to identify risk factors for intussusception with a special focus on rotavirus vaccines. Children with place of birth and residence in Germany who had been treated for intussusception from 2010 to 2014 and who had been less than 1 year old at the time of intussusception were recruited. Case report forms were independently validated by two pediatricians according to the criteria of intussusception defined by the Brighton Collaboration (BC). Cases with the highest diagnostic certainty (level 1) were matched with population-based controls by age, gender, federal state, and place of residence. Information on vaccine exposures originated from vaccination certificates. One hundred and sixteen cases were matched with 272 controls. A significantly increased adjusted odds ratio (aOR) for intussusception (5.74, 95% CI: 1.51-21.79) was detected in individuals immunized with rotavirus vaccine dose 1 prior to symptom onset as compared to non-exposed individuals. Age at the start of the rotavirus immunization series did not modify the risk of intussusception. The odds for intussusception were not increased postdose 2 and 3 as well as any dose. One further risk factor for intussusception, family history of intussusception (aOR 3.26, 95% CI 1.09 - 9.77) was identified. Breastfeeding was found to have a protective effect (aOR 0.54, 95% CI 0.33 - 0.88). Rotavirus vaccine dose 1 was associated with a 5.7-fold increased risk to develop intussusception regardless of age at immunization whereas the overall risk for intussusception in the first year of life was not increased.

Retrospective multicenter matched case-control study on the risk factors for narcolepsy with special focus on vaccinations (including pandemic influenza vaccination) and infections in Germany.

OBJECTIVE: Studies associate pandemic influenza vaccination with narcolepsy. In Germany, a retrospective, multicenter, matched case-control study was performed to identify risk factors for narcolepsy, particularly regarding vaccinations (seasonal and pandemic influenza vaccination) and infections (seasonal and pandemic influenza) and to quantify the detected risks. METHODS: Patients with excessive daytime sleepiness who had been referred to a sleep center between April 2009 and December 2012 for multiple sleep latency test (MSLT) were eligible. Case report forms were validated according to the criteria for narcolepsy defined by the Brighton Collaboration (BC). Confirmed cases of narcolepsy (BC level of diagnostic certainty 1-4a) were matched with population-based controls by year of birth, gender, and place of residence. A second control group was established including patients in whom narcolepsy was definitely excluded (test-negative controls). RESULTS: A total of 103 validated cases of narcolepsy were matched with 264 population-based controls. The second control group included 29 test-negative controls. A significantly increased odd ratio (OR) to develop narcolepsy (crude OR [cOR] = 3.9, 95% confidence interval [CI] = 1.8-8.5; adjusted OR [aOR] = 4.5, 95% CI = 2.0-9.9) was detected in individuals immunized with pandemic influenza A/H1N1/v vaccine prior to symptoms onset as compared to nonvaccinated individuals. Using test-negative controls, in individuals immunized with pandemic influenza A/H1N1/v vaccine prior to symptoms onset, a nonsignificantly increased OR of narcolepsy was detected when compared to nonvaccinated individuals (whole study population, BC levels 1-4a: cOR = 1.9, 95% CI = 0.5-6.9; aOR = 1.8, 95% CI = 0.3-10.1). CONCLUSIONS: The findings of this study support an increased risk for narcolepsy after immunization with pandemic influenza A/H1N1/v vaccine.

Anaphylaxis After Immunization of Children and Adolescents in Germany.

BACKGROUND: Anaphylaxis is a life-threatening event. The aim of this study was to estimate the annual frequency of anaphylaxis after immunization in individuals younger than 18 years in Germany leading to hospitalization. METHODS: All suspected cases of postvaccination anaphylaxis involving individuals aged 0-17 years reported to the German surveillance unit for rare pediatric diseases (Erhebungseinheit für seltene pädiatrische Erkrankungen in Deutschland) from June 2008 through May 2010, and all suspected cases of anaphylaxis as an adverse event following immunization in the same age group reported to the Paul-Ehrlich-Institut during the observational period were classified according to the Brighton collaboration case definition. Only hospitalized cases of anaphylaxis fulfilling Brighton collaboration case definition level 1-3 criteria were eligible. Estimates for the annual frequency were calculated by using capture-recapture methods. RESULTS: A total of 22 reports were eligible. Median age of the affected individuals (13 males, 9 females) was 7.0 years (range: 2 months to 17 years). Anaphylaxis occurred most frequently after administration of AS03 adjuvanted A/H1N1 pandemic influenza vaccine (n = 8). The annual frequency of anaphylaxis after vaccination (excluding pandemic influenza vaccine as well as monovalent measles and rubella vaccines) was estimated to be 6.8 (95% confidence interval: 6.1-10.9). The estimated incidence of anaphylaxis after administration of specific vaccines ranged from 0.4 to 127.6 cases per 1,000,000 doses administered. CONCLUSIONS: This study confirms that anaphylaxis after immunization in children and adolescents is a rare event. AS03 adjuvanted A/H1N1 pandemic influenza vaccine seems to be associated with a higher risk of anaphylaxis when compared with other vaccines.