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During the pandemic, hospitals implemented disaster plans to conserve resources while maintaining patient care. It was unclear how these plans impacted injury care and trauma surgeons.A 16 question survey assessing COVID-related hospital policy and resource allocation pre-COVID-19 peak (March), and a 19 question post-peak (June) survey was distributed to Trauma/Critical Care attending's via social media and the Western Trauma Association member email list.There were 120 pre- and 134 post-peak respondents. Most (95%) altered trauma PPE components, a nd 67% noted changes in their admission population pre-peak while 80% did so post-peak. Penetrating injury increased 56% at Level 1 centers and 27% at Level 2 centers. Altered ICU and transfusion criteria were noted with 25% relocating TBI patients, 17% revised rib fracture admission criteria, and 23% adjusted transfusion practices. Importantly, 12% changed their massive transfusion protocol, with 11% reducing the symptomatic transfusion threshold from 7 g/dL to 6 g/dL. Half (50%) disclosed impediments to patient care including PPE shortages and COVID test-related procedural delay (Fig. 2). While only 14% felt their institution was overwhelmed by COVID, the vast majority (81%) shared durable concerns about personal health and safety.Disparate approaches to COVID-19 preparedness and response characterize survey respondent facility actions. These disparities, especially between Level 1 and Level 2 centers, represent opportunities for the trauma community to coordinate best-practice planning and implementation in light of future consequence infection or pandemic care.

Objective In the absence of head-to-head comparisons, the objective of this study was to conduct a network meta-analysis (NMA) to indirectly compare the relative efficacy and safety of rimegepant, ubrogepant, and lasmiditan for the acute treatment of migraine. Methods A systematic literature review was conducted to identify randomized controlled trials (RCTs) of rimegepant, ubrogepant, and lasmiditan in adults with acute migraine. Outcomes included sustained pain freedom and -relief 2-48 hours post-dose, and adverse events. No RCTs were identified that directly compared these interventions. Therefore, a fixed-effects Bayesian NMA was conducted by identifying a connected (via comparison to placebo) network of RCTs. Results Five RCTs were identified as follows: rimegepant study 303 (n = 1,466), ubrogepant ACHIEVE I and II (n = 1,672 and n = 1,686, respectively), and lasmiditan SAMURAI and SPARTAN (n = 2,231 and n = 3,005, respectively). Efficacy outcomes (pain freedom and relief at 2, 24, 48 hours) tended to be highest for lasmiditan 200 mg and rimegepant followed lower doses of lasmiditan and all doses of ubrogepant. However, lasmiditan 200 mg was also associated with higher rates of adverse events, particularly somnolence and dizziness. Conclusions Lasmiditan, rimegepant, and ubrogepant all performed significantly better than placebo with respect to pain freedom and pain relief. Efficacy results were similar for rimegepant and lasmiditan with rimegepant having higher rates of pain freedom and relief than lower doses of lasmiditan, while somnolence and dizziness outcomes were lower for rimegepant than higher doses of lasmiditan.

Objective Rimegepant is an orally administered small‐molecule calcitonin gene‐related peptide (CGRP) receptor antagonist, with demonstrated efficacy in the acute treatment of migraine. Recent estimates from a single‐arm trial (BHV3000‐201) have also shown evidence of long‐term preventive effects in monthly migraine days (MMDs) and health‐related quality of life (HRQoL). This study aimed to compare MMDs and HRQoL data for oral rimegepant to those obtained in placebo‐controlled trials for injectable anti‐CGRP monoclonal antibodies (mAbs) galcanezumab and erenumab. Methods Matching‐adjusted indirect comparisons (MAICs) were conducted using rimegepant subject‐level data and published aggregate‐level results from mAb trials. Rimegepant baseline characteristics were matched to the pooled subject characteristics from EVOLVE‐I/II (galcanezumab vs. placebo; n = 1773) and STRIVE (ereumab vs. placebo; n = 955) by reweighting the rimegepant subjects to more closely match the distributions observed in these trials. To align with inclusion criteria of the mAb trials, only the subset of rimegepant subjects with a history of 4–14 MMDs were included (n = 257). Weighted mean differences were used to calculate adjusted change in MMDs, Migraine Disability Assessment Test (MIDAS) score, and Migraine‐Specific Quality of Life Questionnaire version 2 (MSQv2) scores from baseline to week 12. Results When matched to the EVOLVE trials, rimegepant was superior to placebo with a mean difference in MMD change from baseline [95% confidence interval] of −1.16 [−1.80, −0.52] and was not statistically significantly different from galcanezumab 0.59 [−0.13, 1.32]. When matched to the STRIVE trial, rimegepant was superior to placebo −1.59 [−2.15, −1.03] and was not statistically significantly different from erenumab −0.06 [−0.61, 0.50]. Rimegepant showed superior MIDAS and MSQv2 results compared with placebo in both EVOLVE trials and in the STRIVE trial, no statistically significant differences from galcanezumab and erenumab regarding MIDAS, and favorable results compared with erenumab across all MSQv2 domains, while being generally similar to galcanezumab across all MSQv2 domains. Conclusions When adjustments were made to reflect baseline characteristics in published literature, supporting data from BHV3000‐201 suggest that rimegepant every other day is an effective therapy in reducing disability and MMDs and enhancing migraine‐specific HRQoL. These data support the preventive benefit observed in randomized trials of rimegepant and further validate its efficacy for both acute and preventive treatment of migraine.

Background: PERTINENT is an active hospital-based surveillance system for pertussis in infants. In 2019, four of the six participating European countries recommended pertussis vaccination in pregnancy. Among infants aged 14 days before symptom onset. We excluded infants with unknown maternal or PV status or with mothers vaccinated ≤14 days before delivery. We calculated pooled VE as 100 * (1-odds ratio of vaccination) adjusted for study site, onset date in quarters and infants’ age group. Results: Of 829 infants presenting with pertussis-like symptoms, 336 (41%) were too young for PV. For the VE in pregnancy analysis, we included 75 cases and 201 controls. Vaccination in pregnancy was recorded for 9 cases (12%) and 92 controls (46%), adjusted VE was between 75% [95%CI: 35–91%] and 88% [95%CI: 57–96%]. Of 493 infants eligible for PV, we included 123 cases and 253 controls. Thirty-one cases and 98 controls recorded both PV with ≥ 1 dose and vaccination in pregnancy, adjusted VE was between 74% [95%CI: 33–90] and 95% [95%CI: 69–99]; 27 cases and 53 controls recorded PV only, adjusted VE was between 68% [95%CI: 27–86] and 94% [95%CI: 59–99]. Conclusion: Our findings suggest that vaccination in pregnancy reduces pertussis incidence in infants too young for PV. In infants aged 2–11 months, PV only and both PV and vaccination in pregnancy provide significant protection against severe pertussis. info:eu-repo/semantics/publishedVersion

Introduction PERTINENT is a pilot active surveillance system of infants hospitalised with pertussis in six European Union/European Economic Area countries (37 hospitals, seven sites). Aim This observational study aimed to estimate annual pertussis incidence per site from 2016 to 2018 and respective trends between 2017 and 2018. Pertussis cases were described, including their severity. Methods We developed a generic protocol and laboratory guidelines to harmonise practices across sites. Cases were hospitalised infants testing positive for Bordetella pertussis by PCR or culture. Sites collected demographic, clinical, laboratory data, vaccination status, and risk/protective factors. We estimated sites’ annual incidences by dividing case numbers by the catchment populations. Results From December 2015 to December 2018, we identified 469 cases (247 males; 53%). The median age, birthweight and gestational age were 2.5 months (range: 0–11.6; interquartile range (IQR): 2.5), 3,280 g (range: 700–4,925; IQR: 720) and 39 weeks (range: 25–42; IQR: 2), respectively. Thirty cases (6%) had atypical presentation either with cough or cyanosis only or with absence of pertussis-like symptoms. Of 330 cases with information, 83 (25%) were admitted to intensive care units including five deceased infants too young to be vaccinated. Incidence rate ratios between 2018 and 2017 were 1.43 in Czech Republic (p = 0.468), 0.25 in Catalonia (p = 0.002), 0.71 in France (p = 0.034), 0.14 in Ireland (p = 0.002), 0.63 in Italy (p = 0.053), 0.21 in Navarra (p = 0.148) and zero in Norway. Conclusions Incidence appeared to decrease between 2017 and 2018 in all but one site. Enhanced surveillance of hospitalised pertussis in Europe is essential to monitor pertussis epidemiology and disease burden.

BACKGROUND: During the 2015/16 influenza season in Europe, the cocirculating influenza viruses were A(H1N1)pdm09 and B/Victoria, which was antigenically distinct from the B/Yamagata component in the trivalent influenza vaccine. METHODS: We used the test-negative design in a multicentre case-control study in twelve European countries to measure 2015/16 influenza vaccine effectiveness (VE) against medically attended influenza-like illness (ILI) laboratory-confirmed as influenza. General practitioners swabbed a systematic sample of consulting ILI patients and a random sample of influenza-positive swabs was sequenced. We calculated adjusted VE against influenza A(H1N1)pdm09, A(H1N1)pdm09 genetic group 6B.1 and influenza B overall and by age group. RESULTS: We included 11 430 ILI patients, of which 2272 were influenza A(H1N1)pdm09 and 2901 were influenza B cases. Overall VE against influenza A(H1N1)pdm09 was 32.9% (95% CI: 15.5-46.7). Among those aged 0-14, 15-64 and ≥65 years, VE against A(H1N1)pdm09 was 31.9% (95% CI: -32.3 to 65.0), 41.4% (95% CI: 20.5-56.7) and 13.2% (95% CI: -38.0 to 45.3), respectively. Overall VE against influenza A(H1N1)pdm09 genetic group 6B.1 was 32.8% (95% CI: -4.1 to 56.7). Among those aged 0-14, 15-64 and ≥65 years, VE against influenza B was -47.6% (95% CI: -124.9 to 3.1), 27.3% (95% CI: -4.6 to 49.4) and 9.3% (95% CI: -44.1 to 42.9), respectively. CONCLUSIONS: Vaccine effectiveness (VE) against influenza A(H1N1)pdm09 and its genetic group 6B.1 was moderate in children and adults, and low among individuals ≥65 years. Vaccine effectiveness (VE) against influenza B was low and heterogeneous among age groups. More information on effects of previous vaccination and previous infection is needed to understand the VE results against influenza B in the context of a mismatched vaccine. ECDC has contributed fund for the coordination and some study sites under the Framework contract no. ECDC/2014/026 for the individuals aged less than 65 years. The I‐MOVE/I‐MOVE+ study team is very grateful to all patients, general practitioners, paediatricians, hospital teams, laboratory teams and regional epidemiologists who have contributed to the study. We acknowledge the authors, originating and submitting laboratories of the sequences from GISAID's EpiFlu Database used for this study. All submitters of data may be contacted directly via the GISAID website http://www.gisaid.org. Sí

Data from household surveys serve as the backbone to sustainable development planning. For the first time, questions on surgery have been included in a nationwide Demographic and Health Survey, showing that it is feasible to integrate these questions into a large-scale survey., Key Findings Based on this pilot survey, which responded to the call to collect, aggregate, and analyze global anesthesia and surgery data, we conclude that it is feasible to integrate surgical questions into a large-scale sample survey to provide insight into surgical needs at a national level.Approximately 5% of women and 2% of men had undergone an operation in Zambia in the past 5 years. Among women, cesarean delivery was the most common surgery, while circumcision was the most common procedure among men.The diagnosed unmet need for surgical care in Zambia is estimated to be 65%. Key Implications For health system strengthening, baseline data and monitoring of progress are necessary. Improved data capabilities allow for mapping out and understanding systems.Data collection mechanisms pertinent to surgical care need to become part of routine data collection processes.There is a need to build on existing data collection mechanisms to avoid adding unnecessary burden, information overload, and data collection fatigue.The replicable design of the Demographic and Health Survey allows for the systematic collection of comparable surgical data in other settings. Similar questions could be included in other surveys as well.There is a need to establish data pathways to ensure clear responsibilities among national and international institutions and integrate surgical metrics into existing mechanisms for sustainable data collection., Background: While primary data on the unmet need for surgery in low- and middle-income countries is lacking, household surveys could provide an entry point to collect such data. We describe the first development and inclusion of questions on surgery in a nationally representative Demographic and Health Survey (DHS) in Zambia. Method: Questions regarding surgical conditions were developed through an iterative consultative process and integrated into the rollout of the DHS survey in Zambia in 2018 and administered to a nationwide sample survey of eligible women aged 15–49 years and men aged 15–59 years. Results: In total, 7 questions covering 4 themes of service delivery, diagnosed burden of surgical disease, access to care, and quality of care were added. The questions were administered across 12,831 households (13,683 women aged 15–49 years and 12,132 men aged 15–59 years). Results showed that approximately 5% of women and 2% of men had undergone an operation in the past 5 years. Among women, cesarean delivery was the most common surgery; circumcision was the most common procedure among men. In the past 5 years, an estimated 0.61% of the population had been told by a health care worker that they might need surgery, and of this group, 35% had undergone the relevant procedure. Conclusion: For the first time, questions on surgery have been included in a nationwide DHS. We have shown that it is feasible to integrate these questions into a large-scale survey to provide insight into surgical needs at a national level. Based on the DHS design and implementation mechanisms, a country interested in including a set of questions like the one included in Zambia, could replicate this data collection in other settings, which provides an opportunity for systematic collection of comparable surgical data, a vital role in surgical health care system strengthening.

Background Antenatal booking has potential to reduce infant and maternal health inequalities; yet, those most in need are least likely to access timely care. This audit describes late referral and antenatal booking across London in 2015–16, according to maternal characteristics. Methods Referral Results Of 122 275 antenatal bookings, 27.1% were before 10 weeks’ gestation and 72.8% by 12 + 6 weeks. Characteristics associated with late booking were living in more deprived areas, age Conclusions Post-referral delays can compound late referral for some women, exacerbating health inequalities, but should be amenable to provider interventions. Different patterns of pre- and post-referral delay suggest that a tailored approach is needed to address inequalities in access to antenatal care.

Influenza A(H3N2), A(H1N1)pdm09 and B viruses co-circulated in Europe in 2017-18, predominated by influenza B. WHO-recommended, trivalent vaccine components were lineage-mismatched for B. The I-MOVE hospital network measured 2017-18 seasonal influenza vaccine effectiveness (IVE) against influenza A(H3N2) and B among hospitalised patients (≥65 years) in Europe. Following the same generic protocol for test-negative design, hospital teams in nine countries swabbed patients ≥65 years with recent onset (≤7 days) severe acute respiratory infection (SARI), collecting information on demographics, vaccination status and underlying conditions. Cases were RT-PCR positive for influenza A(H3N2) or B; controls: negative for any influenza. "Vaccinated" patients had SARI onset >14 days after vaccination. We measured pooled IVE against influenza, adjusted for study site, age, sex, onset date and chronic conditions. We included 3483 patients: 376 influenza A(H3N2) and 928 B cases, and 2028 controls. Most (>99%) vaccinated patients received the B lineage-mismatched trivalent vaccine. IVE against influenza A(H3N2) was 24% (95% CI: 2 to 40); 35% (95% CI: 6 to 55) in 65- to 79-year-olds and 14% (95% CI: -22 to 39) in ≥80-year-olds. Against influenza B, IVE was 30% (95% CI: 16 to 41); 37% (95% CI: 19 to 51) in 65- to 79-year-olds and 19% (95% CI: -7 to 38) in ≥80-year-olds. IVE against influenza B was similar to A(H3N2) in hospitalised older adults, despite trivalent vaccine and circulating B lineage mismatch, suggesting some cross-protection. IVE was lower in those ≥80 than 65-79 years. We reinforce the importance of influenza vaccination in older adults as, even with a poorly matched vaccine, it still protects one in three to four of this population from severe influenza. This study received funding from the European Union's Horizon 2020 research and innovation programme under grant agreement No. 634446. The I‐MOVE study team is very grateful to all patients, hospital teams, laboratory teams and regional epidemiologists who have contributed to the studies. Sí

Introduction Influenza A(H3N2) clades 3C.2a and 3C.3a co-circulated in Europe in 2018/19. Immunological imprinting by first childhood influenza infection may induce future birth cohort differences in vaccine effectiveness (VE). Aim The I-MOVE multicentre primary care test-negative study assessed 2018/19 influenza A(H3N2) VE by age and genetic subgroups to explore VE by birth cohort. Methods We measured VE against influenza A(H3N2) and (sub)clades. We stratified VE by usual age groups (0–14, 15–64, ≥ 65-years). To assess the imprint-regulated effect of vaccine (I-REV) hypothesis, we further stratified the middle-aged group, notably including 32–54-year-olds (1964–86) sharing potential childhood imprinting to serine at haemagglutinin position 159. Results Influenza A(H3N2) VE among all ages was −1% (95% confidence interval (CI): −24 to 18) and 46% (95% CI: 8–68), −26% (95% CI: −66 to 4) and 20% (95% CI: −20 to 46) among 0–14, 15–64 and ≥ 65-year-olds, respectively. Among 15–64-year-olds, VE against clades 3C.2a1b and 3C.3a was 15% (95% CI: −34 to 50) and −74% (95% CI: −259 to 16), respectively. VE was −18% (95% CI: −140 to 41), −53% (95% CI: −131 to −2) and −12% (95% CI: −74 to 28) among 15–31-year-olds (1987–2003), 32–54-year-olds (1964–86) and 55–64-year-olds (1954–63), respectively. Discussion The lowest 2018/19 influenza A(H3N2) VE was against clade 3C.3a and among those born 1964–86, corresponding to the I-REV hypothesis. The low influenza A(H3N2) VE in 15–64-year-olds and the public health impact of the I-REV hypothesis warrant further study.

Background Clostridium difficile infection (CDI) is a common cause of healthcare associated infections contributing to morbidity and mortality. Our objective was to evaluate the impact of the implementation of a CDI bundle along with probiotic utilization. Methods A retrospective review of trauma admissions from 2008 to 2014 was performed. The CDI bundle was implemented in stages from 2009 through 2014 with probiotics initiated in 2010. The bundle included changes in cleaning practices, education, screening, and contact precautions. Results 4632 (49%) patients received antibiotics with 21% receiving probiotics. Probiotic use was associated with increased age, male sex, more severely injured, and antibiotic use. CDI incidence decreased from 11.2 to 4.8 per 1000 admissions, p = .03. Among patients who received antibiotics CDI incidence decreased from 2.2% to 0.7%, p = .01. Conclusions We report the largest series of a CDI bundle implementation including probiotics. During the period of adoption of these interventions, the incidence of CDI decreased significantly.

Summary Objectives Summary evidence of influenza vaccine effectiveness (IVE) against hospitalized influenza is lacking. We conducted a meta-analysis of studies reporting IVE against laboratory-confirmed hospitalized influenza among adults. Methods We searched Pubmed (January 2009 to November 2016) for studies that used test-negative design (TND) to enrol patients hospitalized with influenza-associated conditions. Two independent authors selected relevant articles. We calculated pooled IVE against any and (sub)type specific influenza among all adults, and stratified by age group (18–64 and 65 years and above) using random-effects models. Results We identified 3411 publications and 30 met our inclusion criteria. Between 2010–11 and 2014–15, the pooled seasonal IVE was 41% (95%CI:34;48) for any influenza (51% (95%CI:44;58) among people aged 18–64y and 37% (95%CI:30;44) among ≥65 years). IVE was 48% (95%CI:37;59),37% (95%CI:24;50) and 38% (95%CI:23;53) against influenza A(H1N1)pdm09, A(H3N2) and B, respectively. Among persons aged ≥65 year, IVE against A(H3N2) was 43% (95%CI:33;53) in seasons when circulating and vaccine strains were antigenically similar and 14% (95%CI:-3;30) when A(H3N2) variant viruses predominated. Conclusions Influenza vaccines provided moderate protection against influenza-associated hospitalizations among adults. They seemed to provide low protection among elderly in seasons where vaccine and circulating A(H3N2) strains were antigenically variant.

Between September 2017 and February 2018, influenza A(H1N1)pdm09, A(H3N2) and B viruses (mainly B/Yamagata, not included in 2017/18 trivalent vaccines) co-circulated in Europe. Interim results from five European studies indicate that, in all age groups, 2017/18 influenza vaccine effectiveness was 25 to 52% against any influenza, 55 to 68% against influenza A(H1N1)pdm09, -42 to 7% against influenza A(H3N2) and 36 to 54% against influenza B. 2017/18 influenza vaccine should be promoted where influenza still circulates. Funding: The five studies have received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No 634446 to conduct the study in individuals aged 65 years or more. ECDC has contributed to fund some study sites of the EU-PC study under the Framework contract No ECDC/2014/026 for the individuals aged less than 65 years. All study teams are very grateful to all patients, general practitioners, paediatricians, hospital teams, laboratory teams, regional epidemiologists who have contributed to the studies. We acknowledge the authors, originating and submitting laboratories of the sequences from GISAID’s EpiFlu Database used for this study. All submitters of data may be contacted directly via the GISAID website www.gisaid.org Sí

Trauma transfer patients routinely undergo repeat imaging because of inefficiencies within the radiology system. In 2009, the virtual private network (VPN) telemedicine system was adopted throughout Oregon allowing virtual image transfer between hospitals. The startup cost was a nominal $3,000 per hospital.A retrospective review from 2007 to 2012 included 400 randomly selected adult trauma transfer patients based on a power analysis (200 pre/200 post). The primary outcome evaluated was reduction in repeat computed tomography (CT) scans. Secondary outcomes included cost savings, emergency department (ED) length of stay (LOS), and spared radiation. All data were analyzed using Mann-Whitney U and chi-square tests. P less than .05 indicated significance. Spared radiation was calculated as a weighted average per body region, and savings was calculated using charges obtained from Oregon Health and Science University radiology current procedural terminology codes.Four-hundred patients were included. Injury Severity Score, age, ED and overall LOS, mortality, trauma type, and gender were not statistically different between groups. The percentage of patients with repeat CT scans decreased after VPN implementation: CT abdomen (13.2% vs 2.8%, P.01) and cervical spine (34.4% vs 18.2%, P.01). Post-VPN, the total charges saved in 2012 for trauma transfer patients was $333,500, whereas the average radiation dose spared per person was 1.8 mSV. Length of stay in the ED for patients with Injury Severity Score less than 15 transferring to the ICU was decreased (P.05).Implementation of a statewide teleradiology network resulted in fewer total repeat CT scans, significant savings, decrease in radiation exposure, and decreased LOS in the ED for patients with less complex injuries. The potential for health care savings by widespread adoption of a VPN is significant.

International audience; We conducted a multicentre test negative case control study to estimate the 2013–14 influenza vaccine effectiveness (IVE) against hospitalised laboratory confirmed influenza in 12 hospitals in France, Italy and Spain. We included all ≥18 years hospitalised patients targeted by local influenza vaccination campaign reporting an influenza-like illness within 7 days before admission. We defined as cases patients RT-PCR positive for influenza and as controls those negative for all influenza virus. We used a logistic regression to calculate IVE adjusted for country, month of onset, chronic diseases and age. We included 104 A(H1N1)pdm09, 157 A(H3N2) cases and 585 controls. The adjusted IVE was 42.8% (95%CI: 6.3;65;0) against A(H1N1)pdm09. It was respectively 61.4% (95%CI: −1.9;85.4), 39.4% (95%CI: −32.2;72.2) and 19.7% (95%CI:-148.1;74.0) among patients aged 18–64, 65–79 and ≥80 years. The adjusted IVE against A(H3N2) was 38.1% (95%CI: 8.3;58.2) overall. It was respectively 7.8% (95%CI: −145.3;65.4), 25.6% (95%CI: −36.0;59.2) and 55.2% (95%CI: 15.4;76.3) among patients aged 18–64, 65–79 and ≥80 years. These results suggest a moderate and age varying effectiveness of the 2013–14 influenza vaccine to prevent hospitalised laboratory-confirmed influenza. While vaccination remains the most effective prevention measure, developing more immunogenic influenza vaccines is needed to prevent severe outcomes among target groups. © 2016 Taylor & Francis.

Free PMC Article: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6086844/ I‐MOVE primary care multicentre case‐control team - Portugal: Baltazar Nunes, Ausenda Machado, Ana Paula Rodrigues, Verónica Gomez (Departamento de Epidemiologia, Instituto Nacional de Saúde Dr. Ricardo Jorge); Raquel Guiomar, Pedro Pechirra, Paula Cristóvão, Patrícia Conde, Inês Costa (Departamento de Doenças Infeciosas, Instituto Nacional de Saúde Dr. Ricardo Jorge) BACKGROUND: Results of previous influenza vaccination effects on current season influenza vaccine effectiveness (VE) are inconsistent. OBJECTIVES: To explore previous influenza vaccination effects on current season VE among population targeted for vaccination. METHODS: We used 2011/2012 to 2016/2017 I-MOVE primary care multicentre test-negative data. For each season, we compared current season adjusted VE (aVE) between individuals vaccinated and unvaccinated in previous season. Using unvaccinated in both seasons as a reference, we then compared aVE between vaccinated in both seasons, current only, and previous only. RESULTS: We included 941, 2645 and 959 influenza-like illness patients positive for influenza A(H1N1)pdm09, A(H3N2) and B, respectively, and 5532 controls. In 2011/2012, 2014/2015 and 2016/2017, A(H3N2) aVE point estimates among those vaccinated in previous season were -68%, -21% and -19%, respectively; among unvaccinated in previous season, these were 33%, 48% and 46%, respectively (aVE not computable for influenza A(H1N1)pdm09 and B). Compared to current season vaccination only, VE for both seasons' vaccination was (i) similar in two of four seasons for A(H3N2) (absolute difference [ad] 6% and 8%); (ii) lower in three of four seasons for influenza A(H1N1)pdm09 (ad 18%, 26% and 29%), in two seasons for influenza A(H3N2) (ad 27% and 39%) and in two of three seasons for influenza B (ad 26% and 37%); (iii) higher in one season for influenza A(H1N1)pdm09 (ad 20%) and influenza B (ad 24%). CONCLUSIONS: We did not identify any pattern of previous influenza vaccination effect. Prospective cohort studies documenting influenza infections, vaccinations and vaccine types are needed to understand previous influenza vaccinations' effects. European Centre for Disease Prevention and Control. Grant Number: ECDC/2014/026 European Union's Horizon 2020 research and innovation programme. Grant Number: 634446 WHO‐EURO info:eu-repo/semantics/publishedVersion

Members of the I-Move+hospital working group - Portugal: B. Nunes, I. Kislaya, A.P. Rodrigues (National Health Institute Doutor Ricardo Jorge, Lisbon), V. Gomes, R. Côrte-Real (Centro Hospitalar de Lisboa Central, Lisbon), J. Poças, M.J. Peres (Centro Hospitalar de Setúbal, Setúbal). In a multicentre European hospital study we measured influenza vaccine effectiveness (IVE) against A(H3N2) in 2016/17. Adjusted IVE was 17% (95% confidence interval (CI): 1 to 31) overall; 25% (95% CI: 2 to 43) among 65-79-year-olds and 13% (95% CI: -15 to 30) among those ≥ 80 years. As the A(H3N2) vaccine component has not changed for 2017/18, physicians and public health experts should be aware that IVE could be low where A(H3N2) viruses predominate. Funding: The I-MOVE+ project has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No 634446. The Lithuanian I-MOVE+ study sites were supported by a grant from the Research Council of Lithuania (SEN-03/2015). info:eu-repo/semantics/publishedVersion

et al., Coenzyme Q (CoQ) plays a crucial role in mitochondria as an electron carrier within the mitochondrial respiratory chain (MRC) and is an essential antioxidant. Mutations in genes responsible for CoQ biosynthesis (COQ genes) cause primary CoQ deficiency, a rare and heterogeneous mitochondrial disorder with no clear genotype–phenotype association, mainly affecting tissues with high-energy demand including brain and skeletal muscle (SkM). Here, we report a four-year-old girl diagnosed with minor mental retardation and lethal rhabdomyolysis harboring a heterozygous mutation (c.483G > C (E161D)) in COQ4. The patient's fibroblasts showed a decrease in [CoQ], CoQ biosynthesis, MRC activity affecting complexes I/II + III, and respiration defects. Bona fide induced pluripotent stem cell (iPSCs) lines carrying the COQ4 mutation (CQ4-iPSCs) were generated, characterized and genetically edited using the CRISPR-Cas9 system (CQ4-iPSCs). Extensive differentiation and metabolic assays of control-iPSCs, CQ4-iPSCs and CQ4-iPSCs demonstrated a genotype association, reproducing the disease phenotype. The COQ4 mutation in iPSC was associated with CoQ deficiency, metabolic dysfunction, and respiration defects. iPSC differentiation into SkM was compromised, and the resulting SkM also displayed respiration defects. Remarkably, iPSC differentiation in dopaminergic or motor neurons was unaffected. This study offers an unprecedented iPSC model recapitulating CoQ deficiency-associated functional and metabolic phenotypes caused by COQ4 mutation., This work was supported by the ISCIII/FEDER (E-Rare-2 Call PI12/03112 to P.M.), FIS/ISCIII/FEDER project (PI14/01962 to P.N.) and the European Research Council (ERC-2014-CoG646903 to P.M.). D.R.M. and C.P. are supported by PFIS scholarships (FI11/0511 and FI12/00468, respectively). C.B is supported by a Miguel Servet II contract (CPII13/00011). P.M. also acknowledges the financial support from The Obra Social La Caixa-Fundacio Josep Carreras and The Generalitat de Catalunya (SGR330). P.M. and J.L.-B. are investigators of the Spanish Cell Therapy cooperative network (TERCEL). A.G. is supported by Ramon y Cajal Program (RyC-2013–13221).

Introduction: Following the 2005-6 chikungunya outbreak, a project to strengthen regional Public Health preparedness in the Indian Ocean was implemented. It includes the Comoros, Madagascar, Mauritius, Reunion (France) and Seychelles. A Field Epidemiology Training Programme (FETPOI) was started in 2011 to develop a pool of well-trained intervention epidemiologists. Methods: The FETP-OI consists of two years of supervised, learning-by-doing, on-the-job training at national sites involved in disease surveillance and response. It includes work placements at the Madagascar Pasteur Institute and the French regional epidemiology unit in Reunion and up to three training courses per year. Training objectives include epidemiological surveillance, outbreak investigations, research studies, scientific communication and transfer of competencies. Results: In four years, two cohorts of in total 15 fellows originating from four countries followed the FETP-OI. They led 42 surveillance projects (71% routine management, 14% evaluations, 12% setup, 3% other) and investigated 36 outbreak alerts, 58% of them in Madagascar; most investigations (72%) concerned foodborne pathogens, plague or malaria. Fellows performed 18 studies (44% descriptive analyses, 22% disease risk factors, and 34% on other subjects), and presented results during regional and international conferences through 26 oral and 15 poster presentations. Four articles were published in regional Public Health bulletins and several scientific manuscripts are in process. Conclusion: The FETP-OI has created a regional force of intervention consisting of field epidemiologists and trained supervisors using the same technical language and epidemiological methods. The third cohort is now ongoing. Technically and financially sustainable FETP-OI projects help addressing public health priorities of the Indian Ocean.

In Europe, annual influenza vaccination is recommended to elderly. From 2011 to 2014 and in 2015-16, we conducted a multicentre test negative case control study in hospitals of 11 European countries to measure influenza vaccine effectiveness (IVE) against laboratory confirmed hospitalised influenza among people aged ≥65years. We pooled four seasons data to measure IVE by past exposures to influenza vaccination. We swabbed patients admitted for clinical conditions related to influenza with onset of severe acute respiratory infection ≤7days before admission. Cases were patients RT-PCR positive for influenza virus and controls those negative for any influenza virus. We documented seasonal vaccination status for the current season and the two previous seasons. We recruited 5295 patients over the four seasons, including 465A(H1N1)pdm09, 642A(H3N2), 278 B case-patients and 3910 controls. Among patients unvaccinated in both previous two seasons, current seasonal IVE (pooled across seasons) was 30% (95%CI: -35 to 64), 8% (95%CI: -94 to 56) and 33% (95%CI: -43 to 68) against influenza A(H1N1)pdm09, A(H3N2) and B respectively. Among patients vaccinated in both previous seasons, current seasonal IVE (pooled across seasons) was -1% (95%CI: -80 to 43), 37% (95%CI: 7-57) and 43% (95%CI: 1-68) against influenza A(H1N1)pdm09, A(H3N2) and B respectively. Our results suggest that, regardless of patients' recent vaccination history, current seasonal vaccine conferred some protection to vaccinated patients against hospitalisation with influenza A(H3N2) and B. Vaccination of patients already vaccinated in both the past two seasons did not seem to be effective against A(H1N1)pdm09. To better understand the effect of repeated vaccination, engaging in large cohort studies documenting exposures to vaccine and natural infection is needed. The Lithuanian I-MOVE+ study sites were supported by a grant from the Research Council of Lithuania (SEN-03/2015). The IMOVE+ project has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No 634446. GlaxoSmithKline, Sanofi Pasteur and Sanofi Pasteur MSD financially supported the InNHOVE network. They had no role in study design, data collection, pooled analysis, and publication. We are grateful to all patients, medical staff, study nurses and epidemiologists from the twelve study sites who actively participated in the study. info:eu-repo/semantics/publishedVersion

The growing proportion of elderly people represents an increasing economic burden, not least because of age-associated diseases that pose a significant cost to the health service. Finding possible interventions to age-associated disorders therefore have wide ranging implications. A number of genetically defined accelerated aging diseases have been characterized that can aid in our understanding of aging. Interestingly, all these diseases are associated with defects in the maintenance of our genome. A subset of these disorders, Cockayne syndrome, Xeroderma pigmentosum group A and ataxia-telangiectasia, show neurological involvement reminiscent of what is seen in primary human mitochondrial diseases. Mitochondria are the power plants of the cells converting energy stored in oxygen, sugar, fat, and protein into ATP, the energetic currency of our body. Emerging evidence has linked this organelle to aging and finding mitochondrial dysfunction in accelerated aging disorders thereby strengthens the mitochondrial theory of aging. This theory states that an accumulation of damage to the mitochondria may underlie the process of aging. Indeed, it appears that some accelerated aging disorders that show neurodegeneration also have mitochondrial dysfunction. The mitochondrial alterations may be secondary to defects in nuclear DNA repair. Indeed, nuclear DNA damage may lead to increased energy consumption, alterations in mitochondrial ATP production and defects in mitochondrial recycling, a term called mitophagy. These changes may be caused by activation of poly-ADP-ribose-polymerase 1 (PARP1), an enzyme that responds to DNA damage. Upon activation PARP1 utilizes key metabolites that attenuate pathways that are normally protective for the cell. Notably, pharmacological inhibition of PARP1 or reconstitution of the metabolites rescues the changes caused by PARP1 hyperactivation and in many cases reverse the phenotypes associated with accelerated aging. This implies that modulation of PARP1 or the downstream metabolites may be a therapeutic strategy for treating accelerated aging disorders and potentially age-associated neurological decline seen in the normal population.

Coenzyme Q

The Academy of Breastfeeding Medicine is a worldwide organization of physicians dedicated to the promotion, protection, and support of breastfeeding and human lactation. Our mission is to unite into one association members of the various medical specialties with this common purpose.

Influenza vaccines are currently the best method available to prevent seasonal influenza infection. In most European countries one dose (or two doses for children) of seasonal vaccine is given from September to December to the elderly and other target groups for vaccination. In Europe, influenza seasons can last until mid-May (1), and it is expected that vaccination conveys protection on the individual for the duration of the season. In 13/15 reviewed studies on the length of vaccine-induced protection among the elderly, using anti-haemagglutination antibody titres as a proxy for seroprotection levels, seroprotection rates lasted at least >4 months after vaccination (2). However in the 2011-12 influenza season various studies in Europe reported a decrease in influenza vaccine effectiveness (VE) against A(H3N2) over time within the season (3–5). In the United States, a decrease in VE against A(H3N2) with time since vaccination was suggested in the 2007-8 influenza season (6). The observed decrease of VE over time can be explained by viral change (notably antigenic drift) occurring in the season. Drift in B viruses may be slower than in A viruses (7), and A(H3N2) viruses undergo antigenic drift more frequently than A(H1N1)pdm09 viruses (8). The decrease of VE over time can also be explained by a waning of the immunity conferred by the vaccine independently from viral changes. If vaccine-induced protection wanes more rapidly during the season, then depending on the start and duration of the influenza season, the decline of VE may cause increases in overall incidence, hospitalisations and deaths. Changes to vaccination strategies (timing and boosters) may be needed. As anti-haemagglutination antibody titres are not well defined as a correlate of protection (9,10), vaccine efficacy (as measured in trials) or vaccine effectiveness observational studies may be one way to measure vaccine-induced protection. These studies require a large sample size to model VE by time since vaccination and currently, most of the seasonal observational studies lack the precision required to provide evidence for waning immunity. In this study we pooled data across five post-pandemic seasons (2010/11-2014/15) from the I-MOVE (Influenza - Monitoring Vaccine Effectiveness) multicentre case control studies (1,3,11,12), to obtain a greater sample size to study the effects of time since vaccination on influenza type/subtype-specific VE. We measure influenza type/subtype-specific VE by time since vaccination for the overall season, but also in the early influenza phase; under the hypothesis that virological changes are fewer in the early season, but waning of the vaccine effect should be present regardless of time within the influenza phase.

Influenza A(H3N2), A(H1N1)pdm09 and B viruses co-circulated in Europe in 2014/15. We undertook a multicentre case-control study in eight European countries to measure 2014/15 influenza vaccine effectiveness (VE) against medically-attended influenza-like illness (ILI) laboratory-confirmed as influenza. General practitioners swabbed all or a systematic sample of ILI patients. We compared the odds of vaccination of ILI influenza positive patients to negative patients. We calculated adjusted VE by influenza type/subtype, and age group. Among 6,579 ILI patients included, 1,828 were A(H3N2), 539 A(H1N1)pdm09 and 1,038 B. VE against A(H3N2) was 14.4% (95% confidence interval (CI): -6.3 to 31.0) overall, 20.7% (95%CI: -22.3 to 48.5), 10.9% (95%CI -30.8 to 39.3) and 15.8% (95% CI: -20.2 to 41.0) among those aged 0-14, 15-59 and ≥60 years, respectively. VE against A(H1N1)pdm09 was 54.2% (95%CI: 31.2 to 69.6) overall, 73.1% (95%CI: 39.6 to 88.1), 59.7% (95%CI: 10.9 to 81.8), and 22.4% (95%CI: -44.4 to 58.4) among those aged 0-14, 15-59 and ≥60 years respectively. VE against B was 48.0% (95%CI: 28.9 to 61.9) overall, 62.1% (95%CI: 14.9 to 83.1), 41.4% (95%CI: 6.2 to 63.4) and 50.4% (95%CI: 14.6 to 71.2) among those aged 0-14, 15-59 and ≥60 years respectively. VE against A(H1N1)pdm09 and B was moderate. The low VE against A(H3N2) is consistent with the reported mismatch between circulating and vaccine strains. Sí

The development of noncaseating granulomas in a patient with underlying malignancy and no symptoms or signs suggestive of systemic sarcoid is often referred to as a sarcoidlike reaction and is estimated to occur in a small but significant portion of cancer patients. The pathogenesis is poorly understood, but the entity is hypothesized to be an immune phenomenon representing a host defense mechanism against the spread of tumor cells. Sarcoidlike reactions can occur at any time from the time of diagnosis to several years afterward and may occur in lymph nodes draining a malignant tumor, in the tumor itself, and even in nonregional tissues. Like sarcoid, sarcoidlike reactions of neoplasia can demonstrate hypermetabolic lymph nodes on (18)F-FDG PET imaging and thus be readily confused with metastatic disease. We describe 2 cases of a sarcoidlike reaction of neoplasia presenting as hypermetabolic thoracic lymph nodes on (18)F-FDG PET/CT obtained for follow-up of extrathoracic malignancies: one a 73-y-old woman with a history of stage III head and neck squamous cell carcinoma and the other a 34-y-old woman with recurrent giant cell tumor of the sacrum. In both instances, the differential diagnosis for the finding of hypermetabolic thoracic lymph nodes included the possibility of a sarcoidlike reaction, though tissue sampling was pursued to exclude the more worrisome presence of metastatic disease or, less likely, a new primary malignancy. We review the topic of sarcoidlike reactions of neoplasia as well as the analytic approach to hypermetabolic mediastinal and hilar lymph nodes encountered on (18)F-FDG PET/CT.

Massive transfusion (MT) is classically defined as greater than 10 U of packed red blood cells (PRBCs) in 24 hours. This fails to capture the most severely injured patients. Extending the previous work of Savage and Rahbar, a rolling hourly rate-based definition of MT may more accurately define critically injured patients requiring early, aggressive resuscitation.The Prospective Observational Multicenter Major Trauma Transfusion (PROMMTT) trial collected data from 10 Level 1 trauma centers. Patients were placed into rate-based transfusion groups by maximal number of PRBCs transfused in any hour within the first 6 hours. A nonparametric analysis using classification trees partitioned data according to mortality at 24 hours using a predictor variable of maximum number PRBC units transfused in an hour. Dichotomous variables significant in previous scores and models as predictors of MT were used to identify critically ill patients: a positive finding on Focused Assessment with Sonography in Trauma (FAST) examination, Glasgow Coma Scale (GCS) score less than 8, heart rate greater than 120 beats/min, systolic blood pressure less than 90 mm Hg, penetrating mechanism of injury, international normalized ratio greater than 1.5, hemoglobin less than 11, and base deficit greater than 5. These critical indicators were then compared among the nodes of the classification tree. Patients omitted included those who did not receive PRBCs (n = 24) and those who did not have all eight critical indicators reported (n = 449).In a population of 1,245 patients, the classification tree included 772 patients. Analysis by recursive partitioning showed increased mortality among patients receiving greater than 13 U/h (73.9%, p0.01). In those patients receiving less than or equal to 13 U/h, mortality was greater in patients who received more than 4 U/h (16.7% vs. 6.0%, p0.01) (Fig. 1). Nodal analysis showed that the median number of critical indicators for each node was 3 (2-4) (≤4 U/h), 4 (3-5) (4 U/h and ≤13 U/h), and 5 (4-5.5) (13 U/h).A rate-based transfusion definition identifies a difference in mortality in patients who receive greater than 4 U/h of PRBCs. Redefining MT to greater than 4 U/h allows early identification of patients with a significant mortality risk who may be missed by the current definition.Prognostic/epidemiologic study, level III.

Background We hypothesize that night float rotations in the third-year surgical clerkship improve student learning and perceptions of team cohesion. Methods A 1-week night float (NF) system was implemented during the 2013 to 2014 academic year for students. Each student completed 1 week of NF with the Trauma/Emergency General Surgery service. The Perceived Cohesion Scale survey was prospectively administered and National Board of Medical Examiners academic performance retrospectively reviewed. Results We surveyed 70 medical students, 37 traditional call and 33 NF students, with 91% response rate. Perception of team cohesion increased significantly, without perceived loss of educational benefit. Examination scores increased significantly comparing pre- and postintervention groups, with this trend continuing in the following academic year. Conclusions A week-long student NF experience significantly improved perception of team cohesion and standardized examination results. A dedicated period of NF during the surgical clerkship may improve its overall educational value.

Background Little research has investigated cancer care in UK prisons. We wished to identify the number of new cases and the most common cancer diagnoses occurring each year in London prisoners, and the place of death for those who died from their disease. Methods Using the database of the Thames Cancer Registry, we identified cancer diagnoses in residents of seven London prisons from 1986 to 2005 and the place of death of patients dying from their disease between 1996 and 2005. Results On average, 31 patients were recorded as diagnosed with cancer while in prison within each 5-year period. In women, 83% (85/102) of diagnoses were in situ carcinoma of the cervix, and in men, 19% (11/57) were of lung cancer. None of the 25 patients recorded as dying from their disease died in prison. Most died in hospitals (48%, 12/25) or in hospices (28%, 7/25). Conclusions London prisons contribute a small number of patients each year who require NHS cancer care, including those with advanced cancer who are released before death. Future studies should investigate cancer incidence for the national prison population, methods for improving screening coverage and follow-up, the timeliness of access to cancer treatments and end-of-life care, and prisoners’ and health professionals’ experiences of care.

Objective— The purpose of this study was to analyze the consequences of HDL oxidation for paraoxonase-1 metabolism and function. Methods and Results— HDL was oxidized with AAPH, copper ions, and hypochlorite. Secretion studies were performed using human paraoxonase-1–transfected cells lines and primary rat hepatocytes. Stability studies were performed with recombinant paraoxonase. Conditioned medium had significantly reduced paraoxonase-1 when Cu or AAPH-oxidized HDL was the acceptor complex ( P Conclusions— AAPH and copper, but not hypochlorite, oxidation of HDL compromises its ability to promote release of paraoxonase-1 and stabilize enzyme activity. HDL-associated paraoxonase-1 is highly sensitive to hypochlorite. Reducing paraoxonase-1 renders HDL susceptible to oxidation, which may compromise HDL function. It provides a novel example at the HDL level of the detrimental effects of oxidative stress, and underlines the need for further evaluation of the consequences of HDL oxidation.

Incorporating deliberate practice (DP) into residency curricula may optimize education. DP includes educationally protected time, continuous expert feedback, and a focus on a limited number of technical skills. It is strongly associated with mastery level learning.Determine if a multidisciplinary breast rotation (MDB) increases DP opportunities.Beginning in 2010, interns completed the 4-week MDB. Three days a week were spent in surgery and surgical clinic. Half-days were in breast radiology, pathology, medical oncology, and didactics. The MDB was retrospectively compared with a traditional community rotation (TCR) and a university surgical oncology service (USOS) using rotation feedback and resident operative volume. Data are presented as mean ± standard deviation.Oregon Health and Science University in Portland, Oregon; an academic tertiary care general surgery residency program.General surgery residents at Oregon Health and Science University participating in either the MDB, TCR or USOS.A total of 31 interns rated the opportunity to perform procedures significantly higher for MDB than TCR or USOS (4.6 ± 0.6 vs 4.2 ± 0.9 and 4.1 ± 1.0, p0.05). MDB was rated higher than TCR on quality of faculty teaching and educational materials (4.5 ± 0.7 vs 4.1 ± 0.9 and 4.0 ± 1.2 vs 3.5 ± 1.0, p0.05). Interns operated more on the MDB than on the USOS and were more focused on breast resections, lymph node dissections, and port placements than on the traditional surgical rotation or USOS.The MDB incorporates multidisciplinary care into a unique, disease-specific, and educationally focused rotation. It is highly rated and affords a greater opportunity for DP than either the USOS or TCR. DP is strongly associated with mastery learning and this novel rotation structure could maximize intern education in the era of limited work hours.

Background Changing residency structure emphasizes the need for formal instruction on team leadership and intraoperative teaching skills. A high fidelity, multi-learner surgical simulation may offer opportunities for senior learners (SLs) to learn these skills while teaching technical skills to junior learners (JLs). Methods We designed and optimized a low-cost inguinal hernia model that paired JLs and SLs as an operative team. This was tested in 3 pilot simulations. Participants' feedback was analyzed using qualitative methods. Results JL feedback to SLs included the themes "guiding and instructing" and "allowing autonomy." Senior Learner feedback to JLs focused on "mechanics," "knowledge," and "perspective/flow." Both groups focused on "communication" and "professionalism." Conclusions A multi-learner simulation can successfully meet the technical learning needs of JLs and the teaching and communication learning needs of SLs. This model of resident-driven simulation may illustrate future opportunities for operative simulation.

Characterizing high density lipoprotein (HDL) particles and their relevance to HDL function is a major research objective. One aim is to identify functionally distinct particles. To try to limit both functional and compositional heterogeneity the present study focused on paraoxonase-1 (PON1) as a target for isolation of a minor HDL subfraction.Immunoaffinity techniques were applied to isolate PON1-containing HDL (P-HDL) and total HDL (T-HDL), which were subsequently characterized and compared.Analyses of the lipidomes showed significant differences between the fractions in the relative concentrations of individual lipid subspecies, notably reduced levels of unsaturated lysophosphatidylcholine (p0.05) in P-HDL (reflected in a significantly reduced total lysophosphatidylcholine polyunsaturated fatty acid content, p0.004). Significant differences were also observed for the proteomes. P-HDL was highly enriched in the anti-coagulant, vitamin K activated protein S (prot S) (p0.0001), and alpha2 macroglobulin (p0.01), compared to T-HDL. Conversely, procoagulant proteins kininogen 1 and histidine-rich glycoprotein were largely excluded from P-HDL. Immunoabsorption of PON1 from plasma significantly reduced prot S anti-coagulant activity.The P-HDL lipidome and proteome showed significant differences from T-HDL. Enrichment in anti-coagulation proteins indicates complementary functionalities within P-HDL particles and underlines their anti-atherosclerotic potential.

Objectives To analyse the HDL associated anti-oxidant enzyme paraoxonase-1, during postprandial hyperlipaemia. Methods and results Type 2 diabetic patients (n = 72), glucose intolerant patients (n = 10) and controls (n = 38) consumed a high fat:high carbohydrate meal. Blood samples were collected up to 4 h and analysed for lipids and paraoxonase-1. In vitro studies examined HDL function with respect to the enzyme. There were significant postprandial increases in serum triglycerides. Paraoxonase-1 activity decreased significantly throughout the postprandial phase. Concentrations of the enzyme initially decreased significantly, but returned to fasting concentrations at 4 h. Specific activities were significantly lower at 4 h, compared to fasting. The decrease in specific activity was linked to the dynamic phase of postprandial lipoprotein metabolism. Apo AI limited loss of paraoxonase-1. HDL isolated after being subjected to postprandial conditions in vitro had reduced capacity to associate with and stabilise PON1. Conclusions Postprandial hyperlipaemia was associated with changes to serum paraoxonase-1, consistent with a reduced anti-oxidant potential of HDL. No differences were observed between diabetic and non-diabetic patients, suggesting that the effect was linked to postprandial hyperlipaemia. Modifications to paraoxonase-1 could contribute to increased risk of vascular disease associated with postprandial lipaemia, particularly in diabetic patients, who are already deficient in serum paraoxonase-1.

Using survey data from former Head Start children in the third grade from 15 sites across the nation (n = 576), this study examines the relationship between maternal subjective neighborhood attributions and their children's behavioral problems. Maternal perceptions of neighborhood characteristics were measured across five domains, including collective efficacy, barriers to services, negative neighbor affects, probability of child status attainment success, and overall neighborhood rating. Children's problem behaviors, measured with the Social Skills Rating System, includes externalizing and internalizing outcomes. Our results suggest that the worse the maternal assessments on each neighborhood construct, the greater the extent of children's problem behavior, holding constant child demographic factors and parental socioeconomic status. In addition, we find that family income effects on children's problem behavior are partially mediated by these perceived neighborhood domains. Taken together, these results suggest that neighborhood deprivation is related to problematic behavioral outcomes in children.

Do virtual communities in cyberspace foster social capital and social support? Using participant observation and discourse analysis, we examine a mothering board on a parent's website and investigate whether social capital was present, and if so, how it was developed and used. We find three main types of communication emerge from our analysis: emotional support, instrumental support – both formal and informal, and community building/protection, all of which contribute to the creation and maintenance of social capital. Additionally, using sampling with replacement, we created a final data set of 180 mothers and report descriptive statistics to identify characteristics of those on the board.

Paraoxonase-1 (PON1) requires a suitable acceptor complex for its secretion from producing cells. The serum lipoprotein, high-density lipoprotein (HDL) has been shown to accomplish this function, whereas low-density lipoproteins are ineffective. The present study examined the influence of the third serum lipoprotein subclass, very low density lipoproteins (VLDL), on PON1 secretion. VLDL were shown to promote secretion of PON1 from a transfected Chinese hamster ovary model and from transfected hepatocytes in a high-affinity, saturable manner. The effects of HDL and VLDL were not additive, suggesting that they may employ a common secretion pathway. VLDL was able to stabilise secreted PON1 enzyme activity, but less effectively than stabilisation by HDL. Following co-incubation of VLDL and HDL, the majority of PON1 accumulated in HDL even if HDL was added after initial association of the enzyme with VLDL. VLDL to HDL transfer of PON1 was rapid and did not require lipolysis of VLDL. Low levels of active PON1 were associated with VLDL in human serum, and VLDL-associated enzyme activity was proportional to serum triglyceride concentrations. Serum triglycerides were positively associated with whole serum PON1 mass but negatively associated with specific activity. PON1-enriched VLDL was more resistant to oxidation in vitro. The present study suggests that the triglyceride transport vector, VLDL, can modulate PON1 metabolism and activity. This is due, in part, to an influence of the lipoprotein on PON1 secretion. PON1 was associated with VLDL in human serum, where triglycerides correlated independently with variations in serum mass and activity of the enzyme. VLDL-associated PON1 exerted an anti-oxidative effect, which may be of physiological benefit.

The accurate diagnosis of Dementia of the Alzheimer's Type (DAT) continues to be an area of difficulty for the fields of neuropsychology and neurology. The introduction of new medications that appear to mediate the insidious progression of the disorder increases the need for timely differentiation of DAT from other dementia-related disorders. The present study examined the relationship between hemispheric differences in regional cerebral blood flow with corresponding lateral neuropsychological processing deficits in patients with DAT. Eighty patients with a diagnosis of DAT were administered Single Photon Emission Computerized Tomography (SPECT) scans and a battery of left and right hemisphere neuropsychological-based tasks. The results of ANOVA indicated that patients with DAT who were not suffering from perfusion deficits exhibited significantly fewer neuropsychological deficits than did patients with DAT who had perfusion deficits. The neuropsychological tests that measured verbal ability, logical memory, word-pair learning, reading, arithmetic, and visual-perceptual organization were all significantly lower in the group with perfusion deficits. Further analysis indicated that patients with left hemisphere perfusion deficits tended to have poorer neuropsychological skills than did individuals with right hemisphere perfusion deficits, diffuse perfusion deficits, and no perfusion deficits. A Stepwise Discriminant Analysis was unable to use the neuropsychological variables to classify patients accurately into perfusion deficit groups.

A retrospective cohort study was conducted to investigate an outbreak of Norwalk-like viral gastroenteritidis that occurred in Irish holidaymakers visiting Andorra, in January–February 2002. Preliminary results showed the risk exposure was higher for tourists who stayed in Soldeu and consumed ice cubes in their drinks (OR = 2.5, 95% CI [1.3–4.6)], after logistic regression and adjusting for sex and water consumption).

In the fifth season of Influenza Monitoring Vaccine Effectiveness in Europe (I-MOVE), we undertook a multicentre case-control study (MCCS) in seven European Union (EU) Member States to measure 2012/13 influenza vaccine effectiveness against medically attended influenza-like illness (ILI) laboratory confirmed as influenza. The season was characterised by substantial co-circulation of influenza B, A(H1N1)pdm09 and A(H3N2) viruses. Practitioners systematically selected ILI patients to swab ≤7 days of symptom onset. We compared influenza-positive by type/subtype to influenza-negative patients among those who met the EU ILI case definition. We conducted a complete case analysis using logistic regression with study as fixed effect and calculated adjusted vaccine effectiveness (AVE), controlling for potential confounders (age, sex, symptom onset week and presence of chronic conditions). We calculated AVE by type/subtype. Study sites sent 7,954 ILI/acute respiratory infection records for analysis. After applying exclusion criteria, we included 4,627 ILI patients in the analysis of VE against influenza B (1,937 cases), 3,516 for A(H1N1)pdm09 (1,068 cases) and 3,340 for influenza A(H3N2) (730 cases). AVE was 49.3% (95% confidence interval (CI): 32.4 to 62.0) against influenza B, 50.4% (95% CI: 28.4 to 65.6) against A(H1N1)pdm09 and 42.2% (95% CI: 14.9 to 60.7) against A(H3N2). Our results suggest an overall low to moderate AVE against influenza B, A(H1N1)pdm09 and A(H3N2), between 42 and 50%. In this season with many co-circulating viruses, the high sample size enabled stratified AVE by type/subtype. The low estimates indicate seasonal influenza vaccines should be improved to achieve acceptable protection levels. .

Background Endothelial cells play a complex role in the pathobiology of cancer. This role is not limited to the making of blood vessels to allow for influx of oxygen and nutrients required for the high metabolic demands of tumor cells. Indeed, it has been recently shown that tumor-associated endothelial cells secrete molecules that enhance tumor cell survival and cancer stem cell self-renewal. The hypothesis underlying this work is that specific disruption of endothelial cell-initiated signaling inhibits tumor growth. Methods Conditioned medium from primary human dermal microvascular endothelial cells (HDMEC) stably transduced with silencing RNA for IL-6 (or controls) was used to evaluate the role of endothelial-derived IL-6 on the activation of key signaling pathways in tumor cells. In addition, these endothelial cells were co-transplanted with tumor cells into immunodefficient mice to determine the impact of endothelial cell-derived IL-6 on tumor growth and angiogenesis. Results We observed that tumor cells adjacent to blood vessels show strong phosphorylation of STAT3, a key mediator of tumor progression. In search for a possible mechanism for the activation of the STAT3 signaling pathway, we observed that silencing interleukin (IL)-6 in tumor-associated endothelial cells inhibited STAT3 phosphorylation in tumor cells. Notably, tumors vascularized with IL-6-silenced endothelial cells showed lower intratumoral microvessel density, lower tumor cell proliferation, and slower growth than tumors vascularized with control endothelial cells. Conclusions Collectively, these results demonstrate that IL-6 secreted by endothelial cells enhance tumor growth, and suggest that cancer patients might benefit from targeted approaches that block signaling events initiated by endothelial cells.

The aim of the present study was to develop a neuropsychological test battery for patients with juvenile neuronal ceroid lipofuscinosis (JNCL) and to study the development of cognitive functions during the first 5 years after diagnosis. Fourteen patients with JNCL entered the study. Nine patients were homozygous for the major mutation, whereas five were compound heterozygotes. All patients were studied annually with a special neuropsychological test battery (NEPSY) adapted from Luria's neuropsychological test, and modified for the visually handicapped; the Wechsler Intelligence Scale for Children - Revised (WISC-R) was also included. The neurological examinations were scored. Furthermore, 1.OT magnetic resonance imaging scan was performed at the beginning of follow-up and after a mean of 5 years. A decline in verbal IQ (WISC-R) during the follow-up period was found in all subjects except one compound heterozygous male. Short-term memory and digit memory span were already impaired at an early stage of the disease. Orientation to time was found to decline more than orientation to person and place. Motor speed usually became impaired after 10 years of age. Spatial orientation was impaired only in the patients homozygous for the major mutation. The test battery was found to be reliable and easy to use, and offered valuable information on the progress of the disease. It also provided important guidelines for rehabilitation.

Aims: To evaluate the association between thyroid problems and glaucoma. Methods: A population-based cross-sectional sample with 12,376 participants from the 2002 National Health Interview Survey. Odds ratios (OR) and 95% confidence intervals (CIs) were used to quantify the association between a self-reported diagnosis of glaucoma and a self-reported history of thyroid problems, controlling for demographic characteristics and smoking status. Results: The overall prevalence of glaucoma was 4.6%; 11.9% reported a history of thyroid problems. The prevalence of glaucoma among those who did and did not report thyroid problems was 6.5% and 4.4%, respectively (p = 0.0003). Following adjustment for differences in age, gender, race and smoking status, the association between glaucoma and thyroid problems remained (OR 1.38, 95% CI 1.08 to 1.76). Conclusions: The results of this study lend support to the hypothesis that thyroid disorders may increase the risk of glaucoma. Research should continue evaluating potential mechanisms underlying this relationship and whether the treatment of thyroid problems reduces subsequent glaucoma risk.

Background, An Expanded Programme on Immunization was started in late 1987 in Niger, including vaccination against measles with one dose of standard titer Schwarz vaccine given to infants after 9 months of age. During epidemics an early two-dose strategy was implemented (one dose between 6 and 8 months and one dose after 9 months). From January 1, 1995, until May 7, 1995, 13 892 measles cases were reported in Niamey, Niger. Methods. A retrospective cohort study was conducted in a crowded area of Niamey at the end of the outbreak to assess the effectiveness of measles vaccine in standard (after 9 months) and early (before 9 months) immunization strategies under field conditions. Results. Highest measles incidence rates were observed among children < 1 year of age. Vaccine effectiveness estimates increased with age at vaccination from 78% with a single dose administered at 6 months of age to 95% at 9 months. Vaccine effectiveness with the early two dose strategy was 93%. Conclusions. Immunization with a single dose of standard titer Schwarz vaccine before 9 months of age provided higher clinical protection than expected from seropositivity studies. The early two dose strategy is justified in contexts where measles incidence is high before 9 months of age. Our results raise the issue of lowering the recommended age for measles vaccination in developing countries.

Nonsteroidal antiinflammatory drugs (NSAIDs) decrease the postoperative requirements for opioid analgesic medication. To determine whether NSAIDs potentiate the respiratory effects of opioids, we studied the effects of ketoprofen (K), an NSAID, on respiratory depression induced by morphine (M) in volunteers. After ethics committee approval, 12 healthy male volunteers received infusions of K (1.5 mg/kg), M (0.1 mg/ kg), and KM (1.5 mg/kg + 0.1 mg/kg) in a double-blind, randomized, three-treatment, three-period cross-over trial. During the three sessions, CO2 rebreathing challenges for ventilatory and occlusion pressure responses to CO2 were performed immediately before and 10, 70, 130, 190, and 250 min after drug infusion over 10 min. Venous blood samples for plasma drug concentrations were withdrawn at the same times. Comparisons were made on slopes of ventilatory and occlusion pressure responses to CO2. Venous blood samples confirmed that morphine plasma concentrations were similar when subjects had received morphine alone and when they had received the combination of drugs. Morphine alone induced a respiratory depression with a decrease in both ventilatory and occlusion pressure responses to CO2. Ketoprofen alone did not produce any respiratory effects. The combination of drugs induced a decrease in ventilatory responses to CO2, but intergroup comparisons showed that this was significantly less marked than the decrease induced by morphine alone. In conclusion, for similar morphine plasma concentrations, respiratory depression was less marked with the combination of drugs than with morphine alone. Therefore, ketoprofen may reduce the respiratory depression induced by morphine.

Three outbreaks of meningitis caused by Neisseria meningitidis serogroup A (subgroup III) are described: Niger (1991), Burundi (1992), and Guinea (1993). These outbreaks showed unusual characteristics: a shorter inter-epidemic interval (Niger), unusual geographical location outside the meningitis belt (Burundi and Guinea), and high age-specific attack rates in all age groups (Burundi and Guinea). Mass immunization campaigns mobilized considerable human and financial means (US$ 322000 and 3000 person-days of work for health personnel to immunize 629000 people in Guinea). The vaccination coverage was over 80% in densely populated areas (Burundi and urban Guinea), but below 50% in less populated areas ( 24 27 and 26 30 sub-districts in Niger and Guinea, respectively). The preventive fraction (proportion of cases prevented by vaccination) was substantial in Guinea (35% for a vaccine efficacy of 85%) and was higher where the campaign was initiated earlier. An ‘alert’ threshold indicating the onset of an epidemic of 15 100000 cases in one week showed good sensitivity (94%), specificity (98%) and positive predictive value (89%) in Burundi, permitting quick decision making outside the meningitis belt. These 3 meningococcal meningitis outbreaks show the need for epidemic emergency preparedness and for vigilance on the whole African continent.

CONTEXT: Serum IGF-I levels are often low in patients with short stature (SS) without defined etiology. Hence, genetic investigations have focused on the GH-IGF-I axis.OBJECTIVE: Our objectives were to characterize IGF-I axis status and search for a broader range of genetic associations in children with SS and normal GH.DESIGN AND SETTING: We conducted a prospective, cross-sectional, epidemiogenetic case-control study in 9 European countries (2008-2010).PARTICIPANTS: Children (n = 275) aged ≥2 years with SS without defined etiology (≤-2.5 height SD score [SDS]) and ≥1 peak GH ≥7 μg/L) were recruited.METHODS: Serum IGF-I, IGF-binding protein-3 (IGFBP-3), and acid-labile subunit (ALS) levels were measured in a central laboratory. Candidate gene exome sequencing was performed in this cohort and ethnicity-matched controls.RESULTS: Serum IGF-I, IGFBP-3, and ALS levels were highly correlated, but there was a discrepancy between prevalence of IGF-I, IGFBP-3, and ALS deficiencies (53%, 30%, and 0.8%, respectively). An insertion-deletion (Indel) on the IGF1 gene (P = 1.2 × 10(-5), Bonferroni-corrected; case vs control frequency: 0.04 vs 0.112), an Indel on NFKB1 (P = 1.36 × 10(-10); case vs control frequency: 0.464 vs 0.272), and 2 single-nucleotide polymorphisms on ZBTB38 (P < 2.3 × 10(-6)) were associated with SS. At P < 10(-4), single-nucleotide polymorphisms on genes related to protein kinase regulation, MAPK, and Fanconi pathways were also associated with SS.CONCLUSIONS: IGF-I deficiency is a common feature in SS without defined etiology; an Indel in the IGF1 gene was associated with SS. However, genes involved in transcriptional regulation (NFKB1 and ZBTB38) and growth factor signaling were also associated, providing further candidates for genetic investigations on individual patients.

BackgroundInfluenza vaccination strategies aim at protecting high-risk population from severe outcomes. Estimating the effectiveness of seasonal vaccines against influenza related hospitalisation is important to guide these strategies. Large sample size is needed to have precise estimate of influenza vaccine effectiveness (IVE) against severe outcomes. We assessed the feasibility of measuring seasonal IVE against hospitalisation with laboratory confirmed influenza through a network of 21 hospitals in the European Union.MethodsWe conducted a multicentre study in France (seven hospitals), Italy (one hospital), and Navarra (four hospitals) and Valencia (nine hospitals) regions in Spain. All ≥18 years hospitalised patients presenting an influenza-like illness within seven days were swabbed. Cases were patients RT-PCR positive for influenza A (H3N2); controls were patients negative for any influenza virus. Using logistic regression with study site as a fixed effect we calculated IVE adjusted for potential confounders. We restricted the analyses to those swabbed within four days.ResultsWe included, 375 A(H3N2) cases and 770 controls. The overall adjusted IVE was 24.9% (95%CI-1.8;44.6). Among the target group for vaccination (N = 1058) the adjusted IVE was 28.8% (95%CI:2.8;47.9); it was respectively 36.8% (95%CI:-48.8; 73.1), 42.6% (95%CI:-16.5;71.7), 17.8%(95%CI:-40.8; 52.1) and 37.5% (95%CI:-22.8;68.2) in the age groups 18-64, 65-74, 75-84 and more than 84 years.DiscussionEstimation of IVE based on the pooling of data obtained through a European network of hospitals was feasible. Our results suggest a low IVE against hospitalised confirmed influenza in 2011-12. The low IVE may be explained by a poor immune response in the high-risk population, imperfect match between vaccine and circulating strain or waning immunity due to a late season. Increased sample size within this network would allow more precise estimates and stratification of the IVE by time since vaccination and vaccine types or brands.

Once a vaccine is licensed and introduced in the population, post-licensure studies are required to measure vaccine effectiveness and impact of vaccination programmes on the population at large. However, confusion still prevails around these concepts, making it difficult to discern which effects are measured in such studies and how their findings should be interpreted. We review from the public health evaluation perspective the effects of vaccine-related exposures, describe the methods used to measure them and their assumptions. We distinguish effects due to exposure to individual vaccination from those due to exposure to a vaccination programme, as the latter depends on vaccine coverage, other population factors and includes indirect effects as well. Vaccine (direct) effectiveness is estimated by comparing vaccinated and unvaccinated individuals exposed to the same vaccination programme. The impact of a vaccination programme, defined here as the population prevented fraction when exposure is the programme, is measured by comparing populations with and without a vaccination programme, most commonly the same population before and after vaccination. These designs are based on a number of assumptions for valid inference. In particular, they assume that vaccinees and non-vaccinees do not differ in terms of susceptibility and exposure to the disease or in ascertainment of vaccination and disease status. In pre and post-vaccination design, the population is assumed to have similar baseline transmission, case detection and reporting, risk factors and medical practices in both periods. These principles are frequently violated in post-licensure studies. Potential confounding and biases must be minimized in study design and analyses, or taken into account during result interpretation. It is also essential to define which exposure is evaluated (individual vaccination or vaccination programme) and which effect is measured. This may help decision-makers clarify which type of study is needed and how to interpret the results. (C) 2013 Elsevier Ltd. All rights reserved.

A randomized prospective trial on the effect of the length of initial hospital stay (23 +/- 4 days and 9 +/- 3 days) in 61 consecutive children with newly diagnosed diabetes was carried out. Since the metabolic outcome was similar in the treatment groups for the first two years, we analyzed the adjustment and subjective well-being of families to the diabetes after a two-year follow-up period. A semi-structured interview by a psychologist who was blinded to the initial treatment length and medical history of the child showed that 74% of the families in the short-term and 58% in the long-term treatment groups had good overall psychosocial ability to function (ns); there were no unusual fears in 37% and 15% of the families (ns), respectively. After short-term treatment, families needed slightly but not significantly less time to be confident about the management of diabetes in the family. These findings show that the short-term initial hospital stay does not unfavorably affect the adjustment of the family to diabetes and should probably be preferred over the long-term initial hospital stay.