Serious asthma events with fluticasone plus salmeterol versus fluticasone alone

Background: the safe and appropriate use of long-acting beta-agonists (LABAs) for the treatment of asthma has been widely debated. In two large clinical trials, investigators found a potential risk of serious asthma-related events associated with LABAs. This study was designed to evaluate the risk of administering the LABA salmeterol in combination with an inhaled glucocorticoid, fluticasone propionate. Methods: in this multicenter, randomized, double-blind trial, adolescent and adult patients (age, ≥12 years) with persistent asthma were assigned to receive either fluticasone with salmeterol or fluticasone alone for 26 weeks. All the patients had a history of a severe asthma exacerbation in the year before randomization but not during the previous month. Patients were excluded from the trial if they had a history of life-threatening or unstable asthma. The primary safety end point was the first serious asthma-related event (death, endotracheal intubation, or hospitalization). Noninferiority of fluticasone-salmeterol to fluticasone alone was defined as an upper boundary of the 95% confidence interval for the risk of the primary safety end point of less than 2.0. The efficacy end point was the first severe asthma exacerbation. Results: of 11,679 patients who were enrolled, 67 had 74 serious asthma-related events, with 36 events in 34 patients in the fluticasone-salmeterol group and 38 events in 33 patients in the fluticasone-only group. The hazard ratio for a serious asthma-related event in the fluticasone-salmeterol group was 1.03 (95% confidence interval [CI], 0.64 to 1.66), and noninferiority was achieved (P=0.003). There were no asthma-related deaths; 2 patients in the fluticasone-only group underwent asthma-related intubation. The risk of a severe asthma exacerbation was 21% lower in the fluticasone-salmeterol group than in the fluticasone-only group (hazard ratio, 0.79; 95% CI, 0.70 to 0.89), with at least one severe asthma exacerbation occurring in 480 of 5834 patients (8%) in the fluticasone-salmeterol group, as compared with 597 of 5845 patients (10%) in the fluticasone-only group (P<0.001). Conclusions: patients who received salmeterol in a fixed-dose combination with fluticasone did not have a significantly higher risk of serious asthma-related events than did those who received fluticasone alone. Patients receiving fluticasone-salmeterol had fewer severe asthma exacerbations than did those in the fluticasone-only group. (AUSTRI ClinicalTrials.gov number, NCT01475721)

Obstetric fistula in Burundi: a comprehensive approach to managing women with this neglected disease.

BACKGROUND: In Burundi, the annual incidence of obstetric fistula is estimated to be 0.2-0.5% of all deliveries, with 1000-2000 new cases per year. Despite this relatively high incidence, national capacity for identifying and managing obstetric fistula is very limited. Thus, in July 2010, Medecins Sans Frontieres (MSF) set up a specialised Obstetric Fistula Centre in Gitega (Gitega Fistula Centre, GFC), the only permanent referral centre for obstetric fistula in Burundi. A comprehensive model of care is offered including psychosocial support, conservative and surgical management, post-operative care and follow-up. We describe this model of care, patient outcomes and the operational challenges. METHODS: Descriptive study using routine programme data. RESULTS: Between July 2010 and December 2011, 470 women with obstetric fistula presented for the first time at GFC, of whom 458 (98%) received treatment. Early urinary catheterization (conservative management) was successful in four out of 35 (11%) women. Of 454 (99%) women requiring surgical management, 394 (87%) were discharged with a closed fistula, of whom 301 (76%) were continent of urine and/or faeces, while 93 (24%) remained incontinent of urine and/or faeces. In 59 (13%) cases, the fistula was complex and could not be closed. Outcome status was unknown for one woman. Median duration of stay at GFC was 39 days (Interquartile range IQR, 31-51 days). CONCLUSION: In a rural African setting, it is feasible to implement a comprehensive package of fistula care using a dedicated fistula facility, and satisfactory surgical repair outcomes can be achieved. Several operational challenges are discussed

"I am nothing": experiences of loss among women suffering from severe birth injuries in Tanzania

\ud Despite the increased attention on maternal mortality during recent decades, which has resulted in maternal health being defined as a Millennium Development Goal (MDG), the disability and suffering from obstetric fistula remains a neglected issue in global health. Continuous leaking of urine and the physical, emotional and social suffering associated with it, has a profound impact on women's quality of life. This study seeks to explore the physical, cultural and psychological dimensions of living with obstetric fistula, and demonstrate how these experiences shape the identities of women affected by the condition. A cross-sectional study with qualitative and quantitative components was used to explore the experiences of Tanzanian women living with obstetric fistula and those of their husbands. The study was conducted at the Comprehensive Community Based Rehabilitation Tanzania hospital in Dar es Salaam, Bugando Medical Centre in Mwanza, and Mpwapwa district, in Dodoma region. Conveniently selected samples of 16 women were interviewed, and 151 additional women responded to a questionnaire. In addition, 12 women affected by obstetric fistula and six husbands of these affected women participated in a focus group discussions. Data were analysed using content data analysis framework and statistical package for the social sciences (SPSS) version 15 for Microsoft windows. The study revealed a deep sense of loss. Loss of body control, loss of the social roles as women and wives, loss of integration in social life, and loss of dignity and self-worth were located at the core of these experiences. The women living with obstetric fistula experience a deep sense of loss that had negative impact on their identity and quality of life. Acknowledging affected women's real-life experiences is important in order to understand the occurrence and management of obstetric fistula, as well as prospects after treatment. This knowledge will help to improve women's sense of self-worth and maintain their identity as women, wives, friends and community members. Educational programmes to empower women socially and economically and counselling of families of women living with obstetric fistula may help these women receive medical and social support that is necessary.\u

Serious Asthma Events with Fluticasone plus Salmeterol versus Fluticasone Alone

BACKGROUND The safe and appropriate use of long-acting beta-agonists (LABAs) for the treatment of asthma has been widely debated. In two large clinical trials, investigators found a potential risk of serious asthma-related events associated with LABAs. This study was designed to evaluate the risk of administering the LABA salmeterol in combination with an inhaled glucocorticoid, fluticasone propionate. METHODS In this multicenter, randomized, double-blind trial, adolescent and adult patients (age, .12 years) with persistent asthma were assigned to receive either fluticasone with salmeterol or fluticasone alone for 26 weeks. All the patients had a history of a severe asthma exacerbation in the year before randomization but not during the previous month. Patients were excluded from the trial if they had a history of lifethreatening or unstable asthma. The primary safety end point was the first serious asthma-related event (death, endotracheal intubation, or hospitalization). Noninferiority of fluticasone.salmeterol to fluticasone alone was defined as an upper boundary of the 95% confidence interval for the risk of the primary safety end point of less than 2.0. The efficacy end point was the first severe asthma exacerbation. RESULTS Of 11,679 patients who were enrolled, 67 had 74 serious asthma-related events, with 36 events in 34 patients in the fluticasone.salmeterol group and 38 events in 33 patients in the fluticasone-only group. The hazard ratio for a serious asthmarelated event in the fluticasone.salmeterol group was 1.03 (95% confidence interval [CI], 0.64 to 1.66), and noninferiority was achieved (P = 0.003). There were no asthma-related deaths; 2 patients in the fluticasone-only group underwent asthmarelated intubation. The risk of a severe asthma exacerbation was 21% lower in the fluticasone.salmeterol group than in the fluticasone-only group (hazard ratio, 0.79; 95% CI, 0.70 to 0.89), with at least one severe asthma exacerbation occurring in 480 of 5834 patients (8%) in the fluticasone.salmeterol group, as compared with 597 of 5845 patients (10%) in the fluticasone-only group (P&lt;0.001). CONCLUSIONS Patients who received salmeterol in a fixed-dose combination with fluticasone did not have a significantly higher risk of serious asthma-related events than did those who received fluticasone alone. Patients receiving fluticasone.salmeterol had fewer severe asthma exacerbations than did those in the fluticasone-only group. (AUSTRI ClinicalTrials.gov number, NCT01475721.

Obstetric fistula in Southern Sudan: situational analysis and Key Informant Method to estimate prevalence.

BACKGROUND: Obstetric fistula is a severe condition which can have devastating consequences for a woman's life. Despite a considerable literature, very little is known about its prevalence. This project was conducted to carry out a situational analysis of fistula services in South Sudan and to pilot test the Key Informant Method (KIM) to estimate the prevalence of fistula in a region of South Sudan. METHODS: Key stakeholder interviews, document reviews and fistula surgery record reviews were undertaken. A KIM survey was conducted in a district of Western Bahr-el-Ghazal in January 2012. One hundred sixty-six community-based distributors, traditional birth attendants and village midwives were trained as key informants to identify women with fistula in the community. Women identified were subsequently examined by an obstetrician and nurse to verify whether they had a fistula. RESULTS: There were limited fistula repair services in South Sudan. Approximately 50-80 women per year attend periodic campaigns, with around half having a fistula and receiving a repair. On average a further 5 women a year received fistula repair from hospital services. Ten women with potential fistula were identified via KIM; all confirmed by the obstetrician. Of these, three were from the survey area, which had 8,865 women of reproductive age (15-49 years). This gives a minimal estimated prevalence of at least 30 fistulas per 100,000 women of reproductive age (95% CI 10-100). CONCLUSIONS: Routine fistula repair services available do not meet the population's needs. The pilot study suggests that KIM can be used to identify women with fistula in the community. Data on fistula are generally poor; the KIM methodology we used in South Sudan yielded a lower fistula prevalence than estimates reported previously in the region

Enhanced passive surveillance of influenza vaccination in England, 2016-2017- an observational study using an adverse events reporting card

Influenza is a major public health burden, mainly prevented by vaccination. Recommendations on influenza vaccine composition are updated annually and constant benefit-risk monitoring is therefore needed. We conducted near-real-time enhanced passive surveillance (EPS) for the influenza vaccine, Fluarix Tetra, according to European Medicines Agency guidance, in 10 volunteer general practices in England using Fluarix Tetra as their principal influenza vaccine brand, from 1-Sep to 30-Nov-2016. The EPS method used a combination of routinely collected data from electronic health records (EHR) and a customized adverse events reporting card (AERC) distributed to participants vaccinated with Fluarix Tetra. For participants vaccinated with a different influenza vaccine, data were derived exclusively from the EHR. We reported weekly and cumulative incidence of pre-defined adverse events of interest (AEI) occurring within 7 days post-vaccination, adjusted for clustering effect. Of the 97,754 eligible participants, 19,334 (19.8%) received influenza vaccination, of whom 13,861 (71.7%) received Fluarix Tetra. A total of 1,049 participants receiving Fluarix Tetra reported AEIs; 703 (67%) used the AERC (adjusted cumulative incidence rate 4.96% [95% CI: 3.92-6.25]). Analysis by individual pre-specified AEI categories identified no safety signal for Fluarix Tetra. A total of 62 individuals reported an AEI with a known brand of non-GSK influenza vaccine and 54 with an unknown brand (adjusted cumulative incidence rate 2.59% [1.93-3.47] and 1.77% [1.42-2.20], respectively). In conclusion, the study identified no safety signal for Fluarix Tetra and showed that the AERC was a useful tool that complemented routine pharmacovigilance by allowing more comprehensive capture of AEIs