Safety and protection of plasma donors: A scoping review and evidence gap map.

BACKGROUND AND OBJECTIVES: As part of a large-scale project to safely increase plasma collection in Europe, the current scoping review identifies the existing evidence (gaps) on adverse events (AEs) and other health effects in plasmapheresis donors, as well as factors that may be associated with such events/effects. MATERIALS AND METHODS: We searched six databases and three registries. Study characteristics (publication type, language, study design, population, outcomes, associated factors, time of assessment, duration of follow-up, number and frequency of donations, convalescent plasma [y/n], setting and location) were synthesized narratively and in an interactive evidence gap map (EGM). RESULTS: Ninety-four research articles and five registrations were identified. Around 90% were observational studies (57 controlled and 33 uncontrolled), and most of them were performed in Europe (55%) or the United States (20%). Factors studied in association with donor health included donor characteristics (e.g., sex, age) (n = 27), cumulative number of donations (n = 21), donation frequency (n = 11), plasma collection device or programme (n = 11), donor status (first time vs. repeat) (n = 10), donation volume per session (n = 8), time in donation programme (n = 3), preventive measures (n = 2) or other (n = 9). CONCLUSION: The current scoping review provides an accessible tool for researchers and policymakers to identify the available evidence (gaps) concerning plasmapheresis donation safety. Controlled prospective studies with long-term donor follow-up are scarce. Furthermore, additional experimental studies comparing the health effects of different donation frequencies are required to inform a safe upper limit for donation frequency.

Effects of plasmapheresis frequency on health status and exercise performance in men: A randomized controlled trial.

BACKGROUND AND OBJECTIVES: Most research studies on the effects of repeated plasma donation are observational with different study limitations, resulting in high uncertainty on the link between repeated plasma donation and health consequences. Here, we prospectively investigated the safety of intensive or less intensive plasma donation protocols. MATERIALS AND METHODS: Sixty-three male subjects participated in this randomized controlled trial and were divided into low-frequency (LF, once/month, n = 16), high-frequency (HF, three times/month, n = 16), very high-frequency (VHF, two times/week, n = 16) and a placebo (P, once/month, n = 15) groups. Biochemical, haematological, clinical, physiological and exercise-related data were collected before (D0), after 1½ months (D42) and after 3 months (D84) of donation. RESULTS: In VHF, red blood cells, haemoglobin and haematocrit levels decreased while reticulocyte levels increased from D0 to D84. In both HF and VHF, plasma ferritin levels were lower at D42 and D84 compared to D0. In VHF, plasma levels of albumin, immunoglobulin G (IgG), immunoglobulin A (IgA) and immunoglobulin M (IgM) dropped from D0 to D42 and remained lower at D84 than at D0. In HF, plasma IgG, IgA and IgM were lower at D42, and IgG and IgM were lower at D84, compared to D0. Few adverse events were reported in HF and VHF. Repeated plasma donation had no effect on blood pressure, body composition or exercise performance. CONCLUSION: VHF plasmapheresis may result in a large reduction in ferritin and IgG levels. HF and VHF plasmapheresis may result in little to no difference in other biochemical, haematological, clinical, physiological and exercise-related parameters.

Systematic reviews on platelet transfusions: Is there unnecessary duplication of effort? A scoping review.

BACKGROUND AND OBJECTIVES: Platelet transfusions are used across multiple patient populations to prevent and correct bleeding. This scoping review aimed to map the currently available systematic reviews (SRs) and evidence-based guidelines in the field of platelet transfusion. MATERIALS AND METHODS: A systematic literature search was conducted in seven databases for SRs on effectiveness (including dose and timing, transfusion trigger and ratio to other blood products), production modalities and decision support related to platelet transfusion. The following data were charted: methodological features of the SR, population, concept and context features, outcomes reported, study design and number of studies included. Results were synthesized in interactive evidence maps. RESULTS: We identified 110 SRs. The majority focused on clinical effectiveness, including prophylactic or therapeutic transfusions compared to no platelet transfusion (34 SRs), prophylactic compared to therapeutic-only transfusion (8 SRs), dose, timing (11 SRs) and threshold for platelet transfusion (15 SRs) and the ratio of platelet transfusion to other blood products in massive transfusion (14 SRs). Furthermore, we included 34 SRs on decision support, of which 26 evaluated viscoelastic testing. Finally, we identified 22 SRs on platelet production modalities, including derivation (4 SRs), pathogen inactivation (6 SRs), leucodepletion (4 SRs) and ABO/human leucocyte antigen matching (5 SRs). The SRs were mapped according to concept and clinical context. CONCLUSION: An interactive evidence map of SRs and evidence-based guidelines in the field of platelet transfusion has been developed and identified multiple reviews. This work serves as a tool for researchers looking for evidence gaps, thereby both supporting research and avoiding unnecessary duplication.

Predicting medical usage rate at mass gathering events in Belgium: development and validation of a nonlinear multivariable regression model.

BACKGROUND: Every year, volunteers of the Belgian Red Cross provide onsite medical care at more than 8000 mass gathering events and other manifestations. Today standardized planning tools for optimal preventive medical resource use during these events are lacking. This study aimed to develop and validate a prediction model of patient presentation rate (PPR) and transfer to hospital rate (TTHR) at mass gatherings in Belgium. METHODS: More than 200,000 medical interventions from 2006 to 2018 were pooled in a database. We used a subset of 28 different mass gatherings (194 unique events) to develop a nonlinear prediction model. Using regression trees, we identified potential predictors for PPR and TTHR at these mass gatherings. The additional effect of ambient temperature was studied by linear regression analysis. Finally, we validated the prediction models using two other subsets of the database. RESULTS: The regression tree for PPR consisted of 7 splits, with mass gathering category as the most important predictor variable. Other predictor variables were attendance, number of days, and age class. Ambient temperature was positively associated with PPR at outdoor events in summer. Calibration of the model revealed an R2 of 0.68 (95% confidence interval 0.60-0.75). For TTHR, the most determining predictor variables were mass gathering category and predicted PPR (R2 = 0.48). External validation indicated limited predictive value for other events (R2 = 0.02 for PPR; R2 = 0.03 for TTHR). CONCLUSIONS: Our nonlinear model performed well in predicting PPR at the events used to build the model on, but had poor predictive value for other mass gatherings. The mass gathering categories "outdoor music" and "sports event" warrant further splitting in subcategories, and variables such as attendance, temperature and resource deployment need to be better recorded in the future to optimize prediction of medical usage rates, and hence, of resources needed for onsite emergency medical care.

Mass gathering events: a retrospective analysis of the triage categories, type of injury or medical complaint and medical usage rates.

BACKGROUND: Adequate on-site first aid delivery at mass gatherings (MGs) is one of the cornerstones to ensure safe and healthy MGs. We investigated medical usage rates, frequency of triage categories and type of injury or medical complaint, among attendees at MGs in Belgium. METHODS: We analysed the Medical Triage and Registration Informatics System database, which includes prospectively collected person-level data regarding individuals visiting on-site posts at MGs in Belgium. MGs attended by >10 000 people and organised ≥5 times between 2009 and 2018 were included. We determined the proportion of patients in each triage category ('first aid' vs 'medical condition' vs 'medical emergency' vs 'no treatment') and each type of injury or medical complaint, and we calculated patient presentation rate (PPR) and transfer to hospital rate (TTHR). RESULTS: Twenty-eight MGs, totalling 194 events, were included involving 148 265 patient visits. 'First aid' was the most common triage category (80%, n=118 514). The need for a nurse/physician ('medical condition'), and for the treatment of life-threatening conditions ('medical emergency') was rare (8.9%, n=13 052, and 0.6%, n=860, of all patient presentations, respectively), but remarkably higher during indoor electronic dance music (EDM) events (17.8% (n=26 391) and 4.0% (n=5930), of all patient presentations, respectively). 'Skin wounds' were the most common injury category (42.4%, n=62 275). 'Respiratory problems', 'neurological problems', 'intoxication', 'heart complaints' and 'gastrointestinal complaints' were more frequent during indoor (electronic) dance, whereas 'burns', 'fracture/contusion' and 'skin wounds' were higher during outdoor music, sports events and city festivals, respectively. PPR (per 10 000 attendees) was highest for outdoor EDM and outdoor music (median 130 (IQR 79) and 129 (IQR 104), respectively). TTHR (per 10 000 attendees) was highest for indoor EDM (median 4.4 (IQR 8.5)). CONCLUSION: Medical usage rates, proportion of patients in triage and injury or medical complaint categories varied across different MG categories, suggesting opportunities for planning medical coverage at these events.

Hepatitis B virus prevalence in first-time blood donors in Flanders, Belgium: Impact of universal vaccination and migration.

BACKGROUND: Transfusion-transmissible infections such as hepatitis B virus (HBV) remain a major concern for the safety of blood transfusion. This cross-sectional study aimed to assess the trend of HBV prevalence and associated risk factors among a first-time donor population in a low endemic country. STUDY DESIGN AND METHODS: Between 2010 and 2018, blood samples were collected from first-time donors presented at donor collection sites of Belgian Red Cross-Flanders. They were tested for hepatitis B surface antigen (HBsAg), hepatitis B core antibodies (anti-HBc), and HBV DNA, HIV and hepatitis virus C (HCV) antibodies and RNA, and syphilis antibodies. RESULTS: A total of 211,331 first-time blood donors (43.7% males, median age 25 years) were analyzed. HBsAg prevalence decreased from 0.06% in 2010 to 0.05% in 2018 (p = .004) and this declining trend was accompanied by an increased number of donors in the HBV vaccinated birth cohort (p < .001). HBsAg prevalence was 0.33% in foreign-born donors and 0.02% in Belgian natives (p < .001). Multivariate risk profiling showed that anti-HBc positivity was significantly associated with mainly foreign-born donors (odds ratio [OR] = 9.24) but also with older age (OR = 1.06), male gender (OR = 1.32), year of blood donation (OR = 0.94), and co-infections with HCV (OR = 4.31) or syphilis (OR = 4.91). DISCUSSION: The decreasing trend in HBV prevalence could mainly be explained by the introduction of the universal HBV vaccination. Being born in endemic areas was the most important predictor for HBV infection while the co-infections with syphilis suggest unreported sexual risk contacts.

The effect of hand hygiene promotion programs during epidemics and pandemics of respiratory droplet-transmissible infections on health outcomes: a rapid systematic review.

BACKGROUND: Public health strategies in the context of respiratory droplet-transmissible diseases (such as influenza or COVID-19) include intensified hand hygiene promotion, but a review on the effectiveness of different ways of promoting hand hygiene in the community, specifically for this type of infections, has not been performed. This rapid systematic review aims to summarize the effectiveness of community-based hand hygiene promotion programs on infection transmission, health outcomes and behavioral outcomes during epidemic periods in the context of respiratory droplet-transmissible diseases. We also included laboratory-confirmed health outcomes for epidemic-prone disease during interepidemic periods. METHODS: We searched for controlled experimental studies. A rapid systematic review was performed in three databases and a COVID-19 resource. Following study selection (in which studies performed in the (pre-)hospital/health care setting were excluded), study characteristics and effect measures were synthesized, using meta-analyses of cluster-RCTs where possible. Risk of bias of each study was assessed and the certainty of evidence was appraised according to the GRADE methodology. RESULTS: Out of 2050 unique references, 12 cluster-RCTs, all in the context of influenza, were selected. There were no controlled experimental studies evaluating the effectiveness of hand hygiene promotion programs in the context of COVID-19 that met the in-/exclusion criteria. There was evidence that preventive hand hygiene promotion interventions in interepidemic periods significantly decreased influenza positive cases in the school setting. However, no improvement could be demonstrated for programs implemented in households to prevent secondary influenza transmission from previously identified cases (epidemic and interepidemic periods). CONCLUSIONS: The data suggest that proactive hand hygiene promotion interventions, i.e. regardless of the identification of infected cases, can improve health outcomes upon implementation of such a program, in contrast to reactive interventions in which the program is implemented after (household) index cases are identified.

Translation and validation of PubMed and Embase search filters for identification of systematic reviews, intervention studies, and observational studies in the field of first aid.

OBJECTIVE: The aim of this project was to validate search filters for systematic reviews, intervention studies, and observational studies translated from Ovid MEDLINE and Embase syntax and used for searches in PubMed and Embase.com during the development of evidence summaries supporting first aid guidelines. We aimed to achieve a balance among recall, specificity, precision, and number needed to read (NNR). METHODS: Reference gold standards were constructed per study type derived from existing evidence summaries. Search filter performance was assessed through retrospective searches and measurement of relative recall, specificity, precision, and NNR when using the translated search filters. Where necessary, search filters were optimized. Adapted filters were validated in separate validation gold standards. RESULTS: Search filters for systematic reviews and observational studies reached recall of ≥85% in both PubMed and Embase. Corresponding specificities for systematic review filters were ≥96% in both databases, with a precision of 9.7% (NNR 10) in PubMed and 5.4% (NNR 19) in Embase. For observational study filters, specificity, precision, and NNR were 68%, 2%, and 51 in PubMed and 47%, 0.8%, and 123 in Embase, respectively. These filters were considered sufficiently effective. Search filters for intervention studies reached a recall of 85% and 83% in PubMed and Embase, respectively. Optimization led to recall of ≥95% with specificity, precision, and NNR of 49%, 1.3%, and 79 in PubMed and 56%, 0.74%, and 136 in Embase, respectively. CONCLUSIONS: We report validated filters to search for systematic reviews, observational studies, and intervention studies in guideline projects in PubMed and Embase.com.

Is sexual risk behaviour associated with an increased risk of transfusion-transmissible infections in blood donors from Western and Pacific countries? A systematic review and meta-analysis.

BACKGROUND AND OBJECTIVES: The donor medical questionnaire is designed to aid blood establishments in supporting a safe blood supply. According to blood donor deferral policies, sexual risk behaviour (SRB) leads to a (temporary) deferral from blood donation. This systematic review aimed to scientifically underpin these policies by identifying the best available evidence on the association between SRB and the risk of transfusion transmissible infections (TTIs). MATERIALS & METHODS: Studies from three databases investigating the link between SRB (excluding men who have sex with men (MSM)) and TTIs (HBV, HCV, HIV, Treponema pallidum) in donors from Western and Pacific countries were obtained and assessed on eligibility by two reviewers independently. The association between SRB and TTIs was expressed by calculating pooled effect measures via meta-analyses. The GRADE methodology (Grades of Recommendation, Assessment, Development and Evaluation) was used to assess the quality of evidence. RESULTS: We identified 3750 references and finally included 15 observational studies. Meta-analyses showed that there is a significant (P < 0·05) positive association between the following SRB and HBV and/or HCV infection: having sex with an intravenous drug user (high-certainty evidence), receiving money or goods for sex (moderate-high certainty evidence), having a sex partner with hepatitis/HIV (moderate-certainty evidence) and paid for sex or anal sex (low-certainty evidence). CONCLUSION: Sexual risk behaviour (including having sex with an intravenous drug user, receiving money or goods for sex or having a sex partner with hepatitis/HIV) is probably associated with an increased risk of HBV/HCV infection in blood donors from Western and Pacific countries.

The systematic use of evidence-based methodologies and technologies enhances shared decision-making in the 2018 International Consensus Conference on Patient Blood Management.

BACKGROUND AND OBJECTIVES: Patient Blood Management (PBM) aims to optimize the care of patients who might need a blood transfusion. The International Consensus Conference on PBM (ICC-PBM) aimed to develop evidence-based recommendations on three topics: preoperative anaemia, red blood cell transfusion thresholds and implementation of PBM programmes. This paper reports how evidence-based methodologies and technologies were used to enhance shared decision-making in formulating recommendations during the ICC-PBM. MATERIALS & METHODS: Systematic reviews on 17 PICO (Population, Intervention, Comparison, Outcomes) questions were conducted by a Scientific Committee (22 international topic experts and one methodologist) according to GRADE (Grades of Recommendation, Assessment, Development and Evaluation) methodology. Evidence-based recommendations were formulated using Consensus Development Conference methodology. RESULTS: We screened 17 607 references and included 145 studies. The overall certainty in the evidence of effect estimates was generally low or very low. During the ICC, plenary sessions (100-200 stakeholders from a range of clinical disciplines and community representatives) were followed by closed sessions where multidisciplinary decision-making panels (>50 experts and patient organizations) formulated recommendations. Two chairs (content-expert and methodologist) moderated each session and two rapporteurs documented the discussions. The Evidence-to-Decision template (GRADEpro software) was used as the central basis in the process of formulating recommendations. CONCLUSION: This ICC-PBM resulted in 10 clinical and 12 research recommendations supported by an international stakeholder group of experts in blood transfusion. Systematic, rigorous and transparent evidence-based methodology in a formal consensus format should be the new standard to evaluate (cost-) effectiveness of medical treatments, such as blood transfusion.

Health status deterioration in subjects with mild to moderate airflow obstruction, a six years observational study.

BACKGROUND: Patients with COPD need to cope with a disabling disease, which leads to health status impairment. AIM: To investigate the long term change of health status in subjects with mild to moderate airflow obstruction and to compare this to subjects without airflow obstruction, with and without a smoking history. Second, to investigate the factors potentially associated to rapid health status decline in our total cohort. METHODS: Two hundred and one subjects were included. Generic [Short form 36 health survey (SF36) and EuroQol - 5 dimensions (EQ-5D)] and disease specific [Clinical COPD questionnaire (CCQ) and COPD Assessment Test (CAT)] health status questionnaires were regularly repeated over a six years period. Other functional outcomes comprised measures of lung function, physical fitness, physical activity and emotional state. RESULTS: On average, health status decline did not differ between groups with the exception of the EQ-5D index, which deteriorated faster in subjects with airflow obstruction compared to the never smoking control group [- 0.018(0.008) versus 0.00006(0.003), p = 0.03]. Subjects presenting at least one exacerbation had faster rate of deterioration measured with CAT [0.91(0.21) versus - 0.26(0.25), p < 0.01]. Characteristics of the fast declining group were older age, worse lung function, physical fitness, physical activity and disease specific baseline health status. Subjects with airflow obstruction had a 2.5 (95% CI 1.36-4.71) higher risk of presenting fast overall health status decline. Fast overall decline was associated with the presence of acute exacerbation(s) (44% of the subjects with exacerbation(s) versus 17% of subjects without exacerbation, p = 0.03). Changes in fat free mass, functional exercise capacity and in symptoms of anxiety and depression correlated weakly to changes in health status measured with all questionnaires. CONCLUSION: Subjects with mild airflow obstruction present a significant deterioration of health status, which is generally not much faster compared to smoking and never smoking controls. Subjects with fast decline in overall health status are older and more likely to have airflow obstruction, acute respiratory exacerbation(s), reduced physical fitness, physical activity and impaired COPD specific health status at baseline. TRIAL REGISTRATION: NCT01314807 - retrospectively registered on March 2011.

Is there a risk of transfusion-transmissible infections after percutaneous needle treatments in blood donors? A systematic review and meta-analysis.

BACKGROUND AND OBJECTIVES: The donor medical questionnaire identifies a blood donor's history of known blood safety risks. Current Australian, Canadian, European and USA legislation temporarily defers blood donors who received different percutaneous needle treatments (i.e. tattooing, acupuncture and piercing) from blood donation. This systematic review aimed to scientifically underpin these deferrals by identifying the best available evidence on the association between percutaneous needle treatments and the risk of transfusion-transmissible infections (TTIs). MATERIALS AND METHODS: Studies from three databases investigating the link between percutaneous needle treatments and TTIs (HBV, HCV and HIV infection) in blood donors were retained and assessed on eligibility by two reviewers independently. The association between percutaneous needle treatments and TTIs was expressed by conducting meta-analyses and calculating pooled effect measures (odds ratios (ORs) and 95% CIs). The GRADE methodology (Grades of Recommendation, Assessment, Development and Evaluation) was used to assess the quality of evidence. RESULTS: We identified 1242 references and finally included 21 observational studies. Twenty studies assessed the link between percutaneous needle treatments and HCV infection and found that blood donors receiving these treatments had an increased risk of HCV infection (tattooing: pooled OR 5·28, 95% CI [4·33, 6·44], P < 0·00001 (low-quality evidence); acupuncture: pooled OR 1·56, 95% CI [1·17, 2·08], P = 0·03 (very low-quality evidence); and piercing: pooled OR 3·25, 95% CI [1·68, 6·30], P = 0·0005 (low-quality evidence)). CONCLUSION: Percutaneous needle treatments may be associated with an increased HCV infection risk. Further high-quality studies are required to formulate stronger evidence-based recommendations on percutaneous needle treatments as a blood donor deferral criterion.

Patient Blood Management: Recommendations From the 2018 Frankfurt Consensus Conference.

IMPORTANCE: Blood transfusion is one of the most frequently used therapies worldwide and is associated with benefits, risks, and costs. OBJECTIVE: To develop a set of evidence-based recommendations for patient blood management (PBM) and for research. EVIDENCE REVIEW: The scientific committee developed 17 Population/Intervention/Comparison/Outcome (PICO) questions for red blood cell (RBC) transfusion in adult patients in 3 areas: preoperative anemia (3 questions), RBC transfusion thresholds (11 questions), and implementation of PBM programs (3 questions). These questions guided the literature search in 4 biomedical databases (MEDLINE, EMBASE, Cochrane Library, Transfusion Evidence Library), searched from inception to January 2018. Meta-analyses were conducted with the GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) methodology and the Evidence-to-Decision framework by 3 panels including clinical and scientific experts, nurses, patient representatives, and methodologists, to develop clinical recommendations during a consensus conference in Frankfurt/Main, Germany, in April 2018. FINDINGS: From 17 607 literature citations associated with the 17 PICO questions, 145 studies, including 63 randomized clinical trials with 23 143 patients and 82 observational studies with more than 4 million patients, were analyzed. For preoperative anemia, 4 clinical and 3 research recommendations were developed, including the strong recommendation to detect and manage anemia sufficiently early before major elective surgery. For RBC transfusion thresholds, 4 clinical and 6 research recommendations were developed, including 2 strong clinical recommendations for critically ill but clinically stable intensive care patients with or without septic shock (recommended threshold for RBC transfusion, hemoglobin concentration <7 g/dL) as well as for patients undergoing cardiac surgery (recommended threshold for RBC transfusion, hemoglobin concentration <7.5 g/dL). For implementation of PBM programs, 2 clinical and 3 research recommendations were developed, including recommendations to implement comprehensive PBM programs and to use electronic decision support systems (both conditional recommendations) to improve appropriate RBC utilization. CONCLUSIONS AND RELEVANCE: The 2018 PBM International Consensus Conference defined the current status of the PBM evidence base for practice and research purposes and established 10 clinical recommendations and 12 research recommendations for preoperative anemia, RBC transfusion thresholds for adults, and implementation of PBM programs. The relative paucity of strong evidence to answer many of the PICO questions supports the need for additional research and an international consensus for accepted definitions and hemoglobin thresholds, as well as clinically meaningful end points for multicenter trials.

Is an endoscopic examination associated with transfusion-transmissible infections? A systematic review and meta-analysis.

BACKGROUND: The purpose of a donor medical questionnaire is to identify the blood donor's history relative to the current known blood-safety risks. A temporary deferral from blood donation after an endoscopic examination is enforced because of the reusable nature of the endoscope and close contact with the inner body. The objective of this systematic review was to find the best available evidence on the association between an endoscopic examination and the risk of transfusion-transmissible infections. METHODS: Studies from five databases investigating the link between an endoscopic examination and transfusion-transmissible infections (hepatitis B virus, hepatitis C virus, human immunodeficiency virus infection, Treponema pallidum) were retained and assessed independently by two reviewers. The association between endoscopy and transfusion-transmissible infections was identified by conducting meta-analyses and calculating pooled effect measures (odds ratios and 95% confidence intervals). The Grading of Recommendations, Assessment, Development, and Evaluation methodology was used to assess the quality of evidence. RESULTS: We identified 7571 references and finally included 29 observational studies. A significant association between an endoscopic examination and hepatitis B virus infection (pooled odds ratio [OR], 2.21; 95% confidence interval [CI], 1.26-3.86; p = 0.005) or hepatitis C virus infection (pooled OR 1.76, 95% CI, 1.45-2.14; p < 0.00001) was found. The level of evidence was considered as "very low" due to the type of study design (i.e., observational) and indirect study populations (i.e., no blood donor populations). CONCLUSION: An endoscopic examination is associated with an increased hepatitis B virus or hepatitis C virus infection risk. Further high-quality trials are required to formulate stronger evidence-based recommendations on endoscopic examination as a blood donor deferral criterion.

Engagement of stakeholders in the development of a Theory of Change for handwashing and sanitation behaviour change.

A Theory of Change (ToC) is an approach to map programmes aimed at inducing change in a specific context, with the goal of increasing their impact. We applied this approach to the specific case of handwashing and sanitation practices in low- and middle-income countries and developed a ToC as part of a systematic review exercise. Different existing sources of information were used to inform the initial draft of the ToC. In addition, stakeholder involvement occurred and peer review took place. Our stakeholders included methodological (ToC/quantitative and qualitative research) and content experts (WASH (Water, Sanitation, Hygiene)/behaviour change), as well as end-users/practitioners, policy-makers and donors. In conclusion, the development of a ToC, and the involvement of stakeholders in its development, was critical in terms of understanding the context in which the promotional programmes are being implemented. We recommend ToC developers to work with stakeholders to create a ToC relevant for practice.

The effect of a standard whole blood donation on oxygen uptake and exercise capacity: a systematic review and meta-analysis.

BACKGROUND: Blood is a life-saving product for many people worldwide. Voluntary blood donation serves the demand for blood but there are concerns among potential donors about the impact of blood loss on exercise performance. This systematic review aimed to collect the best available evidence of the effect of a standard whole blood donation on aerobic exercise performance. STUDY DESIGN AND METHODS: Studies from six databases dealing with a standard whole blood donation (400-500 mL) followed by (sub)maximal exercise were retained. The outcomes included exercise-related blood variables (hemoglobin [Hb] concentration, hematocrit, and red blood cell count) and endurance exercise variables ((sub)maximal oxygen uptake, peak work rate, and time to exhaustion). Overall effects at different time points postdonation were investigated by performing meta-analyses and calculating mean differences (and 95% confidence intervals). The GRADE methodology (Grades of Recommendation, Assessment, Development, and Evaluation) was used to assess the quality of evidence. RESULTS: We identified 6237 references and finally included 18 before-after studies of low quality. Twenty-four to 48 hours after a blood donation, 1) Hb concentration was reduced (7% decrease) until 14 days after the blood donation (4% decrease), 2) maximal oxygen uptake (VO2max ) was lower (7% decrease), and 3) a reduction in maximal exercise capacity (10% decrease) was present. CONCLUSION: The best available evidence indicates that a standard whole blood donation (400-500 mL) leads to small but potentially physiologically important reductions in Hb levels, VO2max , and maximal exercise capacity in the first 2 days after the blood donation.

Methodologic quality assessment of red blood cell transfusion guidelines and the evidence base of more restrictive transfusion thresholds.

BACKGROUND: Recent literature suggests that more restrictive red blood cell (RBC) transfusion practices are equivalent or better than more liberal transfusion practices. The methodologic quality of guidelines recommending more restrictive transfusion thresholds and their underlying scientific evidence is unclear. Therefore, we aimed to evaluate the quality of the development process of RBC transfusion guidelines and to investigate the underlying evidence of guidelines recommending a more restrictive hemoglobin (Hb) threshold. STUDY DESIGN AND METHODS: Via systematic literature screening of relevant databases (NGC, GIN, Medline, and Embase), RBC transfusion guidelines recommending a more restrictive Hb level (<6, <7, or <8 g/dL) were included. Four assessors independently evaluated the methodologic quality by scoring the rigor of development domain (AGREE II checklist). The level of evidence served as a reference for the quality of the underlying evidence. RESULTS: The methodologic quality of 13 RBC transfusion guidelines was variable (18%-72%) but highest for those developed by Advancing Transfusion and Cellular Therapies Worldwide (72%), the Task Force of Advanced Bleeding Care in Trauma (70%), and the Dutch Institute for Healthcare Improvement (61%). A Hb level of less than 7 g/dL (intensive care unit patients) or less than 8 g/dL (postoperative patients) were the only thresholds based on high-quality evidence. Only four of 32 recommendations had a high-quality evidence base. CONCLUSION: Methodologic quality should be guaranteed in future RBC transfusion guideline development to ensure that the best available evidence is captured when recommending restrictive transfusion strategies. More high-quality trials are needed to provide a stronger scientific basis for RBC transfusion guidelines that recommend more restrictive transfusion thresholds.

Effectiveness of insecticide-treated and untreated nets to prevent malaria in India.

OBJECTIVES: India is the most malaria-endemic country in South-East Asia, resulting in a high socio-economic burden. Insecticide-treated or untreated nets are effective interventions to prevent malaria. As part of an Indian first-aid guideline project, we aimed to investigate the magnitude of this effect in India. METHODS: We searched MEDLINE, Embase and Central to systematically review Indian studies on the effectiveness of treated or untreated vs. no nets. Parasite prevalence and annual parasite incidence served as malaria outcomes. The overall effect was investigated by performing meta-analyses and calculating the pooled risk ratios (RR) and incidence rate ratios. RESULTS: Of 479 articles, we finally retained 16 Indian studies. Untreated nets decreased the risk of parasite prevalence compared to no nets [RR 0.69 (95% CI; 0.55, 0.87) in high-endemic areas, RR 0.49 (95% CI; 0.28, 0.84) in low-endemic areas], as was the case but more pronounced for treated nets [RR 0.35 (95% CI; 0.26, 0.47) in high-endemic areas, risk ratio 0.16 (95% CI; 0.06, 0.44) in low-endemic areas]. Incidence rate ratios showed a similar observation: a significantly reduced rate of parasites in the blood for untreated nets vs. no nets, which was more pronounced in low-endemic areas and for those who used treated nets. The average effect of treated nets (vs. no nets) on parasite prevalence was higher in Indian studies (RR 0.16-0.35) than in non-Indian studies (data derived from a Cochrane systematic review; RR 0.58-0.87). CONCLUSIONS: Both treated and untreated nets have a clear protective effect against malaria in the Indian context. This effect is more pronounced there than in other countries.

Risk factors and comorbidities in the preclinical stages of chronic obstructive pulmonary disease.

RATIONALE: There is little information about comorbidities and their risk factors in the preclinical stages of chronic obstructive pulmonary disease (COPD). OBJECTIVES: This study aims to investigate the prevalence of premorbid risk factors and comorbid diseases and its association with daily physical activity in subjects detected with COPD by spirometry screening. METHODS: Sixty subjects with preclinical COPD (63 ± 6 yr; 68% [n = 41] male) were compared with 60 smoking control subjects (62 ± 7 yr; 70% [n = 42] male) and 60 never-smoking control subjects (62 ± 6 yr; 57% [n = 34] male). Comorbidities (cardiovascular, metabolic, and musculoskeletal disease) and daily physical activity (by multisensor activity monitor) were measured objectively. MEASUREMENTS AND MAIN RESULTS: The prevalence of premorbid risk factors and comorbid diseases was significantly higher in preclinical COPD compared with age-matched never-smoking control subjects, but was similar to smoking control subjects not suffering from COPD. In preclinical COPD and smoking control subjects, the combination of cardiovascular disease and musculoskeletal disease was the most prevalent (15% [n = 9] and 12% [n = 7], respectively). In a multivariate logistic regression analysis, physical inactivity and smoking were found to be independent risk factors for having greater than or equal to two comorbidities. CONCLUSIONS: Premorbid risk factors and comorbid diseases were more prevalent in the preclinical stages of COPD and smokers without COPD. Physical inactivity and smoking were more strongly associated with the presence of comorbidities compared with airflow obstruction. Clinical trial registered with www.clinicaltrials.gov (NCT 01314807).