Cutaneous adverse events associated with disease-modifying treatment in multiple sclerosis: A systematic review

Glatiramer acetate and interferon-beta are approved first-line disease-modifying treatments (DMTs) for multiple sclerosis (MS). DMTs can be associated with cutaneous adverse events, which may influence treatment adherence and patient quality of life. In this systematic review, we aimed to provide an overview of the clinical spectrum and the incidence of skin reactions associated with DMTs. A systematic literature search was performed up to May 2011 in Medline, Embase, and Cochrane databases without applying restrictions in study design, language, or publishing date. Eligible for inclusion were articles describing any skin reaction related to DMTs in MS patients. Selection of articles and data extraction were performed by two authors independently. One hundred and six articles were included, of which 41 (39%) were randomized controlled trials or cohort studies reporting incidences of mainly local injection-site reactions. A large number of patients had experienced some form of localized injection-site reaction: up to 90% for those using subcutaneous formulations and up to 33% for those using an intramuscular formulation. Sixty-five case-reports involving 106 MS patients described a wide spectrum of cutaneous adverse events, the most frequently reported being lipoatrophy, cutaneous necrosis and ulcers, and various immune-mediated inflammatory skin diseases. DMTs for MS are frequently associated with local injection-site reactions and a wide spectrum of generalized cutaneous adverse events, in particular, the subcutaneous formulations. Although some of the skin reactions may be severe and persistent, most of them are mild and do not require cessation of DMT

Variability in mortality following caesarean delivery, appendectomy, and groin hernia repair in low-income and middle-income countries: a systematic review and analysis of published data

Background Surgical interventions occur at lower rates in resource-poor settings, and complication and death rates following surgery are probably substantial but have not been well quantifi ed. A deeper understanding of outcomes is a crucial step to ensure that high quality accompanies increased global access to surgical care. We aimed to assess surgical mortality following three common surgical procedures—caesarean delivery, appendectomy, and groin (inguinal and femoral) hernia repair—to quantify the potential risks of expanding access without simultaneously addressing issues of quality and safety. Methods We collected demographic, health, and economic data for 113 countries classifi ed as low income or lower-middle income by the World Bank in 2005. We did a systematic review of Ovid, MEDLINE, PubMed, and Scopus from Jan 1, 2000, to Jan 15, 2015, to identify studies in these countries reporting all-cause mortality following the three commonly undertaken operations. Reports from governmental and other agencies were also identifi ed and included. We modelled surgical mortality rates for countries without reported data using a two-step multiple imputation method. We fi rst used a fully conditional specifi cation (FCS) multiple imputation method to establish complete datasets for all missing variables that we considered potentially predictive of surgical mortality. We then used regression-based predictive mean matching imputation methods, specifi ed within the multiple imputation FCS method, for selected predictors for each operation using the completed dataset to predict mortality rates along with confi dence intervals for countries without reported mortality data. To account for variability in data availability, we aggregated results by subregion and estimated surgical mortality rates. Findings From an initial 1302 articles and reports identifi ed, 247 full-text articles met our inclusion criteria, and 124 provided data for surgical mortality for at least one of the three selected operations. We identifi ed 42 countries with mortality data for at least one of the three procedures. Median reported mortality was 7·9 per 1000 operations for caesarean delivery (IQR 2·8–19·9), 2·2 per 1000 operations for appendectomy (0·0–17·2), and 4·9 per 1000 operations for groin hernia (0·0–11·7). Perioperative mortality estimates by subregion ranged from 2·8 (South Asia) to 50·2 (East Asia) per 1000 caesarean deliveries, 2·4 (South Asia) to 54·0 (Central sub-Saharan Africa) per 1000 appendectomies, and 0·3 (Andean Latin America) to 25·5 (Southern sub-Saharan Africa) per 1000 hernia repairs. Interpretation All-cause postoperative mortality rates are exceedingly variable within resource-constrained environments. Eff orts to expand surgical access and provision of services must include a strong commitment to improve the safety and quality of care