Ashley Bonner

Network meta-analysis (NMA)--a statistical technique that allows comparison of multiple treatments in the same meta-analysis simultaneously--has become increasingly popular in the medical literature in recent years. The statistical methodology underpinning this technique and software tools for implementing the methods are evolving. Both commercial and freely available statistical software packages have been developed to facilitate the statistical computations using NMA with varying degrees of functionality and ease of use. This paper aims to introduce the reader to three R packages, namely, gemtc, pcnetmeta, and netmeta, which are freely available software tools implemented in R. Each automates the process of performing NMA so that users can perform the analysis with minimal computational effort. We present, compare and contrast the availability and functionality of different important features of NMA in these three packages so that clinical investigators and researchers can determine which R packages to implement depending on their analysis needs. Four summary tables detailing (i) data input and network plotting, (ii) modeling options, (iii) assumption checking and diagnostic testing, and (iv) inference and reporting tools, are provided, along with an analysis of a previously published dataset to illustrate the outputs available from each package. We demonstrate that each of the three packages provides a useful set of tools, and combined provide users with nearly all functionality that might be desired when conducting a NMA.

OBJECTIVE: This study was performed to determine the prevalence of elevated C-reactive protein (CRP) levels and the significance of CRP in clinical parameters in systemic sclerosis (SSc; scleroderma) patients. METHODS: Canadian Scleroderma Research Group data were used. Statistical comparisons were made for CRP levels ≤8 mg/liter versus >8 mg/liter, early (≤3 years from first non-Raynaud's phenomenon symptom) versus late SSc, and diffuse cutaneous SSc (dcSSc) versus limited cutaneous SSc (lcSSc). A survival analysis was analyzed between patients with normal versus elevated CRP levels. RESULTS: A total of 1,043 patients (mean ± SD age 55.4 ± 12.1 years, mean ± SD disease duration of 11.0 ± 9.5 years) were analyzed; elevation of CRP level and erythrocyte sedimentation rate (ESR; >20 mm/hour) occurred in 25.7% and 38.2%, respectively. Mean ± SD baseline CRP level in dcSSc (11.98 ± 25.41 mg/liter) was higher than in lcSSc (8.15 ± 16.09 mg/liter; P = 0.016). SSc patients with an early disease duration had a higher mean ± SD CRP level (12.89 ± 28.13 mg/liter) than those with a late disease duration (8.60 ± 17.06 mg/liter; P = 0.041). Although not consistent in all subsets, CRP was significantly associated (P < 0.01) with ESR, modified Rodnan skin score (MRSS), worse pulmonary function parameters, disease activity, damage, and Health Assessment Questionnaire. CRP level seemed to normalize in many SSc patients over time. Total lung capacity <80% predicted, MRSS, and serum creatinine were predictors of elevated CRP levels in SSc (odds ratio [OR] 2.76 [95% confidence interval (95% CI) 1.73-4.40], P = 0.0001; OR 1.03 [95% CI 1.01-1.05], P = 0.005; and OR 1.005 [95% CI 1.001-1.010], P = 0.02, respectively). Survival for patients with elevated CRP levels was less than for patients with normal CRP levels (P = 0.001). CONCLUSION: CRP level is elevated in one-quarter of SSc patients, especially early disease. It is correlated with disease activity, severity, poor pulmonary function, and shorter survival.

INTRODUCTION: Providing optimal critical care in developing countries is limited by lack of recognition of critical illness and lack of essential resources. The Modified Early Warning Score (MEWS), based on physiological parameters, is validated in adult medical and surgical patients as a predictor of mortality. The objective of this study performed in Uganda was to determine the prevalence of critical illness on the wards as defined by the MEWS, to evaluate the MEWS as a predictor of death, and to describe additional risk factors for mortality. METHODS: We conducted a prospective observational study at Mulago National Referral Teaching Hospital in Uganda. We included medical and surgical ward patients over 18 years old, excluding patients discharged the day of enrolment, obstetrical patients, and patients who self-discharged prior to study completion. Over a 72-hour study period, we collected demographic and vital signs, and calculated MEWS; at 7-days we measured outcomes. Patients discharged prior to 7 days were assumed to be alive at study completion. Descriptive and inferential statistical analyses were performed. RESULTS: Of 452 patients, the median age was 40.5 (IQR 29-54) years, 53.3% were male, 24.3% were HIV positive, and 45.1% had medical diagnoses. MEWS ranged from 0 to 9, with higher scores representing hemodynamic instability. The median MEWS was 2 [IQR 1-3] and the median length of hospital stay was 9 days [IQR 4-24]. In-hospital mortality at 7-days was 5.5%; 41.4% of patients were discharged and 53.1% remained on the ward. Mortality was independently associated with medical admission (OR: 7.17; 95% CI: 2.064-24.930; p = 0.002) and the MEWS ≥ 5 (OR: 5.82; 95% CI: 2.420-13.987; p<0.0001) in the multivariable analysis. CONCLUSION: There is a significant burden of critical illness at Mulago Hospital, Uganda. Implementation of the MEWS could provide a useful triage tool to identify patients at greatest risk of death. Future research should include refinement of MEWS for low-resource settings, and development of appropriate interventions for patients identified to be at high risk of death based on early warning scores.

BACKGROUND: Opioids are psychoactive analgesic drugs prescribed for pain relief and palliative care. Due to their addictive potential, effort and vigilance in controlling prescriptions is needed to avoid misuse and dependence. Despite the effort, the prevalence of opioid use disorder continues to rise. Opioid substitution therapies are commonly used to treat opioid dependence; however, there is minimal consensus as to which therapy is most effective. Available treatments include methadone, heroin, buprenorphine, as well as naltrexone. This systematic review aims to assess and compare the effect of all available opioid substitution therapies on the treatment of opioid dependence. METHODS/DESIGN: The authors will search Medline, EMBASE, PubMed, PsycINFO, Web of Science, Cochrane Library, Cochrane Clinical Trials Registry, World Health Organization International Clinical Trials Registry Platform Search Portal, and the National Institutes for Health Clinical Trials Registry. The title, abstract, and full-text screening will be completed in duplicate. When appropriate, multiple treatment comparison Bayesian meta-analytic methods will be performed to deduce summary statistics estimating the effectiveness of all opioid substitution therapies in terms of retention and response to treatment (as measured through continued opioid abuse). DISCUSSION: Using evidence gained from this systematic review, we anticipate disseminating an objective review of the current available literature on the effectiveness of all opioid substitution therapies for the treatment of opioid use disorder. The results of this systematic review are imperative to the further enhancement of clinical practice in addiction medicine. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42013006507.