Change in MRI-PDFF and Histologic Response in Patients With Nonalcoholic Steatohepatitis: A Systematic Review and Meta-Analysis.

BACKGROUND & AIMS: Magnetic resonance imaging proton density fat fraction (MRI-PDFF) offers promise as a non-invasive biomarker of treatment response in early-phase nonalcoholic steatohepatitis (NASH) trials. We performed a systematic review to quantify the association between a ≥ 30% reduction in MRI-PDFF and histologic response in NASH. METHODS: We searched the Cochrane Library, Embase, Medline and trial registries through May 2020 for early-phase clinical trials that incorporated MRI-PDFF and examined histologic response following intervention in adults with NASH. Subjects were classified as MRI-PDFF responders (relative decline in liver fat ≥30%) or non-responders (relative decline in liver fat <30%). MRI-PDFF responders versus non-responders were compared. Primary outcome was histologic response defined as a 2-point improvement in NAFLD Activity Score with at least 1-point improvement in lobular inflammation or ballooning. Secondary outcome was NASH resolution. Proportions and random effects odds ratios (OR) with corresponding 95% confidence intervals (CI) were calculated. RESULTS: Seven studies met inclusion criteria, comprising 346 subjects (median age 51 years; 59% female; 46% with diabetes). MRI-PDFF responders were significantly more likely to have a histologic response (51% vs 14%, P < .001; OR 6.98, 95% CI 2.38-20.43, P < .001) and NASH resolution (41% vs 7%, P < .001; OR 5.45, 95% CI 1.53-19.46, P = .009) compared to non-responders. CONCLUSIONS: This meta-analysis demonstrates that a ≥30% relative decline in MRI-PDFF is associated with higher odds of histologic response and NASH resolution. These results support the use of MRI-PDFF in non-invasive monitoring of treatment response in early-phase NASH clinical trials and provide helpful data for sample-size estimation for histology-based assessment.

Magnetic Resonance vs Transient Elastography Analysis of Patients With Nonalcoholic Fatty Liver Disease: A Systematic Review and Pooled Analysis of Individual Participants.

BACKGROUND & AIMS: Magnetic resonance elastography (MRE) and transient elastography (TE) are noninvasive techniques for detection of liver fibrosis. Single-center studies have compared the diagnostic performance of MRE vs TE in patients with nonalcoholic fatty liver disease (NAFLD). We conducted a pooled analysis of individual participant data from published studies to compare the diagnostic performance of MRE vs TE for staging of liver fibrosis in patients with NAFLD, using liver biopsy as reference. METHODS: We performed a systematic search of publication databases, from 2005 through 2017. We identified 3 studies of adults with NAFLD who were assessed by MRE, TE, and liver biopsy. In a pooled analysis, we calculated the cluster-adjusted area under the curve (AUROC) of MRE and TE for the detection of each stage of fibrosis. AUROC comparisons between MRE and TE were performed using the Delong test. RESULTS: Our pooled analysis included 230 participants with biopsy-proven NAFLD with mean age of 52.2±13.9 years and a body mass index of 31.9±7.5 kg/m2. The proportions of patients with fibrosis of stages 0, 1, 2, 3, and 4 were: 31.7%, 27.8%, 15.7%, 13.9%, and 10.9%, respectively. The AUROC of TE vs MRE for detection of fibrosis stages ≥1 was 0.82 (95% CI, 0.76-0.88) vs 0.87 (95% CI, 0.82-0.91) (P=.04); for stage≥ 2 was 0.87 (95% CI, 0.82-0.91) vs 0.92 (95% CI, 0.88-0.96) (P=.03); for stage ≥3 was 0.84 (95% CI, 0.78-0.90) vs 0.93 (95% CI, 0.89-0.96) (P=.001); for stage ≥ 4 was 0.84 (95% CI, 0.73-0.94) vs 0.94 (95% CI, 0.89-0.99) (P=.005). CONCLUSION: In a pooled analysis of data from individual participants with biopsy-proven NAFLD, we found MRE to have a statistically significantly higher diagnostic accuracy than TE in detection of each stage of fibrosis. MRE and TE each have roles in detection of fibrosis in patients with NAFLD, depending upon the level of accuracy desired.

What is "high risk?" a systematic review of atopy risk and implications for primary prevention.

Atopic diseases are common and becoming more prevalent. Efforts have focused on primary disease prevention by identifying high-risk children and applying preventative strategies. Our aim was to evaluate methods used to identify high-risk children in atopy prevention studies. A literature search for relevant articles published between 1986 and 2006 was conducted, and all abstracts were reviewed. The search yielded 1,535 publications, 133 were reviewed in detail, and 57 met inclusion criteria. High risk was defined by 30 different methods. First-degree relatives with an atopic disorder were included in all methods, but only three publications used referenced questionnaires to determine this. Less frequently included were cord blood immunoglobulin E measurements and skin prick or radioallergosorbent testing, and 16 methods relied on history alone. Family history was the most common method used to predict high risk of atopic disease in a child, but a minority of studies used a tested questionnaire to determine the presence of atopy in family members. The methods used to identify high-risk children are variable, and the development and widespread use of a validated, practical screening tool is needed.

Effect of medication dosing frequency on adherence in chronic diseases.

OBJECTIVE: To systematically review available data on the effect of daily medication dosing frequency on medication adherence in chronic disease states, as assessed by precise medication event monitoring systems (MEMS). STUDY DESIGN: Systematic review of relevant literature published between January 1986 and August 2007. METHODS: Four electronic databases were searched to identify appropriate studies. Study selection criteria included prospective study design, patient population with quiescent chronic disease, medication intervention prescribed to each treatment arm for at least 6 weeks, and the use of MEMS to measure adherence. Data were extracted on the chronic disease being treated, the frequency of medication dosing, and the proportion of days with correct number of doses. RESULTS: Twenty studies met the selection criteria. All studies reported higher adherence rates in patients using less frequently dosed medications, and these differences were statistically significant (P <.05) in 75% (15 of 20) of studies. For 5 of 6 studies comparing once-daily versus thrice-daily dosing, patients receiving once-daily dosing had 22% to 41% more adherent days compared with patients receiving thrice-daily dosing. For studies comparing once-daily versus twice-daily dosing, patients receiving once-daily dosing had 2% to 44% more adherent days compared with patients receiving twice-daily dosing, with most studies clustering around 13% to 26%. CONCLUSION: Patients are more compliant with once-daily compared with twice-daily or thrice-daily treatment regimens.

The socioeconomic impact of atopic dermatitis in the United States: a systematic review.

The aim of this study was to review studies examining the direct and indirect costs of atopic dermatitis in the United States. A search was performed using OVID MEDLINE, MEDLINE In-Process and Other Non-Indexed Citations, EMBASE, the International Agency for Health Technology Assessment (INAHTA) database, and the Cochrane Library. All abstracts were reviewed for the following criteria: original cost data, studies performed in the United States, and English language. The search yielded 418 papers. Fifty-nine papers were reviewed in detail, and four studies were found that met the inclusion criteria. These cost-identification analyses estimated the cost of atopic dermatitis heterogeneously and could not be compared directly. National cost estimates ranged widely, from $364 million to $3.8 billion US dollars per year. The cost of atopic dermatitis is significant and will likely increase in proportion to increasing disease prevalence. Measurement of the cost of atopic dermatitis in the United States has been limited to direct cost-identification analyses, with few studies measuring the indirect cost of disease.

Assessing automated external defibrillators in preventing deaths from sudden cardiac arrest: an economic evaluation.

OBJECTIVES: The aim of this study was to evaluate the cost-effectiveness of on-site automated external defibrillators (AEDs) in the initial management of cardiac arrest in Ontario. METHODS: This was a cost-effectiveness analysis based on published literature and data from the Canadian Institute of Health Information. The participants were fictitious male and female cardiac arrest patients who were initially managed with on-site AEDs, compared with similar patients managed without on-site AEDs. This group included a subgroup of high-risk patients (i.e., heart failure and left ventricular ejection fraction<35 percent). The analysis was conducted in a variety of settings including hospitals and homes in Ontario, Canada. The main outcome evaluated was cost per quality-adjusted life-year (QALY) gained from a payer's perspective. RESULTS: Cost per QALY (all costs reported in Canadian dollars) was $12,768 when AEDs were deployed in hospitals, $511,766 when deployed in office buildings, $2,360,023 when deployed in apartment buildings, $87,569 when deployed in homes of high-risk patients, and $1,529,371 when deployed in homes of people older than 55 years of age. CONCLUSIONS: Indiscriminate deployment of AEDs is not a cost-effective means of improving health outcomes of cardiac arrest. Their use should be restricted to emergency response programs, high-risk sites (such as hospitals), and high-risk patients.