Moderately severe and severe acute pancreatitis : a systematic review of the outcomes in the USA and European Union-5.

BACKGROUND AND OBJECTIVES: The global incidence of hospitalisation due to acute pancreatitis (AP) has been rising in the recent decades. In the USA alone, there was a 13.2% increase between 2009 and 2012 compared with 2002-2005. There remains a lack of approved treatments to prevent disease progression, leaving many liable to developing complications that include multisystem organ failure (OF) and death. This therapeutic deficit raises questions about the scale of the current burden of illness (BOI) associated with severe forms of AP. The aim of the systematic literature review (SLR) was to assess clinical, humanistic, and economic outcomes associated with moderately severe AP (MSAP) and severe AP (SAP) in the USA and the European Union-5 (EU-5). METHODS: Systematic searches were conducted in MEDLINE and Embase to identify studies published in English (between 2007 and 2017) that reported on the BOI of MSAP and/or SAP. Manual searches of 'grey' literature sources were also conducted. RESULTS: The SLR identified 19 studies which indicated that 15%-20% of patients with AP progress to more severe forms of the disease, up to 10.5% of those with SAP require surgery for complications, and up to 40% die during hospitalisation. By contrast, there appears to be a lack of data on the extent to which SAP affects patients' quality of life. CONCLUSION: The available evidence clearly demonstrates that the current management for MSAP and SAP in the USA and EU-5 does not adequately meet patients' needs. Early identification and intervention for AP is crucial, given the evidence of high rates of morbidity and an associated economic burden that is considerable. Since many patients with the condition present to hospitals at a point when multisystem OF or death is highly likely, there is a particularly urgent need for effective treatment options to prevent disease progression.

Systematic review of therapy used in relapsed or refractory diffuse large B-cell lymphoma and follicular lymphoma.

To identify real-world evidence on outcomes from therapies for relapsed/refractory diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL), we systematically reviewed literature in Medline/Embase for DLBCL/FL-related articles on real-world results published during January 2012-May 2016. Among 33 included articles, therapies included stem cell transplant (SCT) and chemotherapy, including experimental regimens. The highest overall survival rates were observed for SCT, long considered an optimal strategy following initial relapse. Prognoses were inferior among DLBCL patients receiving rituximab-based regimens rather than SCT, particularly among studies that exclusively focused on those ineligible for SCT due to age or co-morbidity. A lack of viable treatment options for DLBCL/FL patients ineligible for SCT after relapse remains a significant gap in care.

Effectiveness and Safety of Therapeutic Regimens for Elderly Patients With Acute Myeloid Leukemia: A Systematic Literature Review.

Acute myeloid leukemia (AML) is the second most common leukemia among adults. Although the median age at diagnosis is 67 years, with approximately one third of patients aged 75 years or older, limited treatment options exist for the elderly, who have 5-year survival rates of only 5%. A systematic review was conducted to examine effectiveness and safety outcomes of treatment regimens in elderly (≥60 years old) patients with AML. Published literature on the topic was scant, and the review included only 22 articles examining outcomes. Twelve studies examined treatment-specific outcomes; most of these examined azacitidine or intensive chemotherapy (IC). An international randomized controlled trial found that azacitidine significantly improved overall survival relative to conventional regimens including IC and low-dose cytarabine in patients aged > 65 years. Similar results in favor of azacitidine were demonstrated in 2 other studies. IC was generally associated with longer survival versus lower-intensity therapy or best supportive care. Findings suggest that azacitidine is a viable option for elderly AML patients who are ineligible for IC, and emerging agents used in combination with azacitidine could have a major impact in this difficult-to-treat population.

Systematic Literature Review of Treatment Options and Clinical Outcomes for Patients With Higher-Risk Myelodysplastic Syndromes and Chronic Myelomonocytic Leukemia.

High-dose chemotherapy with allogeneic hematopoietic stem cell transplantation (allo-HSCT) can produce long-term remission in patients with higher-risk myelodysplastic syndromes (HR-MDS) and chronic myelomonocytic leukemia (CMML). However, this treatment regimen is not appropriate for elderly and/or comorbid patients; in these cases, azacitidine is a standard treatment. This systematic review was conducted to evaluate real-world evidence of treatment options for patients with HR-MDS/CMML. Medline and Embase (January 2006 to May 2016) were searched, in addition to conference proceedings and treatment guideline reviews. Studies on clinical effectiveness/efficacy outcomes with a sample size ≥50 patients were included. From 1061 unique citations identified, 87 full-text articles were reviewed, of which 24 articles reported at least 1 outcome of interest. Studies showed that HR-MDS/CMML patients treated with a conventional chemotherapy regimen (CCR) have poorer overall survival (OS). Key findings from individual HR-MDS studies showed improved survival with azacitidine over CCRs and higher overall response rates with clofarabine relative to low-dose cytosine arabinoside (but no significant difference in 2-year OS favoring clofarabine). OS was highest for patients treated with allo-HSCT. Findings indicate limited real-world data on treatment strategies available for HR-MDS/CMML patients. Most studies address the effect of chemotherapy or allo-HSCT on clinical outcomes, so are not applicable to elderly/comorbid patients who are too frail for those treatments. In particular, our analysis revealed limited evidence on viable options after failure of treatment with azacitidine, identifying a significant unmet need in this patient population.

The impact of spatial and temporal availability of alcohol on its consumption and related harms: a critical review in the context of UK licensing policies.

ISSUES: Reviews recommend controlling alcohol availability to limit alcohol-related harm. However, the translation of this evidence into policy processes has proved challenging in some jurisdictions. APPROACH: This paper presents a critical review of empirical spatial and temporal availability research to identify its features and limitations for informing alcohol availability policies. The UK is used as an example jurisdiction. It reviews 138 studies from a 2008 systematic review of empirical availability research and our update of this to January 2014. Data describing study characteristics (settings, measures, design) were extracted and descriptively analysed. KEY FINDINGS: Important limitations in current evidence were identified: (i) outlet-level temporal availability was only measured in three studies, and there has been little innovation in measurement of spatial availability; (ii) empirical analyses focus on acute harms with few studies of longer-term harms; (iii) outlets are typically classified at aggregated levels with little empirical analysis of variation within outlet categories; (iv) evidence comes from a narrow range of countries; and (v) availability away from home, online availability and interactions between availability, price and place are all relatively unexamined. IMPLICATIONS: Greater innovation in study and measure design and enhanced data quality are required. Greater engagement between researchers and policy actors when developing studies would facilitate this. CONCLUSIONS: Research and data innovations are needed to address a series of methodological gaps and limitations in the alcohol availability evidence base, advance this research area and enable findings to be translated effectively into policy processes.

Alcohol tax pass-through across the product and price range: do retailers treat cheap alcohol differently?

BACKGROUND AND AIMS: Effective use of alcohol duty to reduce consumption and harm depends partly on retailers passing duty increases on to consumers via price increases, also known as 'pass-through'. The aim of this analysis is to provide evidence of UK excise duty and sales tax (VAT) pass-through rates for alcohol products at different price points. SETTING: March 2008 to August 2011, United Kingdom. DESIGN AND MEASUREMENTS: Panel data quantile regression estimating the effects of three duty changes, two VAT changes and one combined duty and VAT change on UK alcohol prices, using product-level supermarket price data for 254 alcohol products available weekly. Products were analysed in four categories: beers, ciders/ready to drink (RTDs), spirits and wines. FINDINGS: Within all four categories there exists considerable heterogeneity in the level of duty pass-through for cheaper versus expensive products. Price increases for the cheapest 15% of products fall below duty rises (undershifting), while products sold above the median price are overshifted (price increases are higher than duty increases). The level of undershifting is greatest for beer [0.85 (0.79, 0.92)] and spirits [0.86 (0.83, 0.89)]. Undershifting affects approximately 67% of total beer sales and 38% of total spirits sales. CONCLUSIONS: Alcohol retailers in the United Kingdom appear to respond to increases in alcohol tax by undershifting their cheaper products (raising prices below the level of the tax increase) and overshifting their more expensive products (raising prices beyond the level of the tax increase). This is likely to impact negatively on tax policy effectiveness, because high-risk groups favour cheaper alcohol and undershifting is likely to produce smaller consumption reductions.

Effects of minimum unit pricing for alcohol on different income and socioeconomic groups: a modelling study.

BACKGROUND: Several countries are considering a minimum price policy for alcohol, but concerns exist about the potential effects on drinkers with low incomes. We aimed to assess the effect of a £0·45 minimum unit price (1 unit is 8 g/10 mL ethanol) in England across the income and socioeconomic distributions. METHODS: We used the Sheffield Alcohol Policy Model (SAPM) version 2.6, a causal, deterministic, epidemiological model, to assess effects of a minimum unit price policy. SAPM accounts for alcohol purchasing and consumption preferences for population subgroups including income and socioeconomic groups. Purchasing preferences are regarded as the types and volumes of alcohol beverages, prices paid, and the balance between on-trade (eg, bars) and off-trade (eg, shops). We estimated price elasticities from 9 years of survey data and did sensitivity analyses with alternative elasticities. We assessed effects of the policy on moderate, hazardous, and harmful drinkers, split into three socioeconomic groups (living in routine or manual households, intermediate households, and managerial or professional households). We examined policy effects on alcohol consumption, spending, rates of alcohol-related health harm, and opportunity costs associated with that harm. Rates of harm and costs were estimated for a 10 year period after policy implementation. We adjusted baseline rates of mortality and morbidity to account for differential risk between socioeconomic groups. FINDINGS: Overall, a minimum unit price of £0.45 led to an immediate reduction in consumption of 1.6% (-11.7 units per drinker per year) in our model. Moderate drinkers were least affected in terms of consumption (-3.8 units per drinker per year for the lowest income quintile vs 0.8 units increase for the highest income quintile) and spending (increase in spending of £0.04 vs £1.86 per year). The greatest behavioural changes occurred in harmful drinkers (change in consumption of -3.7% or -138.2 units per drinker per year, with a decrease in spending of £4.01), especially in the lowest income quintile (-7.6% or -299.8 units per drinker per year, with a decrease in spending of £34.63) compared with the highest income quintile (-1.0% or -34.3 units, with an increase in spending of £16.35). Estimated health benefits from the policy were also unequally distributed. Individuals in the lowest socioeconomic group (living in routine or manual worker households and comprising 41.7% of the sample population) would accrue 81.8% of reductions in premature deaths and 87.1% of gains in terms of quality-adjusted life-years. INTERPRETATION: Irrespective of income, moderate drinkers were little affected by a minimum unit price of £0.45 in our model, with the greatest effects noted for harmful drinkers. Because harmful drinkers on low incomes purchase more alcohol at less than the minimum unit price threshold compared with other groups, they would be affected most by this policy. Large reductions in consumption in this group would however coincide with substantial health gains in terms of morbidity and mortality related to reduced alcohol consumption. FUNDING: UK Medical Research Council and Economic and Social Research Council (grant G1000043).

The temporal relationship between per capita alcohol consumption and harm: a systematic review of time lag specifications in aggregate time series analyses.

BACKGROUND: Changes in per capita alcohol consumption are temporally linked to changes in rates of alcohol-related harm. Methodological approaches for analysing this relationship have been suggested, however, the problem of time lags is not well-addressed. This study provides a review of time lag specifications, looking at (a) time to first effect on harm, (b) time to full effect and (c) the functional form of the effect accumulation from first to full effect to inform modelling of the relationship between changes in aggregate alcohol consumption and changes in rates of harm. METHODS: Bibliographic databases were searched and citation and reference checking was used to identify studies. Included studies were time series analyses of the relationship between aggregated population alcohol consumption and rates of alcohol-related harms where time lag specifications had been derived or tested. RESULTS: 36 studies were included with liver cirrhosis, heart disease and suicide dominating the evidence base. For a large number of alcohol-related harms, no literature was identified. There was strong evidence of an immediate first effect following a change in consumption for most harms. Recommended lag specifications are proposed for a set of alcohol-attributable harms. CONCLUSIONS: Research on time lag specifications is under-developed for most harms although we provide suggested specifications based on the findings of the review. Greater methodological attention needs to be given to the rationale for choosing or applying lag specifications and the inherent complexity of the time lag process. More consistent and transparent reporting of methodological decisions would aide progress in the field.