Prognostic factors for chronic post-surgical pain after lung or pleural surgery: a protocol for a systematic review and meta-analysis.

INTRODUCTION: Chronic post-surgical pain (CPSP) after lung or pleural surgery is a common complication and associated with a decrease in quality of life, long-term use of pain medication and substantial economic costs. An abundant number of primary prognostic factor studies are published each year, but findings are often inconsistent, methods heterogeneous and the methodological quality questionable. Systematic reviews and meta-analyses are therefore needed to summarise the evidence. METHODS AND ANALYSIS: The reporting of this protocol adheres to the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P) checklist. We will include retrospective and prospective studies with a follow-up of at least 3 months reporting patient-related factors and surgery-related factors for any adult population. Randomised controlled trials will be included if they report on prognostic factors for CPSP after lung or pleural surgery. We will exclude case series, case reports, literature reviews, studies that do not report results for lung or pleural surgery separately and studies that modified the treatment or prognostic factor based on pain during the observation period. MEDLINE, Scopus, Web of Science, Embase, Cochrane, CINAHL, Google Scholar and relevant literature reviews will be searched. Independent pairs of two reviewers will assess studies in two stages based on the PICOTS criteria. We will use the Quality in Prognostic Studies tool for the quality assessment and the CHARMS-PF checklist for the data extraction of the included studies. The analyses will all be conducted separately for each identified prognostic factor. We will analyse adjusted and unadjusted estimated measures separately. When possible, evidence will be summarised with a meta-analysis and otherwise narratively. We will quantify heterogeneity by calculating the Q and I2 statistics. The heterogeneity will be further explored with meta-regression and subgroup analyses based on clinical knowledge. The quality of the evidence obtained will be evaluated according to the Grades of Recommendation Assessment, Development and Evaluation guideline 28. ETHICS AND DISSEMINATION: Ethical approval will not be necessary, as all data are already in the public domain. Results will be published in a peer-reviewed scientific journal. PROSPERO REGISTRATION NUMBER: CRD42021227888.

Bioreactor Conditioning of Valve Scaffolds Seeded Internally with Adult Stem Cells.

The goal of this study was to test the hypothesis that stem cells, as a response to valve-specific extracellular matrix "niches" and mechanical stimuli, would differentiate into valvular interstitial cells (VICs). Porcine aortic root scaffolds were prepared by decellularization. After verifying that roots exhibited adequate hemodynamics in vitro, we seeded human adipose-derived stem cells (hADSCs) within the interstitium of the cusps and subjected the valves to in vitro pulsatile bioreactor testing in pulmonary pressures and flow conditions. As controls we incubated cell-seeded valves in a rotator device which allowed fluid to flow through the valves ensuring gas and nutrient exchange without subjecting the cusps to significant stress. After 24 days of conditioning, valves were analyzed for cell phenotype using immunohistochemistry for vimentin, alpha-smooth muscle cell actin (SMA) and prolyl-hydroxylase (PHA). Fresh native valves were used as immunohistochemistry controls. Analysis of bioreactor-conditioned valves showed that almost all seeded cells had died and large islands of cell debris were found within each cusp. Remnants of cells were positive for vimentin. Cell seeded controls, which were only rotated slowly to ensure gas and nutrient exchange, maintained about 50% of cells alive; these cells were positive for vimentin and negative for alpha-SMA and PHA, similar to native VICs. These results highlight for the first time the extreme vulnerability of hADSCs to valve-specific mechanical forces and also suggest that careful, progressive mechanical adaptation to valve-specific forces might encourage stem cell differentiation towards the VIC phenotype.

Development and initial characterization of a chemically stabilized elastin-glycosaminoglycan-collagen composite shape-memory hydrogel for nucleus pulposus regeneration.

Nucleus pulposus (NP) is a resilient and hydrophilic tissue which plays a significant role in the biomechanical function of the intervertebral disc (IVD). Destruction of the NP extracellular matrix (ECM) is observed during the early stages of IVD degeneration. Herein, we describe the development and initial characterization of a novel biomaterial which attempts to recreate the resilient and hydrophilic nature of the NP via the construction of a chemically stabilized elastin-glycosaminoglycan-collagen (EGC) composite hydrogel. Results demonstrated that a resilient, hydrophilic hydrogel which displays a unique "shape-memory" sponge characteristic could be formed from a blend of soluble elastin aggregates, chondroitin-6-sulfate, hyaluronic acid and collagen following freeze-drying, stabilization with a carbodiimide and penta-galloyl glucose-based fixative, and subsequent partial degradation with glycosaminoglycan degrading enzymes. The resultant material exhibited the ability to restore its original dimensions and water content following multi-cycle mechanical compression and illustrated resistance to accelerated enzymatic degradation. Preliminary in vitro studies utilizing human adipose derived stem cells (hADSCs) demonstrated that the material was cytocompatible and supported differentiation towards an NP cell-like phenotype. In vivo biocompatibility studies illustrated host cell infiltration and evidence of active remodeling following 4 weeks of implantation. Feasibility studies demonstrated that the EGC hydrogel could be delivered via minimally invasive methods.

Risks of alcohol-attributable hospitalisation and death in Australia over time: Evidence of divergence by region, age and sex.

BACKGROUND: Past reports on trends of alcohol consumption and related harm have generally been descriptive in nature and have not provided evidence of whether changes over time are significant. AIMS: We investigated whether: (i) the risk of alcohol-attributable hospitalisation and death between 1994 and 2005 for three different age groups changed significantly across all Australian jurisdictions; and (ii) the relative rates of hospitalisation for males and females changed over time. METHOD: Estimates of alcohol-attributable hospitalisations and deaths were calculated using the aetiologic fraction method. Hospitalisations and deaths were grouped by age: 15-29 years, 30-44 years and 45+ years. Risk estimates and risk differences were analysed using Poisson regression. RESULTS: Risk of alcohol-attributable hospital separations increased nationally and across most jurisdictions throughout the study period. Male and female rates converged over time. Alcohol-attributable deaths decreased nationally across the three age groups and across several jurisdictions beginning in the mid-1990s. CONCLUSION: Nationally, alcohol-attributable deaths declined while hospitalisations rose. However, states with higher population density tended to drive national rates, with considerable variation by jurisdiction. The conditions which dominated hospitalisations (e.g. alcohol dependence, falls) differed substantially from those underlying alcoholattributable deaths (e.g. alcoholic liver cirrhosis, road crashes). Jurisdictional variation in death and hospitalisations rates as well as changes over time may be partly due to differences in: regulation of alcohol supply; patterns and levels of alcohol consumption; the nature and effectiveness of law enforcement; demographic characteristics of general and sub-populations; and medical health services and screening for chronic conditions.

Estimating alcohol-attributable mortality among Indigenous Australians: towards Indigenous-specific alcohol aetiologic fractions.

INTRODUCTION AND AIMS: Past estimates of Indigenous alcohol-attributable health in Australia have been based on drinking prevalence estimates from the general population, rather than prevalence figures from the Indigenous population. The purpose of this paper is to demonstrate the efficacy of using Indigenous-specific drinking prevalence to estimate alcohol-attributable deaths among Indigenous Australians. DESIGN AND METHODS: Estimates of Indigenous alcohol-attributable deaths between 2000 and 2004 were obtained using both (i) national general-population drinking prevalence estimates and (ii) national Indigenous-specific drinking prevalence. Estimates were calculated using the 'aetiologic fraction' method. RESULTS: By using national general-population drinking prevalence figures, past reports on Indigenous health have underestimated alcohol-attributable deaths for the national Indigenous population. Female deaths due to alcohol-attributable haemorrhagic stroke were estimated to be approximately four times higher and alcohol-attributable suicides among men were estimated to be 30% higher than was previously held, when Indigenous-specific drinking prevalence figures were used. DISCUSSION AND CONCLUSIONS: By substituting Indigenous-specific alcohol consumption prevalence estimates for general-population drinking prevalence, the accuracy of estimates of alcohol-related harm among Indigenous Australians can be significantly improved.

Alcohol use and prostate cancer: a meta-analysis.

Past reviews have concluded that there is no association between alcohol use and prostate cancer incidence. We performed a meta-analysis of existing epidemiological studies finding, in contrast, evidence to suggest that prostate incidence is positively linearly associated with heavier alcohol use. This finding was largely due to the contribution of population case-control studies and those measuring men recruited before age 60. No relationship between alcohol consumption and prostate cancer was found for cohort and hospital case-control studies. Analyses of design effects modestly suggests that population case-control studies were probably better suited to identify potential alcohol-prostate cancer relationships due to the close temporal proximity of the measurement of level of alcohol consumption to diagnosis. Future efforts should be made to exclude all ill subjects from control groups/baseline samples in addition to accounting for changes in consumption with advancing age and the onset of illness. The alcohol-prostate cancer association remained significant despite controlling for the degree to which studies endeavored to eliminate false negatives from their control groups.

The impact of the Northern Territory's Living With Alcohol program, 1992-2002: revisiting the evaluation.

AIMS: To evaluate the effects of the Living With Alcohol (LWA) program and the LWA Alcoholic Beverage Levy on alcohol-attributable deaths in the Northern Territory (NT) controlling for simultaneous trends in death rates from a control region and non-alcohol related death trends in the NT, between 1985 and 2002. DESIGN: The LWA program was introduced in 1992 with funding from a special NT tax (Levy) on beverages with greater than 3% alcohol content by volume. The Levy was removed in 1997 but the LWA program continued to be funded by the federal government until 2002. Trends in age standardised rates of acute and chronic alcohol-attributable deaths in the NT were examined before, during and after the combined implementation of the LWA program and Levy and before and during the full length of the LWA program. Auto-regressive integrated moving average (ARIMA) time series analyses included internal and external control series and adjustments for possible confounders. Separate estimates were made for Indigenous and non-Indigenous NT residents. FINDINGS: When combined, the Levy and the LWA program were associated with significant declines in acute alcohol-attributable deaths in the NT as well as Indigenous deaths between 1992 and 1997. A significant but delayed decline in chronic deaths was evident towards the end of the study period between 1998 and 2002. CONCLUSIONS: The combined impact of the LWA program Levy and the programs and services funded by the Levy reduced the burden of alcohol-attributable injury to the NT in the short term and may have contributed to a reduction in chronic illness in the longer term. The results of this study present a strong argument for the effectiveness of combining alcohol taxes with comprehensive programs and services designed to reduce the harm from alcohol, and underline the need to distinguish between the acute and chronic effects of alcohol in population level studies.