Sodium-glucose cotransporter 2 (SGLT2) inhibitor initiation and hepatocellular carcinoma prognosis.

INTRODUCTION: Sodium-glucose cotransporter 2 (SGLT2) inhibitors are a relatively new class of antidiabetic drugs. Emerging findings from laboratory studies indicate that SGLT2 inhibitors can improve liver function and suppress the proliferation of hepatocellular carcinoma (HCC) cells. The aim of this study was to test the hypothesis that initiation of SGLT2 inhibitors improves HCC prognosis in a human population. METHODS: We used National Surveillance, Epidemiology and End Results (SEER)-Medicare linked data in the United States to evaluate the role of SGLT2 inhibitor initiation on the survival of HCC patients. 3,185 HCC patients newly diagnosed between 2014 and 2017 aged 66 years or older with pre-existing type 2 diabetes were included and followed to the end of 2019. Information on SGLT2 inhibitor initiation was extracted from the Medicare Part D file. RESULTS: SGLT2 inhibitor initiation was associated with significantly lower mortality risk after adjusting for potential confounders (HR = 0.68, 95% CI = 0.54-0.86) with stronger association for longer duration of use (HR = 0.60, 95% CI = 0.41-0.88). Further, we found that SGLT2 inhibitor initiation was associated with a lower risk mortality risk ranging from 14% to 60% regardless of patient demographic variables, tumor characteristics, and cancer treatments. CONCLUSION: Our large SEER-Medicare linked data study indicates that SGLT2 inhibitor initiation was associated with improved overall survival of HCC patients with pre-existing type 2 diabetes compared with no SGLT2 inhibitor use. Further studies are needed to confirm our findings and elucidate the possible mechanisms behind the association.

Scalable psychological interventions for Syrian refugees in Europe and the Middle East: STRENGTHS study protocol for a prospective individual participant data meta-analysis.

INTRODUCTION: The World Health Organization's (WHO) scalable psychological interventions, such as Problem Management Plus (PM+) and Step-by-Step (SbS) are designed to be cost-effective non-specialist delivered interventions to reduce symptoms of common mental disorders, such as anxiety, depression and post-traumatic stress disorder (PTSD). The STRENGTHS consortium aims to evaluate the effectiveness, cost-effectiveness and implementation of the individual format of PM+ and its group version (gPM+), as well as of the digital SbS intervention among Syrian refugees in seven countries in Europe and the Middle East. This is a study protocol for a prospective individual participant data (IPD) meta-analysis to evaluate (1) overall effectiveness and cost-effectiveness and (2) treatment moderators of PM+, gPM+ and SbS with Syrian refugees. METHODS AND ANALYSIS: Five pilot randomised controlled trials (RCTs) and seven fully powered RCTs conducted within STRENGTHS will be combined into one IPD meta-analytic dataset. The RCTs include Syrian refugees of 18 years and above with elevated psychological distress (Kessler Psychological Distress Scale (K10>15)) and impaired daily functioning (WHO Disability Assessment Schedule 2.0 (WHODAS 2.0>16)). Participants are randomised into the intervention or care as usual control group, and complete follow-up assessments at 1-week, 3-month and 12-month follow-up. Primary outcomes are symptoms of depression and anxiety (25-item Hopkins Symptom Checklist). Secondary outcomes include daily functioning (WHODAS 2.0), PTSD symptoms (PTSD Checklist for DSM-5) and self-identified problems (PSYCHLOPS). We will conduct a one-stage IPD meta-analysis using linear mixed models. Quality of evidence will be assessed using the GRADE approach, and the economic evaluation approach will be assessed using the CHEC-list. ETHICS AND DISSEMINATION: Local ethical approval has been obtained for each RCT. This IPD meta-analysis does not require ethical approval. The results of this study will be published in international peer-reviewed journals.

Feasibility and Assessment of a Cascade Traceback Screening Program (FACTS): Protocol for a Multisite Study to Implement and Assess an Ovarian Cancer Traceback Cascade Testing Program.

Ovarian cancer (OVCA) patients may carry genes conferring cancer risk to biological family; however, fewer than one-quarter of patients receive genetic testing. "Traceback" cascade testing -outreach to potential probands and relatives-is a possible solution. This paper outlines a funded study (U01 CA240747-01A1) seeking to determine a Traceback program's feasibility, acceptability, effectiveness, and costs. This is a multisite prospective observational feasibility study across three integrated health systems. Informed by the Conceptual Model for Implementation Research, we will outline, implement, and evaluate the outcomes of an OVCA Traceback program. We will use standard legal research methodology to review genetic privacy statutes; engage key stakeholders in qualitative interviews to design communication strategies; employ descriptive statistics and regression analyses to evaluate the site differences in genetic testing and the OVCA Traceback testing; and assess program outcomes at the proband, family member, provider, system, and population levels. This study aims to determine a Traceback program's feasibility and acceptability in a real-world context. It will account for the myriad factors affecting implementation, including legal issues, organizational- and individual-level barriers and facilitators, communication issues, and program costs. Project results will inform how health care providers and systems can develop effective, practical, and sustainable Traceback programs.

Performance and workflow assessment of six nucleic acid extraction technologies for use in resource limited settings.

Infectious disease nucleic acid amplification technologies (NAAT) have superior sensitivity, specificity, and rapid time to result compared to traditional microbiological methods. Recovery of concentrated, high quality pathogen nucleic acid (NA) from complex specimen matrices is required for optimal performance of several NA amplification/detection technologies such as polymerase chain reaction (PCR). Fully integrated NAAT platforms that enable rapid sample-to-result workflows with minimal user input are generally restricted to larger reference lab settings, and their complexity and cost are prohibitive to widespread implementation in resource limited settings (RLS). Identification of component technologies for incorporation of reliable and affordable sample preparation with pathogen NA amplification/detection into an integrated platform suitable for RLS, is a necessary first step toward achieving the overarching goal of reducing infectious disease-associated morbidity and mortality globally. In the current study, we evaluate the performance of six novel NA extraction technologies from different developers using blinded panels of stool, sputum and blood spiked with variable amounts of quality-controlled DNA- and/or RNA-based microbes. The extraction efficiencies were semi-quantitatively assessed using validated real-time reverse transcription (RT)-PCR assays specific for each microbe and comparing target-specific RT-PCR results to those obtained with reference NA extraction methods. The technologies were ranked based on overall diagnostic accuracy (analytical sensitivity and specificity). Sample input and output volumes, total processing time, user-required manual steps and cost estimates were also examined for suitability in RLS. Together with the performance analysis, these metrics were used to select the more suitable candidate technologies for further optimization of integrated NA amplification and detection technologies for RLS.

Assessment of eight nucleic acid amplification technologies for potential use to detect infectious agents in low-resource settings.

Nucleic acid amplification technologies (NAATs) are high-performance tools for rapidly and accurately detecting infectious agents. They are widely used in high-income countries to diagnose disease and improve patient care. The complexities associated with test methods, reagents, equipment, quality control and assurance require dedicated laboratories with trained staff, which can exclude their use in low-resource and decentralized healthcare settings. For certain diseases, fully integrated NAAT devices and assays are available for use in environmentally-controlled clinics or emergency rooms where relatively untrained staff can perform testing. However, decentralized settings in many low- and middle-income countries with large burdens of infectious disease are challenged by extreme environments, poor infrastructure, few trained staff and limited financial resources. Therefore, there is an urgent need for low-cost, integrated NAAT tools specifically designed for use in low-resource settings (LRS). Two essential components of integrated NAAT tools are: 1) efficient nucleic acid extraction technologies for diverse and complex sample types; and 2) robust and sensitive nucleic acid amplification and detection technologies. In prior work we reported the performance and workflow capacity for the nucleic acid extraction component. In the current study we evaluated performance of eight novel nucleic acid amplification and detection technologies from seven developers using blinded panels of RNA and/or DNA from three pathogens to assess both diagnostic accuracy and suitability as an essential component for low-cost NAAT in LRS. In this exercise, we noted significant differences in performance among these technologies and identified those most promising for potential further development.

Trends and determinants of the Flynn effect in cognitive functioning among older individuals in 10 European countries.

BACKGROUND: Although cognitive performance levels in old age have increased in most countries, recent evidence documents a slowing down or even decline in cohort gains in highly developed countries. The aim of this study was to assess trends and determinants in secular cohort gains in cognitive functioning among older individuals and whether cohort gains are levelling off in most advanced countries. METHODS: Data for individuals aged between 50 and 84 years from the Survey of Health, Ageing and Retirement in Europe in 10 European countries between 2004 and 2013 (n=92 739) were used to assess country and age-specific changes in immediate word recall. Multivariate random intercept models were used to assess associations between secular cohort changes in immediate word recall, initial performance levels and changes in country-level socio-demographic characteristics. RESULTS: Performance in immediate word recall improved in all countries between 2004 and 2013 (from 4.40 to 5.08 words, P<0.05). However, secular cohort gains were significantly smaller in countries with initially higher performance levels (coeff.=-0.554, 95% CI -0.682 to -0.426). Changes in socio-demographic and health conditions, including decreases in cardiovascular disease, physical activity and educational achievement, were associated with larger secular cohort gains. CONCLUSIONS: Results may either reflect that some countries are approaching the limits of cognitive plasticity, are slowing in their progress or that societal structures have not yet been optimised to improve cognitive abilities in midlife and beyond, or a combination of these interpretations.

A rotating-slit-collimator-based gamma radiation mapper.

For situations with radioactive material out of control where it may be physically difficult or prohibited to access areas close to the source, measurements from distance may be the only way to assess the radiation environment. Using collimated detectors will provide means to locate the direction of the radiation from the source. To investigate the possibilities of mapping gamma emitting radioactive material in a closed non-enterable area, a tentative system for mapping radioactive materials from a distance was built. The system used a computer controlled cylindrical rotating slit collimator with a high purity germanium detector placed in the cylinder. The system could be placed on a car-towed trailer, with the centre of the detector about 1.4 m above ground. Mapping was accomplished by the use of a specially developed image reconstruction algorithm that requires measurements from two or more locations around the area to be investigated. The imaging capability of the system was tested by mapping an area, 25 by 25 m2, containing three 330 MBq 137Cs point sources. Using four locations outside the area with about 20 min measuring time in each location and applying the image reconstruction algorithm on the deconvoluted data, the system indicated the three source locations with an uncertainty of 1-3 m. The results demonstrated the potential of using collimated mobile gamma radiometry combined with image reconstruction to localize gamma sources inside non-accessible areas.

Comparison of Bruch's Membrane Opening Minimum Rim Width and Peripapillary Retinal Nerve Fiber Layer Thickness in Early Glaucoma Assessment.

PURPOSE: To compare the diagnostic value of Bruch's membrane opening minimum rim width (BMO-MRW) and retinal nerve fiber layer thickness (RNFLT) in patients with ocular hypertension, preperimetric, and perimetric glaucoma. METHODS: One hundred eighty-one eyes consisting of 40 healthy controls, 41 ocular hypertensive subjects, 50 subjects with preperimetric glaucoma and 50 with perimetric glaucoma were included. One randomly selected eye was included. All patients underwent slit-lamp examination, funduscopy, achromatic perimetry, and 24-hour IOP profile. Bruch's membrane opening-MRW and RNFLT (3 peripapillary circle scans, 12°/14°/16°) data were obtained using spectral domain optical coherence tomography. Areas under the receiver operating characteristics curves (AUROC) as well as sensitivity at fixed specificity were computed globally and for six vertical split sectors. Venn diagrams were plotted to identify patients that were diagnosed by one of the two parameters only. RESULTS: For RNFLT the smallest circle diameter showed highest diagnostic accuracy and was used for comparison with BMO-MRW. Distinguishing perimetric glaucoma, RNFLT and BMO-MRW showed comparable AUROCs in global (AUROC, 95% confidence interval: 0.954, 0.911-0.996 and 0.929, 0.872-0.986) and sectoral (0.929, 0.877-0.981 and 0.946, 0.904-0.996) analysis. For preperimetric glaucoma BMO-MRW and RNFLT also demonstrated comparable performance in global (0.839, 0.757-0.921 and 0.821, 0.731-0.912) and sectoral (0.860, 0.782-0.938 and 0.835, 0.750-0.920) analysis. When identifying ocular hypertensive eyes AUROCs were lower for global RNFLT and BMO-MRW (0.493, 0.365-0.621 and 0.562, 0.433-0.691). A combined parameter showed an AUROC of 0.959, 0.921 to 0.996 for perimetric and 0.849, 0.770 to 0.929 for preperimetric glaucoma. CONCLUSIONS: Bruch's membrane opening-MRW and RNFLT are comparably useful parameters for discrimination of preperimetric and perimetric glaucomatous eyes and show potential to assist each other in glaucoma diagnosis. (www.ClinicalTrials.gov number, NTC00494923; Erlangen Glaucoma Registry.).

How much of the variation in mortality across Norwegian municipalities is explained by the socio-demographic characteristics of the population?

The goal was to find out whether much of the variation in mortality between the 430 Norwegian municipalities could be attributed to socio-demographic characteristics of the population - operating through individual- or aggregate-level mechanisms. Two-level discrete-time hazard models were estimated for women and men at age 60-89 in 2000-2008, using registers covering the entire population. Year, age and a municipality-level random term were included in the first step. When socio-demographic characteristics of the individual and others in the municipality were added, the variance of the random term was reduced by 73-80% almost exclusively because of aggregate-level effects. Policy implications of these findings are discussed.

Analysis of hospitalizations comparing rifaximin versus lactulose in the management of hepatic encephalopathy.

INTRODUCTION: Patients with end-stage liver disease often develop hepatic encephalopathy. The loss in cognitive abilities results in marked economic loss to the patient and health care community. We report hospital admission rates and economic impact of patients with end-stage liver disease suffering from hepatic encephalopathy. METHODS: The medical records were reviewed involving liver transplant patients started on lactulose or rifaximin therapy after presenting with stage 2 hepatic encephalopathy from January 2004 to November 2005. Information collected included demographics, hospitalizations required for hepatic encephalopathy, economic data, and Model for End-stage Liver Disease (MELD) score. RESULTS: Thirty-nine patients met study criteria: 24 patients treated with lactulose (group one) and 15 with rifaximin (group two). Group one included 18 men and six women of mean age 48 (range 39 to 58), average MELD 14 (range 10 to 19). Group two included 10 men and five women of mean age 47 (range 42 to 58), average MELD 15 (range 10 to 19). Group one patients required 19 hospitalizations overall: three patients with three hospitalizations, four patients with two hospitalizations, and two patients required one hospitalization. Total drug cost per month was 50 dollars(group one) and 620 dollars(group two). The average annual cost of hospitalization, emergency room visit, and drug per patient treated was 13,284.96 dollars for a total of 318,839 dollars (range 5005 dollars to 26,255 dollars, including drug cost and hospital care). Group two required three hospitalizations, all three with one visit. The average annual cost of hospitalization, emergency room visit, and drug per patient treated was 7958.13 dollars for a total of 119,372 dollars (range 6005 dollars to 19,255 dollars, including drug cost and hospital care). The total cost of therapy per patient per year was 13,285 dollars (group one) versus 7958 dollars (group two). The average length of stay was shorter in group two [3.5 days (range 3 to 4)] versus group 1 [5.0 days (range 3 to 10); P < .0001]. CONCLUSION: These pilot data demonstrate the marked difference in economic costs for the treatment of hepatic encephalopathy. The results also show that in comparative groups, the economic gains are quickly lost when using lactulose.

Pioneers in the development of neurological surgery in Auckland, New Zealand: Robertson, Wrightson, and Mackenzie.

OBJECTIVE: To demonstrate the development of neurosurgery in Auckland, New Zealand, which has diverse roots and was influenced by geographical, socioeconomic, and international forces. METHODS: Historical records were examined, and interviews were conducted to determine the factors that shaped the development of neurological surgery in Auckland, New Zealand. RESULTS: Sir Carrick Robertson, a Scotsman, was one of the more enterprising general surgeons in Auckland. As early as the 1920s, he performed and published the results of several neurosurgical procedures. Later, Donald Mackenzie, another Auckland general surgeon, went abroad to gain neurosurgical experience from his North American and British colleagues. He returned and founded the Auckland Neurosurgical Department in 1945. David Robertson and Phillip Wrightson later joined the department, and they were instrumental in conducting early research on shunt systems, head injury, and pituitary tumors. The neurosurgical department Mackenzie founded went on to become the largest in New Zealand and presently serves metropolitan Auckland as well as both rural areas of New Zealand's North Island and many smaller Pacific island nations. CONCLUSION: Neurological surgery in Auckland was influenced largely by Great Britain, Australia, and North America, as well as by geographical and socioeconomic factors unique to the South Pacific. The achievements of these earlier pioneers in neurosurgery highlight their tremendous abilities and sheer determination to succeed.

[On the prognosis of hip fractures. Assessment of mortality after hip fractures by analyzing overlapping segments of longitudinal data]. / Zur Prognose der Schenkelhalsfraktur. Beurteilung der Mortalität nach Schenkelhalsfraktur durch sektorübergreifende Datenzusammenführung.

BACKGROUND: Data on the treatment of hip fractures in acute care settings have been collected in a report card system for quality assurance in Germany since the beginning of the 1990s. However, there are no data on the long-term outcome and long-term quality of care. MATERIAL AND METHOD: In a retrospective study, data on 1393 patients from 1999 were collected from different sources: from the department of quality assurance at the medical association of Westfalia-Lippe, the Statutory Health Insurance Funds (AOK), and the Medical Review Board of the Statutory Health Insurance Funds (Medizinischer Dienst der Krankenkasse, MDK). Statistical analyses were performed by the Center for Clinical Studies of the University of Düsseldorf. RESULTS: Uni- and multivariate analyses reveal the following prognostic parameters for survival after hip fracture: sex, age, nursing care dependency, living in a nursing home, risk stratification according to ASA, and postoperative complications. Timing of the operation had no affect on survival. CONCLUSIONS: Prognostic factors for the outcome after hip fracture can only be obtained by analyzing data from the hospital stay and the post-hospital setting as well. Chances of survival can be significantly improved by rehabilitative care.

Assessment of pseudohypertrophy as a measure of left-ventricular compression in patients with cardiac tamponade.

BACKGROUND: Left-ventricular pseudohypertrophy reflecting left-ventricular compression was reported in a selected group of patients with cardiac tamponade. HYPOTHESIS: Criteria for the presence of pseudohypertrophy can be established to guide its use as a sign of left-ventricular compression in patients with cardiac tamponade. METHODS: Left-ventricular wall thickness, diameters, relative diastolic wall thickness (%) = (posterior wall thickness/end diastolic radius) x 100 and estimated left-ventricular mass were measured in patients with small, moderate and large pericardial effusion, in patients with cardiac tamponade before and after pericardiocentesis (16 patients in each group) and in 30 control subjects with normal echocardiograms. RESULTS: Left-ventricular posterior wall thickness was increased (12 +/- 2 vs. 9 +/- 1 mm, p < 0.001), left-ventricular end-diastolic diameter was reduced (3.9 +/- 0.5 vs. 4.6 +/- 0.3 cm, p < 0.001) and relative left-ventricular diastolic wall thickness was increased (61 +/- 13 vs. 41 +/- 4.5%, p < 0.001) only in patients with cardiac tamponade compared to controls, but not in patients with small, moderate and large effusions, respectively (relative wall thickness: 42 +/- 5, 41 +/- 7 and 44 +/- 7%, p = NS). Mean values of the estimated left-ventricular mass were similar in all groups. Following pericardiocentesis all parameters were normal. CONCLUSIONS: Despite normal left-ventricular mass, relative left-ventricular diastolic wall thickness is elevated in patients with cardiac tamponade. In contrast it is normal in patients with various degrees of pericardial effusion supporting its use as a quantitative measure of left-ventricular compression in patients with suspected cardiac tamponade.

Interferon-alpha for viral hepatitis.

IFN-alpha has emerged as a promising treatment of chronic viral hepatitis. Although therapeutic response to IFN is far from universal, efficacy has been demonstrated; and studies combining IFN-alpha with other agents, as well as trials with new preparations of IFN-alpha, are under way. Children do not represent a large part of the identified population with chronic viral hepatitis. Yet children, by simple virtue of age, are more recently infected. In addition, longer life expectancies can be expected to be associated with greater morbidity from chronic viral hepatitis. Children seem to tolerate therapy with IFN-alpha well. Treatment of children with chronic viral hepatitis should be strongly considered, with protocols designed to ascertain specific pediatric safety and efficacy.