Investigation of Inflammation in Lewy Body Dementia: A Systematic Scoping Review.

Inflammatory mechanisms are increasingly recognized as important contributors to the pathogenesis of neurodegenerative diseases, including Lewy body dementia (LBD). Our objectives were to, firstly, review inflammation investigation methods in LBD (dementia with Lewy bodies and Parkinson's disease dementia) and, secondly, identify alterations in inflammatory signals in LBD compared to people without neurodegenerative disease and other neurodegenerative diseases. A systematic scoping review was performed by searching major electronic databases (MEDLINE, Embase, Web of Science, and PSYCHInfo) to identify relevant human studies. Of the 2509 results screened, 80 studies were included. Thirty-six studies analyzed postmortem brain tissue, and 44 investigated living subjects with cerebrospinal fluid, blood, and/or brain imaging assessments. Largely cross-sectional data were available, although two longitudinal clinical studies investigated prodromal Lewy body disease. Investigations were focused on inflammatory immune cell activity (microglia, astrocytes, and lymphocytes) and inflammatory molecules (cytokines, etc.). Results of the included studies identified innate and adaptive immune system contributions to inflammation associated with Lewy body pathology and clinical disease features. Different signals in early and late-stage disease, with possible late immune senescence and dystrophic glial cell populations, were identified. The strength of these associations is limited by the varying methodologies, small study sizes, and cross-sectional nature of the data. Longitudinal studies investigating associations with clinical and other biomarker outcomes are needed to improve understanding of inflammatory activity over the course of LBD. This could identify markers of disease activity and support therapeutic development.

Geriatric home-based rehabilitation in Australia: Preliminary data from an inpatient bed-substitution model.

BACKGROUND: The REStORing health of acutely unwell adulTs (RESORT) is an observational longitudinal cohort, including geriatric rehabilitation inpatients aged ≥65 years admitted to a geriatrician-led rehabilitation service at a tertiary hospital. The aim of this study is to describe a home-based bed-substitution rehabilitation model for geriatric inpatients, including patient phenotype, and health outcomes at preadmission, admission, discharge, and three-month follow-up. METHODS: A standardized Comprehensive Geriatric Assessment was performed on admission and discharge, including demographics (home situation, cognitive impairment, medical diagnoses, etc.), frailty (Clinical Frailty Scale (CFS)), mobility (patient-reported and Functional Ambulation Classification), physical performance (Short Physical Performance Battery (SPPB), handgrip strength), and functional independence (Activities of Daily Living (ADL), Instrumental ADL (IADL)). Service provision data (health care staff visits, length of stay (LOS), and negative events (e.g., falls)) were extracted from medical records. Three-month outcomes included mobility, ADL and IADL scores, institutionalization, and mortality. RESULTS: Ninety-two patients were included with a mean age of 81.1 ± 7.8 years, 56.5% female. Twenty-nine (31.5%) patients lived alone, 39 (42.4%) had cognitive impairment and the commonest geriatric rehabilitation admission reason was falls (n = 30, 32.6%). Patients received care from nurses, physicians, and a median of four (interquartile range (IQR) 3-6) allied health disciplines for a median LOS of 13.0 days (IQR 10.0-15.0). On a population level, patient mobility and functional independence worsened from preadmission to admission. CFS, SPPB, ADL, and IADL scores improved from admission to discharge, and seven (7.6%) patients fell. At three-month follow-up, patient-reported mobility was comparable to preadmission baseline, but functional independence (ADL, IADL) scores worsened for 27/69 (39.1%) and 28/63 (44.4%), respectively. CONCLUSIONS: Hospitalization-associated decline in mobility and functional independence improved at discharge and three-months, but was not fully reversed in the multidisciplinary home-based geriatric rehabilitation bed-substitution service. Future research should compare outcomes to equivalent hospital-based geriatric rehabilitation and evaluate patient perspectives.

Diagnostic challenges for dementia in Australia: are blood-based biomarkers the solution?

The burden of dementia will increase as the Australian population ages and grows in coming decades. Early and accurate diagnosis remains challenging, and disproportionately so for particular groups, including rural communities. Recent advances in technology, however, now allow reliable measurement of blood biomarkers that could improve diagnosis in a range of settings. We discuss the most promising biomarker candidates for translation into clinical practice and research in the near future.

Subfascial endoscopic perforator surgery (SEPS) for treating venous leg ulcers.

BACKGROUND: Venous leg ulcers are complex, costly, and their prevalence is expected to increase as populations age. Venous congestion is a possible cause of venous leg ulcers, which subfascial endoscopic perforator surgery (SEPS) attempts to address by removing the connection between deep and superficial veins (perforator veins). The effectiveness of SEPS in the treatment of venous leg ulcers, however, is unclear. OBJECTIVES: To assess the benefits and harms of subfascial endoscopic perforator surgery (SEPS) for the treatment of venous leg ulcers. SEARCH METHODS: In March 2018 we searched the Cochrane Wounds Specialised Register; the Cochrane Central Register of Controlled Trials (CENTRAL); Ovid MEDLINE (including In-Process & Other Non-Indexed Citations); Ovid Embase and EBSCO CINAHL Plus. We also searched clinical trials registries for ongoing and unpublished studies, and scanned reference lists of included studies as well as reviews, meta-analyses and health technology reports to identify additional studies. There were no restrictions with respect to language, date of publication or study setting. SELECTION CRITERIA: We included randomised controlled trials (RCTs) of interventions that examined the use of SEPS independently or in combination with another intervention for the treatment of venous leg ulcers. DATA COLLECTION AND ANALYSIS: Two review authors independently selected studies for inclusion, extracted data, assessed risk of bias, and assessed the certainty of evidence using the GRADE approach. MAIN RESULTS: We included four RCTs with a total of 322 participants. There were three different comparators: SEPS plus compression therapy versus compression therapy (two trials); SEPS versus the Linton procedure (a type of open surgery) (one trial); and SEPS plus saphenous surgery versus saphenous surgery (one trial). The age range of participants was 30 to 82, with an equal spread of male and female participants. All trials were conducted in hospital settings with varying durations of follow-up, from 18 months to 6 years. One trial included participants who had both healed and active ulcers, with the rest including only participants with active ulcers.There was the potential for reporting bias in all trials and performance bias and detection bias in three trials. Participants in the fourth trial received one of two surgical procedures, and this study was at low risk of performance bias and detection bias.SEPS + compression therapy versus compression therapy (2 studies; 208 participants)There may be an increase in the proportion of healed ulcers at 24 months in people treated with SEPS and compression therapy compared with compression therapy alone (risk ratio (RR) 1.17, 95% confidence interval (CI) 1.03 to 1.33; 1 study; 196 participants); low-certainty evidence (downgraded twice, once for risk of bias and once for imprecision).It is uncertain whether SEPS reduces the risk of ulcer recurrence at 24 months (RR 0.85, 95% CI 0.26 to 2.76; 2 studies; 208 participants); very low-certainty evidence (downgraded three times, twice for very serious imprecision and once for risk of bias).The included trials did not measure or report the following outcomes; time to complete healing, health-related quality of life (HRQOL), adverse events, pain, duration of hospitalisation, and district nursing care requirements.SEPS versus Linton approach (1 study; 39 participants)It is uncertain whether there is a difference in ulcer healing at 24 months between participants treated with SEPS and those treated with the Linton procedure (RR 0.95, 95% CI 0.83 to 1.09; 1 study; 39 participants); very low-certainty evidence (downgraded three times, twice for very serious imprecision and once for risk of bias).It is also uncertain whether there is a difference in risk of recurrence at 60 months: (RR 0.47, 95% CI 0.10 to 2.30; 1 study; 39 participants); very low-certainty evidence (downgraded three times, twice for very serious imprecision and once for risk of bias).The Linton procedure is possibly associated with more adverse events than SEPS (RR 0.04, 95% CI 0.00 to 0.60; 1 study; 39 participants); very low-certainty evidence (downgraded three times, twice for very serious imprecision and once for risk of bias).The outcomes time to complete healing, HRQOL, pain, duration of hospitalisation and district nursing care requirements were either not measured, reported or data were not available for analysis.SEPS + saphenous surgery versus saphenous surgery (1 study; 75 participants)It is uncertain whether there is a difference in ulcer healing at 12 months between participants treated with SEPS and saphenous surgery versus those treated with saphenous surgery alone (RR 0.96, 95% CI 0.64 to 1.43; 1 study; 22 participants); very low certainty evidence (downgraded three times, twice for very serious imprecision and once for high risk of reporting bias).It is also uncertain whether there is a difference in the risk of recurrence at 12 months: (RR 1.03, 95% CI 0.15 to 6.91; 1 study; 75 participants); very low certainty evidence (downgraded three times, twice for very serious imprecision and once for high risk of reporting bias).Finally, we are uncertain whether there is an increase in adverse events in the SEPS group (RR 2.05, 95% CI 0.86 to 4.90; 1 study; 75 participants); very low certainty evidence (downgraded three times, twice for very serious imprecision and once for high risk of reporting bias).The outcomes time to complete healing, HRQOL, serious adverse events, pain, duration of hospitalisation, and district nursing care requirements were either not measured, reported or data were not available for analysis. AUTHORS' CONCLUSIONS: The role of SEPS for the treatment of venous leg ulcers remains uncertain. Only low or very low-certainty evidence was available for inclusion. Due to small sample sizes and risk of bias in the included studies, we were unable to determine the potential benefits and harms of SEPS for this purpose. Only four studies met our inclusion criteria, three were very small, and one was poorly reported. Further high-quality studies addressing the use of SEPS in venous leg ulcer management are likely to change the conclusions of this review.

Preoperative Staging by EBUS in cN0/N1 Lung Cancer: Systematic Review and Meta-Analysis.

BACKGROUND: Performance of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) for staging the radiologically normal mediastinum has been reported with inconsistent findings. We assessed the sensitivity of systematic staging using EBUS-TBNA for detection of radiologically occult mediastinal metastases in cN0/N1 lung cancer. METHODS: Studies evaluating EBUS-TBNA for systematic mediastinal staging in cN0/N1 lung cancer were identified by systematic review. Data extracted included: participant age and sex; EBUS-TBNA protocol; stage determined by radiology, EBUS-TBNA and surgery; 2×2 tables. Primary outcome was diagnostic accuracy of EBUS-TBNA for detection of unsuspected N2/N3 disease. RESULTS: We identified 1173 articles. In total, 13 were included in a qualitative review and 9 (1146 patients) in a quantitative meta-analysis. Mean prevalence of N2/N3 disease was 15% (6% to 24%). EBUS-TBNA had pooled sensitivity of 49% [95% confidence interval (CI), 41%-57%], pooled specificity of 100% (95% CI, 99%-100%), mean negative predictive value 91% (82% to 100%) for detection of unsuspected N2/N3 metastases. Number needed to test to detect occult N2/N3 disease was 14 (95% CI, 10.8-16.3), which halved with addition of per-esophageal endoscopic ultrasound. CONCLUSION: Preoperative systematic staging by EBUS-TBNA of early lung cancer can reduce postoperative upstaging. Sensitivity for detection of radiologically occult mediastinal metastases seems lower than selective sampling of pathologic lymph nodes. Verification of negative results by mediastinoscopy in selected cases remains of value.