Factors Associated With Increased Health Care Utilization for Patients With Dementia With Lewy Bodies: A Narrative Review.

Numerous studies have demonstrated that dementia is associated with increased utilization of health care services, which in turn results in increased costs of care. Dementia with Lewy bodies (DLB) is associated with greater costs of care relative to other forms of dementia due to higher rates of hospitalization and nursing home placement directly related to neuropsychiatric symptoms, parkinsonism, increased susceptibility to delirium, and elevated rates of caregiver burden. There is a critical need for researchers to identify potentially modifiable factors contributing to increased costs of care and poor clinical outcomes for patients with DLB, which may include comorbidities, polypharmacy/contraindicated medications, and access to specialty care. Previous research has utilized Medicare claims data, limiting the ability to study patients with early-onset (ie, prior to age 65) DLB. Integrated health systems offer the ability to combine electronic medical record data with Medicare, Medicaid, and commercial claims data and may therefore be ideal for utilization research in this population. The goals of this narrative review are to 1) synthesize and describe the current literature on health care utilization studies for patients with DLB, 2) highlight the current gaps in the literature, and 3) provide recommendations for stakeholders, including researchers, health systems, and policymakers. It is important to improve current understanding of potentially modifiable factors associated with increased costs of care among patients with DLB to inform public health policies and clinical decision-making, as this will ultimately improve the quality of patient care.

Efficacy of the iron-chelating agent, deferiprone, in patients with Parkinson's disease: A systematic review and meta-analysis.

INTRODUCTION: Several studies have reported iron accumulation in the basal ganglia to be associated with the development of Parkinson's Disease (PD). Recently, a few trials have examined the efficacy of using the iron-chelating agent Deferiprone (DFP) for patients with PD. We conducted this meta-analysis to summarize and synthesize evidence from published randomized controlled trials about the efficacy of DFP for PD patients. METHODS: A comprehensive literature search of four electronic databases was performed, spanning until February 2023. Relevant RCTs were selected, and their data were extracted and analyzed using the RevMan software. The primary outcome was the change in the Unified Parkinson's Disease Rating Scale (UPDRS-III). RESULTS: Three RCTs with 431 patients were included in this analysis. DFP did not significantly improve UPDRS-III score compared to placebo (Standardized mean difference -0.06, 95% CI [-0.69, 0.58], low certainty evidence). However, it significantly reduced iron accumulation in the substantia nigra, putamen, and caudate as measured by T2*-weighted MRI (with high certainty evidence). CONCLUSION: Current evidence does not support the use of DFP in PD patients. Future disease-modification trials with better population selection, adjustment for concomitant medications, and long-term follow up are recommended.

Triceps Split and Snip Approach for Distal Humerus Fractures.

Background: The senior author adopted a Triceps Split and Snip approach in 2011. This paper details the results of patients for whom this approach was utilised for open reduction and internal fixation of complex AO type C distal humerus fractures. Methods: A retrospective analysis of a single surgeon's cases was conducted. Range of movement, as well as Mayo Elbow Performance Score (MEPS), and QuickDASH scores were evaluated. Two independent consultants with upper extremity practises evaluated pre- and post-operative radiographs. Results: Seven patients were available for clinical review. The mean age at the time of surgery was 47.7 years (range, 20.3-83.2) and the mean follow-up time was 3.6 years (range, 0.58-8). The average QuickDASH score was 15.85 (range, 0-52.3), average MEPS was 86.88 (range, 60-100) and average total arc of movement (TAM) was 103° (range, 70°-145°). All patients demonstrated 5/5 MRC triceps strength compared to the contralateral side. Conclusions: The Triceps Split and Snip approach for complex distal humerus fractures provided comparable mid-term clinical outcomes when compared to other published data regarding distal humerus fractures. It is versatile and does not compromise the intra-operative option of conversion to a total elbow arthroplasty. Level of Evidence: Level IV (Therapeutic).

Altered hemodynamics and vascular reactivity in a mouse model with severe pericyte deficiency.

Pericytes are the mural cells of the microvascular network that are in close contact with underlying endothelial cells. Endothelial-secreted PDGFB leads to recruitment of pericytes to the vessel wall, but this is disrupted in Pdgfbret/ret mice when the PDGFB retention motif is deleted. This results in severely reduced pericyte coverage on blood vessels. In this study, we investigated vascular abnormalities and hemodynamics in Pdgfbret/ret mice throughout the cerebrovascular network and in different cortical layers by in vivo two-photon microscopy. We confirmed that Pdgfbret/ret mice are severely deficient in pericytes throughout the vascular network, with enlarged brain blood vessels and a reduced number of vessel branches. Red blood cell velocity, linear density, and tube hematocrit were reduced in Pdgfbret/ret mice, which may impair oxygen delivery to the tissue. We also measured intravascular PO2 and found that concentrations were higher in cortical Layer 2/3 in Pdgfbret/ret mice, indicative of reduced blood oxygen extraction. Finally, we found that Pdgfbret/ret mice had a reduced capacity for vasodilation in response to an acetazolamide challenge during functional MRI imaging. Taken together, these results suggest that severe pericyte deficiency can lead to vascular abnormalities and altered cerebral blood flow, reminiscent of pathologies such as arteriovenous malformations.

Disruption of proteostasis causes IRE1 mediated reprogramming of alveolar epithelial cells.

Disruption of alveolar type 2 cell (AEC2) protein quality control has been implicated in chronic lung diseases, including pulmonary fibrosis (PF). We previously reported the in vivo modeling of a clinical surfactant protein C (SP-C) mutation that led to AEC2 endoplasmic reticulum (ER) stress and spontaneous lung fibrosis, providing proof of concept for disruption to proteostasis as a proximal driver of PF. Using two clinical SP-C mutation models, we have now discovered that AEC2s experiencing significant ER stress lose quintessential AEC2 features and develop a reprogrammed cell state that heretofore has been seen only as a response to lung injury. Using single-cell RNA sequencing in vivo and organoid-based modeling, we show that this state arises de novo from intrinsic AEC2 dysfunction. The cell-autonomous AEC2 reprogramming can be attenuated through inhibition of inositol-requiring enzyme 1 (IRE1α) signaling as the use of an IRE1α inhibitor reduced the development of the reprogrammed cell state and also diminished AEC2-driven recruitment of granulocytes, alveolitis, and lung injury. These findings identify AEC2 proteostasis, and specifically IRE1α signaling through its major product XBP-1, as a driver of a key AEC2 phenotypic change that has been identified in lung fibrosis.

Clinical effectiveness of patellar resurfacing, no resurfacing and selective resurfacing in primary total knee replacement: systematic review and meta-analysis of interventional and observational evidence.

BACKGROUND: Patellar resurfacing is optional during total knee replacement (TKR). Some surgeons always resurface the patella, some never resurface, and others selectively resurface. Which resurfacing strategy provides optimal outcomes is unclear. We assessed the effectiveness of patellar resurfacing, no resurfacing, and selective resurfacing in primary TKR. METHODS: A systematic review and meta-analysis was performed. MEDLINE, Embase, Web of Science, The Cochrane Library, and bibliographies were searched to November 2021 for randomised-control trials (RCTs) comparing outcomes for two or more resurfacing strategies (resurfacing, no resurfacing, or selective resurfacing) in primary TKR. Observational studies were included if limited or no RCTs existed for resurfacing comparisons. Outcomes assessed were patient reported outcome measures (PROMs), complications, and further surgery. Study-specific relative risks [RR] were aggregated using random-effects models. Quality of the evidence was assessed using GRADE. RESULTS: We identified 33 RCTs involving 5,540 TKRs (2,727 = resurfacing, 2,772 = no resurfacing, 41 = selective resurfacing). One trial reported on selective resurfacing. Patellar resurfacing reduced anterior knee pain compared with no resurfacing (RR = 0.65 (95% CI = 0.44-0.96)); there were no significant differences in PROMs. Resurfacing reduced the risk of revision surgery (RR = 0.63, CI = 0.42-0.94) and other complications (RR = 0.54, CI = 0.39-0.74) compared with no resurfacing. Quality of evidence ranged from high to very low. Limited observational evidence (5 studies, TKRs = 215,419) suggested selective resurfacing increased the revision risk (RR = 1.14, CI = 1.05-1.22) compared with resurfacing. Compared with no resurfacing, selective resurfacing had a higher risk of pain (RR = 1.25, CI = 1.04-1.50) and lower risk of revision (RR = 0.92, CI = 0.85-0.99). CONCLUSIONS: Level 1 evidence supports TKR with patellar resurfacing over no resurfacing. Resurfacing has a reduced risk of anterior knee pain, revision surgery, and complications, despite PROMs being comparable. High-quality RCTs involving selective resurfacing, the most common strategy in the UK and other countries, are needed given the limited observational data suggests selective resurfacing may not be effective over other strategies.

Bearing allostatic load: insights into a more equitable future within cardio-oncology.

Chronic stress is often regarded as a significant cause of morbidity and mortality; however, the mechanistic link between stress and various disease states has not yet been fully characterized. We explore the concept of allostatic load, a measurement of the physiological burden of chronic stress, as well as its potential role in disease pathogenesis as it relates to cardiovascular disease, cancer, and health-related disparities. Building from this framework, we then posit the potential implications of allostatic load on patient care and research in cardio-oncology. We identify allostatic load as a potential clinically actionable tool to improve health equity in cardio-oncology.

Cardio-Oncology: Understanding the Intersections Between Cardiac Metabolism and Cancer Biology.

An important priority in the cardiovascular care of oncology patients is to reduce morbidity and mortality, and improve the quality of life in cancer survivors through cross-disciplinary efforts. The rate of survival in cancer patients has improved dramatically over the past decades. Nonetheless, survivors may be more likely to die from cardiovascular disease in the long term, secondary, not only to the potential toxicity of cancer therapeutics, but also to the biology of cancer. In this context, efforts from basic and translational studies are crucial to understanding the molecular mechanisms causal to cardiovascular disease in cancer patients and survivors, and identifying new therapeutic targets that may prevent and treat both diseases. This review aims to highlight our current understanding of the metabolic interaction between cancer and the heart, including potential therapeutic targets. An overview of imaging techniques that can support both research studies and clinical management is also provided. Finally, this review highlights opportunities and challenges that are necessary to advance our understanding of metabolism in the context of cardio-oncology.

Incidence, temporal trends and potential risk factors for aseptic loosening following primary unicompartmental knee arthroplasty: A meta-analysis of 96,294 knees.

BACKGROUND: Aseptic loosening (AL) is among the major reasons for revision of failed primary unicompartmental knee arthroplasty (UKA). There is an ongoing temporal increase in the use of UKA with a resultant increase in the revision burden. We aimed to evaluate the incidence of, temporal trends and risk factors for AL. METHODS: Longitudinal studies reporting the incidence of AL following primary UKA were sought from MEDLINE, Embase, Web of Science and Cochrane Library up to 6th April 2020. Incidence and relative risks (RR) (with 95% confidence intervals) were calculated. RESULTS: We identified 62 studies for inclusion. Overall, 96,294 primary UKA procedures accounting for 1752 AL cases were included. AL incidence ranged from 0.00% to 22.70% over a 7.7 year weighted mean follow-up. The pooled random effects incidence (95% CI) was 1.77% (1.34-2.25) in the same follow-up period. The annual rate of AL was 0.10% (0.02-0.22). AL incidence increased with length of follow-up, but there was a temporal decrease from the 1970s onwards. Tibial loosening was more common than femoral component loosening: incidence (95% CI) of 1.63% (0.96-2.44) and 0.58% (0.20-1.09) respectively over a weighted follow-up of 6.6 years. Fixed bearing implant design and cemented fixation were both associated with increased AL risk, whereas robotic-assisted surgery was associated with decreased risk. CONCLUSION: The overall incidence of AL following primary UKA is primarily driven by tibial component loosening and there is a temporal decline in rates. The use of mobile bearing, uncemented implants inserted with robotic assisted surgery may reduce the risk of AL.

Hemiepiphysiodesis: when should it be considered a day-case procedure?

Hemiepiphysiodesis is usually planned as a day-case but patients may stay overnight for pain control. In this study, we assessed the required level of analgesia (LOA) and length of stay (LOS) in patients undergoing hemiepiphysiodesis about the knee joint. We conducted a retrospective cohort study of patients that underwent temporary hemiepiphysiodesis of the distal femur or proximal tibia using hemiepiphysiodesis plates (eight-plates) for coronal plane deformities between January 2012 and October 2019. Demographics, type of procedure, anatomical site, anaesthetic time, preoperative, intraoperative and postoperative analgesia, and time of surgery were collected. Anterior hemiepiphysiodesis and permanent drill epiphysiodesis procedures were excluded. In this series of 79 patients, those with increased American Society of Anesthesiologists Score >1 and patients that were operated on >2 sites required increased LOA, (P < 0.05) and prolonged LOS (P < 0.05). The timing of surgery (morning vs. afternoon list) did not influence LOS or LOA. Patient-controlled analgesia (PCA) was required in 8 of 14 (57%) patients with four growth plates operated on. All (n = 12) patients that received PCA remained in hospital for at least one night. The use of local infiltration intraoperatively played a significant role in early discharge of the patients and t lower the LOA postoperatively (P < 0.05). Parameters including the number of growth plates operated on, use of tourniquet and intraoperative local infiltration can independently influence LOS and LOA postoperatively and at discharge. These parameters should be taken into consideration when consulting with the patient and family and when planning the postoperative course.

Clinical Effectiveness of Treatment Strategies for Prosthetic Joint Infection Following Total Ankle Replacement: A Systematic Review and Meta-analysis.

Prosthetic joint infection (PJI) after total ankle replacement (TAR) is a challenging complication, which often requires debridement and implant retention (DAIR) with or without polyethylene exchange, revision surgery, implantation of a cement spacer, conversion to arthrodesis, or even amputation. The optimum treatment for ankle PJI is not well established. We conducted a systematic review and meta-analysis to compare the clinical effectiveness of various treatment strategies for infected ankle prostheses. We searched MEDLINE, Embase, Web of Science, and the Cochrane Library up to December 2018 for studies evaluating the impact of treatment in patient populations with infected ankle prostheses following TAR. Binary data were pooled after arcsine transformation. Six citations comprising 17 observational design comparisons were included. The reinfection rates (95% confidence intervals) for DAIR with or without polyethylene exchange, 1-stage revision, 2-stage revision, cement spacer, and arthrodesis were 39.8% (24.4 to 56.1), 0.0% (0.0 to 78.7), 0.0% (0.0 to 8.5), 0.2% (0.0 to 17.9), and 13.6% (0.0 to 45.8), respectively. Rates of amputation for DAIR with or without polyethylene exchange and cement spacer were 5.6% (0.0 to 16.9) and 22.2% (6.3 to 54.7), respectively. Measures of function, pain, and satisfaction could not be compared because of limited data. One- and 2-stage revision strategies seem to be associated with the lowest reinfection rates, but these findings are based on limited data. Arthrodesis and DAIR with or without polyethylene exchange appear to be commonly used in treating infected ankle prosthesis, but are associated with poor infection control. Clear gaps exist in the literature, and further research is warranted to evaluate treatment strategies for infected ankle prosthesis.

Venous thromboembolism following 672,495 primary total shoulder and elbow replacements: Meta-analyses of incidence, temporal trends and potential risk factors.

BACKGROUND: There is wide variability in reported venous thromboembolism (VTE) incidence following total shoulder replacement (TSR) or total elbow replacement (TER). It is uncertain which risk factors influence the risk of VTE following TSR or TER. We conducted a PRISMA compliant meta-analysis to evaluate the incidence, temporal trends and potential risk factors for VTE following primary TSR and TER. METHODS: MEDLINE, Embase, Web of Science, and Cochrane Library were searched to September 2019 for longitudinal studies reporting VTE outcomes after TSR or TER. Incidence and relative risks (RR) (95% confidence intervals) were estimated. RESULTS: We identified 43 articles with data on 672,495 TSRs and TERs (668,699 TSRs and 3796 TERs). The overall pooled 3-month VTE incidence following TSR was 0.85% (0.39-1.46). For TER, the 3-month incidence of VTE was 0.23% (0.08-0.44). Older age, body mass index (BMI) ≥25 kg/m2, and alcohol abuse were each associated with increased VTE risk following TSR. Comorbidities associated with increased VTE risk following TSR were chronic pulmonary disease, previous VTE, heart failure, anaemia, coagulopathy, arrhythmia, epilepsy, urinary tract infection, sleep apnoea, and fluid & electrolyte imbalance. Anatomic and outpatient TSR were each associated with decreased VTE risk. CONCLUSIONS: The average 3-month incidence of VTE following TSR or TER is <1%. High risk groups such as older patients, those with a previous VTE history and those undergoing reverse or inpatient TSR may need close monitoring. Modifiable factors such as high BMI, alcohol abuse, and comorbidities could be identified and addressed prior to surgery. SYSTEMATIC REVIEW REGISTRATION: PROSPERO 2019: CRD42019134096.

Incidence, temporal trends and potential risk factors for prosthetic joint infection after primary total shoulder and elbow replacement: Systematic review and meta-analysis.

OBJECTIVES: We conducted a systematic meta-analysis to evaluate the incidence, temporal trends and potential risk factors for prosthetic joint infection (PJI) following primary total shoulder replacement (TSR) and elbow replacement (TER). METHODS: Longitudinal studies reporting infection outcomes following primary TSR or TER were sought from MEDLINE, Embase and Cochrane Library up to June 2019. Incidence rates and relative risks (with 95% CIs) were calculated. RESULTS: The search identified 105 eligible articles (108 non-overlapping studies). There were 631,854 TSRs (1,751 PJIs) and 17,485 TERs (525 PJIs). The pooled PJI incidence following TSR was 0.61% (0.34-0.93) over a follow-up period of 1.1 years. The corresponding incidence following TER was 2.53% (1.99-3.12) over a follow-up period of 3.3 years. Shoulder and elbow PJI incidence declined from the 1990s to 2010 and beyond. Males, younger age (<75 years), previous shoulder surgery, reverse TSR, rotator cuff arthropathy and inpatient TSR increased shoulder PJI risk. For TER, high body mass index, psychiatric illness, and previous elbow surgery increased PJI risk. CONCLUSIONS: Shoulder and elbow PJI may be on a temporal decline. Caution should be taken for patients at high PJI risk following primary TSR such as younger males and patients with a previous shoulder surgery.

Host-related factors for venous thromboembolism following total joint replacement: A meta-analysis of 89 observational studies involving over 14 million hip and knee replacements.

BACKGROUND: Venous thromboembolism, a potential complication of total joint replacement, is associated with preventable mortality and morbidity and is likely to be influenced by host-related factors such as sociodemographic characteristics, body mass index, medical and surgical histories, as well as circulating biomarkers. We conducted a systematic review and meta-analysis to assess the associations between host-related factors and venous thromboembolism risk following total hip and knee replacements. METHODS: We searched MEDLINE, Embase, Web of Science, and Cochrane Library to March 2018 for longitudinal studies reporting these associations. Summary measures of association were relative risks (95% confidence intervals). RESULTS: We identified 89 studies with data on 14,763,963 joint replacements and 150,086 venous thromboembolism events. Comparing males to females, age ≥70 to <70 years, and blacks to whites, relative risks for venous thromboembolism were 0.83 (0.75-0.91), 1.24 (1.03-1.50), and 1.26 (1.20-1.31) respectively. Comparing body mass indices ≥25 vs. <25; ≥30 vs. <30; and ≥50 vs. <50 kg/m2, relative risks were 1.40 (1.24-1.57); 1.65 (1.23-2.22); and 1.72 (1.10-2.67) respectively. Histories of venous thromboembolism; cardiovascular disease; congestive heart failure; cardiac arrhythmia; chronic pulmonary disease; renal disease; neurological disease; fluid & electrolyte imbalance; bariatric surgery; and comorbidity indices were associated with increased venous thromboembolism risk. Comparing a total knee with a hip replacement, the relative risk for venous thromboembolism was 1.69 (1.32-2.15). CONCLUSIONS: Enhanced venous thromboembolism prophylaxis should be considered in those with nonmodifiable risk factors such as older black female knee replacement patients. Modifiable risk factors such as high body mass index and fluid & electrolyte imbalance should be addressed prior to elective surgery. SYSTEMATIC REVIEW REGISTRATION: PROSPERO 2018: CRD42018089625.

Comparison of Parkinson's Disease Patients' Characteristics by Indication for Deep Brain Stimulation: Men Are More Likely to Have DBS for Tremor.

Background: We investigated whether the characteristics of Parkinson's disease (PD) patients differ based on the primary indication for deep brain stimulation (DBS). Methods: We reviewed data for 149 consecutive PD patients who underwent DBS at the University of Virginia. Patients were categorized based on primary surgical indication, and clinical characteristics were compared between groups. Results: Twenty-nine (93.5%) of 31 PD patients who underwent DBS for medication refractory tremor were men, and 66 (62.3%) of 106 PD patients who underwent DBS for motor fluctuations were men (p = 0.001). Other primary indications for DBS were tremor and fluctuations (n = 5), medication intolerance (n = 5), and dystonia (n = 2). Discussion: Patients who underwent DBS for medication refractory tremor were predominantly men, while patients who had DBS for motor fluctuations approximated the gender distribution of PD. Possible explanations are that men with PD are more likely to develop medication refractory tremor or undergo surgery for medication refractory tremor in PD compared to women.

The outcomes of total knee arthroplasty in morbidly obese patients: a systematic review of the literature.

INTRODUCTION: The increasing prevalence of obesity has led to an increase in total knee arthroplasties (TKAs) being undertaken in patients with a higher body mass index (BMI). TKA in morbidly obese patients can be technically challenging due to numerous anatomical factors and patient co-morbidities. The long-term outcomes in this patient group are unclear. This systematic review aims to compare the long-term revision rates, functional outcomes and complication rates of TKAs in morbidly obese versus non-obese patients. METHODS: A search of PubMed, EMBASE and PubMed Central was conducted to identify studies that reported revision rates in a cohort of morbidly obese patients (BMI ≥ 40 kg/m2) that underwent primary TKA, compared to non-obese patients (BMI ≤ 30 kg/m2). Secondary outcomes included Knee Society Objective Scores (KSOS), Knee Society Functional Scores (KSFS), and complication rates between the two groups. The difference in revision rates was assessed using the Chi-squared test. The Wilcoxon signed-rank test was used to compare pre-operative and post-operative functional scores for each group. KSOS and KSFS for morbidly obese and non-obese patients were compared using the Mann-Whitney test. Statistical significance was defined as p ≤ 0.05. RESULTS: Nine studies were included in this review. There were 624 TKAs in morbidly obese patients and 9,449 TKAs in non-obese patients, average BMI values were 45.0 kg/m2 (range 40-66 kg/m2) and 26.5 kg/m2 (range 11-30 kg/m2) respectively. The average follow-up time was 4.8 years (range 0.5-14.1) and 5.2 years (range 0.5-13.2) respectively, with a revision rate of 7% and 2% (p < 0.001) respectively. All functional scores improved after TKA (p < 0.001). Pre- and post-operative KSOS and KSFS were poorer in morbidly obese patients, however, mean improvement in KSOS was the same in both groups and comparable between groups for KSFS (p = 0.78). Overall complication rates,  including infection, were higher in morbidly obese patients. CONCLUSIONS: This review suggests an increased mid to long-term revision rate following primary TKA in morbidly obese patients, however, these patients have a functional recovery which is comparable to non-obese individuals. There is also an increased risk of perioperative complications, such as superficial wound infection. Morbidly obese patients should be fully informed of these issues prior to undergoing primary TKA.

Persistence and stochasticity are key determinants of genetic diversity in plants associated with banded iron formation inselbergs.

The high species endemism characteristic of many of the world's terrestrial island systems provides a model for studying evolutionary patterns and processes, yet there has been no synthesis of studies to provide a systematic evaluation of terrestrial island systems in this context. The banded iron formations (BIFs) of south-western Australia are ancient terrestrial island formations occurring within a mosaic of alluvial clay soils, sandplains and occasional granite outcropping, across an old, gently undulating, highly weathered, plateau. Notably, these BIFs display exceptionally high beta plant diversity. Here, we address the determinants and consequences of genetic diversity for BIF-associated plant species through a comprehensive review of all studies on species distribution modelling, phylogenetics, phylogeography, population genetics, life-history traits and ecology. The taxa studied are predominantly narrowly endemic to individual or a few BIF ranges, but some have more regional distributions occurring both on and off BIFs. We compared genetic data for these BIF-endemic species to other localised species globally to assess whether the unique history and ancestry of BIF landscapes has driven distinct genetic responses in plants restricted to this habitat. We also assessed the influence of life-history parameters on patterns of genetic diversity. We found that BIF-endemic species display similar patterns of genetic diversity and structure to other species with localised distributions. Despite often highly restricted distributions, large effective population size or clonal reproduction appears to provide these BIF-endemic species with ecological and evolutionary resilience to environmental stochasticity. We conclude that persistence and stochasticity are key determinants of genetic diversity and its spatial structure within BIF-associated plant species, and that these are key evolutionary processes that should be considered in understanding the biogeography of inselbergs worldwide.

Risk factors for dislocation after primary total hip replacement: meta-analysis of 125 studies involving approximately five million hip replacements.

BACKGROUND: Dislocation following total hip replacement (THR) is associated with repeated hospitalisations and substantial costs to the health system. Factors influencing dislocation following primary THR are not well understood. We aimed to assess the associations of patient-, surgery-, implant- and hospital-related factors with dislocation risk following primary THR. METHODS: We did a systematic review and meta-analysis of all longitudinal studies reporting these associations. We searched MEDLINE, Embase, Web of Science, and Cochrane Library to March 8, 2019. Summary measures of association were calculated using relative risks (RRs) (with 95% confidence intervals, CIs). The review is registered on PROSPERO, number CRD42019121378. FINDINGS: We identified 149 articles based on 125 unique studies with data on 4 633 935 primary THRs and 35 264 dislocations. The incidence rates of dislocation ranged from 0·12% to 16·13%, with an overall pooled rate of 2·10% (1·83-2·38) over a weighted mean follow-up duration of 6 years. Using median year of data collection, there was a significant decline in dislocation rates from 1971 to 2015. Comparing males vs females, age ≥70 vs <70 years, and high vs low income, RRs (95% CIs) for dislocation were 0·97 (0·88-1·08), 1·27 (1·02-1·57), and 0·79 (0·74-0·85) respectively. White ethnicity, drug use disorder, and social deprivation were each associated with an increased dislocation risk. Comparing body mass index (BMI) ≥30 vs. <30 kg/m2, the RR (95% CI) for dislocation was 1·38 (1·03-1·85). Medical and surgical history-related factors associated with dislocation risk included neurological disorder, psychiatric disease, comorbidity indices, previous surgery including spinal fusion, and surgical indications including avascular necrosis, rheumatoid arthritis, inflammatory arthritis, and osteonecrosis. Surgical factors such as the anterolateral, direct anterior, or lateral approach and posterior with short external rotator and capsule repair were each associated with reduced dislocation risk. At the implant level, larger femoral head diameters, elevated acetabular liners, dual mobility cups, cemented fixations and standard femoral neck lengths reduced the risk of dislocation. Hospital-related factors such as experienced surgeons and high surgeon procedure volume each reduced the risk of dislocation. INTERPRETATION: Dislocation following primary THR is on a temporal decline. Surgical approaches that reduce dislocation risk can be used by clinicians when performing primary THR. Alternative bearings such as dual mobility can be used in individuals at high risk of dislocation. Modifiable risk factors such as high BMI and comorbidities may be amenable to optimisation prior to surgery. FUNDING: National Institute for Health Research.

Risk factors for dislocation after primary total hip replacement: a systematic review and meta-analysis of 125 studies involving approximately five million hip replacements.

BACKGROUND: Dislocation following total hip replacement is associated with repeated admissions to hospital and substantial costs to the health system. Factors influencing dislocation following primary total hip replacement are not well understood. We aimed to assess the association of various factors with dislocation risk following primary total hip replacement. METHODS: We did a systematic review and meta-analysis of longitudinal studies reporting associations of patient-related, surgery-related, implant-related, and hospital-related factors with dislocation risk after primary total hip replacement. We searched MEDLINE, Embase, Web of Science, and the Cochrane Library for all relevant articles published up to March 8, 2019. Summary measures of association were calculated with relative risks (RRs) and 95% CIs. This study is registered on PROSPERO, number CRD42019121378. FINDINGS: We identified 149 articles based on 125 unique studies with data on 4 633 935 primary total hip replacements and 35 264 dislocations. The incidence of dislocation ranged from 0·12% to 16·13%, with an overall pooled incidence of 2·10% (95% CI 1·83-2·38) over a weighted mean follow-up duration of 6 years. Based on the median year of data collection, a significant decline in dislocation rates was observed from 1971 to 2015. The risk of dislocation did not differ significantly between male versus female patients (RR 0·97; 95% CI 0·88-1·08), was higher in those aged 70 years and older than in those younger than 70 years (1·27; 1·02-1·57), and was lower in those from high versus low income groups (0·79; 0·74-0·85). White ethnicity (only when compared with Asian ethnicity), drug use disorder, and social deprivation were significantly associated with increased dislocation risk. The risk of dislocation was higher in patients with body-mass index (BMI) of 30 kg/m2 or higher than in those with BMI lower than 30 kg/m2 (RR 1·38; 95% CI 1·03-1·85). Medical factors and those related to surgical history that were significantly associated with increased dislocation risk included neurological disorder, psychiatric disease, comorbidity indices, previous surgery including spinal fusion, and surgical indications including avascular necrosis, rheumatoid arthritis, inflammatory arthritis, and osteonecrosis. Surgical factors such as the anterolateral, direct anterior, or lateral approach, and posterior approach with short external rotator and capsule repair were significantly associated with reduced dislocation risk. At the implant level, larger femoral head diameters, elevated acetabular liners, dual mobility cups, cemented fixations, and standard femoral neck lengths significantly reduced the risk of dislocation. Hospital-related factors such as experienced surgeons and high surgeon procedure volume significantly reduced the risk of dislocation. INTERPRETATION: Dislocation following primary total hip replacement has declined over time. Surgical approaches that reduce dislocation risk can be used by clinicians during primary total hip replacement, and alternative bearings such as dual mobility can be used in individuals at high risk of dislocation. Modifiable risk factors such as high BMI and comorbidities might also be amenable to optimisation before surgery. FUNDING: National Institute for Health Research.

Intravitreal AAV-Delivery of Genetically Encoded Sensors Enabling Simultaneous Two-Photon Imaging and Electrophysiology of Optic Nerve Axons.

Myelination of axons by oligodendrocytes is a key feature of the remarkably fast operating CNS. Oligodendrocytes not only tune axonal conduction speed but are also suggested to maintain long-term axonal integrity by providing metabolic support to the axons they ensheath. However, how myelinating oligodendrocytes impact axonal energy homeostasis remains poorly understood and difficult to investigate. Here, we provide a method of how to study electrically active myelinated axons expressing genetically encoded sensors by combining electrophysiology and two-photon imaging of acutely isolated optic nerves. We show that intravitreal adeno-associated viral (AAV) vector delivery is an efficient tool to achieve functional sensor expression in optic nerve axons, which is demonstrated by measuring axonal ATP dynamics following AAV-mediated sensor expression. This novel approach allows for fast expression of any optical sensor of interest to be studied in optic nerve axons without the need to go through the laborious process of producing new transgenic mouse lines. Viral-mediated biosensor expression in myelinated axons and the subsequent combination of nerve recordings and sensor imaging outlines a powerful method to investigate oligodendroglial support functions and to further interrogate cellular mechanisms governing axonal energy homeostasis under physiological and pathological conditions.