Biomarkers of neurodegeneration in schizophrenia: systematic review and meta-analysis.

QUESTION: Does neurodegenerative disease underlie the increased rate of dementia observed in older people with schizophrenia? Several studies have reported a higher prevalence of dementia in people with schizophrenia compared with the general population. This may reflect a higher risk of developing neurodegenerative diseases such as vascular dementia or Alzheimer's disease (AD). Alternatively, this may reflect non-pathological, age-related cognitive decline in a population with low cognitive reserve. STUDY SELECTION AND ANALYSIS: We reviewed papers that compared postmortem findings, hippocampal MRI volume or cerebrospinal fluid (CSF) markers of AD, between patients with schizophrenia with evidence of cognitive impairment (age ≥45 years) with controls. We subsequently performed a meta-analysis of postmortem studies that compared amyloid-ß plaques (APs) or neurofibrillary tangles (NFTs) in cognitively impaired patients with schizophrenia to normal controls or an AD group. FINDINGS: No studies found a significant increase of APs or NFTs in cognitively impaired patients with schizophrenia compared with controls. All postmortem studies that compared APs or NFTs in patients with schizophrenia to an AD group found significantly more APs or NFTs in AD. No studies found a significant differences in CSF total tau or phosphorylated tau between patients with schizophrenia and controls. The two studies which compared CSF Aß42 between patients with schizophrenia and controls found significantly decreased CSF Aß42 in schizophrenia compared with controls. Hippocampal volume findings were mixed. CONCLUSIONS: Studies have not found higher rates of AD-related pathology in cognitively impaired individuals with schizophrenia compared with controls. Higher rates of dementia identified in population studies may reflect a lack of specificity in clinical diagnostic tools used to diagnose dementia.

How can event attribution science underpin financial decisions on Loss and Damage?

With climate extremes hitting nations across the globe, disproportionately burdening vulnerable developing countries, the prompt operation of the Loss and Damage fund is of paramount importance. As decisions on resource disbursement at the international level, and investment strategies at the national level, loom, the climate science community's role in providing fair and effective evidence is crucial. Attribution science can provide useful information for decision makers, but both ethical implications and deep uncertainty cannot be ignored. Considering these aspects, we articulate a vision that integrates established attribution methods and multiple lines of evidence within a coherent logical framework.

Leveraging data science and machine learning for urban climate adaptation in two major African cities: a HE2AT Center study protocol.

INTRODUCTION: African cities, particularly Abidjan and Johannesburg, face challenges of rapid urban growth, informality and strained health services, compounded by increasing temperatures due to climate change. This study aims to understand the complexities of heat-related health impacts in these cities. The objectives are: (1) mapping intraurban heat risk and exposure using health, socioeconomic, climate and satellite imagery data; (2) creating a stratified heat-health forecast model to predict adverse health outcomes; and (3) establishing an early warning system for timely heatwave alerts. The ultimate goal is to foster climate-resilient African cities, protecting disproportionately affected populations from heat hazards. METHODS AND ANALYSIS: The research will acquire health-related datasets from eligible adult clinical trials or cohort studies conducted in Johannesburg and Abidjan between 2000 and 2022. Additional data will be collected, including socioeconomic, climate datasets and satellite imagery. These resources will aid in mapping heat hazards and quantifying heat-health exposure, the extent of elevated risk and morbidity. Outcomes will be determined using advanced data analysis methods, including statistical evaluation, machine learning and deep learning techniques. ETHICS AND DISSEMINATION: The study has been approved by the Wits Human Research Ethics Committee (reference no: 220606). Data management will follow approved procedures. The results will be disseminated through workshops, community forums, conferences and publications. Data deposition and curation plans will be established in line with ethical and safety considerations.

Limited slot femorotomy for removal of proximally coated cementless stems. A 10-year follow-up of an unreported surgical technique.

We present a technique of single posterior longitudinal slot femorotomy. This technique allows the expansion of the metaphyseal-diaphyseal region of the proximal femur facilitating extraction of proximally coated uncemented femoral components while leaving the metaphysis and diaphysis intact. Since 1996 we have performed this technique in 18 revision total hip arthroplasties in 15 patients who had x-ray appearance of bony in-growth/on-growth and where found to have solidly ingrown stems at revision surgery. All were revised to a metaphyseally fitting uncemented stem. At mean follow-up of 122.4 months, there were significant improvements in both pain and function. All revised stems achieved stable boney fixation. There were no complications due to this technique. No patient developed a limp or thigh pain postoperatively. There have been no re-revisions of the stem. With appropriate patient selection, this is a simple, reliable, and extensile technique is useful to assist in the extraction of uncemented proximally coated femoral components whether hydroxyapatite-coated or not.

Large diameter metal on metal articulations. Comparison of total hip arthroplasty and hip resurfacing arthroplasty.

The use of large diameter metal bearing total hip arthroplasty (THA) and hip resurfacing arthroplasty (HRA) increased in popularity in the last decade. More recent literature has highlighted the effect of head size in patient outcomes. Data was obtained from the Australian Orthopaedic Association National Joint Replacement Registry (AOA-NJRR) to evaluate the Birmingham (MoM) bearing surface when used with THA and HRA. There is no difference in the overall rate of revision between the THA and HRA but head size has a significant effect on revision rate. The data show that small diameter metal bearings in HRA (below 50mm) have a higher rate of revision than large diameter metal bearings in HRA (equal to and above 50mm) (P<.001). Conversely the large diameter metal bearings in THA have a higher rate of revision than the small diameter metal bearings in THA (P=.027). The revision rate for large diameter HRA compared to small diameter THA is not significantly different P=.670. We recommend caution when choosing either a large diameter (≥50mm) metal on metal THA or small diameter (<50mm) HRA.

Cognitive impairment and pain relief following hip fractures: a case control study.

Hip fractures represent a significant workload of both emergency and orthopaedic departments within the National Health Service (NHS). Pain relief is key in treating hip fractures as highlighted by both National Institute of Clinical Excellence (NICE) and British Orthopaedic Association Standards for Trauma (BOAST) guidelines. However, the literature shows that patients with cognitive impairment tend to have inconsistent pain management, leading to worse outcomes. We conducted a case-control study looking at 296 patients who presented with hip fractures to a major trauma centre between 1 December 2019 and 30 May 2020. Cognition was assessed using pre-recorded Abbreviated Mental Test Scores (AMTS). There was no significant difference between pain relief provided to patients with or without cognitive impairment in both the pre-hospital (p = 0.208) and Accident & Emergency (A&E) (p = 0.154) setting. A larger proportion of patients in A&E did not receive any pain relief (18.6% versus 42.2%). Pre-hospital, the higher the pain score, the stronger the analgesia given (R = 0.435, p = 0.000). This relationship was present in both the cognitively impaired (R = 0.572, p = 0.000) and cognitively intact groups (R = 0.390 p = 0.000). Strength of analgesia and pain scores did not correlate in A&E (R = 0.014, p = 0.826). Cognition did not impact the time to analgesia both pre-hospital (p = 0.291) and in A&E (p = 0.332); however, patients waited significantly longer to receive pain relief in A&E (29.61 minutes versus 150.28 minutes). Fascia-iliaca blocks were administered to 58.4% of the cohort, with no significant difference noted between cognition status. Overall, cognition does not impact pain management both pre-hospital and in A&E. There is still room for improvement, particularly in the assessment of pain in the cognitively impaired. A possible solution is the utilisation of the Bolton Pain Assessment Tool, a validated pain assessment tool for the cognitively impaired that has been utilised in the trauma setting with good effect.

Monitoring a changing Arctic: Recent advancements in the study of sea ice microbial communities.

Sea ice continues to decline across many regions of the Arctic, with remaining ice becoming increasingly younger and more dynamic. These changes alter the habitats of microbial life that live within the sea ice, which support healthy functioning of the marine ecosystem and provision of resources for human-consumption, in addition to influencing biogeochemical cycles (e.g. air-sea CO2 exchange). With the susceptibility of sea ice ecosystems to climate change, there is a pressing need to fill knowledge gaps surrounding sea ice habitats and their microbial communities. Of fundamental importance to this goal is the development of new methodologies that permit effective study of them. Based on outcomes from the DiatomARCTIC project, this paper integrates existing knowledge with case studies to provide insight on how to best document sea ice microbial communities, which contributes to the sustainable use and protection of Arctic marine and coastal ecosystems in a time of environmental change.

Emerging climate change-related public health challenges in Africa: A case study of the heat-health vulnerability of informal settlement residents in Dar es Salaam, Tanzania.

Heat has the potential to become one of the most significant public health impacts of climate change in the coming decades. Increases in temperature have been linked to both increasing mortality and morbidity. Cities have been recognized as areas of particular vulnerability to heat's impacts on health, and marginalized groups, such as the poor, appear to have higher heat-related morbidity and mortality. Little research has examined the heat vulnerability of urban informal settlements residents in Africa, even though surface temperatures across Africa are projected to increase at a rate faster than the global average. This paper addresses this knowledge gap through a mixed-methods analysis of the heat-health vulnerability of informal settlement residents in Dar es Salaam, Tanzania. The heat exposure, sensitivity and adaptive capacity of informal settlement residents were assessed through a combination of climate analyses, semi-structured interviews with local government actors and informal settlement residents, unstructured interviews with health sector respondents, a health impacts literature review, and a stakeholder engagement workshop. The results suggest that increasing temperatures due to climate change will likely be a significant risk to human health in Dar es Salaam, even though the city does not reach extreme temperature conditions, because informal settlement residents have high exposure, high sensitivity and low adaptive capacity to heat, and because the heat-health relationship is currently an under-prioritized policy issue. While numerous urban planning approaches can play a key role in increasing the resilience of citizens to heat, Dar es Salaam's past and current growth and development patterns greatly complicate the implementation and enforcement of such approaches. For African cities, the findings highlight an urgent need for more research on the vulnerability and resilience of residents to heat-health impacts, because many African cities are likely to present similar characteristics to those in Dar es Salaam that increase resident's vulnerability.

Range of Normal and Abnormal Syndesmotic Measurements Using Weightbearing CT.

BACKGROUND: Early recognition of syndesmotic instability is critical for optimizing clinical outcome. Injuries causing a more subtle instability, however, can be difficult to diagnose. The purpose of this study was to evaluate both distal tibiofibular articulations using weightbearing computed tomography (CT) in patients with known syndesmotic instability, thereafter comparing findings between the injured and uninjured sides. We also aimed to define the range of normal measurement variation among patients without syndesmotic injury. METHODS: Patients with unilateral syndesmotic instability requiring operative fixation (n = 12) underwent preoperative bilateral ankle weightbearing CT. A separate cohort of patients without ankle injury who also underwent bilateral ankle weightbearing CT were included as comparative controls (n = 24). For each weightbearing CT, a series of 7 axial plane tibiofibular joint measurements, including 1 angular measurement, were utilized to evaluate parameters of the syndesmotic anatomy at a level 1 cm above the tibial plafond. Values were recorded by 2 independent observers to assess for interobserver reliability. RESULTS: Among those with unilateral syndesmotic instability, values differed between the injured and uninjured sides in 4 of the 7 measurements performed including the syndesmotic area: direct anterior, middle, and posterior differences, and sagittal translation (P < .001, < .001, < .001, and < .001, respectively). In the control population without ankle injury, no differences were identified between any of the bilateral measurements (P value range, .172-.961). CONCLUSION: This study highlights the ability of weightbearing CT to effectively differentiate syndesmotic diastasis among patients with surgically confirmed syndesmotic instability from those without syndesmotic instability. It underscores the substantial utility and importance of using the contralateral, uninjured side as a valid internal control whenever the need for confirming potential syndesmotic instability arises. Prospective studies are necessary to fully understand the accuracy of weightbearing CT in diagnosing occult syndesmotic instability among patients for whom the diagnosis remains in question. LEVEL OF EVIDENCE: Level III, comparative diagnostic study.

Cementless total hip replacements in sickle cell disease.

BACKGROUND: Sickle cell disease (SCD) affects around 80,000 people in the USA and 12,000 in the UK. Up to 40% of patients will get osteonecrosis of the femoral head. Cemented acetabular components yield poor results with the rate of osteolysis ranging from 13.5 to 46%. We report on a consecutive cohort of patients with SCD who underwent uncemented THA with ceramic-on-ceramic (CoC) bearings. METHODS: Since 2002 52 primary THAs were carried out in 40 patients. The average age was 36.1 years (17-54). 48 cases had exchange blood transfusion preoperatively and 3 had top-up transfusions.An S-ROM was used in 47 hips a Solutions stem in 4 hips and an AML in 1. It was necessary to drill the femur during 12 hips. There were 5 intra-operative peri-prosthetic fractures. 2 dislocations were observed. 2 superficial infections were detected. RESULTS: All components have in-grown. There have been no cases of radiographic osteolysis, migration or loosening of the hip with average 5-year (2-10.1) follow-up. CONCLUSIONS: The combination of a multidisciplinary team approach and uncemented implants, with ceramic-on-ceramic bearings used, has made THA in patients with SCD a safe and reliable procedure in our hospital.

Utility of tuberculosis directly observed therapy programs as sites for access to and provision of antiretroviral therapy in resource-limited countries.

The overwhelming share of the global human immunodeficiency virus (HIV) infection and disease burden is borne by resource-limited countries. The explosive spread of HIV infection and growing burden of disease in these countries has intensified the need to find solutions to improved access to treatment for HIV infection. The epidemic of HIV infection and acquired immune deficiency syndrome (AIDS) has been accompanied by a severe epidemic of tuberculosis. Tuberculosis has become the major cause of morbidity and mortality in patients with HIV disease worldwide. Among the various models of provision of HIV/AIDS care, one logical but unexplored strategy is to integrate HIV/AIDS and tuberculosis care and treatment, including highly active antiretroviral therapy, through existing tuberculosis directly observed therapy programs. This strategy could address the related issues of inadequate access and infrastructure and need for enhanced adherence to medication and thereby potentially improve the outcome for both diseases.

Fretting and corrosion in modular-neck total hip arthroplasty femoral stems.

BACKGROUND: During total hip arthroplasty, use of a modular femoral neck on a stemmed implant allows optimization of neck anteversion, length, and offset, resulting in more accurate balance. We performed a retrospective analysis of a consecutive cohort of patients who had undergone total hip arthroplasty with a modular-neck hip system with ceramic-on-ceramic bearings. METHODS: We reviewed the results in fifteen patients who had received an ABG II dual modular hip system (Stryker Orthopaedics, Mahwah, New Jersey) from May 2007 to August 2008. Anteroposterior radiographs of the pelvis were reviewed and scored with regard to medial calcar erosion. Magnetic resonance imaging (MRI) was performed to assess for adverse local tissue reaction around the hip joint. Calcar resorption was correlated with subsequent MRI findings. Retrieval analysis was performed on the implants removed at revision. RESULTS: The mean duration of follow-up for all patients was 42.3 months (range, thirty-three to sixty months). Cobalt-ion levels were elevated in all patients; chromium levels were within the normal range. Medial femoral calcar erosion was noted in seven of the fifteen cases. All patients with grade-2 or 3 calcar erosion on radiographs had positive MRI findings consistent with adverse local tissue reaction. At the time of writing, seven patients had undergone revision arthroplasty. Intraoperatively, tissue staining with tissue and bone necrosis and pseudotumor formation were observed in all revision cases. Histological analysis confirmed the presence of metal-on-metal synovitis, with changes similar to those seen with metal-on-metal bearings. CONCLUSIONS: The ABG II dual modular hip system is associated with a high rate of early failure secondary to fretting and corrosion at the femoral neck-stem taper. The component has subsequently been recalled and is no longer in use. Surgeons using modular hip systems with a titanium stem and cobalt-chromium neck should be vigilant about annual follow-up with radiographs, and use of MRIs as indicated.

The impact of snow on orthopaedic trauma referrals.

Adverse weather has been shown to increase orthopaedic referrals and place strain on services. This retrospective study undertaken at a teaching hospital concerned referrals between April 2009 and April 2010 comparing days when snow fell to days when it did not. Referrals increased significantly on snow days (to 74.9 per day) in comparison to normal weather days (33.5 per day). During snow days there were significant increases in the number of distal radius and ankle fractures referred but not of fractured necks of femur. Complications during the snow fall period were related to procedures performed outside of the trauma unit with further difficulties related to a lack of operating equipment and implant availability. As a result of our study, we recommend that during periods of heavy snow fall orthopaedic and trauma units should place senior orthopaedic trainees in Accident and Emergency to review patients as a triage service, organise trauma lists related to surgeon specific expertise and avoid sending trauma patients outside the unit for operation.

The surgical anatomy of intra-abdominal prosthetic dislocation during hip arthroplasty.

Hip replacement surgery remains one of the most successful and common operations in modern orthopaedics. Many surgical approaches to the hip have been described. A potential anatomical weakness exists between the hip joint and the retroperitoneal space. We describe this potential space, which lies superficial to iliopsoas and its importance in hip replacement surgery. The clinical relevance of this space is illustrated by 2 cases of retro-peritoneal migration of prosthetic femoral heads and the consequences of these.

Post-operative stress fractures complicating surgery for painful forefoot conditions.

A stress fracture is caused by repetitive or unusual loading of a bone leading to mechanical failure. Fatigue type stress fractures occur in normal bone exposed to abnormally high repetitive loads, whereas insufficiency type stress fractures occur in abnormal bone exposed to normal loads. We describe three cases of insufficiency stress fractures that have complicated surgery for painful forefoot conditions. The diagnosis and management of these cases are discussed. Stress fractures should be included in the differential diagnosis of any patient who continues or develops pain after surgery to the forefoot.

A case report of three peripheral schwannomas attached to the Achilles paratenon.

BACKGROUND: Schwannomas are uncommon slow growing tumours arising from the nerve sheath or Schwann cell. OBJECTIVE: To report a case of multiple schwannomas arising form the achilles paratenon. METHODS: A 38 year old man presented lumps on the dorsum of his leg. He was clinically evaluated, subjected to imaging studies and surgery. RESULTS: 3 separate lumps where removed measuring 10, 12, and 12mm. They here confirmed to be schwannomas on hitochemical staining. CONCLUSION: A schwannoma must be considered in the differential of lumps in the lower leg. This is the first report of schwanommas associated with the paratenon. Removal of such masses is warranted to prevent local erosion.

Administration of efavirenz (600 mg/day) with rifampicin results in highly variable levels but excellent clinical outcomes in patients treated for tuberculosis and HIV.

OBJECTIVES: Pharmacokinetic interactions between rifampicin and antiretroviral therapy (ART), including efavirenz, are problematic and need to be better defined to determine proper dose and to be correlated with short-term and long-term clinical outcomes. PATIENTS AND METHODS: Consenting patients with smear-positive pulmonary TB and HIV received once daily didanosine + lamivudine + efavirenz (600 mg), with rifampicin-containing TB regimen by directly observed therapy and self-administration at TB therapy completion. Trough efavirenz levels were measured by HPLC at 1, 2, 4 and 6 months while on rifampicin and after discontinuation. HIV and TB outcomes were monitored. RESULTS: Twenty African patients were enrolled [15 female, mean age 31 years, baseline weight 59.4 kg (range 45-97), viral load 5.75 log10 copies/mL and CD4 230 cells/mm3]. Seventy-two efavirenz concentrations were available from 19 patients (58 on, 14 after rifampicin). The geometric mean efavirenz concentration was 1730 ng/mL (range 354-27,179) on and 1377 ng/mL (range 572-3975) off rifampicin (P = 0.55). Inter-subject variability in efavirenz concentrations was greater on rifampicin (CV 157% versus 58% off) with relatively consistent intra-subject variation over time (median CV 24%). Over half of patients had efavirenz concentrations above or below the expected therapeutic range (1000-4000 ng/mL). Efavirenz levels were not predicted by weight or gender and were not associated with HIV clinical outcomes. Overall 80% of patients had non-detectable viral loads at 6 months and 65% at 21 months with a cumulative CD4 cell increase of 196 cells/mm3. CONCLUSIONS: In this longitudinal study, despite wide variability in plasma efavirenz concentrations during rifampicin administration, excellent clinical outcomes were obtained. In African patients treated for HIV and TB, our data support the routine use of efavirenz at 600 mg/day when receiving rifampicin.

A pilot study of once-daily antiretroviral therapy integrated with tuberculosis directly observed therapy in a resource-limited setting.

To determine the feasibility and effectiveness of integrating highly active antiretroviral therapy (HAART) into existing tuberculosis directly observed therapy (TB/DOT) programs, we performed a pilot study in an urban TB clinic in South Africa. Patients with smear-positive pulmonary TB were offered HIV counseling and testing. Twenty HIV-positive patients received once-daily didanosine (400 mg) plus lamivudine (300 mg) plus efavirenz (600 mg) administered concomitantly with standard TB therapy Monday to Friday and self-administered on weekends. After completing TB therapy, patients were referred to an HIV clinic for continued treatment. At baseline, patients had a mean CD4 count of 230 cells/mm(3) (range: 24-499 cells/mm(3)) and a mean viral load of 5.75 log(10) (range: 3.81-7.53 log(10)). Seventeen completed combined standard TB and HIV therapy; 16 of 20 (80%) patients enrolled and 15 of 17 (88%) patients completing standard TB therapy achieved a viral load <50 copies/mL and mean CD4 count increase of 148 cells/mm(3). TB was cured in 17 of 20 (85%) enrolled patients and 17 of 19 (89%) patients with drug-sensitive TB. Treatment was well tolerated, with minimal gastrointestinal, hepatic, skin, or neurologic toxicity. The project was well accepted and integrated into the daily TB clinic functions. This pilot study demonstrates that TB/DOT programs can be feasible and effective sites for HIV identification and the introduction and monitoring of a once-daily HAART regimen in resource-limited settings.