Prevalence, predictors, and outcomes of poststroke falls in acute hospital setting

Abstract—Falls are a serious medical complication following stroke. The objectives of this study were to (1) confirm the prevalence of falls among patients with stroke during acute hospitalization, (2) identify factors associated with falls during the acute stay, and (3) examine whether in-hospital falls were associated with loss of function after stroke (new dependence at discharge). We completed a secondary analysis of data from a retrospective cohort study of patients with ischemic stroke who were hospitalized at one of four hospitals. We used logistic regression to identify factors associated with inpatient falls and examine the association between falls and loss of function. Among 1,269 patients with stroke, 65 (5%) fell during the acute hospitalization period. We found two characteristics independently associated with falls: greater stroke severity (National Institutes of Health Stroke Scale [NIHSS] 8, adjusted odds ratio [OR] = 3.63, 95% confidence interval [CI]: 1.46–9.00) and history of anxiety (adjusted OR = 4.90, 95% CI: 1.70–13.90). Falls were independently associated with a loss of function (adjusted OR = 9.85, 95% CI: 1.22–79.75) even after adjusting for age, stroke severity, gait abnormalities, and past stroke. Stroke severity (NIHSS 8) may be clinically useful during the acute inpatient setting in identifying those at greatest risk of falling. Given the association between falls and poor patient outcomes, rehabilitation interventions should be implemented to prevent falls poststroke

The state of the Martian climate

60°N was +2.0°C, relative to the 1981–2010 average value (Fig. 5.1). This marks a new high for the record. The average annual surface air temperature (SAT) anomaly for 2016 for land stations north of starting in 1900, and is a significant increase over the previous highest value of +1.2°C, which was observed in 2007, 2011, and 2015. Average global annual temperatures also showed record values in 2015 and 2016. Currently, the Arctic is warming at more than twice the rate of lower latitudes

A retrospective analysis of the change in anti-malarial treatment policy: Peru

<p>Abstract</p> <p>Background</p> <p>National malaria control programmes must deal with the complex process of changing national malaria treatment guidelines, often without guidance on the process of change. Selecting a replacement drug is only one issue in this process. There is a paucity of literature describing successful malaria treatment policy changes to help guide control programs through this process.</p> <p>Objectives</p> <p>To understand the wider context in which national malaria treatment guidelines were formulated in a specific country (Peru).</p> <p>Methods</p> <p>Using qualitative methods (individual and focus group interviews, stakeholder analysis and a review of documents), a retrospective analysis of the process of change in Peru's anti-malarial treatment policy from the early 1990's to 2003 was completed.</p> <p>Results</p> <p>The decision to change Peru's policies resulted from increasing levels of anti-malarial drug resistance, as well as complaints from providers that the drugs were no longer working. The context of the change occurred in a time in which Peru was changing national governments, which created extreme challenges in moving the change process forward. Peru utilized a number of key strategies successfully to ensure that policy change would occur. This included a) having the process directed by a group who shared a common interest in malaria and who had long-established social and professional networks among themselves, b) engaging in collaborative teamwork among nationals and between nationals and international collaborators, c) respect for and inclusion of district-level staff in all phases of the process, d) reliance on high levels of technical and scientific knowledge, e) use of standardized protocols to collect data, and f) transparency.</p> <p>Conclusion</p> <p>Although not perfectly or fully implemented by 2003, the change in malaria treatment policy in Peru occurred very quickly, as compared to other countries. They identified a problem, collected the data necessary to justify the change, utilized political will to their favor, approved the policy, and moved to improve malaria control in their country. As such, they offer an excellent example for other countries as they contemplate or embark on policy changes.</p

Exploiting a subtype-specific mitochondrial vulnerability for successful treatment of colorectal peritoneal metastases

Peritoneal metastases (PMs) from colorectal cancer (CRC) respond poorly to treatment and are associated with unfavorable prognosis. For example, the addition of hyperthermic intraperitoneal chemotherapy (HIPEC) to cytoreductive surgery in resectable patients shows limited benefit, and novel treatments are urgently needed. The majority of CRC-PMs represent the CMS4 molecular subtype of CRC, and here we queried the vulnerabilities of this subtype in pharmacogenomic databases to identify novel therapies. This reveals the copper ionophore elesclomol (ES) as highly effective against CRC-PMs. ES exhibits rapid cytotoxicity against CMS4 cells by targeting mitochondria. We find that a markedly reduced mitochondrial content in CMS4 cells explains their vulnerability to ES. ES demonstrates efficacy in preclinical models of PMs, including CRC-PMs and ovarian cancer organoids, mouse models, and a HIPEC rat model of PMs. The above proposes ES as a promising candidate for the local treatment of CRC-PMs, with broader implications for other PM-prone cancers

The evolving SARS-CoV-2 epidemic in Africa: Insights from rapidly expanding genomic surveillance.

Investment in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequencing in Africa over the past year has led to a major increase in the number of sequences that have been generated and used to track the pandemic on the continent, a number that now exceeds 100,000 genomes. Our results show an increase in the number of African countries that are able to sequence domestically and highlight that local sequencing enables faster turnaround times and more-regular routine surveillance. Despite limitations of low testing proportions, findings from this genomic surveillance study underscore the heterogeneous nature of the pandemic and illuminate the distinct dispersal dynamics of variants of concern-particularly Alpha, Beta, Delta, and Omicron-on the continent. Sustained investment for diagnostics and genomic surveillance in Africa is needed as the virus continues to evolve while the continent faces many emerging and reemerging infectious disease threats. These investments are crucial for pandemic preparedness and response and will serve the health of the continent well into the 21st century

The evolving SARS-CoV-2 epidemic in Africa: Insights from rapidly expanding genomic surveillance

INTRODUCTION Investment in Africa over the past year with regard to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequencing has led to a massive increase in the number of sequences, which, to date, exceeds 100,000 sequences generated to track the pandemic on the continent. These sequences have profoundly affected how public health officials in Africa have navigated the COVID-19 pandemic. RATIONALE We demonstrate how the first 100,000 SARS-CoV-2 sequences from Africa have helped monitor the epidemic on the continent, how genomic surveillance expanded over the course of the pandemic, and how we adapted our sequencing methods to deal with an evolving virus. Finally, we also examine how viral lineages have spread across the continent in a phylogeographic framework to gain insights into the underlying temporal and spatial transmission dynamics for several variants of concern (VOCs). RESULTS Our results indicate that the number of countries in Africa that can sequence the virus within their own borders is growing and that this is coupled with a shorter turnaround time from the time of sampling to sequence submission. Ongoing evolution necessitated the continual updating of primer sets, and, as a result, eight primer sets were designed in tandem with viral evolution and used to ensure effective sequencing of the virus. The pandemic unfolded through multiple waves of infection that were each driven by distinct genetic lineages, with B.1-like ancestral strains associated with the first pandemic wave of infections in 2020. Successive waves on the continent were fueled by different VOCs, with Alpha and Beta cocirculating in distinct spatial patterns during the second wave and Delta and Omicron affecting the whole continent during the third and fourth waves, respectively. Phylogeographic reconstruction points toward distinct differences in viral importation and exportation patterns associated with the Alpha, Beta, Delta, and Omicron variants and subvariants, when considering both Africa versus the rest of the world and viral dissemination within the continent. Our epidemiological and phylogenetic inferences therefore underscore the heterogeneous nature of the pandemic on the continent and highlight key insights and challenges, for instance, recognizing the limitations of low testing proportions. We also highlight the early warning capacity that genomic surveillance in Africa has had for the rest of the world with the detection of new lineages and variants, the most recent being the characterization of various Omicron subvariants. CONCLUSION Sustained investment for diagnostics and genomic surveillance in Africa is needed as the virus continues to evolve. This is important not only to help combat SARS-CoV-2 on the continent but also because it can be used as a platform to help address the many emerging and reemerging infectious disease threats in Africa. In particular, capacity building for local sequencing within countries or within the continent should be prioritized because this is generally associated with shorter turnaround times, providing the most benefit to local public health authorities tasked with pandemic response and mitigation and allowing for the fastest reaction to localized outbreaks. These investments are crucial for pandemic preparedness and response and will serve the health of the continent well into the 21st century

Sexually dimorphic control of regulatory T cell function and autoimmunity protection through B7-H1 and estrogen signals (123.50)

Abstract CD4+CD25hi regulatory T cells (Tregs) mediate peripheral tolerance and defend against autoimmunity. Among immune sexual dimorphisms, autoimmunity is more common in females but underlying mechanism(s) are poorly understood. We show that B7-H1 signals dampen estrogen-driven Treg mTOR activation through estrogen receptor beta, reducing Treg function independent of PTEN. Poorly functional Tregs from B7-H1 deficient hosts appeared phenotypically normal and did not produce IL-17. B7-H1-deficient female mice (but not males or WT of either sex) were prone to anti-CTLA-4-induced autoimmunity. Autoimmune propensity was rescued by estrogen withdrawal or B7-H1-sufficient dendritic cell transfer. B7-H1-mediated effects on estrogen signals were also mediated by B or T lymphocytes or monocytes, and occurred during induced Treg generation, with no effect on differentiated Tregs. CD80 and PD-1 were not ligands for these effects nor was Treg B7-H1 expression required. Estrogen affected male Tregs in vitro and in vivo provided B7-H1 was blocked. Strikingly, B7-H1 and estrogen did not affect thymic Treg differentiation or function, suggesting differential control of natural Tregs and a potential role for induced Tregs in autoimmunity protection. Similar Treg results were seen in BL6 and Balb/c mice. We thus show a mechanistic basis for the female propensity to autoimmunity, and data are consistent with proposed roles for B7-H1 in female-predominant autoimmune disorders, particularly lupus.</jats:p

Prevalence, predictors, and outcomes of poststroke falls in acute hospital setting

Abstract—Falls are a serious medical complication following stroke. The objectives of this study were to (1) confirm the prevalence of falls among patients with stroke during acute hospitalization, (2) identify factors associated with falls during the acute stay, and (3) examine whether in-hospital falls were associated with loss of function after stroke (new dependence at discharge). We completed a secondary analysis of data from a retrospective cohort study of patients with ischemic stroke who were hospitalized at one of four hospitals. We used logistic regression to identify factors associated with inpatient falls and examine the association between falls and loss of function. Among 1,269 patients with stroke, 65 (5%) fell during the acute hospitalization period. We found two characteristics independently associated with falls: greater stroke severity (National Institutes of Health Stroke Scale [NIHSS] 8, adjusted odds ratio [OR] = 3.63, 95% confidence interval [CI]: 1.46–9.00) and history of anxiety (adjusted OR = 4.90, 95% CI: 1.70–13.90). Falls were independently associated with a loss of function (adjusted OR = 9.85, 95% CI: 1.22–79.75) even after adjusting for age, stroke severity, gait abnormalities, and past stroke. Stroke severity (NIHSS 8) may be clinically useful during the acute inpatient setting in identifying those at greatest risk of falling. Given the association between falls and poor patient outcomes, rehabilitation interventions should be implemented to prevent falls poststroke

Prevalence, predictors, and outcomes of poststroke falls in acute hospital setting

Abstract—Falls are a serious medical complication following stroke. The objectives of this study were to (1) confirm the prevalence of falls among patients with stroke during acute hospitalization, (2) identify factors associated with falls during the acute stay, and (3) examine whether in-hospital falls were associated with loss of function after stroke (new dependence at discharge). We completed a secondary analysis of data from a retrospective cohort study of patients with ischemic stroke who were hospitalized at one of four hospitals. We used logistic regression to identify factors associated with inpatient falls and examine the association between falls and loss of function. Among 1,269 patients with stroke, 65 (5%) fell during the acute hospitalization period. We found two characteristics independently associated with falls: greater stroke severity (National Institutes of Health Stroke Scale [NIHSS] 8, adjusted odds ratio [OR] = 3.63, 95% confidence interval [CI]: 1.46–9.00) and history of anxiety (adjusted OR = 4.90, 95% CI: 1.70–13.90). Falls were independently associated with a loss of function (adjusted OR = 9.85, 95% CI: 1.22–79.75) even after adjusting for age, stroke severity, gait abnormalities, and past stroke. Stroke severity (NIHSS 8) may be clinically useful during the acute inpatient setting in identifying those at greatest risk of falling. Given the association between falls and poor patient outcomes, rehabilitation interventions should be implemented to prevent falls poststroke

Recommendations for pathologic staging (pTNM) of cancer of the esophagus and esophagogastric junction for the 8th edition AJCC/UICC staging manuals

SUMMARY We report analytic and consensus processes that produced recommendations for pathologic stage groups (pTNM) of esophageal and esophagogastric junction cancer for the AJCC/UICC cancer staging manuals, 8th edition. The Worldwide Esophageal Cancer Collaboration provided data for 22,654 patients with epithelial esophageal cancers; 13,300 without preoperative therapy had pathologic assessment after esophagectomy or endoscopic treatment. Risk‐adjusted survival for each patient was developed using random survival forest analysis to identify data‐driven pathologic stage groups wherein survival decreased monotonically with increasing group, was distinctive between groups, and homogeneous within groups. The AJCC Upper GI Task Force, by smoothing, simplifying, expanding, and assessing clinical applicability, produced consensus pathologic stage groups. For pT1‐3N0M0 squamous cell carcinoma (SCC) and pT1‐2N0M0 adenocarcinoma, pT was inadequate for grouping; subcategorizing pT1 and adding histologic grade enhanced staging; cancer location improved SCC staging. Consensus eliminated location for pT2N0M0 and pT3N0M0G1 SCC groups, and despite similar survival, restricted stage 0 to pTis, excluding pT1aN0M0G1. Metastases markedly reduced survival; pT, pN, and pM sufficiently grouped advanced cancers. Stage IIA and IIB had different compositions for SCC and adenocarcinoma, but similar survival. Consensus stage IV subgrouping acknowledged pT4N+ and pN3 cancers had poor survival, similar to pM1. Anatomic pathologic stage grouping, based on pTNM only, produced identical consensus stage groups for SCC and adenocarcinoma at the cost of homogeneity in early groups. Pathologic staging can neither direct pre‐treatment decisions nor aid in prognostication for treatment other than esophagectomy or endoscopic therapy. However, it provides a clean, single therapy reference point for esophageal cancer