Corrigendum: Plasticity in One Hemisphere, Control From Two: Adaptation in Descending Motor Pathways After Unilateral Corticospinal Injury in Neonatal Rats

After injury to the corticospinal tract (CST) in early development there is large-scale adaptation of descending motor pathways. Some studies suggest the uninjured hemisphere controls the impaired forelimb, while others suggest that the injured hemisphere does; these pathways have never been compared directly. We tested the contribution of each motor cortex to the recovery forelimb function after neonatal injury of the CST. We cut the left pyramid (pyramidotomy) of postnatal day 7 rats, which caused a measurable impairment of the right forelimb. We used pharmacological inactivation of each motor cortex to test its contribution to a skilled reach and supination task. Rats with neonatal pyramidotomy were further impaired by inactivation of motor cortex in both the injured and the uninjured hemispheres, while the forelimb of uninjured rats was impaired only from the contralateral motor cortex. Thus, inactivation demonstrated motor control from each motor cortex. In contrast, physiological and anatomical interrogation of these pathways support adaptations only in the uninjured hemisphere. Intracortical microstimulation of motor cortex in the uninjured hemisphere of rats with neonatal pyramidotomy produced responses from both forelimbs, while stimulation of the injured hemisphere did not elicit responses from either forelimb. Both anterograde and retrograde tracers were used to label corticofugal pathways. There was no increased plasticity from the injured hemisphere, either from cortex to the red nucleus or the red nucleus to the spinal cord. In contrast, there were very strong CST connections to both halves of the spinal cord from the uninjured motor cortex. Retrograde tracing produced maps of each forelimb within the uninjured hemisphere, and these were partly segregated. This suggests that the uninjured hemisphere may encode separate control of the unimpaired and the impaired forelimbs of rats with neonatal pyramidotomy

The Views of Mental Health Manager Towards the Use of a Family Work Model for Psychosis in Guangzhou, China

Family Interventions in Psychosis (FIP) have been promoted internationally but have been criticised for being based on western cultural models. This paper reports on a focus group study with 10 Integrated Mental Health Service Managers in Guangzhou, China using thematic analysis. Managers believed FIP might benefit families but identified potential difficulties due to (a) families avoiding services due to the ‘shame’ of mental illness (b) unrealistic expectations of services amongst families (c) deferral to ‘key decision-makers’ within families when discussing family issues with workers. The findings indicate that FIP work should focus on interaction between carers in the first instance with service users being introduced into sessions at a later date and that more attention needs to be given by the research community to how FIP may be adapted to cultural norms within China

The importance of organizational characteristics for improving outcomes in patients with chronic disease: a systematic review of congestive heart failure

Luci K. Leykum, Jacqueline Pugh, Valerie Lawrence, and Polly H. Noel are with the South Texas Veterans Health Care System and Department of Medicine, University of Texas Health Science Center at San Antonio, San Antonio TX, 78229, USA -- Michael Parchman is with the South Texas Veterans Health Care System and Department of Family and Community Medicine, University of Texas Health Science Center at San Antonio, San Antonio TX, 78229, USA -- Reuben R. McDaniel Jr. is with the McComb's School of Business, University of Texas at Austin, Austin TX, USABackground: Despite applications of models of care and organizational or system-level interventions to improve patient outcomes for chronic disease, consistent improvements have not been achieved. This may reflect a mismatch between the interventions and the nature of the settings in which they are attempted. The application of complex adaptive systems (CAS) framework to understand clinical systems and inform efforts to improve them may lead to more successful interventions. We performed a systematic review of interventions to improve outcomes of patients with congestive heart failure (CHF) to examine whether interventions consistent with CAS are more likely to be effective. We then examine differences between interventions that are most effective for improving outcomes for patients with CHF versus previously published data for type 2 diabetes to explore the potential impact of the nature of the disease on the types of interventions that are more likely to be effective. Methods: We conducted a systematic review of the literature between 1998 and 2008 of organizational interventions to improve care of patients with CHF. Two independent reviewers independently assessed studies that met inclusion criteria to determine whether each reported intervention reflected one or more CAS characteristics. The effectiveness of interventions was rated as either 0 (no effect), 0.5 (mixed effect), or 1.0 (effective) based on the type, number, and significance of reported outcomes. Fisher's exact test was used to examine the association between CAS characteristics and intervention effectiveness. Specific CAS characteristics associated with intervention effectiveness for CHF were contrasted with previously published data for type 2 diabetes. Results and discussion: Forty-four studies describing 46 interventions met eligibility criteria. All interventions utilized at least one CAS characteristic, and 85% were either 'mixed effect' or 'effective' in terms of outcomes. The number of CAS characteristics present in each intervention was associated with effectiveness (p < 0.001), supporting the idea that interventions consistent with CAS are more likely to be effective. The individual CAS characteristics associated with CHF intervention effectiveness were learning, self-organization, and co-evolution, a finding different from our previously published analysis of interventions for diabetes. We suggest this difference may be related to the degree of uncertainty involved in caring for patients with diabetes versus CHF. Conclusion: These results suggest that for interventions to be effective, they must be consistent with the CAS nature of clinical systems. The difference in specific CAS characteristics associated with intervention effectiveness for CHF and diabetes suggests that interventions must also take into account attributes of the disease.McCombs School of [email protected]

Plasticity in One Hemisphere, Control From Two: Adaptation in Descending Motor Pathways After Unilateral Corticospinal Injury in Neonatal Rats

After injury to the corticospinal tract (CST) in early development there is large-scale adaptation of descending motor pathways. Some studies suggest the uninjured hemisphere controls the impaired forelimb, while others suggest that the injured hemisphere does; these pathways have never been compared directly. We tested the contribution of each motor cortex to the recovery forelimb function after neonatal injury of the CST. We cut the left pyramid (pyramidotomy) of postnatal day 7 rats, which caused a measurable impairment of the right forelimb. We used pharmacological inactivation of each motor cortex to test its contribution to a skilled reach and supination task. Rats with neonatal pyramidotomy were further impaired by inactivation of motor cortex in both the injured and the uninjured hemispheres, while the forelimb of uninjured rats was impaired only from the contralateral motor cortex. Thus, inactivation demonstrated motor control from each motor cortex. In contrast, physiological and anatomical interrogation of these pathways support adaptations only in the uninjured hemisphere. Intracortical microstimulation of motor cortex in the uninjured hemisphere of rats with neonatal pyramidotomy produced responses from both forelimbs, while stimulation of the injured hemisphere did not elicit responses from either forelimb. Both anterograde and retrograde tracers were used to label corticofugal pathways. There was no increased plasticity from the injured hemisphere, either from cortex to the red nucleus or the red nucleus to the spinal cord. In contrast, there were very strong CST connections to both halves of the spinal cord from the uninjured motor cortex. Retrograde tracing produced maps of each forelimb within the uninjured hemisphere, and these were partly segregated. This suggests that the uninjured hemisphere may encode separate control of the unimpaired and the impaired forelimbs of rats with neonatal pyramidotomy

Will they participate? Predicting patients’ response to clinical trial invitations in a pediatric emergency department

Objective (1) To develop an automated algorithm to predict a patient’s response (ie, if the patient agrees or declines) before he/she is approached for a clinical trial invitation; (2) to assess the algorithm performance and the predictors on real-world patient recruitment data for a diverse set of clinical trials in a pediatric emergency department; and (3) to identify directions for future studies in predicting patients’ participation response. Materials and Methods We collected 3345 patients’ response to trial invitations on 18 clinical trials at one center that were actively enrolling patients between January 1, 2010 and December 31, 2012. In parallel, we retrospectively extracted demographic, socioeconomic, and clinical predictors from multiple sources to represent the patients’ profiles. Leveraging machine learning methodology, the automated algorithms predicted participation response for individual patients and identified influential features associated with their decision-making. The performance was validated on the collection of actual patient response, where precision, recall, F-measure, and area under the ROC curve were assessed. Results Compared to the random response predictor that simulated the current practice, the machine learning algorithms achieved significantly better performance (Precision/Recall/F-measure/area under the ROC curve: 70.82%/92.02%/80.04%/72.78% on 10-fold cross validation and 71.52%/92.68%/80.74%/75.74% on the test set). By analyzing the significant features output by the algorithms, the study confirmed several literature findings and identified challenges that could be mitigated to optimize recruitment. Conclusion By exploiting predictive variables from multiple sources, we demonstrated that machine learning algorithms have great potential in improving the effectiveness of the recruitment process by automatically predicting patients’ participation response to trial invitations

Global variation in postoperative mortality and complications after cancer surgery: a multicentre, prospective cohort study in 82 countries

© 2021 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 licenseBackground: 80% of individuals with cancer will require a surgical procedure, yet little comparative data exist on early outcomes in low-income and middle-income countries (LMICs). We compared postoperative outcomes in breast, colorectal, and gastric cancer surgery in hospitals worldwide, focusing on the effect of disease stage and complications on postoperative mortality. Methods: This was a multicentre, international prospective cohort study of consecutive adult patients undergoing surgery for primary breast, colorectal, or gastric cancer requiring a skin incision done under general or neuraxial anaesthesia. The primary outcome was death or major complication within 30 days of surgery. Multilevel logistic regression determined relationships within three-level nested models of patients within hospitals and countries. Hospital-level infrastructure effects were explored with three-way mediation analyses. This study was registered with ClinicalTrials.gov, NCT03471494. Findings: Between April 1, 2018, and Jan 31, 2019, we enrolled 15 958 patients from 428 hospitals in 82 countries (high income 9106 patients, 31 countries; upper-middle income 2721 patients, 23 countries; or lower-middle income 4131 patients, 28 countries). Patients in LMICs presented with more advanced disease compared with patients in high-income countries. 30-day mortality was higher for gastric cancer in low-income or lower-middle-income countries (adjusted odds ratio 3·72, 95% CI 1·70–8·16) and for colorectal cancer in low-income or lower-middle-income countries (4·59, 2·39–8·80) and upper-middle-income countries (2·06, 1·11–3·83). No difference in 30-day mortality was seen in breast cancer. The proportion of patients who died after a major complication was greatest in low-income or lower-middle-income countries (6·15, 3·26–11·59) and upper-middle-income countries (3·89, 2·08–7·29). Postoperative death after complications was partly explained by patient factors (60%) and partly by hospital or country (40%). The absence of consistently available postoperative care facilities was associated with seven to 10 more deaths per 100 major complications in LMICs. Cancer stage alone explained little of the early variation in mortality or postoperative complications. Interpretation: Higher levels of mortality after cancer surgery in LMICs was not fully explained by later presentation of disease. The capacity to rescue patients from surgical complications is a tangible opportunity for meaningful intervention. Early death after cancer surgery might be reduced by policies focusing on strengthening perioperative care systems to detect and intervene in common complications. Funding: National Institute for Health Research Global Health Research Unit

Effects of hospital facilities on patient outcomes after cancer surgery: an international, prospective, observational study

© 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 licenseBackground: Early death after cancer surgery is higher in low-income and middle-income countries (LMICs) compared with in high-income countries, yet the impact of facility characteristics on early postoperative outcomes is unknown. The aim of this study was to examine the association between hospital infrastructure, resource availability, and processes on early outcomes after cancer surgery worldwide. Methods: A multimethods analysis was performed as part of the GlobalSurg 3 study—a multicentre, international, prospective cohort study of patients who had surgery for breast, colorectal, or gastric cancer. The primary outcomes were 30-day mortality and 30-day major complication rates. Potentially beneficial hospital facilities were identified by variable selection to select those associated with 30-day mortality. Adjusted outcomes were determined using generalised estimating equations to account for patient characteristics and country-income group, with population stratification by hospital. Findings: Between April 1, 2018, and April 23, 2019, facility-level data were collected for 9685 patients across 238 hospitals in 66 countries (91 hospitals in 20 high-income countries; 57 hospitals in 19 upper-middle-income countries; and 90 hospitals in 27 low-income to lower-middle-income countries). The availability of five hospital facilities was inversely associated with mortality: ultrasound, CT scanner, critical care unit, opioid analgesia, and oncologist. After adjustment for case-mix and country income group, hospitals with three or fewer of these facilities (62 hospitals, 1294 patients) had higher mortality compared with those with four or five (adjusted odds ratio [OR] 3·85 [95% CI 2·58–5·75]; p<0·0001), with excess mortality predominantly explained by a limited capacity to rescue following the development of major complications (63·0% vs 82·7%; OR 0·35 [0·23–0·53]; p<0·0001). Across LMICs, improvements in hospital facilities would prevent one to three deaths for every 100 patients undergoing surgery for cancer. Interpretation: Hospitals with higher levels of infrastructure and resources have better outcomes after cancer surgery, independent of country income. Without urgent strengthening of hospital infrastructure and resources, the reductions in cancer-associated mortality associated with improved access will not be realised. Funding: National Institute for Health and Care Research