"Dovie": A Creative Exploration Of The Effects Of The Economy And Progress On One Woman's Life In Post Civil War Appalachia Prior To World War II

The period between the Civil War and World War II brought sweeping changes and extreme circumstances to the entire country, and many of these events were intensified by the isolation and harsh realities of life in Appalachia. In this work I propose to address the life of a fictional woman who lived in the mountainous regions of North Carolina. In doing so I intend to explore how many people thrived in spite of conditions, and why some towns have vanished from existence

A Phase III Randomized Trial of Gemcitabine–Oxaliplatin versus Carboplatin–Paclitaxel as First-Line Therapy in Patients with Advanced Non-small Cell Lung Cancer

Purpose:This phase III study compared the efficacy and tolerability of gemcitabine and oxaliplatin (GEMOX) with paclitaxel and carboplatin (PCb) in chemotherapy-naive patients with stage IIIB/IV non-small cell lung cancer.Patients and Methods:Patients aged 18 years or older were randomized to PCb (paclitaxel 225 mg/m2 followed by carboplatin area under the curve = 6 on day 1 every 3 weeks) or GEMOX (gemcitabine 1,000 mg/m2 on days 1 and 8 followed by oxaliplatin 130 mg/m2 on day 1 every 3 weeks) for up to six cycles. The primary end point was progression-free survival (PFS), with tumor response rate, overall survival (OS), and quality of life as secondary end points.Results:The study was terminated after 383 patients had been randomized (371 received treatment) as the incidence of adverse events had exceeded the protocol-specified safety threshold (≥20% in either arm). No formal statistical comparisons were conducted. Median PFS was 4.44 months and 4.67 months in the GEMOX and PCb groups, respectively. Objective response rates (complete or partial) were 15.2% and 22.4% in the GEMOX and PCb arms, respectively. Median OS was 9.90 months (GEMOX) and 9.24 months (PCb); post hoc analyses showed median OS in patients aged 70 years or older to be similar to those younger than 70 years. PFS was similar in both groups of patients with adenocarcinoma histology, although OS favored the GEMOX group. Quality of life was improved from baseline in both groups. Toxicity profiles were comparable between the groups.Conclusion:PFS, OS, and objective response rates with GEMOX were similar to PCb. Nevertheless, toxicities limit the adoption of this regimen for routine use in advanced non-small cell lung cancer

Study protocol for a randomised controlled trial of brief, habit-based, lifestyle advice for cancer survivors: exploring behavioural outcomes for the Advancing Survivorship Cancer Outcomes Trial (ASCOT)

Introduction Positive health behaviours such as regular physical activity and a healthy diet have significant effects on cancer outcomes. There is a need for simple but effective behaviour change interventions with the potential to be implemented within the cancer care pathway. Habit-based advice encourages repetition of a behaviour in a consistent context so that the behaviour becomes increasingly automatic in response to a specific contextual cue. This approach therefore encourages long-term behaviour change and can be delivered through printed materials. ‘Healthy Habits for Life’ is a brief intervention based on habit theory, and incorporating printed materials plus a personally tailored discussion, that has been designed specifically for patients with a diagnosis of cancer. The aim of this trial was to test the effect of ‘Healthy Habits for Life’ on a composite health behaviour risk index (CHBRI) over 3 months in patients with a diagnosis of breast, colorectal or prostate cancer. Method and analysis A 2-arm, individually randomised controlled trial in patients with breast, colorectal and prostate cancer. Patients will be recruited over 18 months from 7 National Health Service Trusts in London and Essex. Following baseline assessments and allocation to intervention or usual care, patients are followed up at 3 and 6 months. The primary outcome will be change in CHBRI at 3 months. Maintenance of any changes over 6 months, and changes in individual health behaviours (including dietary intake, physical activity, alcohol consumption and smoking status) will also be explored. Ethics and dissemination Ethical approval was obtained through the National Research Ethics Service Committee South Central—Oxford B via the Integrated Research Application System (reference number 14/SC/1369). Results of this study will be disseminated through peer-reviewed publications and scientific presentation

Perioperative exercise programmes to promote physical activity in the medium to long term: systematic review and qualitative research

Background: In England, more than 4 million hospital admissions lead to surgery each year. The perioperative encounter (from initial presentation in primary care to postoperative return to function) offers potential for substantial health gains in the wider sense and over the longer term. Objectives: The aim was to identify, examine and set in context a range of interventions applied perioperatively to facilitate physical activity in the medium to long term. Data sources: The following databases were searched – Cochrane Central Register of Controlled Trials, MEDLINE, the Cumulative Index to Nursing and Allied Health Literature, EMBASE, PsycINFO and SPORTDiscus in October 2020. Clinical trials databases were also searched, and backward and forward citation searches were conducted. Review methods: We undertook a systematic review; ran database searches in October 2020; extracted data; conducted risk-of-bias assessments of studies; and used Grading of Recommendations Assessment, Development and Evaluation assessments. We conducted focus groups and interviews with people running services designed to promote physical activity, to understand the practical and contextual factors that make such interventions ‘work’. Although the two streams of work were conducted independently, we considered overlapping themes from their findings. Results: In the review, we found 51 randomised controlled trials and two quasi-randomised trials; nine non-randomised studies formed a supplementary data set. Studies included 8604 adults who had undergone (or were undergoing) surgery, and compared 67 interventions facilitating physical activity. Most interventions were started postoperatively and included multiple components, grouped as follows: education and advice, behavioural mechanisms and physical activity instruction. Outcomes were often measured using different tools; pooling of data was not always feasible. Compared with usual care, interventions may have slightly increased the amount of physical activity, engagement in physical activity and health-related quality of life at the study’s end (moderate-certainty evidence). We found low-certainty evidence of an increase in physical fitness and a reduction in pain, although effects generally favoured interventions. Few studies reported adherence and adverse events; certainty of these findings was very low. Although infrequently reported, participants generally provided positive feedback. For the case studies, we conducted two online focus groups and two individual interviews between November 2020 and January 2021, with nine participants from eight services of physical activity programmes. Conceptual and practical aspects included how the promotion of physical activity can be framed around the individual to recruit and retain patients; how services benefit from committed and compassionate staff; how enthusiasts, data collection and evidence play key roles; and how digital delivery could work as part of a blended approach, but inequalities in access must be considered. Limitations: Outcome measures in the review varied and, despite a large data set, not all studies could be pooled. This also limited the exploration of differences between interventions; components of interventions often overlapped between studies, and we could not always determine what ‘usual care’ involved. The case study exploration was limited by COVID-19 restrictions; we were unable to visit sites and observe practice, and the range of services in the focus groups was also limited. Conclusions: Evidence from the review indicates that interventions delivered in the perioperative setting, aimed at enhancing physical activity in the longer term, may have overall benefit. The qualitative analysis complemented these findings and indicated that interventions should be focused around the individual, delivered locally and compassionately, and promoted by a patient’s full clinical team. There is a need to develop a core outcome set for similar studies to allow quantitative synthesis. Future work should also investigate the experiences of patients in different contexts, such as different communities, and with different surgical indications

Effectiveness of the perioperative encounter in promoting regular exercise and physical activity: a systematic review and meta-analysis

Background Low levels of physical activity (PA) are associated with poorer health outcomes. The perioperative encounter (extending from initial contact in primary care to beyond discharge from hospital) is potentially a good time to intervene, but data regarding the effectiveness of interventions are scarce. To address this, we systematically reviewed existing literature to evaluate the effectiveness of interventions applied perioperatively to facilitate PA in the medium to long-term (at least six months after the intervention). Methods In this systematic review and meta-analysis, we searched Central Register of Controlled Trials (CENTRAL, Cochrane Library), MEDLINE, CINAHL, Embase, PsycInfo, and SPORTDiscus from database inception to October 22nd 2020, with an updated search done on August 4th 2022. We searched clinical trials registers, and conducted forward- and backward-citation searches. We included randomised controlled trials and quasi-randomised trials comparing PA interventions with usual care, or another PA intervention, in adults who were scheduled for, or had recently undergone, surgery. We included trials which reported our primary outcomes: amount of PA or whether participants were engaged in PA at least six months after the intervention. A random effects meta-analysis was used to pool data across studies as risk ratios (RR), or standardised mean differences (SMDs), which we interpreted using Cohen. We used the Cochrane risk of bias tool and used GRADE to assess the certainty of the evidence. This study is registered with PROSPERO, CRD42019139008. Findings We found 57 trials including 8548 adults and compared 71 interventions facilitating PA. Most interventions were started postoperatively and included multiple components. Compared with usual care, interventions may slightly increase the number of minutes of PA per day or week (SMD 0.17, 95% CI 0.09–0.26; 14 studies, 2172 participants; I2 = 0%), and people's engagement in PA at the study's end (RR 1.19, 95% CI 0.96–1.47; 9 studies, 882 participants; I2 = 25%); this was moderate-certainty evidence. Some studies compared two different types of interventions but it was often not feasible to combine data in analysis. The effect estimates generally indicated little difference between intervention designs and we judged all the evidence for these comparisons to be very low certainty. Thirty-six studies (63%) had low risk of selection bias for sequence generation, 27 studies (47%) had low risk of bias for allocation concealment, and 56 studies (98%) had a high risk of performance bias. For detection bias for PA outcomes, we judged 30 studies (53%) that used subjective measurement tools to have a high risk of detection bias. Interpretation Interventions delivered in the perioperative setting, aimed at enhancing PA in the medium to long-term, may have overall benefit. However, because of imprecision in some of the findings, we could not rule out the possibility of no change in PA

Colloids versus crystalloids for fluid resuscitation in critically ill people

Background Critically ill people may lose fluid because of serious conditions, infections (e.g. sepsis), trauma, or burns, and need additional fluids urgently to prevent dehydration or kidney failure. Colloid or crystalloid solutions may be used for this purpose. Crystalloids have small molecules, are cheap, easy to use, and provide immediate fluid resuscitation, but may increase oedema. Colloids have larger molecules, cost more, and may provide swifter volume expansion in the intravascular space, but may induce allergic reactions, blood clotting disorders, and kidney failure. This is an update of a Cochrane Review last published in 2013. Objectives To assess the effect of using colloids versus crystalloids in critically ill people requiring fluid volume replacement on mortality, need for blood transfusion or renal replacement therapy (RRT), and adverse events (specifically: allergic reactions, itching, rashes). Search methods We searched CENTRAL, MEDLINE, Embase and two other databases on 23 February 2018. We also searched clinical trials registers. Selection criteria We included randomised controlled trials (RCTs) and quasi‐RCTs of critically ill people who required fluid volume replacement in hospital or emergency out‐of‐hospital settings. Participants had trauma, burns, or medical conditions such as sepsis. We excluded neonates, elective surgery and caesarean section. We compared a colloid (suspended in any crystalloid solution) versus a crystalloid (isotonic or hypertonic). Data collection and analysis Independently, two review authors assessed studies for inclusion, extracted data, assessed risk of bias, and synthesised findings. We assessed the certainty of evidence with GRADE. Main results We included 69 studies (65 RCTs, 4 quasi‐RCTs) with 30,020 participants. Twenty‐eight studied starch solutions, 20 dextrans, seven gelatins, and 22 albumin or fresh frozen plasma (FFP); each type of colloid was compared to crystalloids. Participants had a range of conditions typical of critical illness. Ten studies were in out‐of‐hospital settings. We noted risk of selection bias in some studies, and, as most studies were not prospectively registered, risk of selective outcome reporting. Fourteen studies included participants in the crystalloid group who received or may have received colloids, which might have influenced results. We compared four types of colloid (i.e. starches; dextrans; gelatins; and albumin or FFP) versus crystalloids. Starches versus crystalloids We found moderate‐certainty evidence that there is probably little or no difference between using starches or crystalloids in mortality at: end of follow‐up (risk ratio (RR) 0.97, 95% confidence interval (CI) 0.86 to 1.09; 11,177 participants; 24 studies); within 90 days (RR 1.01, 95% CI 0.90 to 1.14; 10,415 participants; 15 studies); or within 30 days (RR 0.99, 95% CI 0.90 to 1.09; 10,135 participants; 11 studies). We found moderate‐certainty evidence that starches probably slightly increase the need for blood transfusion (RR 1.19, 95% CI 1.02 to 1.39; 1917 participants; 8 studies), and RRT (RR 1.30, 95% CI 1.14 to 1.48; 8527 participants; 9 studies). Very low‐certainty evidence means we are uncertain whether either fluid affected adverse events: we found little or no difference in allergic reactions (RR 2.59, 95% CI 0.27 to 24.91; 7757 participants; 3 studies), fewer incidences of itching with crystalloids (RR 1.38, 95% CI 1.05 to 1.82; 6946 participants; 2 studies), and fewer incidences of rashes with crystalloids (RR 1.61, 95% CI 0.90 to 2.89; 7007 participants; 2 studies). Dextrans versus crystalloids We found moderate‐certainty evidence that there is probably little or no difference between using dextrans or crystalloids in mortality at: end of follow‐up (RR 0.99, 95% CI 0.88 to 1.11; 4736 participants; 19 studies); or within 90 days or 30 days (RR 0.99, 95% CI 0.87 to 1.12; 3353 participants; 10 studies). We are uncertain whether dextrans or crystalloids reduce the need for blood transfusion, as we found little or no difference in blood transfusions (RR 0.92, 95% CI 0.77 to 1.10; 1272 participants, 3 studies; very low‐certainty evidence). We found little or no difference in allergic reactions (RR 6.00, 95% CI 0.25 to 144.93; 739 participants; 4 studies; very low‐certainty evidence). No studies measured RRT. Gelatins versus crystalloids We found low‐certainty evidence that there may be little or no difference between gelatins or crystalloids in mortality: at end of follow‐up (RR 0.89, 95% CI 0.74 to 1.08; 1698 participants; 6 studies); within 90 days (RR 0.89, 95% CI 0.73 to 1.09; 1388 participants; 1 study); or within 30 days (RR 0.92, 95% CI 0.74 to 1.16; 1388 participants; 1 study). Evidence for blood transfusion was very low certainty (3 studies), with a low event rate or data not reported by intervention. Data for RRT were not reported separately for gelatins (1 study). We found little or no difference between groups in allergic reactions (very low‐certainty evidence). Albumin or FFP versus crystalloids We found moderate‐certainty evidence that there is probably little or no difference between using albumin or FFP or using crystalloids in mortality at: end of follow‐up (RR 0.98, 95% CI 0.92 to 1.06; 13,047 participants; 20 studies); within 90 days (RR 0.98, 95% CI 0.92 to 1.04; 12,492 participants; 10 studies); or within 30 days (RR 0.99, 95% CI 0.93 to 1.06; 12,506 participants; 10 studies). We are uncertain whether either fluid type reduces need for blood transfusion (RR 1.31, 95% CI 0.95 to 1.80; 290 participants; 3 studies; very low‐certainty evidence). Using albumin or FFP versus crystalloids may make little or no difference to the need for RRT (RR 1.11, 95% CI 0.96 to 1.27; 3028 participants; 2 studies; very low‐certainty evidence), or in allergic reactions (RR 0.75, 95% CI 0.17 to 3.33; 2097 participants, 1 study; very low‐certainty evidence). Authors' conclusions Using starches, dextrans, albumin or FFP (moderate‐certainty evidence), or gelatins (low‐certainty evidence), versus crystalloids probably makes little or no difference to mortality. Starches probably slightly increase the need for blood transfusion and RRT (moderate‐certainty evidence), and albumin or FFP may make little or no difference to the need for renal replacement therapy (low‐certainty evidence). Evidence for blood transfusions for dextrans, and albumin or FFP, is uncertain. Similarly, evidence for adverse events is uncertain. Certainty of evidence may improve with inclusion of three ongoing studies and seven studies awaiting classification, in future updates

Effectiveness of the perioperative encounter in promoting regular exercise and physical activity: a systematic review and meta-analysis

Background: Low levels of physical activity (PA) are associated with poorer health outcomes. The perioperative encounter (extending from initial contact in primary care to beyond discharge from hospital) is potentially a good time to intervene, but data regarding the effectiveness of interventions are scarce. To address this, we systematically reviewed existing literature to evaluate the effectiveness of interventions applied perioperatively to facilitate PA in the medium to long-term (at least six months after the intervention). Methods: In this systematic review and meta-analysis, we searched Central Register of Controlled Trials (CENTRAL, Cochrane Library), MEDLINE, CINAHL, Embase, PsycInfo, and SPORTDiscus from database inception to October 22nd 2020, with an updated search done on August 4th 2022. We searched clinical trials registers, and conducted forward- and backward-citation searches. We included randomised controlled trials and quasi-randomised trials comparing PA interventions with usual care, or another PA intervention, in adults who were scheduled for, or had recently undergone, surgery. We included trials which reported our primary outcomes: amount of PA or whether participants were engaged in PA at least six months after the intervention. A random effects meta-analysis was used to pool data across studies as risk ratios (RR), or standardised mean differences (SMDs), which we interpreted using Cohen. We used the Cochrane risk of bias tool and used GRADE to assess the certainty of the evidence. This study is registered with PROSPERO, CRD42019139008. Findings: We found 57 trials including 8548 adults and compared 71 interventions facilitating PA. Most interventions were started postoperatively and included multiple components. Compared with usual care, interventions may slightly increase the number of minutes of PA per day or week (SMD 0.17, 95% CI 0.09–0.26; 14 studies, 2172 participants; I2 = 0%), and people's engagement in PA at the study's end (RR 1.19, 95% CI 0.96–1.47; 9 studies, 882 participants; I2 = 25%); this was moderate-certainty evidence. Some studies compared two different types of interventions but it was often not feasible to combine data in analysis. The effect estimates generally indicated little difference between intervention designs and we judged all the evidence for these comparisons to be very low certainty. Thirty-six studies (63%) had low risk of selection bias for sequence generation, 27 studies (47%) had low risk of bias for allocation concealment, and 56 studies (98%) had a high risk of performance bias. For detection bias for PA outcomes, we judged 30 studies (53%) that used subjective measurement tools to have a high risk of detection bias. Interpretation: Interventions delivered in the perioperative setting, aimed at enhancing PA in the medium to long-term, may have overall benefit. However, because of imprecision in some of the findings, we could not rule out the possibility of no change in PA. Funding: National Institute for Health Research Health Services and Delivery Research programme (NIHR127879)

HIV-1 glycan density drives the persistence of the mannose patch within an infected individual.

CAPRISA, 2016.Abstract available in pdf

Admixture Mapping of Quantitative Trait Loci for BMI in African Americans: Evidence for Loci on Chromosomes 3q, 5q, and 15q

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/93743/1/oby_1443_sm_2.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/93743/2/oby_1443_sm_1.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/93743/3/oby.2009.24.pd