Point-of-care testing and treatment of sexually transmitted and genital infections to improve birth outcomes in high-burden, low-resource settings (WANTAIM): a pragmatic cluster randomised crossover trial in Papua New Guinea.

BACKGROUND: Chlamydia trachomatis, Neisseria gonorrhoeae, Trichomonas vaginalis, and bacterial vaginosis have been associated with adverse maternal and perinatal outcomes, but there is conflicting evidence on the benefits of antenatal screening and treatment for these conditions. We aimed to determine the effect of antenatal point-of-care testing and immediate treatment of C trachomatis, N gonorrhoeae, T vaginalis, and bacterial vaginosis on preterm birth, low birthweight, and other adverse maternal and perinatal outcomes compared with current standard of care, which included symptom-based treatment without laboratory confirmation. METHODS: In this pragmatic cluster randomised crossover trial, we enrolled women (aged ≥16 years) attending an antenatal clinic at 26 weeks' gestation or earlier (confirmed by obstetric ultrasound), living within approximately 1 h drive of a study clinic, and able to provide reliable contact details at ten primary health facilities and their catchment communities (clusters) in Papua New Guinea. Clusters were randomly allocated 1:1 to receive either the intervention or control (standard care) in the first phase of the trial. Following an interval (washout period) of 2-3 months at the end of the first phase, each cluster crossed over to the other group. Randomisation was stratified by province. Individual participants were informed about trial group allocation only after completing informed consent procedures. The primary outcome was a composite of preterm birth (livebirth before 37 weeks' gestation), low birthweight (<2500 g), or both, analysed according to the intention-to-treat population. This study is registered with ISRCTN Registry, ISRCTN37134032, and is completed. FINDINGS: Between July 26, 2017, and Aug 30, 2021, 4526 women were enrolled (2210 [63·3%] of 3492 women in the intervention group and 2316 [62·8%] of 3687 in the control group). Primary outcome data were available for 4297 (94·9%) newborn babies of 4526 women. The proportion of preterm birth, low birthweight, or both, in the intervention group, expressed as the mean of crude proportions across clusters, was 18·8% (SD 4·7%) compared with 17·8% in the control group (risk ratio [RR] 1·06, 95% CI 0·78-1·42; p=0·67). There were 1052 serious adverse events reported (566 in the intervention group and 486 in the control group) among 929 trial participants, and no differences by trial group. INTERPRETATION: Point-of-care testing and treatment of C trachomatis, N gonorrhoeae, T vaginalis, and bacterial vaginosis did not reduce preterm birth or low birthweight compared with standard care. Within the subgroup of women with N gonorrhoeae, there was a substantial reduction in the primary outcome. FUNDING: UK Department of Health and Social Care; UK Foreign, Commonwealth and Development Office; UK Medical Research Council; the Wellcome Trust; the Australian National Health and Medical Research Council; and Swiss National Science Foundation.

Catheter Tip-Associated Mass With Continuous Infusion of Sufentanil for Persistent Spinal Pain Syndrome Type 2: A Case Report Including Histopathologic Examination and Review of the Associated Basic and Clinical Research.

OBJECTIVES: Intrathecal opioids delivered by implanted pumps are used to treat malignant or nonmalignant chronic pain. In this study, we 1) review a case in which intrathecal infusions of sufentanil along with other adjuvants were used and after an extended period led to an intrathecal mass and 2) compared and contrasted the potential mechanisms for these phenomena. MATERIALS AND METHODS: A woman aged 66 years with a history of scoliosis and multiple spine surgeries was treated with an implantable drug delivery system for treating persistent pain after laminectomy. The patient received intrathecal medication comprising sufentanil, bupivacaine, and clonidine. RESULTS: Intrathecal therapy over approximately ten years served to reduce pain and improve function over the treatment period. After the extended treatment interval, the patient developed an intrathecal mass that was associated with impairment. The mass was surgically removed. Systematic histopathology revealed the space-occupying mass to largely comprise fibroblasts and some inflammatory cells embedded in a collagen mass located proximally to the catheter tip. CONCLUSIONS: To our knowledge, this is the first published case report of sufentanil causing this complication. The science and mechanism of intrathecal catheter tip-associated mass formation and associated clinical research correlates are reviewed in detail, and explanations for this phenomenon are proposed based on histochemical analysis of the patient's pathology findings.

The effect of the Xpert HIV-1 Qual test on early infant diagnosis of HIV in Myanmar and Papua New Guinea: a pragmatic, cluster-randomised, stepped-wedge, open-label trial.

BACKGROUND: Despite proven benefits for child health, coverage of early infant diagnosis of HIV remains suboptimal in many settings. We aimed to assess the effect of a point-of-care early infant diagnosis test on time-to-results communication for infants vertically exposed to HIV. METHODS: This pragmatic, cluster-randomised, stepped-wedge, open-label trial assessed the effect of the Xpert HIV-1 Qual early infant diagnosis test (Cepheid) on time-to-results communication, compared with standard care laboratory-based testing of dried blood spots using PCR. Hospitals were the unit of randomisation for one-way crossover from control to intervention phase. Each site had between 1 month and 10 months of control phase before transitioning to the intervention, with a total of 33 hospital-months in the control phase and 45 hospital-months in the intervention phase. We enrolled infants vertically exposed to HIV at six public hospitals: four in Myanmar and two in Papua New Guinea. Infants had to have mothers with confirmed HIV infection, be younger than 28 days, and required HIV testing to be eligible for enrolment. Health-care facilities providing prevention of vertical transmission services were eligible for participation. The primary outcome was communication of early infant diagnosis results to the infant's caregiver by 3 months of age, assessed by intention to treat. This completed trial was registered with the Australian and New Zealand Clinical Trials Registry, 12616000734460. FINDINGS: In Myanmar, recruitment took place between Oct 1, 2016, and June 30, 2018; in Papua New Guinea, recruitment was between Dec 1, 2016, and Aug 31, 2018. A total of 393 caregiver-infant pairs were enrolled in the study across both countries. Independent of study time, the Xpert test reduced time to early infant diagnosis results communication by 60%, compared with the standard of care (adjusted time ratio 0·40, 95% CI 0·29-0·53, p<0·0001). In the control phase, two (2%) of 102 study participants received an early infant diagnosis test result by 3 months of age compared with 214 (74%) of 291 in the intervention phase. No safety and adverse events were reported related to the diagnostic testing intervention. INTERPRETATION: This study reinforces the importance of scaling up point-of-care early infant diagnosis testing in resource-constrained and low HIV-prevalence settings, typical of the UNICEF East Asia and Pacific region. FUNDING: National Health and Medical Research Council of Australia.

EPA's Unprecedented Interim Drinking Water Health Advisories for PFOA and PFOS.

Per- and polyfluoroalkyl substances (PFAS) are persistent and widely distributed in the environment from commercial products and waste process residues, including in surface waters usually at low parts per trillion (ppt) levels. Groundwaters near contaminated locations can have higher parts per trillion or parts per billion (ppb) concentrations. Interim EPA Drinking Water Health Advisories (HAs) for perfluorooctanoic acid (PFOA) and perfluorooctanesulfonic acid (PFOS) that were originally 70 ppt were recently reduced to 0.004 and 0.020 ppt, respectively. Final HAs for perfluorobutane sulfonic acid and its potassium salt (PFBS) and hexafluoropropylene oxide (HFPO) dimer acid and its ammonium salt ("GenX chemicals") were established at 2000 and 10 ppt, respectively. The minimum reporting levels (MRLs) for PFOA and PFOS are currently 4 ppt. The scientific basis for these very low and unmeasurable HA values for PFOA and PFOS is debatable and up to about five orders of magnitude below many other worldwide national recommendations (e.g., Australia, UK, Canada), which are in the range of 100 ppt and above.

Point-of-care HPV DNA testing of self-collected specimens and same-day thermal ablation for the early detection and treatment of cervical pre-cancer in women in Papua New Guinea: a prospective, single-arm intervention trial (HPV-STAT).

BACKGROUND: WHO recommends human papillomavirus (HPV) testing and same-day treatment for cervical screening in low-income and middle-income countries (LMICs); however, few published data exist on the validity of the strategy. We aimed to evaluate the clinical performance, treatment completion rates, adverse events profile, and acceptability of a fully integrated strategy, comprising point-of-care HPV DNA testing of self-collected specimens and same-day thermal ablation, for screening of cervical cancer in women in Papua New Guinea. METHODS: HPV-STAT was a large-scale, prospective, single-arm intervention trial conducted at two clinical sites in Papua New Guinea. Cervical screening clinics with an on-site consultant gynaecologist were selected in consultation with national and provincial health authorities, church health services, and local stakeholders. Eligible participants were women aged 30-59 years attending cervical screening services at the two clinics, who were willing to comply with study procedures and able to provide written informed consent. Women self-collected vaginal specimens for point-of-care GeneXpert testing (Cepheid, Sunnyvale, CA, USA) for oncogenic HPV types. Women testing positive for HPV underwent pelvic examination followed by same-day thermal ablation or referral for gynaecology review. All HPV-positive women and a 15% random sample of HPV-negative women provided a clinician-collected cervical specimen for liquid-based cytology. The primary outcome was clinical performance (ie, sensitivity, specificity, positive predictive value [PPV], and negative predictive value [NPV]) of the strategy for the detection of high-grade squamous intraepithelial lesion (HSIL) or worse. This trial is registered with ISRCTN, ISRCTN13476702. FINDINGS: Between June 5, 2018, and Jan 6, 2020, we recruited 4285 women, 3638 (84·9%) of whom tested negative for HPV and 647 (15·1%) tested positive for one or more oncogenic HPV type. Sensitivity of the algorithm to detect HSIL or worse was 85·4% (95% CI 81·0-89·6), with specificity 89·6% (88·6-90·6), PPV 35·2% (31·6-39·0), and NPV 98·9% (98·6-99·2). Among HPV-positive women, 602 (93·0%) received same-day thermal ablation and 42 (6·5%) were referred for gynaecology review, 37 (88·1%) of whom attended. Acceptability was high among both HPV-positive and HPV-negative women. Among the 329 HPV-positive women who attended a 3-month follow-up visit, 51 (15·5%) reported mild adverse symptoms that resolved in all cases by the follow-up visit. There were no serious adverse events. INTERPRETATION: We conducted the first real-world evaluation of a fully integrated point-of-care HPV self-collect, test, and treat strategy for same-day cervical screening in a LMIC and found it to be effective, acceptable, and safe when implemented at scale in primary health-care facilities in Papua New Guinea. Our findings support the introduction and scale-up of HPV screening and treatment for the control and elimination of cervical cancer in LMICs, as recommended by WHO. FUNDING: Australian National Health and Medical Research Council.

Discovery of Autoantibodies Targeting Nephrin in Minimal Change Disease Supports a Novel Autoimmune Etiology.

BACKGROUND: Failure of the glomerular filtration barrier, primarily by loss of slit diaphragm architecture, underlies nephrotic syndrome in minimal change disease. The etiology remains unknown. The efficacy of B cell-targeted therapies in some patients, together with the known proteinuric effect of anti-nephrin antibodies in rodent models, prompted us to hypothesize that nephrin autoantibodies may be present in patients with minimal change disease. METHODS: We evaluated sera from patients with minimal change disease, enrolled in the Nephrotic Syndrome Study Network (NEPTUNE) cohort and from our own institutions, for circulating nephrin autoantibodies by indirect ELISA and by immunoprecipitation of full-length nephrin from human glomerular extract or a recombinant purified extracellular domain of human nephrin. We also evaluated renal biopsies from our institutions for podocyte-associated punctate IgG colocalizing with nephrin by immunofluorescence. RESULTS: In two independent patient cohorts, we identified circulating nephrin autoantibodies during active disease that were significantly reduced or absent during treatment response in a subset of patients with minimal change disease. We correlated the presence of these autoantibodies with podocyte-associated punctate IgG in renal biopsies from our institutions. We also identified a patient with steroid-dependent childhood minimal change disease that progressed to end stage kidney disease; she developed a massive post-transplant recurrence of proteinuria that was associated with high pretransplant circulating nephrin autoantibodies. CONCLUSIONS: Our discovery of nephrin autoantibodies in a subset of adults and children with minimal change disease aligns with published animal studies and provides further support for an autoimmune etiology. We propose a new molecular classification of nephrin autoantibody minimal change disease to serve as a framework for instigation of precision therapeutics for these patients.

European Health Care Systems and the Emerging Influence of European Union Competition Policy.

CONTEXT: Since the 1990s, the EU's influence over national health care policy has been limited to European internal market law or social policy coordination mechanisms. The introduction of EU competition law into health care is more recent and underdeveloped; however, its introduction would potentially be much more far-reaching and disruptive. METHODS: Three EU competition law (state-aid) cases are used and comprise both Court of Justice and European Commission decisions. One is from Ireland, one is from the Netherlands, and the third is from Belgium. FINDINGS: The Belgian (Iris-H) case sees EU institutions scrutinize a clearly "social" (nonmarket) health care model with EU competition law for the first time. This is a highly significant development. It is clear, however, that the European Commission is more reluctant to use EU competition law to scrutinize health care systems than the European courts are. CONCLUSIONS: This intent on the part of EU institutions will have to be assessed in future cases, as considerable uncertainty about its shape and outer contours remains. However, EU competition law, and the EU's state-aid investigation apparatus, encroaching into the national health care systems for the first time is highly significant.

A High-Content Screen for Mucin-1-Reducing Compounds Identifies Fostamatinib as a Candidate for Rapid Repurposing for Acute Lung Injury.

Drug repurposing has the advantage of identifying potential treatments on a shortened timescale. In response to the pandemic spread of SARS-CoV-2, we took advantage of a high-content screen of 3,713 compounds at different stages of clinical development to identify FDA-approved compounds that reduce mucin-1 (MUC1) protein abundance. Elevated MUC1 levels predict the development of acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) and correlate with poor clinical outcomes. Our screen identifies fostamatinib (R788), an inhibitor of spleen tyrosine kinase (SYK) approved for the treatment of chronic immune thrombocytopenia, as a repurposing candidate for the treatment of ALI. In vivo, fostamatinib reduces MUC1 abundance in lung epithelial cells in a mouse model of ALI. In vitro, SYK inhibition by the active metabolite R406 promotes MUC1 removal from the cell surface. Our work suggests fostamatinib as a repurposing drug candidate for ALI.

Anesthetic management of a patient with left ventricular assist device undergoing robotic laparoscopic prostatectomy: a case report.

BACKGROUND: Patients with left ventricular assist devices (LVAD) require specific anesthetic and hemodynamic considerations. We report the specific anesthetic preparation and management in this scenario. CASE PRESENTATION: We present the case of a 66-year-old male with a HeartMate II LVAD undergoing robotic prostatectomy for prostate cancer in the steep Trendelenburg position. We employed central venous and radial arterial access, LVAD pump parameters, near-infrared sensor of cerebral oximetry, and transesophageal echocardiography for monitoring. Hemodynamics were managed with nicardipine, dobutamine, epinephrine, and phenylephrine during abdominal insufflation, operative positioning, and desufflation. The patient had a successful procedure, was discharged on postoperative day 2, and achieved surgical cure of his prostate cancer. DISCUSSION: By presenting the first detailed account of anesthetic management in this scenario, we provide a clinical vignette for use by the clinical anesthesiologist in his or her preparation prior to caring for this type of patient.

Effect of Preoperative Opioid Use on Adverse Outcomes, Medical Spending, and Persistent Opioid Use Following Elective Total Joint Arthroplasty in the United States: A Large Retrospective Cohort Study of Administrative Claims Data.

OBJECTIVE: Between 17% and 40% of patients undergoing elective arthroplasty are preoperative opioid users. This US study analyzed patients in this population to illustrate the relationship between preoperative opioid use and adverse surgical outcomes. DESIGN: Retrospective study of administrative medical and pharmaceutical claims data. SUBJECTS: Adults (aged 18+) who received elective total knee, hip, or shoulder replacement in 2014-2015. METHODS: A patient was a preoperative opioid user if opioid prescription fills occurred in two periods: 1-30 and 31-90 days presurgery. Zero-truncated Poisson (incidence rate ratio [IRR]), logistic (odds ratio [OR]), Cox (hazard ratio [HR]), and quantile regressions modeled the effects of preoperative opioid use and opioid dose, adjusted for demographics, comorbidities, and utilization. RESULTS: Among 34,792 patients (38% hip, 58% knee, 4% shoulder), 6,043 (17.4%) were preoperative opioid users with a median morphine equivalent daily dose of 32 mg. Preoperative opioid users had increased length of stay (IRR = 1.03, 95% CI = 1.02 to 1.05), nonhome discharge (OR = 1.10, 95% CI = 1.00 to 1.21), and 30-day unplanned readmission (OR = 1.43, 95% CI = 1.17 to 1.74); experienced 35% higher surgical site infection (HR = 1.35, 95% CI = 1.14 to 1.59) and 44% higher surgical revision (HR = 1.44, 95% CI = 1.21 to 1.71); had a median $1,084 (95% CI = $833 to $1334) increase in medical spend during the 365 days after discharge; and had a 64% lower rate of opioid cessation (HR = 0.34, 95% CI = 0.33 to 0.35) compared with patients not filling two or more prescriptions across periods. CONCLUSIONS: Preoperative opioid users had longer length of stay, increased revision rates, higher spend, and persistent opioid use, which worsened with dose. Adverse outcomes after elective joint replacement may be reduced if preoperative opioid risk is managed through increased monitoring or opioid cessation.

Embryonic FAP+ lymphoid tissue organizer cells generate the reticular network of adult lymph nodes.

The induction of adaptive immunity is dependent on the structural organization of LNs, which is in turn governed by the stromal cells that underpin LN architecture. Using a novel fate-mapping mouse model, we trace the developmental origin of mesenchymal LN stromal cells (mLNSCs) to a previously undescribed embryonic fibroblast activation protein-α (FAP)+ progenitor. FAP+ cells of the LN anlagen express lymphotoxin ß receptor (LTßR) and vascular cell adhesion molecule (VCAM), but not intercellular adhesion molecule (ICAM), suggesting they are early mesenchymal lymphoid tissue organizer (mLTo) cells. Clonal labeling shows that FAP+ progenitors locally differentiate into mLNSCs. This process is also coopted in nonlymphoid tissues in response to infection to facilitate the development of tertiary lymphoid structures, thereby mimicking the process of LN ontogeny in response to infection.

Verbal memory and sentence comprehension in aphasia: A case series.

This case series explores the relationship between verbal memory capacity and sentence comprehension in four patients with aphasia. Two sentence comprehension tasks showed that two patients, P1 and P2, had impaired syntactic comprehension, whereas P3 and P4's sentence comprehension was intact. The memory assessment tasks showed that P1 and P2 had severely impaired short-term memory, whereas P3 and P4 performed within the normal range in the short-term memory tasks. This finding suggests an association between short-term memory deficit and sentence comprehension difficulties. P1 and P3 exhibited impaired comparable working memory deficits, suggesting a dissociation between working memory and sentence comprehension.

Common elements in opioid use disorder guidelines for buprenorphine prescribing.

OBJECTIVES: This study sought to formulate a consolidation of guidelines representing best practices related to office-based opioid treatment (OBOT) of opioid use disorder (OUD) using buprenorphine. It also demonstrates how a set of evidence-based guidelines may be linked with claims data to leverage analytic techniques that drive cost-effective, positive health outcomes. STUDY DESIGN: Literature review of US and international guidelines for OBOT using buprenorphine for OUD. METHODS: The study conducted a review of currently available US and several international guidelines from 2009 to 2018 published on OUD and the use of buprenorphine in OBOT. Guidelines were consolidated based on common elements. The process of correlating common elements with available commercial and state Medicaid claims data is described, including which elements are amenable to analysis along with relative complexity. RESULTS: Seven guidelines met inclusion criteria and are presented as 3 tables, organized by clinical themes and phase of care related to OBOT use of buprenorphine for OUD. Themes included establishing care, monitoring treatment stability and engagement, and nonpharmacologic treatment to improve outcomes. Areas of agreement and divergence between guidelines are highlighted. Specific components are identified as they relate to metrics of interest to public and private payers. CONCLUSIONS: Among US and international guidelines for treatment of OUD, common themes are readily identified and may indicate agreement in regard to interventions. Linking pharmacy and medical billing claims data to evidence-supported best practices provides public and private payers the ability to track individual patients, facilitate high-quality care, and monitor outcomes.

Effectiveness and cost-effectiveness of humanistic counselling in schools for young people with emotional distress (ETHOS): study protocol for a randomised controlled trial.

BACKGROUND: One in ten children in Britain have been identified as experiencing a diagnosable mental health disorder. School-based humanistic counselling (SBHC) may help young people identify, address, and overcome psychological distress. Data from four pilot trials suggest that SBHC may be clinically effective. However, a fully powered randomised controlled trial (RCT) is needed to provide a robust test of its effectiveness, to assess its cost-effectiveness, and to determine the process of change. METHODS/DESIGN: The Effectiveness and Cost-effectiveness Trial of Humanistic Counselling in Schools (ETHOS) is a two-arm, parallel-group RCT comparing the clinical and cost-effectiveness of SBHC with Pastoral Care as Usual (PCAU) in school settings. Eligibility criteria for young people include being between 13 and 16 years of age and experiencing moderate to severe levels of emotional distress. Participants are randomised to receive either SBHC or PCAU. SBHC is delivered in up to 10 weekly, individual sessions in their school with a qualified, experienced counsellor who has also received training using a clinical practice manual. Adherence to the SBHC model is assessed by a sub-team of auditors and in clinical supervision. PCAU consists of the schools' pre-existing systems for supporting the emotional health and well-being of students. The primary outcomes are psychological distress measured using the Young Person's Clinical Outcomes in Routine Evaluation (YP-CORE) and costs evaluated using the Client Service Receipt Inventory (CSRI). Secondary outcomes include psychological difficulties, levels of depression, anxiety and self-esteem, well-being, school engagement, educational outcomes and achievement of personal goals. Qualitative interviews with participants, parents and school staff will look to identify the mechanisms of change in SBHC. Researchers administering the measures are blind to allocation. The trial requires n = 306 participants (n = 153 in each group), with 90% power to detect a standardised mean difference (SMD) of 0.5. An intention-to-treat analysis will be undertaken. DISCUSSION: This RCT is powered to detect clinically meaningful differences, and will make a major contribution to the evidence base for mental health provision for adolescents. It will have implications for all stakeholders, including policy-makers, statutory advisory bodies for child welfare, head teachers, children and young people practitioners, child welfare and parenting organisations, and young people. TRIAL REGISTRATION: Controlled Trials International Standard Randomised Controlled Trial Number (ISRCTN) Registry, ID: ISRCTN10460622 . Registered on 11 May 2016.

Perioperative Outcomes after Regional Versus General Anesthesia for Above the Knee Amputations.

BACKGROUND: Nontraumatic lower extremity amputation (LEA) remains a common procedure among patients who frequently have significant comorbidities. Patients undergoing above knee amputation (AKA) have the highest rates of mortality in this cohort, yet there is little evidence to support selection between peripheral nerve block or neuraxial regional anesthesia (RA) versus general anesthesia (GA) techniques. The objective of this study was to determine whether RA (neuraxial or peripheral nerve block) techniques were associated with more favorable outcomes versus general anesthesia among patients undergoing AKA. METHODS: This is a retrospective cohort study using propensity-matched groups. Patients undergoing AKA were identified in the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) data set and grouped according to anesthetic type as either RA or GA. Patients undergoing AKA with RA were propensity matched to similar patients who had GA. Primary outcome was 30-day mortality. Secondary outcomes were numerous and included cardiac, pulmonary, infectious, and bleeding complications, as well as length of stay. Among a subset of patients for whom readmission data were available, rate of readmission was compared as a secondary outcome. RESULTS: Nine thousand nine hundred ninety-nine patients were identified in the ACS-NSQIP database. One thousand three hundred twelve received a regional anesthetic, and the remainder had a general anesthetic. Factors significantly associated with GA included younger age (70 vs. 75 years; P < 0.001), higher body mass index (26.5 vs. 25.4; P < 0.001), and ethnically white (62.4% vs. 57%; P < 0.001). Before matching, patients receiving RA were less likely to be smokers (22% vs. 29%; P < 0.001), have a bleeding disorder (15% vs 30%; P < 0.001), or have a diagnosis of sepsis (26% vs 34%; P < 0.001). Propensity score matching produced a cohort composed of 1,916 patients equally divided between RA and GA. We found no difference with respect to the primary end point of 30-day mortality (11.7% vs 11.7%; odds ratio [OR] 1.01; P = 0.943) nor was there any difference with respect to secondary outcomes. Among patients for whom readmission data were available, there was no statistically significant difference between rates of readmission between the groups (15.6% for RA vs. 12.7% for GA; OR 1.26, confidence interval 0.87-1.828, P = 0.221). CONCLUSIONS: The present investigation did not detect any difference between regional and general anesthetic with respect to morbidity or mortality among patients undergoing AKA. This data set did not allow us to address other relevant markers including pain control or phantom limb syndrome.

More haste less speed: A meta-analysis of thinking latencies during planning in people with psychosis.

Cognitive impairment is a core feature of psychosis, with slowed processing speed thought to be a prominent impairment in schizophrenia and first-episode psychosis. However, findings from the Stockings of Cambridge (SOC) planning task suggest changes in processing speed associated with the illness may include faster responses in early stages of planning, though findings are inconsistent. This review uses meta-analytic methods to assess thinking times in psychosis across the available literature. Studies were identified by searching PubMed, Web of Science and Google Scholar. Eligibility criteria: 1) included a sample of people with non-affective psychosis according to DSM III, DSM IV, DSM V or ICD-10 criteria; 2) employed the SOC task; 3) included a healthy control group; and 4) published in English. We identified 11 studies that employed the SOC task. Results show that people with psychosis have significantly faster initial thinking times than non-clinical participants, but significantly slower subsequent thinking times during problem execution. These findings indicate that differences in processing speed are not limited to slower responses in people with psychosis but may reflect a preference for step-by-step processing rather than planning before task execution. We suggest this style of responding is adopted to compensate for working memory impairment.