Integration of anaerobic digestion with heat Pump: Machine learning-based technical and environmental assessment.

Anaerobic digestion (AD)-based biogas production mitigates the environmental footprint of organic wastes (e.g., food waste and sewage sludge) and facilitates a circular economy. The work proposed an integrated system where the thermal energy demand of an AD is supplied using an air source heat pump (ASHP). The proposed system is compared to a baseline system, where the thermal energy is supplied by a natural gas-based heating system. Several machine learning models are developed for predicting biogas production, among which the Gaussian Process Regression (GPR) showed a superior performance (R2 = 0.84 and RMSE = 0.0755 L gVS-1 day-1). The GPR model further informed a thermodynamic model of the ASHP, which revealed the maximum biogas yield to be approximately 0.585 L.gVS-1.day-1 at an optimal temperature of 55 °C (thermophilic). Subsequently, life cycle assessment showed that ASHP-based AD heating systems achieved 28.1 % (thermophilic) and 36.8 % (mesophilic) carbon abatement than the baseline system.

Cardiac risk assessment with the Revised Cardiac Risk Index index before elective non-cardiac surgery: A retrospective audit from an Australian tertiary hospital.

Clinicians assessing cardiac risk as part of a comprehensive consultation before surgery can use an expanding set of tools, including predictive risk calculators, cardiac stress tests and measuring serum natriuretic peptides. The optimal assessment strategy is unclear, with conflicting international guidelines. We investigated the prognostic accuracy of the Revised Cardiac Risk Index for risk stratification and cardiac outcomes in patients undergoing elective non-cardiac surgery in a contemporary Australian cohort.We audited the records for 1465 consecutive patients 45 years and older presenting to the perioperative clinic for elective non-cardiac surgery in our tertiary hospital. We calculated individual Revised Cardiac Risk Index scores and documented any use of preoperative cardiac tests. The primary outcome was any major adverse cardiac events within 30 days of surgery, including myocardial infarction, pulmonary oedema, complete heart block or cardiac death.Myocardial perfusion imaging was the most common preoperative stress test (4.2%, 61/1465). There was no routine investigation of natriuretic peptide levels for cardiac risk assessment before surgery. Major adverse cardiac events occurred in 1.3% (18/1366) of patients who had surgery. The Revised Cardiac Risk Index score had modest prognostic accuracy for major cardiac complications, area under receiver operator curve 0.73, 95% confidence interval 0.60 to 0.86. Stratifying major adverse cardiac events by the Revised Cardiac Risk Index scores 0, 1, 2 and 3 or greater corresponded to event rates of 0.6% (4/683), 0.8% (4/488), 4.1% (6/145) and 8.0% (4/50), respectively.The Revised Cardiac Risk Index had only modest predictive value in our single-centre experience. Patients with a revised cardiac risk index score of 2 or more had an elevated risk of early cardiac complications after elective non-cardiac surgery.

Exploring why medical students still feel underprepared for clinical practice: a qualitative analysis of an authentic on-call simulation.

BACKGROUND: Current research shows that many UK medical graduates continue to feel underprepared to work as a junior doctor. Most research in this field has focused on new graduates and employed the use of retrospective self-rating questionnaires. There remains a lack of detailed understanding of the challenges encountered in preparing for clinical practice, specifically those faced by medical students, where relevant educational interventions could have a significant impact. Through use of a novel on-call simulation, we set out to determine factors affecting perceived preparation for practice in final year medical students and identify ways in which we may better support them throughout their undergraduate training. METHODS: 30 final year medical students from Imperial College London participated in a 90-minute simulation on hospital wards, developed to recreate a realistic on-call experience of a newly qualified doctor. Students partook in pairs, each observed by a qualified doctor taking field notes on their decisions and actions. A 60-minute semi-structured debrief between observer and student pair was audio-recorded for analysis. Field notes and students' clinical documentation were used to explore any challenges encountered. Debrief transcripts were thematically analysed through a general inductive approach. Cognitive Load Theory (CLT) was used as a lens through which to finalise the evolving themes. RESULTS: Six key themes emerged from the on-call simulation debriefs: information overload, the reality gap, making use of existing knowledge, negative feelings and emotions, unfamiliar surroundings, and learning 'on the job'. CONCLUSIONS: The combination of high fidelity on-call simulation, close observation and personalised debrief offers a novel insight into the difficulties faced by undergraduates in their preparation for work as a junior doctor. In using CLT to conceptualise the data, we can begin to understand how cognitive load may be optimised within this context and, in doing so, we highlight ways in which undergraduate curricula may be adapted to better support students in their preparation for clinical practice. Recommendations are centred around enhancing the expertise of the learner through 'whole task' training approaches and integrated learning, as well as navigating negative emotions and supporting lifelong 'learning while working'.

The rOSCE: A remote clinical examination during COVID lockdown and beyond.

This article was migrated. The article was marked as recommended. The COVID-19 pandemic has created a challenge for all medical educators. There is a clear need to train the next generation of doctors whilst ensuring that patient safety is preserved. The OSCE has long been used as the gold standard for assessing clinical competency in undergraduates ( Khan et al., 2013a). However, social distancing rules have meant that we have had to reconsider our traditional assessment methods. We held a remote eight-station summative OSCE (rOSCE) for three final year resit students using Microsoft Teams. Apart from clinical examinations and practical procedures which are assessed elsewhere in our programme, the content was similar to our standard OSCE. Staff and student training ensured familiarity with the assessment modality. The rOSCE was found to be a feasible tool with high face validity. The rOSCE is a remote assessment tool that can offer an alternative to the traditional face to face OSCEs for use in high stakes examinations. Although further research is needed, we believe that the rOSCE is scalable to larger cohorts of students and is adaptable to the needs of most undergraduate clinical competency assessments.

UK longitudinal integrated clerkships: where are we now?

In this article, we discuss whether it is possible for UK institutions to influence the international longitudinal integrated clerkship (LIC) narrative, in the context of supplying future clinicians to a fragmented health service that is battling a General Practice recruitment crisis. Perhaps more importantly, we will discuss whether the 'LIC model' fits the UK undergraduate framework. We intend to present some emerging evidence of LICs in the UK, informed by a UK-wide survey and observations from a 2019 UK LIC think tank and then discuss whether the global CLIC definition applies to the UK context with possible ways forward.

Genomic Correlates of Disease Progression and Treatment Response in Prospectively Characterized Gliomas.

PURPOSE: The genomic landscape of gliomas has been characterized and now contributes to disease classification, yet the relationship between molecular profile and disease progression and treatment response remain poorly understood.Experimental Design: We integrated prospective clinical sequencing of 1,004 primary and recurrent tumors from 923 glioma patients with clinical and treatment phenotypes. RESULTS: Thirteen percent of glioma patients harbored a pathogenic germline variant, including a subset associated with heritable genetic syndromes and variants mediating DNA repair dysfunctions (29% of the total) that were associated with somatic biallelic inactivation and mechanism-specific somatic phenotypes. In astrocytomas, genomic alterations in effectors of cell-cycle progression correlated with aggressive disease independent of IDH mutation status, arose preferentially in enhancing tumors (44% vs. 8%, P < 0.001), were associated with rapid disease progression following tumor recurrence (HR = 2.6, P = 0.02), and likely preceded the acquisition of alkylating therapy-associated somatic hypermutation. Thirty-two percent of patients harbored a potentially therapeutically actionable lesion, of whom 11% received targeted therapies. In BRAF-mutant gliomas, response to agents targeting the RAF/MEK/ERK signaling axis was influenced by the type of mutation, its clonality, and its cellular and genomic context. CONCLUSIONS: These data reveal genomic correlates of disease progression and treatment response in diverse types of glioma and highlight the potential utility of incorporating genomic information into the clinical decision-making for patients with glioma.

Identifying central tenets needed in our education systems: Results from a pilot integrated clinical apprenticeship.

Purpose: The ability of healthcare systems to deliver world-class compassionate care depends on the quality of training and education of staff. Matching student-centered learning with patient-centered care is the focus for much curricula reform. This study explores the effect a novel longitudinal curriculum had on medical students' attitudes and experiences to better identify central tenets needed in our education system. Methods: Single-center, qualitative focus-group study conducted in 2017 of medical students in a longitudinally integrated clinical apprenticeship at a large UK medical school. Students were randomly assigned to focus groups to describe their educational journey and explore how longitudinal learning prepared them for a medical career, valuing their unique position as student participants in the healthcare system. Results: Four themes emerged from students' experiences: navigating the patient journey, their professional development, their learning journey, and the healthcare system. Conclusions: Listening to student voices lends insights for educators refining educational models to produce doctors of tomorrow. This project identified the educational value of students having authentic roles in helping patients navigate the healthcare system and the benefits of consistent mentorship and greater autonomy. The gulf between gaining skills as a future doctor and gaining skills to pass summative exams calls into question assessment methods.

Multicenter Phase IB Trial of Carboxyamidotriazole Orotate and Temozolomide for Recurrent and Newly Diagnosed Glioblastoma and Other Anaplastic Gliomas.

Purpose Carboxyamidotriazole orotate (CTO) is a novel oral inhibitor of non-voltage-dependent calcium channels with modulatory effects in multiple cell-signaling pathways and synergistic effects with temozolomide (TMZ) in glioblastoma (GBM) models. We conducted a phase IB study combining CTO with two standard TMZ schedules in GBM. Methods In cohort 1, patients with recurrent anaplastic gliomas or GBM received escalating doses of CTO (219 to 812.5 mg/m2 once daily or 600 mg fixed once-daily dose) combined with TMZ (150 mg/m2 5 days during each 28-day cycle). In cohort 2, patients with newly diagnosed GBM received escalating doses of CTO (219 to 481 mg/m2/d once daily) with radiotherapy and TMZ 75 mg/m2/d, followed by TMZ 150 mg to 200 mg/m2 5 days during each 28-day cycle. Results Forty-seven patients were enrolled. Treatment was well tolerated; toxicities included fatigue, constipation, nausea, and hypophosphatemia. Pharmacokinetics showed that CTO did not alter TMZ levels; therapeutic concentrations were achieved in tumor and brain. No dose-limiting toxicities were observed; the recommended phase II dose was 600 mg/d flat dose. Signals of activity in cohort 1 (n = 27) included partial (n = 6) and complete (n = 1) response, including in O6-methylguanine-DNA methyltransferase unmethylated and bevacizumab-refractory tumors. In cohort 2 (n = 15), median progression-free survival was 15 months and median overall survival was not reached (median follow-up, 28 months; 2-year overall survival, 62%). Gene sequencing disclosed a high rate of responses among EGFR-amplified tumors ( P = .005), with mechanisms of acquired resistance possibly involving mutations in mismatch-repair genes and/or downstream components TSC2, NF1, NF2, PTEN, and PIK3CA. Conclusion CTO can be combined safely with TMZ or chemoradiation in GBM and anaplastic gliomas, displaying favorable brain penetration and promising signals of activity in this difficult-to-treat population.

Efficacy Outcome Measures for Pediatric Procedural Sedation Clinical Trials: An ACTTION Systematic Review.

Objective evaluations comparing different techniques and approaches to pediatric procedural sedation studies have been limited by a lack of consistency among the outcome measures used in assessment. This study reviewed those existing measures, which have undergone psychometric analysis in a pediatric procedural sedation setting, to determine to what extent and in what circumstances their use is justified across the spectrum of procedures, age groups, and techniques. The results of our study suggest that a wide range of measures has been used to assess the efficacy and effectiveness of pediatric procedural sedation. Most lack the evidence of validity and reliability that is necessary to facilitate rigorous clinical trial design, as well as the evaluation of new drugs and devices. A set of core pediatric sedation outcome domains and outcome measures can be developed on the basis of our findings. We believe that consensus among all stakeholders regarding appropriate domains and measures to evaluate pediatric procedural sedation is possible and that widespread implementation of such recommendations should be pursued.

Intravenous Magnesium Sulphate for Analgesia after Caesarean Section: A Systematic Review.

OBJECTIVE: To summarise the evidence for use of intravenous magnesium for analgesic effect in caesarean section patients. BACKGROUND: Postcaesarean pain requires effective analgesia. Magnesium, an N-methyl-D-aspartate receptor antagonist and calcium-channel blocker, has previously been investigated for its analgesic properties. METHODS: A systematic search was conducted of PubMed, Scopus, MEDLINE, Cochrane Library, and Google Scholar databases for randomised-control trials comparing intravenous magnesium to placebo with analgesic outcomes in caesarean patients. RESULTS: Ten trials met inclusion criteria. Seven were qualitatively compared after exclusion of three for unclear bias risk. Four trials were conducted with general anaesthesia, while three utilised neuraxial anaesthesia. Five of seven trials resulted in decreased analgesic requirement postoperatively and four of seven resulted in lower serial visual analogue scale scores. CONCLUSIONS: Adjunct analgesic agents are utilised to improve analgesic outcomes and minimise opioid side effects. Preoperative intravenous magnesium may decrease total postcaesarean rescue analgesia consumption with few side effects; however, small sample size and heterogeneity of methodology in included trials restricts the ability to draw strong conclusions. Therefore, given the apparent safety and efficacy of magnesium, its role as an adjunct analgesic in caesarean section patients should be further investigated with the most current anaesthetic techniques.

Biomechanical comparison of expanded polytetrafluoroethylene (ePTFE) and PTFE interpositional patches and direct tendon-to-bone repair for massive rotator cuff tears in an ovine model.

BACKGROUND: Massive irreparable rotator cuff tears are a difficult problem. Modalities such as irrigation and debridement, partial repair, tendon transfer and grafts have been utilized with high failure rates and mixed results. Synthetic interpositional patch repairs are a novel and increasingly used approach. The present study aimed to examine the biomechanical properties of common synthetic materials for interpositional repairs in contrast to native tendon. METHODS: Six ovine tendons, six polytetrafluoroethylene (PTFE) felt sections and six expanded PTFE (ePTFE) patch sections were pulled-to-failure to analyze their biomechanical and material properties. Six direct tendon-to-bone surgical method repairs, six interpositional PTFE felt patch repairs and six interpositional ePTFE patch repairs were also constructed in ovine shoulders and pulled-to-failure to examine the biomechanical properties of each repair construct. RESULTS: Ovine tendon had higher load-to-failure (591 N) and had greater stiffness (108 N/mm) than either PTFE felt (296 N, 28 N/mm) or ePTFE patch sections (323 N, 34 N/mm). Both PTFE felt and ePTFE repair techniques required greater load-to-failure (225 N and 177 N, respectively) than direct tendon-to-bone surgical repairs (147 N) in ovine models. CONCLUSIONS: Synthetic materials lacked several biomechanical properties, including strength and stiffness, compared to ovine tendon. Interpositional surgical repair models with these materials were significantly stronger than direct tendon-to-bone model repairs.

Adverse Event Reporting in Clinical Trials of Intravenous and Invasive Pain Treatments: An ACTTION Systematic Review.

Thorough assessment and reporting of adverse events (AEs) facilitates a detailed understanding of a treatment's risk-benefit profile. Although the Consolidated Standards of Reporting Trials (CONSORT) 2004 statement provides recommendations regarding AE reporting, adherence to these standards is often inadequate. We investigated AE reporting in clinical trials of intravenous and invasive pain treatments published in 6 major anesthesiology and pain journals between 2000 to 2003 and 2006 to 2012. We examined whether AE reporting improved after publication of the 2004 CONSORT recommendations and also comprehensively reviewed AE assessment using the Analgesic, Anesthetic, and Addiction Clinical Trial Translations, Innovations, Opportunities, and Networks (ACTTION) AE reporting recommendations. No improvement was found overall in CONSORT harms reporting scores from pre- to postpublication of the CONSORT recommendations, with only 5 of 10 fulfilled on average. AE reporting assessed using the ACTTION coding manual was generally inadequate, and 8% of articles failed to report any AE information at all. Anesthesiology and pain journals were similar in AE reporting quality, although industry-sponsored trials reported more AE information than nonindustry sponsored trials. Improvement is needed in AE reporting in analgesic clinical trials. The CONSORT checklist and ACTTION AE recommendations can assist investigators and editors in improving clinical trial transparency and quality. PERSPECTIVE: This systematic review of AE reporting in intravenous and invasive pain treatment trials shows that little improvement has been made since the 2004 CONSORT harms reporting guidelines. Better assessment and reporting of treatment AEs is necessary to understand the full clinical effect of intravenous and invasive treatments.

Reporting of cross-over clinical trials of analgesic treatments for chronic pain: Analgesic, Anesthetic, and Addiction Clinical Trial Translations, Innovations, Opportunities, and Networks systematic review and recommendations.

Cross-over trials are typically more efficient than parallel group trials in that the sample size required to yield a desired power is substantially smaller. It is important, however, to consider some issues specific to cross-over trials when designing and reporting them, and when evaluating the published results of such trials. This systematic review evaluated the quality of reporting and its evolution over time in articles of cross-over clinical trials of pharmacologic treatments for chronic pain published between 1993 and 2013. Seventy-six (61%) articles reported a within-subject primary analysis, or if no primary analysis was identified, reported at least 1 within-subject analysis, which is required to achieve the gain in power associated with the cross-over design. For 39 (31%) articles, it was unclear whether analyses conducted were within-subject or between-group. Only 36 (29%) articles reported a method to accommodate missing data (eg, last observation carried forward, n = 29), and of those, just 14 included subjects in the analysis who provided data from only 1 period. Of the articles that identified a within-subject primary analysis, 21 (51%) provided sufficient information for the results to be included in a meta-analysis (ie, estimates of the within-subject treatment effect and variability). These results and others presented in this article demonstrate deficiencies in reporting of cross-over trials for analgesic treatments. Clearer reporting in future trials could improve readers' ability to critically evaluate the results, use these data in meta-analyses, and plan future trials. Recommendations for proper reporting of cross-over trials that apply to any condition are provided.

Deficiencies in reporting of statistical methodology in recent randomized trials of nonpharmacologic pain treatments: ACTTION systematic review.

OBJECTIVE: The goal of this study was to assess the quality of reporting of statistical methods in randomized clinical trials (RCTs), including identification of primary analyses, missing data accommodation, and multiplicity adjustment, in studies of nonpharmacologic, noninterventional pain treatments (e.g., physical therapy, cognitive behavioral therapy, acupuncture, and massage). STUDY DESIGN: Systematic review of 101 articles reporting RCTs of pain treatments that were published between January 2006 and June 2013 in the European Journal of Pain, the Journal of Pain, and Pain. SETTING: Systematic review. RESULTS: Sixty-two percent of studies identified a primary outcome variable, 46% identified a primary analysis, and of those with multiple primary analyses, only 21% adjusted for multiplicity. Slightly over half (55%) of studies reported using at least one method to accommodate missing data. Only four studies reported prespecifying at least one of these four study methods. CONCLUSION: This review identified deficiencies in the reporting of primary analyses and methods to adjust for multiplicity and accommodate missing data in articles disseminating results of nonpharmacologic, noninterventional trials. Investigators should be encouraged to indicate whether their analyses were prespecified and to clearly and completely report statistical methods in clinical trial publications to maximize the interpretability of trial results.

Efficacy Outcome Measures for Procedural Sedation Clinical Trials in Adults: An ACTTION Systematic Review.

Successful procedural sedation represents a spectrum of patient- and clinician-related goals. The absence of a gold-standard measure of the efficacy of procedural sedation has led to a variety of outcomes being used in clinical trials, with the consequent lack of consistency among measures, making comparisons among trials and meta-analyses challenging. We evaluated which existing measures have undergone psychometric analysis in a procedural sedation setting and whether the validity of any of these measures support their use across the range of procedures for which sedation is indicated. Numerous measures were found to have been used in clinical research on procedural sedation across a wide range of procedures. However, reliability and validity have been evaluated for only a limited number of sedation scales, observer-rated pain/discomfort scales, and satisfaction measures in only a few categories of procedures. Typically, studies only examined 1 or 2 aspects of scale validity. The results are likely unique to the specific clinical settings they were tested in. Certain scales, for example, those requiring motor stimulation, are unsuitable to evaluate sedation for procedures where movement is prohibited (e.g., magnetic resonance imaging scans). Further work is required to evaluate existing measures for procedures for which they were not developed. Depending on the outcomes of these efforts, it might ultimately be necessary to consider measures of sedation efficacy to be procedure specific.

Reporting of adverse events and statistical details of efficacy estimates in randomized clinical trials of pain in temporomandibular disorders: Analgesic, Anesthetic, and Addiction Clinical Trial Translations, Innovations, Opportunities, and Networks systematic review.

BACKGROUND: Statistical methods and adverse events (that is, harms) data affect the accuracy of conclusions about the risk-to-benefit ratio of treatments for temporomandibular disorders (TMDs). The authors reviewed the quality of reporting in TMD clinical trials to highlight practices that are in need of improvement. TYPES OF STUDIES REVIEWED: The authors included articles published between 1969 and May 31, 2013, in which the investigators reported randomized clinical trials of TMD treatments with pain as a principal outcome variable. Investigators in trials of nonpharmacologic and noninvasive treatments were required to at least mask the participants and assessors; all others were required to be double masked. RESULTS: Ninety articles qualified for this review: 39 published between 1971 and 2005 (older articles) and 51 published between 2006 and 2013 (newer articles). Specification of primary outcome analyses, methods to accommodate missing data, and adverse event collection methods and rates were generally poor. In some cases, there was apparent improvement from the older to the newer cohort; however, reporting of these methodological details remained inadequate even in the newer articles. PRACTICAL IMPLICATIONS: This review is designed to alert authors, reviewers, editors, and readers of TMD clinical trials to these issues and improve reporting quality in the future.

Quality of pain intensity assessment reporting: ACTTION systematic review and recommendations.

UNLABELLED: Pain intensity assessments are used widely in human pain research, and their transparent reporting is crucial to interpreting study results. In this systematic review, we examined reporting of human pain intensity assessments and related elements (eg, administration frequency, time period assessed, type of pain) in all empirical pain studies with adult participants in 3 major pain journals (ie, European Journal of Pain, Journal of Pain, and Pain) between January 2011 and July 2012. Of the 262 articles identified, close to one-quarter (24%) ambiguously reported the pain intensity assessment. Elements related to the pain intensity assessment were frequently not reported: 31% did not identify the time period participants were asked to rate, 43% failed to report the type of pain intensity rated, and 58% did not report the specific location or pain condition rated. No differences were observed between randomized clinical trials and experimental (eg, studies involving experimental manipulation without random group assignment and blinding) and observational studies in reporting quality. The ability to understand study results, and to compare results between studies, is compromised when pain intensity assessments are not fully reported. Recommendations are presented regarding key details for investigators to consider when conducting and reporting pain intensity assessments in human adults. PERSPECTIVE: This systematic review demonstrates that publications of pain research often incompletely report pain intensity assessments and their details (eg, administration frequency, type of pain). Failure to fully report details of pain intensity assessments creates ambiguity in interpreting research results. Recommendations are proposed to increase transparent reporting.

Instruments to Identify Prescription Medication Misuse, Abuse, and Related Events in Clinical Trials: An ACTTION Systematic Review.

UNLABELLED: Measurement of inappropriate medication use events (eg, abuse or misuse) in clinical trials is important in characterizing a medication's abuse potential. However, no gold standard assessment of inappropriate use events in clinical trials has been identified. In this systematic review, we examine the measurement properties (ie, content validity, cross-sectional reliability and construct validity, longitudinal construct validity, ability to detect change, and responder definitions) of instruments assessing inappropriate use of opioid and nonopioid prescription medications to identify any that meet U.S. and European regulatory agencies' rigorous standards for outcome measures in clinical trials. Sixteen published instruments were identified, most of which were not designed for the selected concept of interest and context of use. For this reason, many instruments were found to lack adequate content validity (or documentation of content validity) to evaluate current inappropriate medication use events; for example, evaluating inappropriate use across the life span rather than current use, including items that did not directly assess inappropriate use (eg, questions about anger), or failing to capture information pertinent to inappropriate use events (eg, intention and route of administration). In addition, the psychometric data across all instruments were generally limited in scope. A further limitation is the heterogeneous, nonstandardized use of inappropriate medication use terminology. These observations suggest that available instruments are not well suited for assessing current inappropriate medication use within the specific context of clinical trials. Further effort is needed to develop reliable and valid instruments to measure current inappropriate medication use events in clinical trials. PERSPECTIVE: This systematic review evaluates the measurement properties of inappropriate medication use (eg, abuse or misuse) instruments to determine whether any meet regulatory standards for clinical trial outcome measures to assess abuse potential.