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Chronic pancreatitis is associated with impaired quality of life, high incidence of comorbidities, serious complications and mortality. Healthcare costs are exorbitant. Some medical societies have developed guidelines for treatment based on scientific evidence, but the gathered level of evidence for any individual topic is usually low and, therefore, recommendations tend to be vague or weak. In the present position papers on chronic pancreatitis from the Societat Catalana de Digestologia and the Societat Catalana de Pàncrees we aimed at providing defined position statements for the clinician based on updated review of published literature and on multidisciplinary expert agreement. The final goal is to propose the use of common terminology and rational diagnostic/therapeutic circuits based on current knowledge. To this end 51 sections related to chronic pancreatitis were reviewed by 21 specialists from 6 different fields to generate 88 statements altogether. Statements were designed to harmonize concepts or delineate recommendations. Part 2 of these paper series discuss topics on treatment and follow-up. The therapeutic approach should include assessment of etiological factors, clinical manifestations and complications. The complexity of these patients advocates for detailed evaluation in multidisciplinary committees where conservative, endoscopic, interventional radiology or surgical options are weighed. Specialized multidisciplinary units of Pancreatology should be constituted. Indications for surgery are refractory pain, local complications, and suspicion of malignancy. Enzyme replacement therapy is indicated if evidence of exocrine insufficiency or after pancreatic surgery. Response should be evaluated by nutritional parameters and assessment of symptoms. A follow-up program should be planned for every patient with chronic pancreatitis. © 2021 Elsevier España, S.L.U.

Objective The purpose of this study was to develop a natural language processing (NLP) pipeline to identify incidental thyroid nodules (ITNs) meeting criteria for sonographic follow-up and to assess both adherence rates to white paper recommendations and downstream outcomes related to these incidental findings. Methods 21583 non-contrast chest CT reports from 2017 and 2018 were retrospectively evaluated to identify reports which included either an explicit recommendation for thyroid ultrasound, a description of a nodule ≥ 1.5 cm, or description of a nodule with suspicious features. Reports from 2018 were used to train an NLP algorithm called fastText for automated identification of such reports. Algorithm performance was then evaluated on the 2017 reports. Next, any patient from 2017 with a report meeting criteria for ultrasound follow-up was further evaluated with manual chart review to determine follow-up adherence rates and nodule-related outcomes. Results NLP identified reports with ITNs meeting criteria for sonographic follow-up with an accuracy of 96.5% (95% CI 96.2-96.7) and sensitivity of 92.1% (95% CI 89.8-94.3). In 10006 chest CTs from 2017, ITN follow-up ultrasound was indicated according to white paper criteria in 81 patients (0.8%), explicitly recommended in 46.9% (38/81) of patients, and obtained in less than half of patients in which it was appropriately recommended (17/35, 48.6%). Discussion NLP accurately identified chest CT reports meeting criteria for ITN ultrasound follow-up. Radiologist adherence to white paper guidelines and subsequent referrer adherence to radiologist recommendations showed room for improvement.

Antimicrobial stewardship programs (ASPs) have made immense strides in optimizing antibiotic, antifungal, and antiviral use in clinical settings. However, although ASPs are required institutionally by regulatory agencies in the United States and Canada, they are not mandated for transplant centers or programs specifically. Despite the fact that solid organ transplant recipients in particular are at increased risk of infections from multidrug-resistant organisms, due to host and donor factors and immunosuppressive therapy, there currently are little rigorous data regarding stewardship practices in solid organ transplant populations, and thus, no transplant-specific requirements currently exist. Further complicating matters, transplant patients have a wide range of variability regarding their susceptibility to infection, as factors such as surgery of transplant, intensity of immunosuppression, and presence of drains or catheters in situ may modify the risk of infection. As such, it is not feasible to have a “one-size-fits-all” style of stewardship for this patient population. The objective of this white paper is to identify opportunities, risk factors, and ASP strategies that should be assessed with solid organ transplant recipients to optimize antimicrobial use, while producing an overall improvement in patient outcomes. We hope it may serve as a springboard for development of future guidance and identification of research opportunities.

Palliative radiation therapy (pRT) is an effective tool for people with incurable cancer, in the treatment of many cancer-related symptoms such as pain, bleeding and dyspnea. As utilization rates for palliative radiation therapy increase, the demands on the healthcare system continue to grow. Radiation Therapists with advanced knowledge, skills and judgements began demonstrating their ability to practice autonomously in 2004, with the development of the Clinical Specialist Radiation Therapist (CSRT) role. Since this time, CSRTs with a specific focus in pRT (pCSRT) have been increasing in both numbers as well as their positive effects on the cancer care system. Integrating a pCSRT into the existing pRT system has resulted in increased access to and quality of pRT being delivered to palliative cancer patients. The benefits of the addition of pCSRTs to the cancer care system include increasing system capacity and increasing quality of care. This white paper provides information related to the improvements that can be realized in a RT program related to the care and treatment of its palliative patients by adding a pCSRT to the interprofessional healthcare team and suggest it as one of many strategies that can be undertaken to make improvements to access and quality of care.

Neonatal and infantile cholestasis (NIC) can represent the onset of a surgically correctable disease and of a genetic or metabolic disorder worthy of medical treatment. Timely recognition of NIC and identification of the underlying etiology are paramount to improve outcomes. Upon invitation by the Italian National Institute of Health (ISS), an expert working grouped was formed to formulate evidence-based positions on current knowledge about the diagnosis of NIC. A systematic literature search was conducted to collect evidence about epidemiology, etiology, clinical aspects and accuracy of available diagnostic tests in NIC. Evidence was scored using the GRADE system. All recommendations were approved by a panel of experts upon agreement of at least 75% of the members. The final document was approved by all the panel components. This position document summarizes the collected statements and defines the best-evidence diagnostic approach to cholestasis in the first year of life.

Objective The objective of this study was to develop the first edition of a Chinese evidence-based position paper on the management of oral leukoplakia (OLK). Study Design The consultant group for drafting the position paper consisted of 31 oral medicine specialists and 2 evidence-based medicine specialists. English studies (searched in PubMed, EMBASE, and the Cochrane Library) and Chinese studies (searched in China National Knowledge Infrastructure and WanFang) published before January 2018 were used. The quality of the study was assessed using the Grading of Recommendations Assessment, Development, and Evaluation grid, and the strength of the recommendations was determined based on the results of 3 rounds of voting among the consultant group members using the Delphi method. Results Twenty-two evidence-based guidelines for clinical management and monitoring of OLK were established in this position paper. A clinical path diagram for oral health practitioners was constructed based on the recommendations. Conclusion Current evidence suggests that management and monitoring of patients with OLK should be performed by experienced clinicians to control the lesion and for early detection of malignant transformation. However, all recommendations are based on evidence of low or extremely low quality and may require further modification as new evidence is produced.

Intra-operative ultrasound has become a relevant imaging modality in neurosurgical procedures. While B-mode, with its intrinsic limitations, is still considered the primary ultrasound modality, intra-operative contrast-enhanced ultrasound (ioCEUS) has more recently emerged as a powerful tool in neurosurgery. Though still not used on a large scale, ioCEUS has proven its utility in defining tumor boundaries, identifying lesion vascular supply and mapping neurovascular architecture. Here we propose a step-by-step procedure for performing ioCEUS analysis of the brain, highlighting its neurosurgical applications. Moreover, we provide practical advice on the use of ultrasound contrast agents and review technical ultrasound parameters influencing ioCEUS imaging.

Human trafficking is a pandemic human rights violation with an emerging paradigm shift that reframes an issue traditionally seen through a criminal justice lens to that of a public health crisis, particularly for children. Children and adolescents who are trafficked or are at risk for trafficking should receive evidence-based, trauma-informed, and culturally responsive care from trained health care providers (HCPs). The purpose of this article was to engage and equip pediatric HCPs to respond effectively to human trafficking in the clinical setting, improving health outcomes for affected and at-risk children. Pediatric HCPs are ideally positioned to intervene and advocate for children with health disparities and vulnerability to trafficking in a broad spectrum of care settings and to optimize equitable health outcomes.

Objectives A recent paper by Doi et al. advocated completely replacing the relative risk (RR) with the odds ratio (OR) as the effect measure in clinical trials and meta-analyses with binary outcomes. Besides some practical advantages of RR over OR, Doi et al.’s key assumption that the OR is “portable” in the meta-analysis, that is, study-specific ORs are likely not correlated with baseline risks, was not well justified. Study designs and settings We summarized Spearman's rank correlation coefficient between study-specific ORs and baseline risks in 40,243 meta-analyses from the Cochrane Database of Systematic Reviews. Results Study-specific ORs tend to be higher in studies with lower baseline risks of disease for most meta-analyses in Cochrane Database of Systematic Reviews. Using an actual meta-analysis example, we demonstrate that there is a strong negative correlation between OR (RR or RD) with the baseline risk and the conditional effects notably vary with baseline risks. Conclusions Replacing RR or RD with OR is currently unadvisable in clinical trials and meta-analyses. It is possible that no effect measure is “portable” in a meta-analysis. In addition to the overall (or marginal) effect, we suggest presenting the conditional effect based on the baseline risk using a bivariate generalized linear mixed model.

Objective This study collected randomized controlled trials (RCTs) published in the social sciences in China and assessed their risk of bias and reporting quality. Study Design and Setting Three databases were systematically searched for publications from January 2000 to June 2020 for RCTs in the social sciences published by Chinese researchers. The risk of bias was assessed using the Cochrane Collaboration Risk of Bias Tool (CCRBT), and reporting quality was assessed using the Consolidated Standards of Reporting Trials for Social and Psychological Interventions (CONSORT-SPI). Results A total of 316 RCTs were identified, including 204 articles in English and 112 articles in Chinese. The most frequently researched interventions focused on education (33.9%), and the most frequently studied population were students (32.9%). Eighty-seven percent of RCTs had intermediate reporting quality. Twenty-four of the 43 CONSORT-SPI sub-items had a compliance rate of less than 50%. Most RCTs had an unclear risk of bias for blinding outcome assessors (84.5%), blinding participants and personnel (82.9%), allocation concealment (73.1%), and random sequence generation (68.0%). A low proportion of CONSORT-SPI items were reported and, high proportion of the papers had unclear risk of bias. Conclusion The quality and reporting of RCTs in the social sciences needs improvement in China, especially for reporting methods and results. Most studies had an unclear risk of bias as they lacked important methodological information.

Pulp and paper mills are known large emitters of air pollution creating potential environmental challenges and human health impacts. This study assesses air pollution and associated impacts from connected pulp and paper facilities which operate in Edmundston, New Brunswick, Canada, and Madawaska, Maine, United States (US). Despite operating within two regulatory jurisdictions on both sides of the international border (in Canada and the US), the mills have exceeded their approvals to operate and national air quality regulations multiple times between 2010 and 2017. Previous studies have linked many types of cancer as well as respiratory and cardiovascular diseases to air pollution emitted by pulp and paper mills, making this an important regional issue in Canada and the US. While potential environmental and community impacts are likely similar on both sides of the international border, emissions from each side are not reported on the other, and few studies have been conducted on either side. Historic and ongoing lack of local epidemiological health and environmental impact studies and recommendations for improvements to mill operations to improve environmental and human health are presented.

Background In Victoria, Australia, public hospitals are administered through a system of devolved governance. Overall, Victoria's public health system has a record of good performance when comparing measurable safety outcomes to the rest of Australia. However, in 2015 a cluster of preventable perinatal deaths were identified at a health service in Melbourne's outer fringes. Questions What were the factors that contributed to these preventable deaths, and what were the outcomes of the four key inquiries commissioned by the Victorian government after the identification of the cluster? What can be learnt by comparing this crisis in one Victorian health service to similar events at other health services in Australia and the United Kingdom? Methods This paper discusses the crisis at the Victorian health service and expands on the factors that contributed to the crisis, the inquiries, subsequent recommendations, and the response from the Victorian state government. Similarities between this case and others in Australia and the United Kingdom are discussed. Findings A common theme in the four inquiries into the crisis at the health service in Victoria was that inadequate clinical governance was a key factor that led to these events. As a result, a number of significant changes were implemented across the state to improve patient safety across all areas of health care. When comparing this Victorian crisis to similar events at other health services across the world, inadequate clinical governance consistently appears as a key contributing factor to poor clinical outcomes. Discussion All cases discussed had a delay in the identification of clusters of poor clinical outcomes. This was found to be a direct result of inadequate clinical governance structures at both a local and government level. Conclusion A robust clinical governance framework that is enacted at both the government and the health organisation level is essential to deliver high quality and safe patient care.

Background Brugada syndrome is a rare inherited arrhythmic syndrome with a coved type 1 ST-segment elevation on ECG and an increased risk of sudden death. Many studies have evaluated risk stratification performance based on ECG-derived parameters. However, since historical Brugada patient cohorts included mostly paper ECGs, most studies have been based on manual ECG parameter measurements. We hypothesized that it would be possible to run automated algorithm-based analysis of paper ECGs. We aimed: 1) to validate the digitization process for paper ECGs in Brugada patients; and 2) to quantify the acute class I antiarrhythmic drug effect on relevant ECG parameters in Brugada syndrome. Methods A total of 176 patients (30% female, 43 ± 13 years old) with induced type 1 Brugada syndrome ECG were included in the study. All of the patients had paper ECGs before and during class I antiarrhythmic drug challenge. Twenty patients also had a digital ECG, in whom printouts were used to validate the digitization process. Paper ECGs were scanned and then digitized using ECGScan software, version 3.4.0 (AMPS, LLC, New York, NY, USA) to obtain FDA HL7 XML format ECGs. Measurements were automatically performed using the Bravo (AMPS, LLC, New York, NY, USA) and Glasgow algorithms. Results ECG parameters obtained from digital and digitized ECGs were closely correlated (r = 0.96 ± 0.07, R2 = 0.93 ± 0.12). Class I antiarrhythmic drugs significantly increased the global QRS duration (from 113 ± 20 to 138 ± 23, p Conclusions Automated algorithm-based measurements of depolarization and repolarization parameters from digitized paper ECGs are reliable and could quantify the acute effects of class 1 antiarrhythmic drug challenge in Brugada patients. Our results support using computerized automated algorithm-based analyses from digitized paper ECGs to establish risk stratification decision trees in Brugada syndrome.

Objective To identify key papers in urology using a novel bibliometric index called the disruption score. Methods A PubMed search was conducted to identify papers published in Journal of Urology, European Urology, Urology, Urologic Oncology, Journal of Endourology, and BJU International, Nature Reviews Urology. Selected urology papers published in other medical journals were also included. Using a validated dataset of disruption scores for all papers published in 1954-2014, the top 100 most-disruptive urology papers, as well as the top 100 most-cited papers, were identified. Comparisons between both lists and across journals were investigated. Results A total of 72,623 published articles were included. Journal of Urology had the most articles in the most-disruptive papers list (n = 69) followed by BJU International (n = 16). New England Journal of Medicine had the most papers in the most-cited papers list (n = 26) followed by Journal of Urology (n = 23). Only 7 papers were common to both the most-disruptive papers and most-cited papers lists. Oncology was highly represented among the most-cited papers (n = 60), whereas the most-disruptive papers included a broader representation of urology. The most common study design among the most disruptive papers was small case-series/case reports, whereas the most common study design among the most-cited papers was randomized controlled trials. Conclusion The disruption score identified landmark papers in urology that have introduced innovative ideas. Disruption score captures a unique profile of scientific impact that may be used in combination with other bibliometric indices to identify scholarly achievements in urology.

Natural and synthetic alkaloids are widely used for several applications, ranging from clinical purposes to criminal activities. Presumptive color tests are considered a leading tool to reveal on-scene substance identification via rapid chemical reactions that result in visual color changes. Colorimetric tests are popular due to their inherent simplicity, low cost, promptitude and portability; however, in many cases the results of such tests may not be predictable, partly because of the interference from similar species. In this proof-of-concept study, we present a paper-based microfluidic optoelectronic tongue - the so-called μOPTO - comprised of 6 indicators in lieu of one specific test and capable of discriminating 8 different alkaloid drugs (i.e. scopolamine, atropine, cocaine, morphine, ephedrine, caffeine, dipyrone and alprazolam) used for recreational, criminal and medical purposes. The wax printing method was employed to fabricate the microfluidic analytical device with six circular spots for reagent accommodation connected to a centered spot to enable simultaneous reactions with one sample injection. Digital images were obtained using an ordinary flatbed scanner, and the RGB information from before and after sample exposure was extracted using appropriate software. The color changes related to each spot were used to build differential maps with a unique fingerprint for each drug. The chemometric tools (i.e. PCA and HCA) showed suitable discrimination of all studied alkaloids in different quantities. To demonstrate a practical application, different alcoholic beverages spiked with scopolamine - a famous substance that causes drug abuse - were analyzed using the optoelectronic tongue. The results showed that small quantities of the drug were identified in different beverages, demonstrating that our device has the potential to be used in situ to prevent ingestion of contaminated samples.

Objectives Unlike the technological advances in cross-sectional imaging, the adoption of CR and DR has been relatively overlooked in terms of the additional radiographer skills and competences required for optimal practice. Furthermore, projection radiography is often referred to as basic, plain or other words suggesting simplicity or entry-level skill requirements. Radiographers’ professional identity is connected with the discourse expressed via the language used in daily practice and consequently, if the perception of projection radiography is regarded as simple practice not requiring much reflection or complex decision-making, apathy and carelessness may arise. The purpose of this narrative review was to raise projection radiography from its longstanding lowly place and re-position it as a specialist imaging field. Key findings Danish pre-registration radiography curricula contain little mention of projection radiography and a low proportion (n = 17/144; 11.8%) of Danish radiography students chose to focus on projection radiography within publicly available BSc. theses between 2016 and 2020 as compared to topics related to CT and MRI (n = 60/144; 41.7%). Conclusion By changing how we as the profession perceive the role and position of projection radiography, we can start to rebuild its lost prestige and demand a greater, more detailed and clinically relevant educational offering from academic partners. For this to commence, the language and terminology we use to describe ourselves and tasks undertaken must reflect the complexity of the profession. Implications for practice Regardless of imaging modality, every patient should be assured that a radiographer with expertise in acquiring images of diagnostic quality undertakes their examination. Reclaiming the prestige of projection radiography may lead students and radiographers to recognize projection radiography as a demanding specialist field for the benefit of the patients.

Background In 2019, a randomized controlled trial (RCT) authored by Dr. Ismail was retracted due to concerns about data integrity. Since there are no policies in place to investigate other publications of authors of retracted studies, we investigated Dr. Ismail’s other trials. Methods We searched for RCTs authored by Dr. Ismail. We made pairwise comparisons of values in baseline and outcome tables between trials. We assessed whether the distributions of baseline characteristics were compatible with properly conducted randomization, using Monte Carlo simulations and the Kolmogorov-Smirnov test. We read the publications carefully for unusual features. Results Dr. Ismail was author in eight published and one unpublished trial. In three of his first author studies we found multiple identical values in the baseline and/or outcome tables from different trials. At least some of the trials were unlikely to have followed a proper randomization process. There were a number of other unusual features in the papers we reviewed. Conclusions It is probable that other trials published by Dr. Ismail contain questionable data. We call for a thorough investigation of the original trial data and related official documents. Our exercise suggests that the practice to assess research integrity should include all publications of authors with retracted fabricated articles.

This position paper, sponsored by the Asociación Española de Gastroenterología [Spanish Association of Gastroenterology], the Sociedad Española de Endoscopia Digestiva [Spanish Gastrointestinal Endoscopy Society] and the Sociedad Española de Anatomía Patológica [Spanish Anatomical Pathology Society], aims to establish recommendations for performing an high quality upper gastrointestinal endoscopy for the screening of gastric cancer precursor lesions (GCPL) in low-incidence populations, such as the Spanish population. To establish the quality of the evidence and the levels of recommendation, we used the methodology based on the GRADE system (Grading of Recommendations Assessment, Development and Evaluation). We obtained a consensus among experts using a Delphi method. The document evaluates different measures to improve the quality of upper gastrointestinal endoscopy in this setting and makes recommendations on how to evaluate and treat the identified lesions. We recommend that upper gastrointestinal endoscopy for surveillance of GCPL should be performed by endoscopists with adequate training, administering oral premedication and use of sedation. To improve the identification of GCPL, we recommend the use of high definition endoscopes and conventional or digital chromoendoscopy and, for biopsies, NBI should be used to target the most suspicious areas of intestinal metaplasia. Regarding the evaluation of visible lesions, the risk of submucosal invasion should be evaluated with magnifying endoscopes and endoscopic ultrasound should be reserved for those with suspected deep invasion. In lesions amenable to endoscopic resection, submucosal endoscopic dissection is considered the technique of choice.

A current osteopathic tenet inherited from Native American principles involves viewing each person as a dynamic interaction of body-mind-spirit (BMS). Because of its traditional medicine heritage and current evidence-based approach, the osteopathic profession is, arguably, uniquely positioned to promote evidence-informed person-centered approaches that transcend improvements in pain and musculoskeletal function. It may be particularly relevant in the context of integrating the BMS tenet into osteopathic care according to the diversity of patients’ values and sociocultural assumptions towards health, symptoms, and subsequent care, which range from the typical Western to complementary and alternative medicine perspectives. There is currently a lack of robust clinical practice frameworks in this area, confusing patients and practitioners and blurring professional identities. The current commentary provides an opportunity to initiate discussions in the profession with a rationale for creating a roadmap to develop an evidence-informed framework for osteopathic care that integrates the BMS tenet.

Multiple myeloma is the second most common hematological malignancy in the USA and Europe. Despite improvements in the 5-year and overall survival rates over the past decade, older adults (aged ≥65 years) with multiple myeloma continue to experience disproportionately worse outcomes than their younger counterparts. These differences in outcomes arise from the increased prevalence of vulnerabilities such as medical comorbidities and frailty seen with advancing age that can influence treatment-delivery and tolerance and impact survival. In general, geriatric assessments can help identify those patients more likely to benefit from enhanced toxicity risk-prediction and aid treatment decision-making. Despite the observed benefits of geriatric assessments and other screening frailty tools, provider and systems-level barriers continue to influence the overall perception of the feasibility of geriatric assessments in clinical practice settings. Clinical trials are underway evaluating the efficacy and safety of various multiple myeloma therapies in less fit/frail older adults, with a minority examining fitness-based/risk-adapted approaches. Thus, significant gaps exist in knowing which myeloma therapies are most appropriate for older and more vulnerable adults with multiple myeloma. The purpose of this Review is to discuss how geriatric assessments can be used to guide the management of transplant-ineligible patients; and to highlight frontline therapies for standard-risk and high-risk cytogenetic abnormalities [i.e., t(4;14), t(14;16), and del(17p)] associated with multiple myeloma. We also discuss the current shortcomings of the existing clinical approaches to care and highlight ongoing clinical trials evaluating newer fitness-based approaches to managing transplant-ineligible patients.

Introduction The disruption score is a new bibliometric tool that has recently been utilized to identify studies that are innovative and shift paradigms. We sought to identify and characterize the top 100 most disruptive publications in pediatric surgery. Methods The 100 most disruptive and cited publications in 17 pediatric surgery journals were identified from a validated dataset and linked with the iCite NIH tool. The top 100 most disruptive publications were reviewed to determine study design, clinical focus, and perceived contribution. Results The publications included in the top 100 list were more disruptive than 99.5% of the entire PubMed universe. Journal of Pediatric Surgery (n = 45) had the most articles included. There was a weak correlation between citation count and disruption score (r = 0.27). Retrospective cohort studies (38%), contributions in clinical outcomes (39%), technical/technological innovations (31%), clinical focus in trauma (18%), and disorders of the gastrointestinal tract (18%) were the most represented. The disruption score identified a unique subset of literature that has created new paradigms with long lasting influence and may be further applied as another tool to measure scientific impact. This wide array of literature highlights both technical and technological innovations as well as key moments in the history of pediatric surgery. Level of evidence V

Bladder duplication is a rare anomaly classified as sagittal or coronal, depending on the axis of the septum. VACTER association involves congenital anomalies affecting the vertebrae, anus, heart, trachea, esophagus, kidney and genitourinary system. This is the first description of a case of coronal bladder duplication in a patient that also presented with anomalies on the foregut and other organs that correspond to VACTER association. Pertinent literature is systematically reviewed and compared with our case.

The development of microfluidic devices for point-of-care (POC) testing has been widely applied for food quality control, environmental monitoring, and clinical diagnoses. Regarding the latter, microfluidic paper-based analytical devices (µPADs) have a great potential in developing portable and disposable platforms for fast disease-relevant biomarker detection in remote areas. In this work, k-nearest neighbors (k-NN) classifiers were applied to demonstrate the reliability of using chemical data obtained from µPADs for diagnosis of diseases like diabetes mellitus and hyperuricemia. Predictors based on glucose, lactate, and uric acid biomarkers were evaluated to reach this goal. Healthy adults were differentiated from the diagnosed patients with a perfect success rate. Metabolic disorders were suitably predicted with 95.0% overall accuracy. This model also showed sensitivities and specificities in the ranges 75–100% and 93–100%, respectively, indicating that the classification protocol is robust. The k-NN modeling proved the potential of the µPADs to be applied in telemedicine for reliable off-site diagnoses.

Most anticancer molecules are administered in body-size-based dosing schedules, bringing up unsolved issues regarding pharmacokinetic data in heavy patients. The worldwide spread of obesity has not been matched by improved methods and strategies for tailored drug dosage in this population. The weight or body surface area (BSA)-based approaches may fail to fully reflect the complexity of the anthropometric features besides obesity in cancer patients suffering from sarcopenia. Likewise, there is a lack of pharmacokinetic data on obese patients for the majority of chemotherapeutic agents as well as for new target drugs and immunotherapy. Therefore, although the available findings point to the role of dose intensity in cancer treatment, and support full weight-based dosing, empirical dose capping often occurs in clinical practice in order to avoid toxicity. Thus a panel of experts of the Associazione Italiana Oncologia Medica (AIOM), Associazione Medici Diabetologi (AMD), Società Italiana Endocrinologia (SIE), and Società Italiana Farmacologia (SIF), provides here a consensus statement for appropriate cytotoxic chemotherapy and new biological cancer drug dosing in obese patients., Highlights • The worldwide spread of obesity is an emerging challenge also in cancer patients • Weight or BSA-based approaches do not adequately address the critical issue of optimal dosing for cancer drugs under obesity • Empirical dose capping is often employed in clinical practice to avoid toxicities among overweight and obese patients • There is a lack of clinical and pharmacokinetic studies in this population • Clinical practice recommendations should guide suitable dosing of cytotoxic and biological cancer drugs in obese patients

Breastfeeding offers one of the most fundamental global health benefits for babies. Breastmilk is lifesaving, providing not only nutrition but immunologic benefits and as such is strongly supported by the World Health Organization and leading healthcare associations worldwide. When the COVID-19 pandemic started in 2020, the impact of the restrictions to prevent the spread of the disease created challenges and questions about provision of safe, quality care, including breastfeeding practices, in a new 'normal' environment. Mothers were temporarily separated from their babies where infection was present or suspected, parents were prevented from being present on neonatal units and vital breastfeeding support was prevented. This discussion paper provides an overview of essential areas of knowledge related to practice for neonatal nurses and midwives who care for breastfeeding mothers and babies, in the context of the COVID-19 pandemic and the latest global guidance. Three areas will be discussed; the protective benefits of breastfeeding, keeping breastfeeding mothers and babies together and supporting mothers to breastfeed their babies. Finally, care recommendations are presented to serve as a summary of key points for application to practice for neonatal nurses and midwives.

During the COVID-19 pandemic, parents with sick or premature babies have faced challenges following admission to a neonatal unit due to the imposed lock-down restrictions on social contact, hospital visitation and the wearing of personal protective equipment. The negative short-term impact on neonatal care in relation to the prevention of close proximity, contact and bonding between parents and babies is potentially significant. However, an interesting finding has been reported of a reduction in premature birth admissions to the neonatal intensive care unit during the pandemic, raising important questions. Why was this? Was it related to the effect of the modifiable risk-factors for premature birth? This discussion paper focuses on an exploration of these factors in the light of the potential impact of COVID-19 restrictions on neonatal care. After contextualising both the effect of premature birth and the pandemic on neonatal and parental short-term outcomes, the discussion turns to the modifiable risk-factors for premature birth and makes recommendations relevant to the education, advice and care given to expectant mothers.

Electrochemical paper-based analytical devices (ePADs) are useful analytical devices that serve as point-of-care testing (POCT) devices for various clinical biomarkers in view of their simplicity, portability, and low-cost format. However, multistep reagent manipulation usually restricts the performance of the device for end users. Herein, we developed a sequential ePAD for sequential immunosensing fluid delivery by integrating dual flow behaviors (fast-flow/delayed) within a single paper platform for the simultaneous detection of hepatitis B surface antigen (HBsAg) and hepatitis C core antigen (HCVcAg). In the present work, a fast-flow channel was used for the automated washing of unbound antigens, while a delayed channel was created to store a redox reagent for further electrochemical analysis with a single buffer loading (the analysis time can be completed within 500 s). Hence, the undesirable complex procedure of multi-step reagent manipulation is scarcely needed by the user. The detection limit of the proposed ePAD was as low as 18.2 pg mL−1 for HBsAg and 1.19 pg mL−1 for HCVcAg. In addition, this proposed ePAD was also proven to be effective in real clinical sera from patients to verify its biological applicability. The ePAD sensor shows high promise as an easy-to-use, portable, and extendable sensor for other multiplex biological assays.

Penetrating head trauma (PHT) includes any traumatic injury where an object pierces the skull and breaches the dural membrane surrounding the brain. PHTs are less prevalent than blunt head injuries. However, they often have more complex damage, worse prognosis, and higher rates of morbidity and mortality. An 83-year-old man fell at his home and hit his head on the right side toward a shoji (a Japanese-style paper sliding door). He reported to the emergency room the following day with his family. He had a small wound before the right ear, which was sutured in the emergency room. A CT scan demonstrated tiny pieces of bone fragments inside the brain, as well as right temporal subcortical hemorrhage and pneumocephalus. He was admitted to the hospital and received intensive prophylaxis with antibiotics. He developed life-threatening skin disease and subsequent acute kidney disease requiring hemodialysis. He fully recovered from his life-threatening condition. Here, we report an unprecedented case of a penetrating head injury of an older adult caused by a shoji.

Small relative effect sizes are common in observational studies of exposure in environmental and public health. However, such effects can still have considerable policy importance when the baseline rate of the health outcome is high, and many persons are exposed. Assessing the certainty of the evidence based on these effect sizes is challenging because they can be prone to residual confounding due to the non-randomized nature of the evidence. When applying GRADE, a precise relative risk >2.0 increases the certainty in an existing effect because residual confounding is unlikely to explain the association. GRADE also suggests rating up when opposing plausible residual confounding exists for other effect sizes. In this concept paper, we propose using the E-value, defined as the smallest effect size of a confounder that still can reduce an observed RR to the null value, and a reference confounder to assess the likelihood of residual confounding. We propose a 4-step approach. 1. Assess the association of interest for relevant exposure levels. 2. Calculate the E-value for this observed association. 3. Choose a reference confounder with sufficient strength and information and assess its effect on the observed association using the E-value. 4. Assess how likely it is that residual confounding will still bias the observed RR. We present three case studies and discuss the feasibility of the approach.

L-tyrosine hydroxylase (TH) is a critical enzyme and involved in the conversion of L-tyrosine to L-3,4-dihydroxyphenylalanine (L-DOPA) in the human body. TH deficiency is a rare autosomal recessive disorder which results in cerebral catecholamine deficiency and causes symptoms of depression, movement disorders, and impaired development. L-DOPA is the common precursor of catecholamine neurotransmitters, therefore how to rapidly and precisely determine the ratio of L-DOPA to L-tyrosine in the bio-matrix is important to the clinical diagnosis of disorder. To response the demand, a low-cost, user-friendly, and on-site detection system is developed herein, which includes a wax-printing paper microfluidics as reaction platform, surface modification with sodium periodate for improving detection performance, an additive manufactured enclosed case for maintaining identical detection environment, and an IOS application (APP) to drive smartphone’s imaging to facilitate high-throughput quantification of multiple biomarkers simultaneously. Multiple experiments were conducted to understand the detection limit, detection range, shelf-life, and specificity of this quantification system even with a complex bio-matrix such as artificial urine or Fetal Bovine Sera (FBS). The experiment results showed that L-DOPA, L-tyrosine, and creatinine can be easily and rapidly quantified with high reliability and repeatability, demonstrating an efficient tool for routine checkup of patients with TH deficiency.

Bacteria identification has predominantly been conducted using specific bioreceptors such as antibodies or nucleic acid sequences. This approach may be inappropriate for environmental monitoring when the user does not know the target bacterial species and for screening complex water samples with many unknown bacterial species. In this work, we investigate the supervised machine learning of the bacteria-particle aggregation pattern induced by the peptide sets identified from the biofilm-bacteria interface. Each peptide is covalently conjugated to polystyrene particles and loaded together with bacterial suspensions onto paper microfluidic chips. Each peptide interacts with bacterial species to a different extent, leading to varying sizes of particle aggregation. This aggregation changes the surface tension and viscosity of the liquid flowing through the paper pores, altering the flow velocity at different extents. A smartphone camera captures this flow velocity without being affected by ambient and environmental conditions, towards a low-cost, rapid, and field-ready assay. A collection of such flow velocity data generates a unique fingerprinting profile for each bacterial species. Support vector machine is utilized to classify the species. At optimized conditions, the training model can predict the species at 93.3% accuracy out of five bacteria: Escherichia coli, Staphylococcus aureus, Salmonella Typhimurium, Enterococcus faecium, and Pseudomonas aeruginosa. Flow rates are monitored for less than 6 s and the sample-to-answer assay time is less than 10 min. The demonstrated method can open a new way of analyzing complex biological and environmental samples in a biomimetic manner with machine learning classification.

The value of incorporating research evidence into clinical practice is in part, to help acknowledge, accept and manage uncertainties. The urgency related to the Covid-19 pandemic has changed usual publication process and information sharing. The rapid knowledge exchange between theory, research and clinical recommendation has occurred with the hope of preventing Covid-19 related mortality and reducing morbidity. However, expediting knowledge transfer should not occur at the expense of accuracy and cautious interpretation of the research evidence. Such carelessness only serves to inundate the public and health professionals with false or misleading information. Such inaccuracies, especially when relating to potential therapeutic strategies for Covid-19 are likely to have severe negative consequence on people's health. There is therefore a need to avoid speculation and favour scientific rigour and intellectual honesty in claims made about evidence on benefits of manual treatment for Covid-19 patients. This letter to the editor questions overstatements found in Marin et al.'s published narrative review and focuses on three avoidable types of errors: misinterpretation, cherry picking and lack of methodological rigour.

Aim To explore a cohort of mental health nurses’ views and experiences in developing and applying critical appraisal of research skills to identify helping and hindering factors. Background In accordance with evidence-based practice principles, there is an expectation that student (mental health) nurses will become competent in understanding research to make judgements about its trustworthiness and applicability in the clinical setting. This process is termed the ‘critical appraisal of research’ and it is deemed important to healthcare professionals because it facilitates the use of evidence from research to underpin practice. Design The study incorporated qualitative secondary research using thematic analysis and a poststructural lens. Methods Following undertaking a module including tuition on the critical appraisal of research, a cohort of student mental health nurses’ submitted essay reflections focusing on critical appraisal experiences were thematically analysed. The thematic analysis included both deductive and inductive components in adjunct to a poststructuralist analysis to explore influencing factors of language, meaning and subjectivity. Results The study identified there are both pedagogical factors and wider societal considerations influencing the critical appraisal of research experiences. Psychological and emotional factors, incorporating anxiety components were identified as a key barrier to engagement and understanding which has not previously been identified in comparable research. Enablers to the understanding and application of critical appraisal skills were identified as peer learning, accessing academic supervision, gaining a satisfaction of personal learning and self-directed learning with library skills support. Conclusions The findings indicate that there are specific pedagogic considerations which can be applied when supporting mental health student nurses in developing and gaining skills in the critical appraisal of research. It is recommended that these are applied universally for nursing students and considered for other populations of healthcare students.