Use Of Standardized Protocol Research Articles

Pro-Tmune, the Next Generation Graft for Allogeneic Hematopoietic Cell Transplantation: Phase 1 Safety and Efficacy Data

ProTmune, an ex vivo modulated mobilized peripheral blood (mPB) graft, has FDA fast track designation for the reduction of incidence and severity of acute graft-versus-host disease (GvHD) in patients undergoing allogeneic hematopoietic cell transplantation (HCT). Despite the use of standard protocols to prevent its occurrence, 50 to 60% of patients receiving an unrelated allogeneic HCT experience acute GvHD within 60 days post-HCT.Here we report early Phase 1 safety and efficacy data from PROTECT, the ongoing Phase 1 open-label / Phase 2 blinded and randomized controlled trial (RCT) of ProTmune in adult subjects with hematologic malignancy undergoing HCT following myeloablative conditioning using a matched unrelated donor and receiving standard GvHD prophylaxis of methotrexate and tacrolimus.As of July 31, 2017, five subjects were administered ProTmune in the Phase 1 portion of PROTECT. Underlying hematologic diseases included ALL, AML and MDS. Subjects were predominantly female (80%), with mean age of 54 (range 34 to 66) and mean weight of 75.2 +/- 14.7 kg. All subjects remain on study as of July 31, 2017 with a median follow-up of 53 days (range 33 to 224 days).ProTmune was manufactured on-site the day of HCT (Day 0) by pharmacologically modulating a mPB graft ex vivo with two small molecules (FT1050 and FT4145) to enhance the biologic properties and therapeutic function of the graft. All manufacturing runs have been successful, maintaining high cell viability (87.9 +/- 10.9%) and CD34+ cell recovery (87.7 +/- 13.5%). Successful pharmacologic modulation was confirmed by the marked increase in the percentage of cells positive for the potency marker CXCR4 (5.0 +/- 0.1% pre-manufacture to 67.3 +/- 7.9% post-manufacture). ProTmune, containing on average 6.8 +/- 3.6 x106 CD34+ cells/kg and 2.5 +/- 0.5 x108 CD3+ cells/kg, was administered on Day 0.ProTmune has been well tolerated in these five subjects. ProTmune-related AEs were limited to two cases of Grade 1 vomiting on the day of administration. No ProTmune-related SAEs have been reported. All subjects engrafted with no reports of secondary graft failure. Median time to neutrophil engraftment was Day 15 (range Day 14 to Day 21). There have been no disease relapse or deaths.The primary efficacy endpoint is incidence of acute GvHD through Day 100. In Phase 1, one subject was reported to have an acute GvHD event by Day 100 (limited to skin with complete recovery on methylprednisolone).The Phase 1 portion of PROTECT is projected to enroll 6-10 subjects. By the 2017 ASH meeting, enrollment will be complete with at least six subjects projected to have reached Day 100+, and the safety and efficacy results will be updated. [Display omitted] DisclosuresMaziarz:Novartis Pharmaceuticals Corporation: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Incyte: Consultancy, Honoraria; Juno Therapeutics: Honoraria; Kite Therapeutics: Honoraria; Athersys, Inc: Patents & Royalties. Saad:Spectrum: Honoraria; Actinium: Consultancy. Diaz:Fate Therapeutics, Inc: Employment. Medcalf:Fate Therapeutics, Inc: Employment, Equity Ownership. Fremgen:Fate Therapeutics, Inc.: Employment. Storgard:Fate Therapeutics, Inc: Employment.

Evidence-Based Guideline on Critical Patient Transport and Handover to ICU.

The perioperative period is a time in which significant physiological change occurs. Improper transfer of information at this point can lead to medical errors. Planning and preparation for critical patient transport to ICU is vital to prevent adverse events. Critical patient transport to ICU must be as safe as possible and should not cause additional risks. It needs good communication, planning, and appropriate staffing with standard monitoring. Evidence shows inconsistency and variability on the use of standardized protocols during critical patient transfer and handover to the ICU. There is a variety of controversial approaches about the need of sedation, use of end-tidal CO2 monitoring, and manual versus mechanical ventilation based on different evidence. The objective of this review was to recommend safer options of critical patient transfer to the ICU that help reduce patient morbidity and mortality. Methods. Google Scholars, PubMed through HINARI, and other search engines were used to search high-quality evidence that help reach appropriate conclusions. Discussion. Critical patient transfer and handover to ICU is a complex procedure that needs experienced hands, availability of appropriate team members, standard monitoring, and necessary emergency and patient-specific medications. Appropriate and adequate transfer of patient information to the receiving team decreases patient morbidity and mortality when the transfer team uses standardized checklist. Conclusion. Involvement of senior physicians, use of standard monitoring, and appropriate transfer of information have been shown to decrease critical patient morbidity and mortality.

Surgical site infections in the COVID-19 era: a comparative cohort study

Background. The COVID-19 pandemic has put an important strain on the healthcare system all over the world. Several strategies to mitigate its impact have been proposed, with the sole purpose to prioritize the finite resources in different healthcare settings, in order to still provide qualitative medical services. As a result, elective surgeries, even for oncologic patients, were postponed or even cancelled, if the patient’s healthcare safety could not be maintained. Surgical site infections (SSIs), as defined by the Centers for Disease Control and Prevention (CDC), are a well-known cause of patient morbidity and of increased healthcare costs. Objectives. To assess the rate and impact of SSIs during the COVID-19 pandemic (the year 2020) compared to the rate during 2019 and to identify the prevention bundle to reduce their incidence in an important academic tertiary center in Romania. Materials and method. We performed a cohort study on operated patients in both obstetrics and gynecology departments, in a third-level maternity unit, the “Filantropia” Clinical Hospital of Obstetrics and Gynecology, Bucharest, regarding the prevalence of surgical site infections during one year of COVID-19 pandemic (2020) versus the prevalence and impact of the previous year (2019). This is an observational cohort retrospective study, analyzing the period from the 1st of January 2019 to the 31st of December 2019 and from the 1st of January 2020 to the 31st of December 2020, with the aim to evaluate the influence of highly surveillance and perioperative guidelines followed during the COVID-19 pandemic and to compare it to the regulations and guidelines followed during 2019. Results. Taking into account both gynecological interventions and caesarean sections, 6998 interventions were performed (3641 in 2019 and 3357 in 2020), with no significant difference regarding patients’ demographics. The number of operations performed were different, with fewer caesarean sections in 2020 (2061) compared to 2273 in 2019. Also, fewer operations for malignancies such as ovarian or endometrial cancers and laparoscopic procedures were performed in 2020 compared to 2019, due to difficulties in maintaining the patients’ and medical personnel safety. No significant difference rates were observed regarding postoperative complications or the length of stay. However, the total SSI complication rate was reduced in 2020 (1.22%) compared to the previous year (1.92%) due to the introduction of higher surveillance protocols and to medical personnel theoretical and hands-on education. Discussion. Risk factors, such as high Body Mass Index, increased blood glucose levels, smoking status, immunodeficiency or MRSA status, have an important role in facilitating the SSIs. Considering the epidemiological context, a reduced referral to medical services during pandemic, excluding emergencies, led to fewer surgeries performed in the gynecology department, fewer caesarean sections and to a total SSI rate decreased compared to 2019. Thus, understanding the multiple factors involved in the pathology, the importance of a responsible care and the existence of a record of these cases may help diminish the rate, especially during pandemic. Conclusions. Beside challenges faced during the pandemic period, we continued to perform surgical procedures with timely planning and meticulous care, keeping a low rate of SSIs (1.22%). The use of standardized protocols and a bundle of preventive strategies may be of great help in the better control of this type of infections.

Safety and monitoring of patient-controlled intravenous analgesia : Clinical practice in German hospitals

HintergrundDie patientenkontrollierte intravenöse Analgesie („patient controlled intravenous analgesia“, PCIA) ist als Verfahren in der Akutschmerztherapie etabliert. Ziel dieser Untersuchung war es, Anwendungspraxis, Überwachung, unerwünschte Vorkommnisse und Komplikationen unter einer PCIA-Therapie an deutschen Krankenhäusern zu erfassen.MethodenAlle 995 bei der Deutschen Gesellschaft für Anästhesie und Intensivmedizin e. V. registrierten Chefärzte wurden zur Teilnahme an der elektronischen Umfrage eingeladen.ErgenisseAus 244 Kliniken wurden Antworten zurückgesandt. In 193 (79 %) dieser Kliniken kam die PCIA zum Einsatz. Alle folgenden Angaben beziehen sich auf diese Krankenhäuser. Das am häufigsten genutzte Opioid war Piritramid. Bei Patienten mit PCIA setzten 94 % der Kliniken zusätzlich Nichtopioidanalgetika ein, 38 % retardierte orale Opioide sowie 4 % parenterale Opioide. Bei Anwendung der PCIA auf Normalstation lag lediglich in 31 % der Kliniken ein standardisiertes Überwachungskonzept vor, das über die Routineversorgung der Stationen hinausging. Insgesamt 82 % der befragten Kliniken berichteten von unerwünschten Vorkommnissen im Zusammenhang mit der PCIA. In 39 % der Kliniken war in den vorangegangenen 6 Monaten mindestens eine potenziell vital bedrohliche Komplikation aufgetreten, insgesamt wurden 335 Einzelfälle berichtet (bei ca. 50.000 durchgeführten PCIAs). Kliniken, die über Komplikationen berichteten, hatten einen höheren Überwachungsstandard als Kliniken, die über keine Komplikationen berichteten.SchlussfolgerungenDie PCIA ist ein verbreitetes, aber durchaus mit Risiken verbundenes Analgesieverfahren. Anwendungs- und Überwachungspraxis sind heterogen. Konsentierte, aktuelle Empfehlungen hinsichtlich Behandlungs- und Überwachungsstandards sowie der systematischen Erfassung von Komplikationen bei Anwendung der PCIA stehen aus.

A systematic approach to contouring and polishing anterior resin composite restorations: A checklist manifesto.

This article presents a systematic, step-by-step checklist approach to be used for contouring and polishing anterior resin composite restorations to achieve maximum esthetics efficiently. This checklist is intended to be used to take the guesswork out and streamline the process to predictably, practically, and repeatedly contour and polish anterior resin composite restorations. The practitioner's knowledge of basic dental anatomy combined with this step-by-step checklist facilitates identifying and modifying the final restoration to an anatomically correct form, thus satisfying the most esthetically demanding patients. This approach is demonstrated with case presentation of direct resin veneers in a young female, which resulted in an improved smile that satisfied her esthetic desires. The use of standardized protocols facilitates and expedites daily procedures in dentistry. Specifically, this checklist protocol, which is geared towards contouring and polishing anterior direct resin composite restorations. The clinical technique presented in this article shows the advantages of using a step-by-step checklist approach to predictably and efficiently obtain ideal esthetics when performing anterior resin composite restorations.

Global Current Practices of Ventilatory Support Management in COVID-19 Patients: An International Survey.

BackgroundAs the global outbreak of COVID-19 continues to ravage the world, it is important to understand how frontline clinicians manage ventilatory support and the various limiting factors.MethodsAn online survey composed of 32 questions was developed and validated by an international expert panel.ResultsOverall, 502 respondents from 40 countries across six continents completed the survey. The mean number (±SD) of ICU beds was 64 ± 84. The most popular initial diagnostic tools used for treatment initiation were arterial blood gas (48%) and clinical presentation (37.5%), while the national COVID-19 guidelines were the most used (61.2%). High flow nasal cannula (HFNC) (53.8%), non-invasive ventilation (NIV) (47%), and invasive mechanical ventilation (IMV) (92%) were mostly used for mild, moderate, and severe COVID-19 cases, respectively. However, only 38.8%, 56.6% and 82.9% of the respondents had standard protocols for HFNC, NIV, and IMV, respectively. The most frequently used modes of IMV and NIV were volume control (VC) (36.1%) and continuous positive airway pressure/pressure support (CPAP/PS) (40.6%). About 54% of the respondents did not adhere to the recommended, regular ventilator check interval. The majority of the respondents (85.7%) used proning with IMV, with 48.4% using it for 12–16 hours, and 46.2% had tried awake proning in combination with HFNC or NIV. Increased staff workload (45.02%), lack of trained staff (44.22%) and shortage of personal protective equipment (PPE) (42.63%) were the main barriers to COVID-19 management.ConclusionOur results show that general clinical practices involving ventilatory support were highly heterogeneous, with limited use of standard protocols and most frontline clinicians depending on isolated and varied management guidelines. We found increased staff workload, lack of trained staff and shortage of PPE to be the main limiting factors affecting global COVID-19 ventilatory support management.

Holistic Approach of Swiss Fetal Progenitor Cell Banking: Optimizing Safe and Sustainable Substrates for Regenerative Medicine and Biotechnology.

Safety, quality, and regulatory-driven iterative optimization of therapeutic cell source selection has constituted the core developmental bedrock for primary fetal progenitor cell (FPC) therapy in Switzerland throughout three decades. Customized Fetal Transplantation Programs were pragmatically devised as straightforward workflows for tissue procurement, traceability maximization, safety, consistency, and robustness of cultured progeny cellular materials. Whole-cell bioprocessing standardization has provided plethoric insights into the adequate conjugation of modern biotechnological advances with current restraining legislative, ethical, and regulatory frameworks. Pioneer translational advances in cutaneous and musculoskeletal regenerative medicine continuously demonstrate the therapeutic potential of FPCs. Extensive technical and clinical hindsight was gathered by managing pediatric burns and geriatric ulcers in Switzerland. Concomitant industrial transposition of dermal FPC banking, following good manufacturing practices, demonstrated the extensive potential of their therapeutic value. Furthermore, in extenso, exponential revalorization of Swiss FPC technology may be achieved via the renewal of integrative model frameworks. Consideration of both longitudinal and transversal aspects of simultaneous fetal tissue differential processing allows for a better understanding of the quasi-infinite expansion potential within multi-tiered primary FPC banking. Multiple fetal tissues (e.g., skin, cartilage, tendon, muscle, bone, lung) may be simultaneously harvested and processed for adherent cell cultures, establishing a unique model for sustainable therapeutic cellular material supply chains. Here, we integrated fundamental, preclinical, clinical, and industrial developments embodying the scientific advances supported by Swiss FPC banking and we focused on advances made to date for FPCs that may be derived from a single organ donation. A renewed model of single organ donation bioprocessing is proposed, achieving sustained standards and potential production of billions of affordable and efficient therapeutic doses. Thereby, the aim is to validate the core therapeutic value proposition, to increase awareness and use of standardized protocols for translational regenerative medicine, potentially impacting millions of patients suffering from cutaneous and musculoskeletal diseases. Alternative applications of FPC banking include biopharmaceutical therapeutic product manufacturing, thereby indirectly and synergistically enhancing the power of modern therapeutic armamentariums. It is hypothesized that a single qualifying fetal organ donation is sufficient to sustain decades of scientific, medical, and industrial developments, as technological optimization and standardization enable high efficiency.

An overview of sexual assault cases in Bangladesh

Sexual assault is defined as any sexual act performed by one (or more) person(s) on another without consent. It may include the use of threat or force. In some cases, the person cannot give consent to sex because he/she is unconscious or otherwise incapacitated. A person may be raped by a stranger, an acquaintance or date or a family member. The purpose of the present study was to find out the medicolegal findings of rape victims in order to point out the visible loopholes of the procedure. This was a cross sectional descriptive type of study which was done in the Dept. of Forensic Medicine, Sir Salimullah Medical College and Mitford Hospital, Dhaka , Bangladesh from January to December 2015 with maintaining ethical issues. Rape cases were sent for medicolegal examination and victims who ultimately agreed to do medicolegal examinations were examined and opinions were given regarding the issues. In this study, majority (70.0%) of the victims was within 11 to 20 years of age and 65.0% of the victims were unmarried. Almost 68.0% of the victims were examined within 7 days followed by 32.0% of the victims after 7 days to beyond one month after rape; however, 48.0% of the victims showed sign of recent hymeneal tear with bruise and abrasion followed by 52.0% showed sign of old hymeneal tear. Spermatozoa were not found in any of the specimen of high vaginal swab. Young adults remain the most vulnerable group, so education related to sex, morality, humanity and different life skills training should be provided to these groups from their school years itself. The benefits of early intervention and comprehensive care of survivors with the use of standardized protocols along with shorter and lesser traumatic period of court processing to the survivors of these cases should be encouraged.

Survey of practices in relation to chronic pulmonary hypertension in neonates in the Canadian Neonatal Network and the National Institute of Child Health and Human Development Neonatal Research Network.

Current knowledge gaps pertaining to diagnosis and management of neonatal chronic pulmonary hypertension (cPH) may result in significant variability in clinical practice. The objective of the study is to understand cPH management practices in neonatal intensive care units affiliated with the Canadian Neonatal Network (CNN) and National Institute of Child Health and Human Development Neonatal Research Network (NRN). A 32-question survey seeking practice details for cPH evaluation, diagnostic criteria, conservative measures, pharmacotherapeutics, and follow-up was e-mailed to a designated physician at each center. Responses were described as frequency (percentage) and compared between CNN and NRN, where appropriate. Overall response rate was 67% (CNN 20/28 (71%), NRN 9/15 (60%)). While 8 (28%) centers had standardized management protocols, 17 (59%) routinely evaluate high-risk patients; moderate-severe chronic lung disease being the commonest indication. While interventricular septal flattening on echocardiography was the commonest listed diagnostic criterion, several adjunctive indices were also identified. Asymptomatic neonates with cPH were managed expectantly (routine care) in 50% of sites, and using various conservative measures in others. Pulmonary vasodilators were prescribed for symptomatic cases, with 60% of sites using them early (86% reporting any use). Seventy-five percent of sites use inhaled nitric oxide and sildenafil citrate as first- and second-line agents, respectively. Use of standard protocols, cardiac catheterization, and conservative measures for asymptomatic cases was more common in NRN units (p < 0.05). While there is relative homogeneity in patient identification and diagnostic criteria used for neonatal cPH, significant interunit inconsistencies still exists in routine evaluation, use of additional investigations, management of asymptomatic cases, frequency and type of conservative measures, and choice of pulmonary vasodilators.

TSCH‐over‐LoRA: long range and reliable IPv6 multi‐hop networks for the internet of things

TSCH‐over‐LoRa is a long range and reliable IPv6 multi‐hop solution that aims at combining the reliability of TSCH (Time‐Slotted, Channel Hopping) together with the long range capabilities of LoRa. TSCH‐over‐LoRa brings mesh IPv6 networking to LoRa devices, enabling the use of standard protocols (such as RPL, UDP, and CoAP) and long range operation to TSCH/6TiSCH industrial wireless IoT networks. We design, implement, and integrate TSCH‐over‐LoRa into the TSCH/6TiSCH networking stack of the Contiki‐NG operating system and experimentally demonstrate its compatibility with higher‐level protocols and its resilience to interference.

The efficacy of myofunctional therapy in patients with atypical swallowing.

The myofunctional treatment (MFT) is a conventional therapy in the treatment of oral disease like atypical swallowing (AS). Functional (standardized surface electromyographic analysis-ssEMG) and clinical ("orofacial muscular evaluation with score" protocol-OMES) analyses were conducted to detect the effects of MFT (10weeks session) in a group of patients with AS. ssEMG was performed to analyze the activity of masseter (MM), temporalis (TA), and submental (SM) muscles before (T1) and after (T2) the MFT in a group of 15 patients. OMES was completed at the same timepoints. A Student-t test was carried out to detect differences between T1 and T2 for ssEMG data, and a signed RANK test was used for OMES ones. One-way ANOVA variance test was performed to detect any differences between the different couples of muscles at each timepoint. After MFT, patients showed a shorter duration of the whole act of swallowing (p < .0001), higher intensity of the SM activity (p < .01) than at T1. At T2 masticatory muscles showed lower values for the activation index (ANOVA, p < .0001) and for the spike position (ANOVA, p < .01) than SM. The OMES protocol showed a significant increase for the total evaluation score (p < .01), appearance-posture (p < .01) and functions (p < .001). MFT permits a shortening of the muscular activation pattern and an increase in SM activity. The improvement of oral functionalities is possible and identifiable thanks to the use of standardized protocols.

Adenovirus-associated Acute Respiratory Distress Syndrome: Need for a Protocol-based Approach

ABSTRACTAimViral causes of acute respiratory distress syndrome (ARDS) are mostly limited to influenza A; however, adenovirus has been emerging as a cause of fulminant ARDS with a high mortality rate and no consensus on its management. Here we present a series of five patients with confirmed adenovirus infection treated for ARDS at our quaternary referral institution.Materials and methodsAll patients were above 18 years old, had confirmed adenovirus infection, and were treated for acute hypoxic respiratory failure requiring mechanical ventilation in our medical intensive care unit (MICU). Demographic and clinical data were collected and analyzed.ResultsAmong these patients, the median age was 28 years, median BMI 28 kg/m2 median sequential organ failure assessment (SOFA) score 9, and median acute physiology and chronic health evaluation (APACHE) III score 74. All patients received lung-protective mechanical ventilation with high positive end-expiratory pressure and low plateau pressures. Three patients developed severe ARDS, two received prone position ventilation, and one was placed on extracorporeal membrane oxygenation. The median duration of mechanical ventilation, MICU length of stay, and hospital length of stay were 24, 19, and 27 days, respectively. One out of five patients died in our study.ConclusionThe mortality rate for adenovirus-associated pneumonia in the literature is estimated to be 40% in those requiring mechanical ventilation. The lower mortality at our institution could be attributed to the use of standardized protocols, which include low tidal volume ventilation, early use of neuromuscular blockade, targeting low plateau pressures, conservative fluid management, and comfort and familiarity with the use of adjunctive and rescue therapies. We recommend testing for adenovirus as part of a routine respiratory viral panel in ARDS patients, and if tested positive, transfer to tertiary or quaternary centers with the experience and rescue modalities needed to manage complicated ARDS patients.How to cite this articleVashisht R, Mirzai S, Koval C, Duggal A. Adenovirus-associated Acute Respiratory Distress Syndrome: Need for a Protocol-based Approach. Indian J Crit Care Med 2020;24(5):367–368.

Methodological Insight Into Mosquito Microbiome Studies.

Symbiotic bacteria affect competence for pathogen transmission in insect vectors, including mosquitoes. However, knowledge on mosquito-microbiome-pathogen interactions remains limited, largely due to methodological reasons. The current, cost-effective practice of sample pooling used in mosquito surveillance and epidemiology prevents correlation of individual traits (i.e., microbiome profile) and infection status. Moreover, many mosquito studies employ laboratory-reared colonies that do not necessarily reflect the natural microbiome composition and variation in wild populations. As a consequence, epidemiological and microbiome studies in mosquitoes are to some extent uncoupled, and the interactions among pathogens, microbiomes, and natural mosquito populations remain poorly understood. This study focuses on the effect the pooling practice poses on mosquito microbiome profiles, and tests different approaches to find an optimized low-cost methodology for extensive sampling while allowing for accurate, individual-level microbiome studies. We tested the effect of pooling by comparing wild-caught, individually processed mosquitoes with pooled samples. With individual mosquitoes, we also tested two methodological aspects that directly affect the cost and feasibility of broad-scale molecular studies: sample preservation and tissue dissection. Pooling affected both alpha- and beta-diversity measures of the microbiome, highlighting the importance of using individual samples when possible. Both RNA and DNA yields were higher when using inexpensive reagents such as NAP (nucleic acid preservation) buffer or absolute ethanol, without freezing for short-term storage. Microbiome alpha- and beta-diversity did not show overall significant differences between the tested treatments compared to the controls (freshly extracted samples or dissected guts). However, the use of standardized protocols is highly recommended to avoid methodological bias in the data.

Introduction: Esophageal Squamous Cell Carcinoma-Current Status and Future Advances.

Esophageal squamous cell carcinoma is the most common histological subtype of esophageal cancer. The carcinoma is more common in high-incidence areas such as in Central and Southeast Asia, Eastern and Southern Africa, South America, etc. Common risk factors associated with the cancer are tobacco smoking and excessive alcohol consumption. Dietary factors, genetic factors, microorganisms, and some other environmental factors may contribute to the etiopathogenesis of the disease. Despite the global incidence of esophageal squamous cell carcinoma decreases slightly in the recent years, esophageal squamous cell carcinoma is still a major cause of cancer-related morbidity and mortality worldwide. Further improvement of the outcomes of the patients with the disease could be achieved by early diagnosis, collaborative efforts of multidisciplinary clinical and research teams, use of standardized protocol for pathological reporting and staging of the disease, proper use of cancer tissue, as well as improvement in clinical, pathological, therapeutic, and research approaches to the cancer.

Standardized Brain MRI Acquisition Protocols Improve Statistical Power in Multicenter Quantitative Morphometry Studies.

In this study, we used power analysis to calculate required sample sizes to detect group-level changes in quantitative neuroanatomical estimates derived from MRI scans obtained from multiple imaging centers. Sample size estimates were derived from (i) standardized 3T image acquisition protocols and (ii) nonstandardized clinically acquired images obtained at both 1.5 and 3T as part of the multicenter Human Epilepsy Project. Sample size estimates were compared to assess the benefit of standardizing acquisition protocols. Cortical thickness, hippocampal volume, and whole brain volume were estimated from whole brain T1-weighted MRI scans processed using Freesurfer v6.0. Sample sizes required to detect a range of effect sizes were calculated using (i) standard t-test based power analysis methods and (ii) a nonparametric bootstrap approach. A total of 32 participants were included in our analyses, aged 29.9 ± 12.62 years. Standard deviation estimates were lower for all quantitative neuroanatomical metrics when assessed using standardized protocols. Required sample sizes per group to detect a given effect size were markedly reduced when using standardized protocols, particularly for cortical thickness changes <.2 mm and hippocampal volume changes <10%. The use of standardized protocols yielded up to a five-fold reduction in required sample sizes to detect disease-related neuroanatomical changes, and is particularly beneficial for detecting subtle effects. Standardizing image acquisition protocols across scanners prior to commencing a study is a valuable approach to increase the statistical power of multicenter MRI studies.

Mixed evidence for adaptation to environmental pollution.

Adaptation to pollution has been studied since the first observations of heavy metal tolerance in plants decades ago. To document micro‐evolutionary responses to pollution, researchers have used phenotypic, molecular genetics, and demographic approaches. We reviewed 258 articles and evaluated the evidence for adaptive responses following exposure to a wide range of pollutants, across multiple taxonomic groups. We also conducted a meta‐analysis to calculate the magnitude of phenotypic change in invertebrates in response to metal pollution. The majority of studies that reported differences in responses to pollution were focused on phenotypic responses at the individual level. Most of the studies that used demographic assays in their investigations found that negative effects induced by pollution often worsened over multiple generations. Our meta‐analysis did not reveal a significant relationship between metal pollution intensity and changes in the traits studied, and this was probably due to differences in coping responses among different species, the broad array of abiotic and biotic factors, and the weak statistical power of the analysis. We found it difficult to make broad statements about how likely or how common adaptation is in the presence of environmental contamination. Ecological and evolutionary responses to contamination are complex, and difficult to interpret in the context of taxonomic, and methodological biases, and the inconsistent set of approaches that have been used to study adaptation to pollution in the laboratory and in the field. This review emphasizes the need for: (a) long‐term monitoring programs on exposed populations that link demography to phenotypic, genetic, and selection assays; (b) the use of standardized protocols across studies especially for similar taxa. Approaches that combine field and laboratory studies offer the greatest opportunity to reveal the complex eco‐evolutionary feedback that can occur under selection imposed by pollution.

Shining a Light: Integrating Protocols Into Clinical Practice for Treatment of Neonatal Abstinence Syndrome.

The epidemic use of opioids is negatively influencing the health of the American people. Pregnant women and their unborn babies have not escaped the ravages of substance use. A dramatic increase in maternal opioid use has led to an increasing number of infants experiencing withdrawal symptoms known as neonatal abstinence syndrome (NAS). The purpose of this article is to highlight best practice for the management of infants with opioid withdrawal. Review of available protocols and treatments revealed wide variation in the treatment of NAS and little use of standardized guidelines or protocols, despite current recommendations of the American Academy of Pediatrics. There is supporting evidence showing that the use of standardized protocols reduces the length of treatment and enhances outcomes in the neonatal population. Evidence-based strategies to address gaps in practice include developing strong protocols to identify infants at risk and implementing standardized plans when treating NAS. Consistent assessment, initial treatment with nonpharmacologic measures, and conservative use of pharmacologic agents are important elements to an NAS treatment protocol. In evaluating the current literature for best practice in the management of the newborn with opioid withdrawal, it is clear that evidence-based standardized protocols need to be in place for the best treatment of the mother-infant dyad, caring for both the infants with NAS as well as the mothers with opioid use disorder.

Minimal difference in phenotype between adolescents and young adults with polycystic ovary syndrome

To test the hypothesis that the polycystic ovary syndrome (PCOS) phenotype, or its component features, is less severe in adolescents than in young adult patients, in a referred (clinical) population. Cross-sectional study. Tertiary-care academic medical center. Two hundred seventy-four adolescents and young adults aged 13.0-24.9years with PCOS according to the National Institute of Health 1990 criteria. Patients were categorized as adolescents (AD: 13.0-18.9years; n = 91) and young adults (YA: 19.0-24.9years; n = 183). Adolescents were further categorized as early adolescents (Early-AD: 13.0-15.9years; n = 31) and late adolescents (Late-AD: 16.0-18.9years; n = 60). History, physical examination, hormonal assays with the use of standardized protocols. Unadjusted and adjusted odds ratios (ORs; adjusted for body mass index [BMI] when applicable) were calculated for biochemical hyperandrogenism (HA), hirsutism (HIR), acne, and degree of oligo/amenorrhea (OA). PCOS phenotypes were classified as HIR+HA+OA, HA+OA, and HIR+OA. Our analysis demonstrated minimal significant difference in the prevalence of the three PCOS phenotypes, or component features, between AD and YA patients. The risks for obesity were higher for YA versus AD, and the risk of acne was lower for YA versus AD. There was no significant difference between Early-AD and Late-AD. BMI-adjusted models did not significantly modify the main findings. The present study suggests that the PCOS phenotype is established in early adolescence, remains constant into adulthood, and is not related to BMI.

Advanced dementia pain management protocols.

Pain management in advanced dementia is complex because of neurological deficits present in these patients, and nurses are directly responsible for providing interventions for the evaluation, management and relief of pain for people suffering from this health problem. In order to facilitate and help decision-makers, pain experts recommend the use of standardized protocols to guide pain management, but in Spain, comprehensive pain management protocols have not yet been developed for advanced dementia. This article reflects the need for an integrated management of pain in advanced dementia. From the review and analysis of the most current and relevant studies in the literature, we performed an approximation of the scales for the determination of pain in these patients, with the observational scale PAINAD being the most recommended for the hospital setting. In addition, we provide an overview for comprehensive management of pain in advanced dementia through the conceptual framework «a hierarchy of pain assessment techniques by McCaffery and Pasero» for the development and implementation of standardized protocols, including a four-phase cyclical process (evaluation, planning/performance, revaluation and recording), which can facilitate the correct management of pain in these patients.

An Overview of Sexual Assault Cases in Nepal

Background: Sexual assault is defined as any sexual act performed by one (or more) person(s) on another without consent. It may include the use of threat or force. In some cases, the person cannot give consent to sex because he/she is unconscious or otherwise incapacitated. A person may be raped by a stranger, an acquaintance or date or a family member.Methods: The study was a retrospective and descriptive analysis of cases of sexual assault victims examined by the author in the Forensic Medicine departments at Institute of Medicine, Maharajgunj and Gandaki Medical College Teaching Hospital, Pokhara, Nepal over a period of four years (2012 to 2016). This includes information regarding the age group of the victim at the time of sexual abuse, relationship of the victim to the perpetrator, genital and extra-genital injuries present over the victim’s body and number of cases attended as an expert witness by the author in various courts of Nepal.Results: In the four years period, a total number of 55 cases were examined as sexual assault cases. It was observed that majority were of the 13 - 15 years of age group (46%) followed by &lt;10 years (20%), 16 - 20 years (16%), &gt;20 years (11%) and 10 - 12 years (7%). Regarding the relationship of the victim to the alleged perpetrator, 87% cases (48 out of 55) were related to acquaintances compared to 13% due to strangers. Surprisingly, 3.6% cases (2 out of 48) were due to the biological fathers of the victims. On physical examination of the victim’s body, 36% cases showed genital injuries compared to only 15% with extra genital injuries. The author attended the court as an expert witness in 33% of these cases. Only 7% of the cases were mentally challenged.Conclusion: Young adults remain the most vulnerable group, so education related to sex, morality, humanity and different life skills training should be provided to these groups from their school years itself. The benefits of early intervention and comprehensive care of survivors with the use of standardized protocols along with shorter and lesser traumatic period of court processing to the survivors of these cases should be encouraged.Journal of Gandaki Medical College Volume, 09, Number 2, July December 2016, Page: 43-46