Effects of increased physical therapy staffing in the neonatal intensive care unit on oral feeding maturation and neurodevelopment of extremely low birth weight infants.

BACKGROUND: It remains a matter of debate as to what extent early intervention may facilitate long-term functional outcomes of preterm infants in the neonatal intensive care unit (NICU). We aimed to examine the effect of increasing physical therapy (PT) staff dedicated to the NICU on temporal changes (initiation, duration) of PT interventions and functional outcomes (acquisition of full oral feeding and Hammersmith Neonatal Neurological Examination). METHODS: Extremely low birth weight infants, retrospectively collected from an academic medical center, were allocated to two subgroups, either a baseline period (N = 48) without NICU-dedicated PT staff (non-dedicated group) or a quality improvement period (N = 42) with additional dedicated staff (dedicated group). RESULTS: Compared to those in the non-dedicated group, NICU infants in the dedicated group started PT earlier and had increased PT treatment for additional 14 min per day when achieving full oral feeding. The infants in the dedicated group significantly achieved full oral feeding earlier than the non-dedicated group. As for Hammersmith Neonatal Neurological Examination, there were significant differences in two items (total and tone) between the groups. CONCLUSIONS: Additional NICU-dedicated PT staff facilitated earlier intervention and increased PT treatment in terms of daily duration. Moreover, the dedication shortened the completion of full oral feeding and improved neurological development, presumably resulting in better developmental outcome.

Critical path activities in clinical trial setup and conduct: How to avoid bottlenecks and accelerate clinical trials.

Most clinical trials are delayed due to scientific and/or operational challenges. Any effort to minimize delays can generate value for patients and sponsors. This article reviews critical path process steps commonly identified by practitioners, such as during protocol development, site contracting, or patient recruitment. Commonly considered measures, such as adding more trial sites or countries, were contrasted with less frequented measures, such as evidence-based feasibility or real-world evidence analysis, to help validate assumptions before clinical trial initiation. In a broad analysis, we integrated a literature review with a practitioner survey into a framework to help decision makers on the most critical process steps when setting up or conducting clinical trials in order to bring critical treatments to patients faster.

A ship-construction dataset for resource leveling optimization in large project management problems.

Resource leveling is a highly complex optimization problem corresponding to adjusting a project's timeline (start and end dates) with the aim of matching resource allocation demands. The problem is particularly complex when a project is large and involves hundreds or even thousands of activities. Its successful solution is equivalent to considerable profits for the involved construction groups through the efficient management of their resources. In literature usually can be found only small-size benchmark problems consisting of a few activities (i.e., ten to twenty) mainly aiming to demonstrate that a new proposed method can operate correctly identifying the optimum (or a near-optimum) solution. This data article provides resource leveling data suitable for testing, corresponding to a very large real-world problem of ship construction (consisting of 1178 activities). According to recent literature, the majority of the proposed methods for solving resource-leveling optimization problems are based on algorithmic approaches, usually artificial intelligence-oriented (evolutionary programming). The reason is that intelligent approaches manage to solve complex problems, producing approximate solutions of high accuracy and thus attractive (profitable) for practical application. The provided data have been tested in the past with intelligent techniques using different evaluation functions. Nevertheless, the specific dataset has never been published before elsewhere and now there is a clear opportunity to provide these data for testing and benchmark experimentation to interested researchers.

Leveraging the regulatory framework to facilitate drug development in Parkinson's disease.

There is an exigent need for disease-modifying and symptomatic treatment approaches for Parkinson's disease. A better understanding of Parkinson's disease pathophysiology and new insights in genetics has opened exciting new venues for pharmacological treatment targets. There are, however, many challenges on the path from discovery to drug approval. These challenges revolve around appropriate endpoint selection, the lack of accurate biomarkers, challenges with diagnostic accuracy, and other challenges commonly encountered by drug developers. The regulatory health authorities, however, have provided tools to provide guidance for drug development and to assist with these challenges. The main goal of the Critical Path for Parkinson's Consortium, a nonprofit public-private partnership part of the Critical Path Institute, is to advance these so-called drug development tools for Parkinson's disease trials. The focus of this chapter will be on how the health regulators' tools were successfully leveraged to facilitate drug development in Parkinson's disease and other neurodegenerative diseases.

A new emergency response of spherical intelligent fuzzy decision process to diagnose of COVID19.

The control of spreading of COVID-19 in emergency situation the entire world is a challenge, and therefore, the aim of this study was to propose a spherical intelligent fuzzy decision model for control and diagnosis of COVID-19. The emergency event is known to have aspects of short time and data, harmfulness, and ambiguity, and policy makers are often rationally bounded under uncertainty and threat. There are some classic approaches for representing and explaining the complexity and vagueness of the information. The effective tool to describe and reduce the uncertainty in data information is fuzzy set and their extension. Therefore, we used fuzzy logic to develop fuzzy mathematical model for control of transmission and spreading of COVID19. The fuzzy control of early transmission and spreading of coronavirus by fuzzy mathematical model will be very effective. The proposed research work is on fuzzy mathematical model of intelligent decision systems under the spherical fuzzy information. In the proposed work, we will develop a newly and generalized technique for COVID19 based on the technique for order of preference by similarity to ideal solution (TOPSIS) and complex proportional assessment (COPRAS) methods under spherical fuzzy environment. Finally, an illustrative the emergency situation of COVID-19 is given for demonstrating the effectiveness of the suggested method, along with a sensitivity analysis and comparative analysis, showing the feasibility and reliability of its results.

Huntington's Disease Regulatory Science Consortium: Accelerating Medical Product Development.

Huntington's disease (HD) is a devastating neurodegenerative disorder that urgently needs disease-modifying therapeutics. To this end, collaboration to standardize clinical research practices in the field and drive progress in addressing drug development challenges is paramount. At a meeting in 2017 organized by CHDI Foundation and the Critical Path Institute, stakeholders across the pharmaceutical industry, academia, regulatory agencies, and patient advocacy groups discussed the need for and potential impact of a consortium dedicated to HD regulatory science. Consequently, the Huntington's Disease Regulatory Science Consortium (HD-RSC) was formed, a precompetitive consortium that is dedicated to building a regulatory strategy to expedite the approval of HD therapeutics.

[PROSTATE-SPECIFIC ANTIGEN LEVEL AT 6 MONTHS AFTER RADICAL PROSTATECTOMY ENABLES STRATIFICATION OF FOLLOW-UP PERIODS IN THE CANCER REGIONAL ALLIANCES CRITICAL PATH].

(Objectives)Factors related to prostate-specific antigen (PSA) recurrence, including PSA at 6 months after radical prostatectomy, were evaluated to determine if the postoperative follow-up period in the cancer regional alliances critical path could be individualized using a coordinated path. (Patients and methods)Among 352 patients who underwent laparoscopic radical prostatectomy at our hospital from May 2009 to June 2015, 331 who did not undergo preoperative hormone therapy were examined retrospectively. Cases with PSA < 0.01 ng/mL at 6 months after surgery (group A, n=209) were compared with those with PSA > 0.01 ng/mL at the same time point (group B, n=122). (Results)PSA recurrence was significantly higher in group B (n=21 (10.0%) vs. n=70 (57.4%), p< 0.001) and the time to recurrence was significantly shorter (44 vs.12.5 months, p< 0.001). In multivariate analysis within group A, the Gleason Grade Group (GGG) and extraprostatic extension in surgical specimens were predictors of PSA recurrence. In group A, all cases (n=30) of GGG1 in surgical specimens had no extraprostatic extension and no PSA recurrence. There were 90 cases of surgical specimens with GGG2 and no extracapsular infiltration, and only 4 of these cases had recurrence (4.4%). (Conclusion)The results of the study indicate that follow-up interval stratification is possible using the PSA level at 6 months after radical prostatectomy, GGG and extraprostatic extension in the surgical specimen.

Driving Factors and Actions Taken by Women to Confront Violence: Qualitative Research Based on Art.

This qualitative study based on art aimed to analyze the critical path of women in coping with situations of violence in the city of Santa Maria/Rio Grande do Sul, Brazil, in these women's perspective. It has as settings the Women's Police Station (DEAM) and the institutional care service for women in situations of violence, named Casa Abrigo (Shelter House). The "talking map" creativity and sensitivity technique was used in conjunction with the in-depth interview to analyze the critical path of 12 women in situations of violence. The driving factors of the critical path of women in coping with situations of violence were related to their knowledge about the DEAM's assistance, their perceptions about the experience of different types of violence, the fact that they can no longer stand the violence and that they worry about their children, as well as the support of their family, of the ex-husband's or ex-partner's relatives, and of their female friends. The decisions executed and actions taken by the women included reporting the aggressor, requesting a restraining order, seeking help from the guardianship council and family members, getting back together with the aggressor, and leaving home. There is a need to strengthen the decision-making process of women in situations of violence to break the silence and the situation of violence. For this purpose, it is urgent to broaden the information for and knowledge of women about where and how to seek help, through access to clear and precise information in all places that compose the assistance network for these women.

Predictors of At-Home Death for Cancer Patients in Rural Clinics in Japan.

BACKGROUND: The prediction of at-home deaths has become an important topic in rural areas of Japan with an advanced aging society. However, there are no well-established predictors to explain how these factors influence intention. This study aims to investigate the possible predictors of at-home death for cancer patients in rural clinics in Japan. METHODS: This is a nationwide cross-sectional survey. A self-administered questionnaire was sent to 493 rural clinics in Japan. The main outcome was the realization of at-home deaths for cancer patients. RESULTS: Among the 264 clinics (54%) that responded to the survey, there were 194 clinics with the realization of at-home death. The use of a clinical pathway (adjusted odds ratio 4.19; 95% confidence interval 1.57-11.19) and the provision of organized palliative care (adjusted odds ratio 19.16; 95% confidence interval 7.56-48.52) were associated with the prediction of at-home death, irrespective of island geography or the number of doctors and nurses. CONCLUSIONS: Having a clinical pathway and systematizing palliative care could be important to determine the possibility of at-home deaths for cancer patients in rural clinics in Japan.

Prehospital Scheduling Management by the Critical Path Method for Burn Mass Casualty Incidents.

In 2015, a dust explosion occurred in New Taipei Water Park in Taiwan, and 499 casualties was appallingly high. In fact, the government spent 208 min of response time from receiving calls for emergency to sending the last wounded person to hospital. To stop a similar accident happening again, a well-prepared strategy, with an aim to reduce the rescue time, to respond to such an emergency is necessary. This study mainly focuses on the execution of mass casualty operations while both efficiency and quality of care are considered. We not only find that there is only 1 h or less to allocate rescue resources after a Burn Mass Casualty Incident (BMCI) happens but also shorten the response time. It is our first time to use a special method, called Critical Path Method (CPM), to analyze the rescue process. But before CPM is created, the benefit of available resources should be maximized, and timely, safe, and effective emergency medical services should be provided. With CPM, the interrelations of every activity can be visualized, and the most time-consuming activity can be found by this efficient time management. If the relationship between the predecessors and its successors operations of the most time-consuming activity item is reshaped, BMCI prehospital scheduling management becomes more effective based on its efficiency and quality of care.

Using the critical path method to rollout and optimise new PMTCT guidelines to eliminate mother-to-child transmission of HIV in Zimbabwe: a descriptive analysis.

BACKGROUND: Achievement of the elimination target for mother-to-child transmission (MTCT) of HIV in selected countries has increased hope to end the HIV epidemic in children across the world. However, MTCT rates remain well above the 5% elimination target in most sub-Saharan Africa countries. These countries require innovative strategies to scale-up their interventions to end paediatric HIV. We describe how the Elizabeth Glaser Paediatric AIDS Foundation (EGPAF) consortium and the Children's Investment Fund Foundation (CIFF) used the critical path method to facilitate rapid expansion and optimization of 2010 and 2013 WHO PMTCT guidelines to reduce Zimbabwe's MTCT rate from 22% in 2010 to 6.4% in 2015. METHODS: We analysed activities implemented and PMTCT programme data for the period before and during the EGPAF-CIFF project. The critical path method involved a cycle of collecting and analysing quarterly PMTCT indicator data and planning and implementing targeted activities to improve the PMTCT indicators. We performed a graphical trend analysis of data that measured availability of PMTCT services. Using Pearson's Chi2 test, we compared results of PMTCT uptake indicators at the start and end of the EGPAF-CIFF project and used regression discontinuity analysis to assess effectiveness of activities implemented to improve the PMTCT service uptake indicators. RESULTS: Zimbabwe rolled out WHO 2010 and 2013 PMTCT guidelines in less than 1 year during the EGPAF-CIFF project, yet it took more than 4 years to roll-out previous guidelines. All PMTCT indicators increased significantly (p < 0.001) comparing the five-year periods before and during the EGPAF-CIFF project. Critical path activities implemented increased five of the seven PMTCT uptake indicators. CONCLUSION: Zimbabwe rapidly rolled-out and optimised new WHO PMTCT guidelines and drastically reduced its MTCT rate using the critical path method. We recommend wider use of the critical path method in public health programmes.

Placebo effect in subjects with cognitive impairment.

Understanding both the placebo response and the underlying disease progression is crucial to designing clinical trials and interpreting results in Alzheimer's disease (AD) research. The disease severity at different stage of disease (e.g., mild cognitive impairment (MCI), early or late AD) is related to the rate of disease progression, which make it even difficult for AD researchers to understand the clinical trial results. A model-based meta-analysis approach using all available historical data provides quantitative understanding of placebo effect and disease progression in AD and offers a useful tool to aid in both trial design and trial interpretation. The Critical Path Institute (C-Path) is a nonprofit organization founded in 2005 as a vehicle to develop tools to accelerate drug development. The drug development tool (DDT) with AD is the first-ever quantitative DDT to be endorsed by FDA and EMA, and is publicly available to researchers through C-Path's website: https://c-path.org/ad-cts-tool-request/.

Quality of Research Tools.

Drug discovery research is a complex undertaking conducted by teams of scientists representing the different areas involved. In addition to a strong familiarity with existing knowledge, key relevant concepts remain unknown as activities start. This is often an accepted risk, mitigated by gaining understanding in real time as the project develops. Chemicals play a role in all biology studies conducted in the context of drug discovery, whether endogenously or exogenously added to the system under study. Furthermore, new knowledge often flourishes at the interface of existing areas of expertise. Due to differences in their training, adding a chemist's perspective to research teams would at least avoid potentially costly mistakes and ideally make any biology research richer. Thus, it would seem natural that one such team member be a chemist. Still, as that may not always be the case, we present some suggestions to minimize the risk of irreproducibility due to chemistry-related issues during biology research supporting drug discovery and make these efforts more robust and impactful. These include discussions on identity and purity, target and species selectivity, and chemical modalities such as orthosteric or allosteric small molecules or antibodies. Given the immense diversity of potential chemical/biological system interactions, we do not intend to provide a foolproof guide to conduct biological experimentation. Investigate at your own peril!

Combinations of Simple Mechanisms Explain Diverse Strategies in the Freehand Writing of Memorized Sentences.

Individual differences in the strategies that control sequential behavior were investigated in an experiment in which participants memorized sentences and then wrote them by hand, in a non-cursive style. Thirty-two participants each wrote eight sentences, which had hierarchical structures with five levels. The dataset included over 31,000 letters. Despite the deliberately constrained nature of the task and stimuli, 23 patterns of behavior were identified from the durations of pauses that occurred before the inscription of letters at four chunk levels, spanning letters, words, phrases, and sentences. A critical path task analytic model, Graphical Production of Memorized Sentences (GPoMS), shows that the control of writing relies on cues that continuously switch between motor actions and chunk retrievals in a just-in-time fashion at the level of letter information. GPoMS explains the individual differences in terms of variants of a motor production mechanism and variants of a chunk retrieval mechanism, which involve varying degrees of parallelism between cognitive actions and motor actions. A graphical technique for constructing GPoMS models was developed that enabled the estimation of ongoing working memory demands during production.

[Selection and optimal sequence of critical elements for medication review: A simulation with hospital pharmacy residents]. / Sélection et séquence optimale des éléments critiques de validation des ordonnances : une simulation avec des résidents en pharmacie hospitalière.

OBJECTIVES: The main objective of this study was to compare the responses of pharmacy residents regarding critical steps for medication order review, in the presence or absence of clinical pharmacists on patient care units, to describe the sequence of these steps and to compare them to an optimal sequence. The secondary objectives were to test this sequence in a simulation and to assess the residents' level of agreement on medication order review. METHODS: Twenty-two validation steps were selected from guidelines. A simulation on order review was organized in three steps: selecting elements judged to be necessary or not for the order review critical path, then organizing this sequence in chronological order, implementation of this critical path on two simulated practical cases, resident perceptions about order review in their training. RESULTS: Forty-one residents participated in the activity. Responses were heterogeneous regarding the elements' sequence and the time required for the review of a simulated case (3-13minutes). A majority of residents considered that their training was insufficient (29/41), that pharmacists validated differently (27/41), and that it was impossible to review the 22 proposed items for each prescription (30/41). CONCLUSIONS: This article highlights heterogeneous medication order review practices among pharmacy residents, due to a lack of training in their curriculum according to them. It is essential to acquire medication order review standard both locally and nationally.

Application of critical path analysis in clinical trials.

Clinical research operates in a strictly regulated environment under various management models, but a distinct management model of clinical trial (CT) still needs exploration and research. Critical path analysis (CPA) is a management approach can be used for monitoring, analysis, and prediction of success of its time-bound operational activities. A model CT was compiled with 78 activities, which were further merged into 35 major activities. After performing dependence analysis, the list was finalized with 25 activities which were taken in activity predecessor to create a network diagram and perform CPA considering patients, conduct, and outcome. Activities were inclusive, described the trial entirely with accuracy, and were in chronological and logical sequences. This approach does not replace an understanding of or adherence to the requirements contained in all applicable regulations, guidelines or standard operating procedures governing clinical studies but ensures the proper use of operational and decisional approaches including optimal resource management. As the need to meet deadlines becomes more important and the need to produce good, stable project plans, CPA is very useful for determining activities that can lead to project delay. With this approach, project may be effectively monitored, and realistic schedules can be maintained.

Rota crítica: a trajetória de uma mulher para romper o ciclo da violênciadoméstica / Critical path: the journey of a woman for breaking the cycle of domestic violence / Ruta crítica: la trayectoria de una mujer para romper el ciclo de la violencia doméstica

Este artigo busca analisar o trajeto percorrido por uma mulher para romper com a violência doméstica. A metodologia consiste em uma análise de discurso do prontuário de uma usuária de um serviço de abrigagem para mulheres em situação de violência doméstica, localizado em Porto Alegre/RS. Investigaram-se fatores impulsores e inibidores envolvidos no processo de superar a violência. A rede socioinstitucional tem um papel importante na rota crítica da usuária. Contudo, se identificou trechos do discurso que estimulam a vitimização ao invés de promover a autonomia da usuária. (AU)

This article aims to analyze the path a woman travels to break away from domestic violence. The methodology consists of a speech analysis of medical records of a user of a shelter service for women in domestic violence situations from Porto Alegre, Brazil. We investigate impellers and inhibiting factors involved in the process of overcoming violence. The socioinstitutional network has an important role in the critical path of the user. However, it was found excerpts from the speech that encourage victimization instead of promoting the autonomy of the user. (AU)

Este artículo analiza el trayecto recorrido por una mujer para romper con la violencia doméstica. La metodología consiste en un análisis de discurso del prontuario de una usuaria de servicio de abrigaje para mujeres en situación de violencia doméstica, localizado en Porto Alegre/RS. Se investigaron factores impulsores e inhibidores que intervienen en el proceso de superación de la violencia. La red socio-institucional tiene un papel importante en la ruta crítica de la usuaria. Sin embargo, se identificó extractos del habla que estimulan victimización en lugar de promover la autonomía del usuario. (AU)

Development of a patient-reported outcome instrument to assess complex activities of daily living and interpersonal functioning in persons with mild cognitive impairment: The qualitative research phase.

INTRODUCTION: As drug development research efforts move toward studying patients earlier in the course of Alzheimer's disease (AD), it is important to incorporate the patient's perspective into measurement of outcomes. METHODS: This article summarizes the qualitative work of the Patient-Reported Outcome Consortium's Cognition Working Group in the development of a new self-reported outcome measure in persons with mild cognitive impairment (MCI) due to suspected AD, herein referred to as MCI. RESULTS: The draft measure captures the patient's voice for two functional domains, complex activities of daily living and interpersonal functioning. DISCUSSION: This work represents a series of initial steps in the development of this rating scale. The next steps are to conduct psychometric analysis and evaluate the role of insight.

Rota crítica: a trajetória de uma mulher para romper o ciclo da violência doméstica / Critical path: the journey of a woman for breaking the cycle of domestic violence / Ruta crítica: la trayectoria de una mujer para romper el ciclo de la violencia doméstica

Este artigo busca analisar o trajeto percorrido por uma mulher para romper com a violência doméstica. A metodologia consiste em uma análise de discurso do prontuário de uma usuária de um serviço de abrigagem para mulheres em situação de violência doméstica, localizado em Porto Alegre/RS. Investigaram-se fatores impulsores e inibidores envolvidos no processo de superar a violência. A rede socioinstitucional tem um papel importante na rota crítica da usuária. Contudo, se identificou trechos do discurso que estimulam a vitimização ao invés de promover a autonomia da usuária.

This article aims to analyze the path a woman travels to break away from domestic violence. The methodology consists of a speech analysis of medical records of a user of a shelter service for women in domestic violence situations from Porto Alegre, Brazil. We investigate impellers and inhibiting factors involved in the process of overcoming violence. The socioinstitutional network has an important role in the critical path of the user. However, it was found excerpts from the speech that encourage victimization instead of promoting the autonomy of the user.

Este artículo analiza el trayecto recorrido por una mujer para romper con la violencia doméstica. La metodología consiste en un análisis de discurso del prontuario de una usuaria de servicio de abrigaje para mujeres en situación de violencia doméstica, localizado en Porto Alegre/RS. Se investigaron factores impulsores e inhibidores que intervienen en el proceso de superación de la violencia. La red socio-institucional tiene un papel importante en la ruta crítica de la usuaria. Sin embargo, se identificó extractos del habla que estimulan victimización en lugar de promover la autonomía del usuario.