Multinational Studies Research Articles

In Vitro Susceptibility of Gram-Negative Pathogens to Cefiderocol in Five Consecutive Annual Multinational SIDERO-WT Surveillance Studies, 2014 to 2019.

ABSTRACTWe report in vitro susceptibility data from five consecutive annual SIDERO-WT surveillance studies (2014 to 2019) for cefiderocol and comparators tested against Gram-negative clinical isolates from North America and Europe. CLSI broth microdilution was used to determine MICs for Enterobacterales (n = 31,896), Pseudomonas aeruginosa (n = 7,700), Acinetobacter baumannii complex (n = 5,225), Stenotrophomonas maltophilia (n = 2,030), and Burkholderia cepacia complex (n = 425). MICs were interpreted by CLSI-approved clinical breakpoints (February 2021). Cefiderocol inhibited 99.8, 96.7, 91.6, and 97.7% of all Enterobacterales, meropenem-nonsusceptible, ceftazidime-avibactam-nonsusceptible, and ceftolozane-tazobactam-nonsusceptible isolates, respectively, at ≤4 μg/mL (susceptible breakpoint). Cefiderocol inhibited 99.9, 99.8, 100, and 99.8% of all P. aeruginosa, meropenem-nonsusceptible, ceftazidime-avibactam-nonsusceptible, and ceftolozane-tazobactam-nonsusceptible isolates, respectively, at ≤4 μg/mL (susceptible breakpoint). Cefiderocol inhibited 96.0% of all A. baumannii complex isolates and 94.2% of meropenem-nonsusceptible isolates at ≤4 μg/mL (susceptible breakpoint) and 98.6% of S. maltophilia isolates at ≤1 μg/mL (susceptible breakpoint). B. cepacia complex isolates were tested with a MIC50 of ≤0.03 μg/mL and MIC90 of 0.5 μg/mL. Annual cefiderocol percent susceptible rates for Enterobacterales (North America range, 99.6 to 100%/year; Europe range, 99.3 to 99.9%/year) and P. aeruginosa (North America range, 99.8 to 100%; Europe range, 99.9 to 100%) were unchanged from 2014 to 2019. Annual percent susceptible rates for A. baumannii complex demonstrated sporadic, nondirectional differences (North America range, 97.5 to 100%; Europe range, 90.4 to 97.5%); the wider range for Europe (∼7%) was due to isolates from Russia. Annual percent susceptible rates for S. maltophilia showed minor, nondirectional differences (North America range, 96.4 to 100%; Europe range, 95.6 to 100%). We conclude that clinical isolates of Enterobacterales (99.8% susceptible), P. aeruginosa (99.9%), A. baumannii (96.0%), and S. maltophilia (98.6%) collected in North America and Europe from 2014 to 2019 were highly susceptible to cefiderocol.

A scoping review of the current evidence on treatment and outcomes following synovial sepsis.

Synovial sepsis is a frequent cause of morbidity and mortality in horses. Despite advances in diagnostics and treatments, persistent infection or chronic lameness can occur. To perform a scoping review to identify and evaluate the current evidence on the factors implicated in the success of treatment for synovial sepsis. Joanna Briggs Institute scoping review. A protocol was registered, and a systematic literature search was performed on CAB abstracts, Medline, Scopus and Embase. Inclusion and exclusion criteria were developed and studies systematically reviewed against this. Studies relating to factors affecting treatment success following synovial sepsis were retained and data was extracted on study method, population characteristics and factors significantly associated with treatment outcome. In total, 2338 studies were identified, and 61 were included to full paper analysis. Eight papers reported significant factors, identifying 15 risk factors associated with two measurements of outcome, either survival and/or return to athletic function. The 15 factors were identified and categorised into pre-, intra- and post-operative factors. Risk factors that were identified included the number or type of synovial structures involved, the presence of pannus, tendon and bone pathology, and the use of systemic antimicrobials. There were many discrepancies in inclusion criteria of cases of synovial sepsis as well as measurement and description of outcome variables. Non-English language studies or conference proceedings were not included. Only small numbers of papers had similar findings. Standardisation of inclusion criteria is essential to enable comparisons and analysis between studies on synovial sepsis. Future studies should use methodologies to reduce bias including multicentre and multinational studies, prospective study design and robust statistical modelling.

Safety, tolerability, pharmacokinetics, and pharmacodynamics of the glucokinase activator PB-201 and its effects on the glucose excursion profile in drug-naïve Chinese patients with type 2 diabetes: a randomised controlled, crossover, single-centre phase 1 trial.

BackgroundPB-201, a partial, pancreas/liver-dual glucokinase activator, showed good tolerance and glycaemic effects in multinational studies. This study determined its optimal dose, safety, pharmacokinetics, and pharmacodynamics in Chinese patients with type 2 diabetes.MethodsIn this double-blind, randomised, four-period, crossover, phase 1 trial in China, conducted at the Peking University Third Hospital, adult patients with drug-naive type 2 diabetes were randomised (1:1:1:1) to four sequence groups using a computer-generated randomisation table. In each period, they received oral placebo or PB-201 (50+50, 100+50, or 100+100 mg split doses) for 7 days. Investigators and patients were masked to treatment assignment. The primary endpoints were safety and pharmacokinetics. Continuous glucose monitoring was used to delineate the glucose excursion profile. Trial registration number: NCT03973515.FindingsBetween August 27, 2019 and December 19, 2019, 16 patients were randomised. PB-201 showed a dose-proportional pharmacokinetic profile without apparent accumulation in the body and induced dose-dependent lowering of blood glucose. PB-201 at 50+50, 100+50, and 100+100 mg increased mean time in range (49·210% [standard deviation 27], 56·130% [25], and 63·330% [20] with three doses, respectively) versus placebo (49·380% [27]) and reduced estimated glycated haemoglobin from baseline (−0·5445% [1·654], −1·063% [1·236], and −1·888% [1·381] vs −0·581% [1·200]). Fifteen patients (93·8%) had treatment-emergent adverse events, which were mild. No patients had hypoglycaemia with venous/capillary glucose <3·9 mmol/L or nocturnal hypoglycaemia.InterpretationPB-201 100 mg twice daily is identified as the optimal dose, which shows promising glucose-lowering effects and low risks of hypoglycaemia and other side effects. Further investigation of PB-201 100 mg twice daily in confirmatory trials is warranted.FundingPegBio.

Severity and case fatality rates of COVID-19: a systematic review, meta-analysis and an exploratory meta-regression of risk factors

Background: We aimed to estimate prevalence of severe or critical illness and case fatality of COVID-19 in a systematic review and meta-analysis and to examine clinical, biochemical and radiological risk factors in a meta-regression.&#x0D; Methods: PRISMA guidelines were followed. PubMed, Scopus and Web of Science were searched using pre-specified keywords. Peer-reviewed empirical studies examining rates of severe illness, critical illness and case fatality among COVID-19 patients were examined. Random-effects meta-analyses were performed and adjusted for publication bias. Meta-regression analyses examined the moderator effects of risk factors.&#x0D; Results: The meta-analysis included 29 studies representing 2,090 individuals. Pooled prevalence rates of severe illness, critical illness and case fatality among COVID-19 patients were 15%, 5% and 0.8% respectively. There were significant heterogeneity and publication bias related with the studies. Meta-regression analyses revealed that increasing age and elevated LDH consistently predicted severe / critical disease and case fatality. Moreover, hypertension; fever and dyspnea at presentation; and elevated CRP predicted increased severity.&#x0D; Conclusions: Emerged predictors of severity and case fatality should inform clinicians to define at-risk endophenotypes. Differences in un-adjusted vs. adjusted pooled estimates indicates limited utility of small-scale studies and underscores the importance of multi-national studies to establish the morbidity and mortality rates in pandemics.

Green Space and Mental Health outcomes: a cross-sectional survey as a starting point to bridge Green Areas' features to the post-pandemic needs

Abstract Background Green space has been associated with health and mental health. Given the high prevalence of mental disorders and costs of worldwide mental ill health and the concurrent rise in mental disorders during the pandemic, there is a need of a better understanding of the impact of different types of green space on mental health. The aim of this study was to assess the impact of characteristics of green space on mental health in a population in a rural area of Germany. Methods We conducted a cross-sectional survey based on face-to-face on an online assessment instrument. The instrument consisted of sociodemographic questions (assessing age, gender, income, education), mental health related question (PHQ - 9). Green space was dichotomized into green space with agrarian features and green space without agrarian features and subsequently geocoded using ATkis TN. Results In total n = 484 persons participated (female: 240 (49, 6%), male: N = 239 (49, 9%), n= missing). Mean age was 58,17 years (SD: 18,83) with an age range of 19-96 years. Depression symptoms showed n = 122 (54.9%) persons. Green space without agrarian features was associated with lower symptom levels of depression (Beta: 0.045, SE: 0.023, p = 0.015). However, green space with agrarian features was not related to depression. Discussion Characteristics of green spaces are associated with better mental health; however, the clear definition of quality green space needs further elaboration. The sample is a rural sample and results need further validation in an urban sample. Outlook: In the post-pandemic era green space itself seems to have no impact on mental health, however quality green space does. These results need further validation in multinational studies.

Management and outcomes in critically ill nonagenarian versus octogenarian patients

BackgroundIntensive care unit (ICU) patients age 90 years or older represent a growing subgroup and place a huge financial burden on health care resources despite the benefit being unclear. This leads to ethical problems. The present investigation assessed the differences in outcome between nonagenarian and octogenarian ICU patients.MethodsWe included 7900 acutely admitted older critically ill patients from two large, multinational studies. The primary outcome was 30-day-mortality, and the secondary outcome was ICU-mortality. Baseline characteristics consisted of frailty assessed by the Clinical Frailty Scale (CFS), ICU-management, and outcomes were compared between octogenarian (80–89.9 years) and nonagenarian (> 90 years) patients. We used multilevel logistic regression to evaluate differences between octogenarians and nonagenarians.ResultsThe nonagenarians were 10% of the entire cohort. They experienced a higher percentage of frailty (58% vs 42%; p < 0.001), but lower SOFA scores at admission (6 + 5 vs. 7 + 6; p < 0.001). ICU-management strategies were different. Octogenarians required higher rates of organ support and nonagenarians received higher rates of life-sustaining treatment limitations (40% vs. 33%; p < 0.001). ICU mortality was comparable (27% vs. 27%; p = 0.973) but a higher 30-day-mortality (45% vs. 40%; p = 0.029) was seen in the nonagenarians. After multivariable adjustment nonagenarians had no significantly increased risk for 30-day-mortality (aOR 1.25 (95% CI 0.90–1.74; p = 0.19)).ConclusionAfter adjustment for confounders, nonagenarians demonstrated no higher 30-day mortality than octogenarian patients. In this study, being age 90 years or more is no particular risk factor for an adverse outcome. This should be considered– together with illness severity and pre-existing functional capacity - to effectively guide triage decisions.Trial registrationNCT03134807 and NCT03370692.

Worldwide epidemiology of neuro-coronavirus disease in children: lessons for the next pandemic.

Purpose of reviewThe severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pandemic has overwhelmed the global community, negatively impacting patient health and research efforts; associated neurological manifestations are a significant cause of morbidity. This review outlines the worldwide epidemiology of neurologic manifestations of different SARS-CoV-2 clinical pediatric phenotypes, including acute coronavirus disease 2019 (COVID-19), multisystem inflammatory syndrome in children (MIS-C) and postacute sequelae of COVID-19 (PASC). We discuss strategies to develop adaptive global research platforms for future investigation into emerging pediatric neurologic conditions.Recent findingsMulticenter, multinational studies show that neurological manifestations of acute COVID-19, such as smell/taste disorders, headache, and stroke, are common in hospitalized adults (82%) and children (22%), associated with increased mortality in adults. Neurological manifestations of MIS-C are reported in up to 20% of children, including headache, irritability, and encephalopathy. Data on PASC are emerging and include fatigue, cognitive changes, and headache. Reports of neurological manifestations in each phenotype are limited by lack of pediatric-informed case definitions, common data elements, and resources.SummaryCoordinated, well resourced, multinational investigation into SARS-CoV-2-related neurological manifestations in children is critical to rapid identification of global and region-specific risk factors, and developing treatment and mitigation strategies for the current pandemic and future health neurologic emergencies.

Clinical Characteristics of Resected Acinar Cell Carcinoma of the Pancreas: A Korean Multi-Institutional Study.

Simple SummaryPancreatic acinar cell carcinoma accounts for less than 1% of primary pancreatic neoplasms. Because of its rarity, its characteristics and clinical outcomes remain unclear. Treatment strategies for pancreatic acinar cell carcinoma have relied on those of pancreatic ductal adenocarcinoma. In previous studies, it has been difficult to identify its characteristics due to the lack of cohort numbers in single institutional studies with detailed data and the lack of detailed data in large cohort multi-institutional studies. This retrospective multicenter cohort used a database founded in 2015 by the Korean Association of Hepato-Biliary Pancreatic Surgery. This database has collected nationwide patient data with details. In the present study, we aimed to better understand clinical outcomes of resected pancreatic acinar cell carcinoma and to lay the groundwork for establishing proper treatment strategies.Given the rare incidence of pancreatic acinar cell carcinoma (PACC), its post-resection clinical outcomes remain unclear. Treatment strategies for PACC have relied on those of pancreatic ductal adenocarcinoma (PDAC). The present study retrospectively investigated clinicopathologic characteristics of resected PACC registered in the Korea Tumor Registry System Biliary Pancreas database. Among 59 patients with a mean age of 59.2 years and a male predominance (83.1%), 43, 5, 7, and 4 had pure PACC, ductal differentiations, mixed neuroendocrine carcinomas, and intraductal and papillary variants, respectively. The mean tumor size was 4.6 cm, consisting of eight at T1, 26 at T2, and 25 at T3 stages. Metastasis to regional lymph node was identified in 15 (25.4%) patients. Thirty-one (52.5%) patients received adjuvant therapy. Five-year survival rate was 57.4%. The median survival was 78.8 months. In survival comparison according to the stage with AJCC system, N stage (lymph node metastasis), but not T stage, showed significant differences (p = 0.027). Resected PACC appeared to have clinical outcomes distinct from those of PDAC in this nationwide study. Therefore, large-scale multinational studies are needed to overcome the rarity of PACC and to establish an appropriate treatment strategies and staging system.

Mental Health in Times of the COVID-19 Pandemic

Abstract. The COVID-19 pandemic is one of the most serious health and economic crises of the 21st century. From a psychological point of view, the COVID-19 pandemic and its consequences can be conceptualized as a multidimensional and potentially toxic stressor for mental health in the general population. This selective literature review provides an overview of longitudinal studies published until June 2021 that have investigated the impact of the COVID-19 pandemic on mental health in the European population. Risk and protective factors identified in the studies are summarized. Forty-two studies that met inclusion and search criteria ( COVID-19, mental health, longitudinal, and Europe) in PubMed, PsycInfo, and Web of Science databases indicate differential effects of the pandemic on mental distress, depression, and anxiety, depending on samples and methods used. Age-specific (e.g., young age), social (e.g., female, ethnical minority, loneliness), as well as physical and mental health-related factors (e.g., pre-pandemic illness) were identified as risk factors for poor mental health. The studies point to several protective factors such as social support, higher cognitive ability, resilience, and self-efficacy. Increasing evidence supports the assumption of the pandemic being a multidimensional stressor on mental health, with some populations appearing more vulnerable than others, although inconsistencies arise. Whether the pandemic will lead to an increase in the prevalence of mental disorders is an open question. Further high-quality longitudinal and multi-national studies and meta-analyses are needed to draw the complete picture of the consequences of the pandemic on mental health.

RIETE: Past and future

There is a lack of knowledge with regards to contemporary presentation, management, and outcomes of patients with venous thromboembolism (VTE). Many clinically important subgroups (including the elderly, those with recent bleeding, and pregnant patients) have been under-represented in clinical trials. Further, design of clinical trials is challenging in some scenarios, such as in those with hemodynamically-unstable pulmonary embolism (PE). RIETE (Registro Informatizado Enfermedad TromboEmbolica) is a large prospective multinational ongoing registry, designed to address these unmet needs using representative data from multiple centers. Initiated in Spain in 2001, RIETE currently includes 206 centers in 28 countries and has enrolled over 87,000 patients with VTE. The overarching goal is to improve the management of VTE through better understanding of prevention, as well as demographics, co-morbidities, treatment patterns, and outcomes of patients with VTE. RIETE has helped characterize the pattern of presentation and outcomes of VTE, including in the aforementioned understudied subgroups, in over 150 research articles. RIETE has recently expanded to collect long-term outcomes data, and has broadened its inclusion criteria to enroll other forms of venous thrombosis (such as cerebral vein thrombosis and splanchnic vein thrombosis). The RIETE platform is also being used to conduct pragmatic comparative effectiveness studies, including randomized trials. Future steps would focus on collaboration with additional centers across the world, and efforts to ensure the quality and expansion of the registry. It is expected that RIETE will continue to provide clinical evidence for understudied subgroups with VTE, and will have more prominent role for facilitation of multicenter (and multinational studies) that could be used for assessment of variations and disparities in care, quality improvement, and conducting comparative effectiveness research. RIETE is a large ongoing registry of patients with VTE and other thrombotic conditions. Its results could be helpful for improving our understanding of the epidemiology, patterns of care and outcomes of patients with thrombotic disease.

Evaluating the performance of ACR, SLICC and EULAR/ACR classification criteria in childhood onset systemic lupus erythematosus

BackgroundThe ACR 1997, SLICC 2012 and EULAR/ACR 2019 classification criteria were validated based on adult patients. To date, there are no classification criteria specific for children with SLE. The aim of the study is to compare the performance characteristics among the three SLE classification criteria (ACR-1997, SLICC-2012 and EULAR/ACR-2019) in childhood onset SLE (cSLE) cohort of Arab ethnicity from Oman.MethodsWe conducted a retrospective multicenter study in Oman of cSLE patients as cases and patients with other rheumatic disease with a positive ANA titer as controls. The cSLE cases recruited were children diagnosed with SLE before 13 years of age. Data was retrospectively collected to establish the ACR-1997, SLICC-2012 and EULAR/ACR-2019 criteria fulfilled at first visit, first year follow up and last follow up.ResultsStudy population included 113 cSLE cases (mean age at diagnosis of 7.3 ± 3.4 years with disease duration of 6.1 ± 4.6 years) and 51 controls (mean age at diagnosis 5.0 ± 3.4 with disease duration 5.7 ± 3.9). The cSLE cases had higher frequency of familial SLE than controls (38% vs 7.8%; p < 0.001). The performance measures demonstrated that EULAR/ACR-2019 criteria had the highest sensitivity (81, 88, 89%) compared to ACR 1997 (49, 57, 66%) and SLICC 2012 (76, 84,86%); while the ACR 1997 had the highest specificity (96%) compared to SLICC 2012 (94%) and EULAR/ACR 2019 (90%) at first visit, first year and last assessment. When we increased the threshold score to ≥13 rather than the traditional score ≥ 10 for ACR/EULAR 2019, there was increased specificity (96%) at the expense of lower sensitivity (76, 83, and 84%) at first visit, first year and last assessment.ConclusionIn this cSLE population, EULAR/ACR 2019 scored better at initial presentation, first year and last assessment follow up. Further multinational studies are needed to validate the appropriate cut off score for the newly proposed ACR/EULAR 2019 classification criteria in cSLE to increase early sensitivity and specificity for cSLE classification.

Systematic review of crisis reactions toward major disease outbreaks: application of the triple helix model in the context of tourism

PurposeWhile academia, industry and government have made various efforts to ameliorate the impacts of Covid-19, no study has hitherto used an integrative framework to assess the reactions of all three of these sectors to previous multinational epidemics. Such fragmentation ignores the holistic nature of crisis management. To better understand the impacts of health crises on tourism, this study aims to examine the past literature related to academic, industrial and governmental responses to multinational epidemics through the lens of the triple helix model.Design/methodology/approachBased on preferred reporting items for systematic reviews and meta-analyzes and the best-fit approach, this paper conducts a systematic review of the literature published between 2000 and 2020 on five multinational epidemics that had significant impacts on the tourism industry: food and mouth disease, severe acute respiratory syndrome, bird flu (novel influenza A and avian flu), Ebola and middle east respiratory syndrome. Thematic analysis was used to identify major themes in the 63 relevant articles identified.FindingsNo substantial increase was found in the quantity of multinational epidemic-related studies after 2010. Collectively, the 10 identified themes strongly emphasized economic recovery.Originality/valueNo existing tourism-related study examines reactions toward multiple health crises by integrating three important sectors: academia, industry and government. This study fills that research gap with a systematic review of past multinational epidemics and proposes an integrative framework. It also provides recommendations for future research and health-crisis management practices.

Vegetation Dynamics and Climatological Drivers in Ethiopia at the Turn of the Century

Global change, particularly climate change, poses a risk of altering vegetation composition and health. The consequences manifest throughout Earth’s system as a change in ecosystem services and socioecological stability. It is therefore critical that vegetation dynamics are monitored to establish baseline conditions and detect shifts. Africa is at high risk of environmental change, yet evaluation of the link between climate and vegetation is still needed for some regions. This work expands on more frequent local and multinational scale studies of vegetation trends by quantifying directional persistence (DP) at a national scale for Ethiopia, based on the normalized difference vegetation index (NDVI) between 2000 and 2016. The DP metric determines cumulative change in vegetation greenness and has been applied to studies of ecological stability and health. Secondary analysis utilizing panel regression methodologies is carried out to measure the effect of climate on NDVI. Models are developed to consider spatial dependence by including fixed effects and spatial weights. Results indicate widespread cumulative declines in NDVI, with the greatest change during the dry season and concentrated in northern Ethiopia. Regression analyses suggest significant control from climatic variables. However, temperature has a larger effect on NDVI, which contrasts with findings of some previous studies.

Clinical remission of rheumatoid arthritis in a multicenter real-world study in Asia-Pacific region.

BackgroundClinical remission is an attainable goal for Rheumatoid Arthritis (RA). However, data on RA remission rates from multinational studies in the Asia-Pacific region are limited. We conducted a cross-sectional multicentric study to evaluate the clinical remission status and the related factors in RA patients in the Asia-Pacific region.MethodsRA patients receiving standard care were enrolled consecutively from 17 sites in 11 countries from APLAR RA SIG group. Data were collected on-site by rheumatologists with a standardized case-report form. Remission was analyzed by different definitions including disease activity score using 28 joints (DAS28) based on ESR and CRP, clinical disease activity index (CDAI), simplified disease activity index (SDAI), Boolean remission definition, and clinical deep remission (CliDR). Logistic regression was used to determine related factors of remission.FindingsA total of 2010 RA patients was included in the study, the overall remission rates were 62•3% (DAS28-CRP), 35•5% (DAS28-ESR), 30•8% (CDAI), 26•5% (SDAI), 24•7% (Boolean), and 17•1% (CliDR), respectively, and varied from countries to countries in the Asia-Pacific region. Biological and targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs) prescription rate was low (17•9%). Compared to patients in non-remission, patients in remission had higher rates of b/tsDMARDs usage and lower rates of GC usage. The favorable related factors were male sex, younger age, fewer comorbidities, fewer extra-articular manifestations (EAM), and use of b/tsDMARDs, while treatment with GC was negatively related to remission.InterpretationRemission rates were low and varied in the Asia-Pacific region. Treatment with b/tsDMARDs and less GC usage were related to higher remission rate. There is an unmet need for RA remission in the Asia-Pacific region.

Pharmacoepidemiological Safety of Drugs Used in Geriatrics: A Systematic Review in Madanapalle and Punganur Region of Andhra Pradesh

In this study, we were provided universal considerations for the setting up and carry out of pharmacoepidemiological studies of drug use for disorders like Osteoarthritis, Hypertension, Hyperlipidemia, Hypothyroidism, Depression, and Osteoporosis in geriatric patient. The study method was focused on monitored and categorized the prescriptions of geriatrics from 650 patient in Madapalle and Puganur region of Andhra Pradesh, Identified and prepare the list of drugs, which were inappropriately prescribed and used in geriatrics by using Revised Beers criteria and also assess the Activities of Daily Living (ADL) by using Modified Barthel Index (MBI). Identify any drug-drug interactions among the drugs used in geriatrics. We were reported the adverse drug reactions appeared in geriatrics and the various treatments that the patients are received with different co-morbidity disease with the assessment of drug exposure, and ascertainment of PIM, PPO STOPP, START criteria and MBI outcomes. Characteristic of statistics sources include evaluation of complete history of drug use in elderly patient with co-morbidity condition, allowing approximate of collective exposure. Result data from beers criteria with PIM, modified barthel index are preferable, but elderly patient treatment data from reliable sources, for example, patient or pathology registries, and medical records are also considered. We present report to showed poly-pharmacy effects of drug use on elderly patient improvement and converse the need for employing STOPP and START criteria of PIM and PPO to avoid undesirable drug reaction causation. We emphasize that a study design of beers criteria always be considered and result of Modified barthel index shows the dependency rate in elderly patient. We also underline the need for Comorbidity analyses in geriatric patient and drug usage, as drug utilization in geriatric are prone to dose and number of drugs in treatment dependent. In the main, studies of Prescription analyses like polypharmacy, PIM, PPO in prescription should explore risk Geriatric patient, the present study reveal the PIM and PPO of in prescription from six hundred and fifty geriatric patient. We conclude the pharmacoepidemiological studies of elderly patient are likely to develop significantly in the coming years, due to the rising mortality of long-term drug exposures and less awareness of poly-pharmacy result, the increasing perform of multinational studies, permiting studies of rare and common disease in elderly people, types of medication and procedural development specifically addressing geriatric treatment and long-term outcomes.

Country-related future research agenda of Lean Manufacturing–A systematic literature review

PurposeMany future research proposals of Lean Manufacturing (LM) are presented in the literature. The purpose of this paper is to determine these future research proposals of LM which are country-related and classify them.Design/methodology/approachA systematic literature review (SLR) of peer-reviewed journal articles in LM was conducted. A total of 145 articles published in 34 journals during 2010–2020 were collected from four major management science publishers namely, Emerald Online, Elsevier/Science Direct, Springer Link and Taylor and Francis. The country-related future research proposals of LM identified in the literature were classified according to, firstly, the continent of the country of reference, and secondly, some form of natural affinity of these proposals creating meaningful themes. The quality tool “affinity diagram” was applied to classify the country-related future research proposals of LM.FindingsThe country-related future research proposals of LM, which are increasing in the literature over time, refer mostly to studies to be conducted in several continents/countries and to multinational studies. Conducting studies specifically in Asia, Europe, South and North America, Africa and Australia–New Zealand is also suggested. The plethora of the country-related future research proposals of LM were classified, based on the affinity of their content, into 18 meaningful themes. These themes were also classified based on their affinity into two broad categories, namely “themes concerning the LM approach itself” and “themes concerning factors outside the LM approach”.Research limitations/implicationsThe restricted number of the databases searched and the subjectivity of classifying the large number of the country-related future research proposals into themes are the main limitations of the present SLR. Based on these limitations, future literature review studies can be carried out.Practical implicationsUseful proposals are provided to researchers of several countries for conducting original and country-specific research studies which can enrich the knowledge of the implementation of LM under the specific circumstances of a country for the benefit of practitioners.Originality/valueThis study goes beyond previous literature review studies on LM by focusing exclusively on the LM future research agenda which is country related. The analytical presentation of the country-related future research proposals as well as the formulation of clusters of these proposals make the present SLR study substantially different from those carried out worldwide so far.

Clinical experience and psychometric properties of the Cardiff Acne Disability Index (CADI).

The Cardiff Acne Disability Index (CADI) is a questionnaire designed to measure the quality of life of teenagers and young adults with acne. It has been used clinically and within therapeutic research globally. This review aims to appraise all published data regarding the clinical and research experience of the CADI, its psychometric properties and validation, from its publication in 1992 until September 2020, in a single reference source. A literature search was conducted using MEDLINE via Ovid, PubMed, EBSCOhost, Web of Science and Scopus. All full articles in the English language were included. A total of 96 clinical studies were identified and analysed. The CADI has been used in 44 different countries, including four multinational studies, and has validated translations in 25 languages. Overall, 29 therapeutic interventions have used the CADI, demonstrating its responsiveness to change. The reliability of the CADI has been assessed in 14 studies through test-retest and internal consistency studies. In total, 57 studies have demonstrated aspects of its validity through correlation to other measures, and five studies have investigated the dimensionality of the CADI. There is evidence of high internal consistency, test-retest reliability, responsiveness to change and significant correlation with other objective measures. The minimal clinically important difference and validated score meaning bands have not yet been reported. This information is needed to improve the interpretability of CADI scores for clinical use and in research. The authors of the CADI have also rephrased Question 2 of the measure to ensure inclusivity.

In vitro activity of the novel siderophore cephalosporin, cefiderocol, in Gram-negative pathogens in Europe by site of infection

ObjectivesWe assessed the activity of the novel siderophore cephalosporin, cefiderocol and selected other antibacterial agents against Gram-negative bacterial isolates in Europe. MethodsIsolates were obtained between 2013 and 2018 from European countries participating in the SIDERO-WT and SIDERO-Proteeae multinational surveillance studies. Isolates were categorised by infection site, focusing on bloodstream infections, hospital-acquired/ventilator-associated bacterial pneumonia (HABP/VABP), complicated intra-abdominal infections and complicated urinary tract infections. Cefiderocol activity was compared with ceftazidime–avibactam, ceftolozane–tazobactam, colistin and meropenem using standard susceptibility testing methods. European Committee on Antimicrobial Susceptibility Testing (EUCAST) breakpoints were used to interpret susceptibility data. ResultsIsolates (n = 20 911) were collected from 145 sites in 24 countries in Europe, the highest proportion (34%) being from patients with HABP/VABP. Enterobacterales (66.6% of isolates) were more frequent than glucose non-fermenting species (33.4%) overall, with some differences between infection sites. Across all infection sites, the MIC50/MIC90 for cefiderocol was ≤0.5/≤2 mg/L for Enterobacter spp., ≤0.25/<2 mg/L for Klebsiella spp., 0.12/2 mg/L for Acinetobacter spp., ≤0.25/1 mg/L for Pseudomonas aeruginosa and ≤0.12/≤0.5 mg/L for Stenotrophomonas maltophilia. Across all infection sites, cefiderocol MICs were ≤2 mg/L for ≥96% of Enterobacter spp., ≥95% of Klebsiella spp., ≥90% of Acinetobacter spp. and ≥99% of Pseudomonas aeruginosa and Stenotrophomonas maltophilia isolates. Cefiderocol maintained high activity in carbapenem-resistant isolates, and the difference in activity between carbapenem-resistant (percentage susceptibility at EUCAST breakpoint: E. coli 77.8%, Klebsiella spp. 69.2%, Pseudomonas aeruginosa 97.5%, Acinetobacter spp. 90.7%, Stenotrophomonas maltophilia 99.6%) and carbapenem-susceptible (percentage susceptibility at EUCAST breakpoint: E. coli 99.4%, Klebsiella spp. 98.0%, Pseudomonas aeruginosa 99.7%, Acinetobacter spp. 94.9%) isolates was lower for cefiderocol than other agents. ConclusionsCefiderocol had excellent activity against all Gram-negative species, independent of key infection site and carbapenem MIC. Cefiderocol is a useful addition to the therapeutic options available for these difficult-to-treat infections.

This Month in Pediatric Urology

You have accessJournal of UrologyThis Month in Pediatric Urology1 Jul 2021This Month in Pediatric Urology Julian Wan Julian WanJulian Wan More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000001820AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail Urinary Tract Infections in Newborns with Spina Bifida Spina bifida is a striking neurosurgical condition affecting growth, mobility and cognition. It is also a significant urological condition with long term effects. The creation of a national registry and multicenter studies have made it possible to analyze these manifestations to a degree heretofore limited by experience of any single practice or institution. The variations in management, the utility of baseline imaging and the frequency of complex bladder reconstruction are among the issues that have been examined in recent articles in The Journal.1–3 In a multicenter study in this issue of The Journal, Wallis et al (page 126) continue this effort.4 They report on a prospective study at 9 institutions participating in the UMPIRE study (Urologic Management to Preserve Initial Renal Function Protocol for Young Children with Spina Bifida). Using data gathered from 2015 to 2019, they followed 299 patients with spina bifida and looked at the utility of using antibiotic prophylaxis during the newborn period. They found that symptomatic culture proven urinary tract infection (UTI) during the first 4 months of life was low (4%) suggesting that antibiotic prophylaxis may not be necessary. The presence of higher grades of hydronephrosis and being on clean intermittent catheterization did increase this risk tenfold and threefold, respectively, and the important effect of urodynamic testing remains to be determined. The refinement of the use of antibiotics and a greater appreciation of the different contributing factors to UTI risk in this manner may help to shape a unified approach to the urological management of spina bifida in newborns. This may help smooth out local and regional variations. Large scale collaborative studies like this provide a framework for future work to identify and refine effective therapies for these complex cases.

Clinical outcomes of patients with resected acinar cell carcinoma of the pancreas: A Korea Tumor Registry System Biliary Pancreas (KOTUS-BP) database analysis

Given the rare incidence of the pancreatic acinar cell carcinoma (PACC), the post-resection clinical outcomes remains still unclear, and treatment strategies have relied on that of pancreatic ductal adenocarcinoma (PDAC). The present study retrospectively investigated the clinicopathologic characteristics of resected PACC of 54 patients registered in the Korea Tumor Registry System Biliary Pancreas (KOTUS-BP) database between March 2003 and March 2020. Among 54 patients, with a mean age of 59 years and a male predominance (81.5%), there were 38 pure PACC (70.4%), five ductal differentiations (9.3%), seven mixed neuroendocrine carcinomas (13.0%), and four intraductal and papillary variants (7.4%). A mean tumor size was 4.6 cm consisting of seven at T1, 25 at T2, and 22 at T3 stages. Metastasis to regional lymph node was identified in 13 patients (24.1%). Twenty-eight patients (51.9%) received adjuvant chemotherapy (5-fluorouracil-based [n = 15]; gemcitabine-based [n = 13]). The 5-year survival rate was 54.6% with a median survival of 78.8 months. In survival comparison according to the stages of American Joint Committee on Cancer system, N stage (lymph node metastasis) showed significant differences (p = 0.008), but T stage did not derive any significant difference. The resected PACC appears to have clinical outcomes distinct from the PDAC in this nation-wide study. Therefore, large-scale multinational studies are needed to overcome the rarity of PACC and to establish appropriate treatment strategies and staging system.