Tag: pubmed

Saudi J Kidney Dis Transpl. 2021 Jan-Feb;32(1):111-117. doi: 10.4103/1319-2442.318512.

ABSTRACT

Studies have reported high prevalence of inappropriate dosing in patients with renal impairment, which was significantly reduced with pharmacists’ interventions. The objective of this study was to assess the proportions of renal drug dosing errors following the implementation of pharmacists-led renal drug dosing adjustment program. This was a quasi-experimental study conducted at the King Abdul Aziz Medical City, a tertiary teaching hospital, Jeddah, Saudi Arabia. The study comprised of 3 phases. The pre-phase and post-phase evaluated drug orders for dosing appropriateness. During the intervention phase, a renal drug dosing adjustment program was implemented, which included educational sessions on dosing in renal insufficiency and a renal drug dosing guidance. The primary outcome was to assess the change in the proportions of dosing errors following the intervention. In the pre-phase, inappropriate dosing was noted in 20.1% (70/348) of orders that required dosing adjustment. Among the total dosing errors, 44.2% (31/70) were further corrected, and pharmacists have documented intervention in 48.3% (15/31) of the corrected orders. In the post-phase, inappropriate dosing was noted in 21.9% (76/346) of orders that required dosing adjustment. Among the total dosing errors, 39.4% (30/76) were further corrected, and pharmacists have documented intervention in 66.6% (20/30) of the corrected orders. There was no statistically significant difference in inappropriate drug dosing between pre-phase and post-phase with a P = 0.56. The intervention was not associated with significant reduction in renal dosing errors, although pharmacist involvement in the corrected orders orders increased after the implementation of the intervention. This may indicate the need to integrate renal dosing guidance into the hospital prescribing system to optimize drug dosing in renal patients.

PMID:34145120 | DOI:10.4103/1319-2442.318512

Saudi J Kidney Dis Transpl. 2021 Jan-Feb;32(1):128-136. doi: 10.4103/1319-2442.318514.

ABSTRACT

Immunosuppressive therapy is the backbone to renal transplantation. Although an adequate level of immunosuppression is required to dampen the immune response to the allograft, the level of chronic immunosuppression is slowly decreased over time (as the risk of acute rejection decreases) to help lower the overall risk of infection and malignancy. Several studies have discussed the clinical use of therapeutic drug monitoring of mycophenolic acid (MPA) in kidney transplant recipients. This prospective single-center study included 88 patients with end-stage renal disease who were transplanted in Mansoura Urology and Nephrology Center from living related donors, from the beginning of February 2016 to the end of December 2016. Eight patients were excluded, the remaining 80 patients were divided into two groups; the study group (40 patients) who were followed up using therapeutic trough level monitoring of MPA and, control group (40 patients) who were followed up using the fixed-dose of Mycophenolate according to our local immunosuppressive protocol. These patients were followed up for one year posttransplantation with regard to graft function, rejection episodes, gastrointestinal (GI), and hematological side effects, the incidence of infection or malignancy, patient survival, and graft survival. Fifteen patients from the study group (37.5%) needed dose reduction of MPA, no patients needed to increase the dose. Our study showed insignificant differences regarding the patients’ characteristics and demographic data. Significantly higher incidence of GI manifestations was noted in the control group (P = 0.001). Although the higher frequency of incidence of infection, anemia, leukopenia and thrombocytopenia was seen in the fixed- dose group, the difference was statistically insignificant. Regarding proteinuria and post-transplant diabetes mellitus, comparable data were obtained. Significantly higher percentage of recipients in the study group is still having normally functioning grafts (P = 0.02). Furthermore, higher percent of recipients in the control group died with functioning graft after one year of follow-up (P = 0.04). There were insignificant differences as regarding patient and graft survival. The decrease in the dose of MPA reduced the annual cost by around six thousand US dollars. Our results suggest that adopting therapeutic dose monitoring strategy during follow-up of kidney transplant recipients is adequate. Longer-term studies with a larger sample size may be needed to support this policy.

PMID:34145122 | DOI:10.4103/1319-2442.318514

Saudi J Kidney Dis Transpl. 2021 Jan-Feb;32(1):209-217. doi: 10.4103/1319-2442.318526.

ABSTRACT

A wide range of causative organisms can cause acute pyelonephritis (APN). However, in recent times, these pathogens have increasingly become resistant to most of the antibiotics making treatment difficult. This was a prospective observational single-center study with a aim to study the microbiological spectrum, resistance patterns, and clinical outcome of patients with APN conducted in a private tertiary care hospital in India. All adult patients hospitalized in the department of nephrology at our institute with a diagnosis of APN from February 2016 to May 2017 were included. Patients <18 years of age, kidney-transplant recipients, and pregnant patients were excluded. Demographic details, clinical symptoms, signs, and radiological and laboratory data including urine and blood cultures of all patients were recorded. The details of treatment received and outcomes in hospital and after discharge were noted. Patients were followed up three months post discharge. Decision of antibiotic and duration of antibiotics was documented by treating nephrologists. Quantitative data were presented in terms of means and standard deviation. Student’s “t” test was used for comparison of quantitative outcome parameters. P <0.05 is considered statistically significant. SPSS software version 23.0 was used for statistical analysis. A total of 89 patients with a mean age of 50.33 ± 13.9 years, of which 61.8% were males and were studied; 82/89 had complicated pyelonephritis. The most common risk factor for APN was diabetes mellitus in 64 (72%). Most common symptom was fever in 80 (90%). A triad of fever, flank pain, and dysuria was present only in 27 (30.33%). Overall, 15 patients (16.8%) had severe pyelonephritis requiring intensive care unit admission. The most common organism isolated was Escherichia coli in 26/49 (53%), followed by Klebsiella pneumoniae in 12 (24.40%). Twenty-two (58%) isolates were extended-spectrum beta lactamase producers. Six (12.20%) were resistant to carbapenems and two (4%) were pan-resistant. All 89 were treated with intravenous antibiotics. Older patients, those with diabetes, with poor glycemic control, and with emphysematous pyelonephritis and patients in whom ESBL organisms were grown had poor outcome. Piperacillin tazobactam, aminopenicillins, cefoperazone sulbactam, and carbapenems (in severe pyelonephritis) can be considered as the empirical antibiotic of choice.

PMID:34145133 | DOI:10.4103/1319-2442.318526

Thorax. 2021 Jun 18:thoraxjnl-2020-216494. doi: 10.1136/thoraxjnl-2020-216494. Online ahead of print.

ABSTRACT

The incidence of and risk factors for recurrent hospitalisation for pneumonia were investigated using data from Hospital Episode Statistics, linked to a UK primary care database. Within 90 days and 1 year of follow-up, 1733 (3.1%) and 5064 (9.0%), developed recurrent pneumonia respectively. Smoking status at the time of hospitalisation with index pneumonia was associated with the risk of readmission with recurrent pneumonia within a year of discharge: current versus never smokers: adjusted subhazard ratio (sHR) 1.42, 95% CI 1.32 to 1.53, p<0.001, and ex smokers versus never smokers: adjusted sHR 1.24, 95% CI 1.15 to 1.34, p<0.001. Other independent risk factors associated with recurrent pneumonia were age, gender, deprivation and underlying comorbidities.

PMID:34145048 | DOI:10.1136/thoraxjnl-2020-216494

Indian J Med Res. 2020 Dec;152(6):648-655. doi: 10.4103/ijmr.IJMR_1582_18.

ABSTRACT

BACKGROUND & OBJECTIVES: As India and other developing countries are scaling up isoniazid preventive therapy (IPT) for people living with HIV (PLHIV) in their national programmes, we studied the feasibility and performance of IPT in terms of treatment adherence, outcome and post-treatment effect when given under programmatic settings.

METHODS: A multicentre, prospective pilot study was initiated among adults living with HIV on isoniazid 300 mg with pyridoxine 50 mg after ruling out active tuberculosis (TB). Symptom review and counselling were done monthly during IPT and for six-month post-IPT. The TB incidence rate was calculated and risk factors were identified.

RESULTS: Among 4528 adults living with HIV who initiated IPT, 4015 (89%) successfully completed IPT. IPT was terminated in 121 adults (3%) due to grade 2 or above adverse events. Twenty five PLHIVs developed TB while on IPT. The incidence of TB while on IPT was 1.17/100 person-years (p-y) [95% confidence interval (CI) 0.8-1.73] as compared to TB incidence of 2.42/100 p-y (95% CI 1.90-3.10) during the pre-IPT period at these centres (P=0.017). The incidence of TB post-IPT was 0.64/100 p-y (95% CI 0.04-1.12). No single factor was significantly associated with the development of TB.

INTERPRETATION & CONCLUSIONS: Under programmatic settings, completion of IPT treatment was high, adverse events minimal with good post-treatment protection. After ruling out TB, IPT should be offered to all PLHIVs, irrespective of their antiretroviral therapy (ART) status. Scaling-up of IPT services including active case finding, periodic counselling on adherence and re-training of ART staff should be prioritized to reduce the TB burden in this community.

PMID:34145105 | DOI:10.4103/ijmr.IJMR_1582_18

BMJ Open. 2021 Jun 18;11(6):e050948. doi: 10.1136/bmjopen-2021-050948.

ABSTRACT

INTRODUCTION: This research project addresses the lack of screening tools for the early detection of high-risk individuals for long-term care, through four individual studies.Study 1 investigates the predictive ability of the ‘Kihon Check List’, study 2 the ‘Cognitive Function instrument’ and EuroQol-5 Dimension (EQ-5D) and study 3 the ‘Cognitive Function instrument’ and EQ-5D as well as the ‘Frail Kenshin’ health check-up, for incident long-term care certification over a follow-up period of up to 4 years. This is the first large prospective study to evaluate the predictive ability of these tools for the outcome measure long-term care certification. The last subsection of this project study four aims to explore a mixed methods intervention for delaying the need for long-term care. This section is purely exploratory, looking for clues for further studies.

METHODS AND ANALYSIS: Baseline data have been collected through local government programs, as well as through postal self-reported questionnaires. The primary outcome variable for all studies is long-term care certification data. Statistical analysis will be carried out using Kaplan-Meier, Multiple Cox regression as well as logistic regression.

CONCLUSION: This project hopes to identify tools effective in predicting long-term care need. This will enable identification of citizens that are of higher risk for long-term care in the near future. This subset of high-risk individuals can in the future be addressed for extra support/intervention.

ETHICS AND DISSEMINATION: All studies have been approved by respective institutional ethical committees and the WHO ethical committee ERC.0002899. In addition, all studies conform to the provisions of the Declaration of Helsinki and are conducted in accordance with Japan’s ‘Ethical Guidelines for Medical and Health Research Involving Human Subjects’. All findings will be disseminated at conferences and published in peer-reviewed journals.

TRIAL REGISTRATION NUMBER: UMIN000023283.

PMID:34145022 | DOI:10.1136/bmjopen-2021-050948

BMJ Open. 2021 Jun 18;11(6):e051417. doi: 10.1136/bmjopen-2021-051417.

ABSTRACT

INTRODUCTION: The global COVID-19 pandemic continues to have wide-ranging implications for health, including psychological well-being. A growing corpus of research reviews has emerged on the topic of psychological resilience in the context of the pandemic. However, this body of work has not been systematically reviewed for its quality, nor with respect to findings on the effectiveness of tools and strategies for psychological resilience. To this end, a meta-review protocol is proposed with the following objectives: (1) identify review work on the topic of psychological resilience during COVID-19; (2) assess the quality of this review work using A MeaSurement Tool to Assess systematic Reviews; (3) assess the risk of bias in this work; (4) generate a narrative summary of the key points, strengths and weaknesses; (5) identify the psychological resilience strategies that have been reviewed; (6) identify how these strategies have been evaluated for their effectiveness; (7) identify what outcomes were measured and (8) summarise the findings on strategies for psychological resilience so far, providing recommendations, if possible.

METHODS AND ANALYSIS: A systematic meta-review will be conducted in accordance with the Preferred Reporting Items for Systematic Reviews for Protocols and Joanna Briggs Institute umbrella review guidelines. Electronic searches of general databases, especially Web of Science, Scopus and PubMed, will be conducted. Only results from January 2020 onwards will be considered, coinciding with the COVID-19 pandemic. Only results in English will be included. Descriptive statistics, thematic analysis and narrative summaries describing the nature of the reviewed work and evaluation of psychological resilience strategies will be carried out.

ETHICS AND DISSEMINATION: Ethical approval is not needed for systematic review protocols. The results of the meta-review will be published in an international peer-reviewed journal. The raw and summarised data will be shared in the journal or other open venues.

PROSPERO REGISTRATION NUMBER: CRD42021235288.

PMID:34145023 | DOI:10.1136/bmjopen-2021-051417

Cancer Res. 2021 Jun 18:canres.3543.2020. doi: 10.1158/0008-5472.CAN-20-3543. Online ahead of print.

ABSTRACT

ENO1 (α-enolase) expression is significantly correlated with reduced survival and poor prognosis in many cancer types, including lung cancer. However, the function of ENO1 in carcinogenesis remains elusive. In this study, we found that high expression of ENO1 is present in metastatic lung cancer cell lines and malignant tumors and is associated with poor overall survival of lung cancer patients. Knockdown of ENO1 decreased cancer cell proliferation and invasiveness, whereas overexpression of ENO1 enhanced these processes. Moreover, ENO1 expression promoted tumor growth in orthotopic models and enhanced lung tumor metastasis in tail-vein injection models. These effects were mediated by upregulation of mesenchymal markers N-cadherin and vimentin and the epithelial-mesenchymal transition (EMT) regulator SLUG, along with concurrent downregulation of E-cadherin. Mechanistically, ENO1 interacted with hepatocyte growth factor receptor (HGFR) and activated HGFR and Wnt signaling via increased phosphorylation of HGFR and the Wnt co-receptor LRP5/6. Activation of these signaling axes decreased GSK-3β activity via Src-PI3K-AKT signaling and inactivation of the β-catenin destruction complex to ultimately upregulate SLUG and β-catenin. Additionally, we generated a chimeric anti-ENO1 monoclonal antibody (chENO1-22) that can decrease cancer cell proliferation and invasion. chENO1-22 attenuated cancer cell invasion by inhibiting ENO1-mediated GSK3β inactivation to promote SLUG protein ubiquitination and degradation. Moreover, chENO1-22 prevented lung tumor metastasis and prolonged survival in animal models. Taken together, these findings illuminate the molecular mechanisms underlying the function of ENO1 in lung cancer metastasis and supports the therapeutic potential of a novel antibody targeting ENO1 for treating lung cancer.

PMID:34145039 | DOI:10.1158/0008-5472.CAN-20-3543

BMJ Open. 2021 Jun 18;11(6):e049339. doi: 10.1136/bmjopen-2021-049339.

ABSTRACT

INTRODUCTION: A 2011 paper proposed a working taxonomy of implementation outcomes, their conceptual distinctions and a two-pronged research agenda on their role in implementation success. Since then, over 1100 papers citing the manuscript have been published. Our goal is to compare the field’s progress to the originally proposed research agenda, and outline recommendations for the next 10 years. To accomplish this, we are conducting the proposed scoping review.

METHODS AND ANALYSIS: Our approach is informed by Arksey and O’Malley’s methodological framework for conducting scoping reviews. We will adhere to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews. We first aim to assess the degree to which each implementation outcome has been investigated in the literature, including healthcare settings, clinical populations and innovations represented. We next aim to describe the relationship between implementation strategies and outcomes. Our last aim is to identify studies that empirically assess relationships among implementation and/or service and client outcomes. We will use a forward citation tracing approach to identify all literature that cited the 2011 paper in the Web of Science (WOS) and will supplement this with citation alerts sent to the second author for a 6-month period coinciding with the WOS citation search. Our review will focus on empirical studies that are designed to assess at least one of the identified implementation outcomes in the 2011 taxonomy and are published in peer-reviewed journals. We will generate descriptive statistics from extracted data and organise results by these research aims.

ETHICS AND DISSEMINATION: No human research participants will be involved in this review. We plan to share findings through a variety of means including peer-reviewed journal publications, national conference presentations, invited workshops and webinars, email listservs affiliated with our institutions and professional associations, and academic social media.

PMID:34145020 | DOI:10.1136/bmjopen-2021-049339

BMJ Open. 2021 Jun 18;11(6):e044242. doi: 10.1136/bmjopen-2020-044242.

ABSTRACT

OBJECTIVES: To develop and validate a rule-out prediction model for the risk of hospitalisation among patients with SARS-CoV-2 infection in the ambulatory setting to derive a simple score to determine outpatient follow-up.

DESIGN: Prospective cohort study.

SETTING: Swiss university hospital.

PARTICIPANTS: 1459 individuals with a positive result for SARS-CoV-2 infection between 2 March and 23 April 2020.

METHODS: We applied the rule of 10 events per variable to construct our multivariable model and included a maximum of eight covariates. We assessed the model performance in terms of discrimination and calibration and performed internal validation to estimate the statistical optimism of the final model. The final prediction model included age, fever, dyspnoea, hypertension and chronic respiratory disease. To develop the OUTCoV score, we assigned points for each predictor that were proportional to the coefficients of the regression equation. Sensitivity, specificity, positive and negative likelihood ratios were estimated, including positive and negative predictive values in different thresholds.

MAIN OUTCOME MEASURE: The primary outcome was COVID-19-related hospitalisation.

RESULTS: The OUTCoV score ranged from 0 to 7.5 points. The two threshold parameters with optimal rule-out and rule-in characteristics for the risk of hospitalisation were 3 and 5.5, respectively. Outpatients with a score <3 (997/1459; 68.3%) had no follow-up as at low risk of hospitalisation (1.8%; 95% CI 1.1 to 2.8). For a score ≥5.5 (20/1459; 1.4%), the hospitalisation risk was higher (30%; 95% CI 11.9 to 54.3).

CONCLUSIONS: The OUTCoV score allows to rule out two-thirds of outpatients with SARS-CoV-2 infection presenting a low hospitalisation risk and to identify those at high risk that require careful follow-up to assess the need for hospitalisation. The model provides a simple decision-making tool for an effective allocation of resources to maintain quality care for outpatient populations.

PMID:34145007 | DOI:10.1136/bmjopen-2020-044242