Tag: nevin manimala

Br J Gen Pract. 2021 Oct 22:BJGP.2021.0311. doi: 10.3399/BJGP.2021.0311. Online ahead of print.

ABSTRACT

BACKGROUND: Numbers of GP locums in the NHS have grown in recent years, yet evidence on the scale and scope of the locum workforce in general practice is sparse.

AIM: To identify characteristics, geographical patterns and drivers of GP locum use.

DESIGN AND SETTING: Observational study of routine data from general practices in England.

METHODS: Descriptive analyses of national GP workforce data betwen December 2017-September 2020, to determine the volume and geographical distribution of locum use and examine the characteristics of locums compared to other GP types. We modelled locum FTE using negative binomial regressions and estimated Incidence Rate Ratios (IRRs) for the association between the outcome and practice and population characteristics.

RESULTS: In December 2019, locums made up 1,217.9 (3.3%) of 33,996.6 total GP FTE which was fewer than other GP types. Median locum age was 42 years (IQR, 36-51), and the majority were UK qualified (660 of 1,034 total locum FTE), were male (642.6 of 1,178.9 locum FTE), and had long-term employment (834.1 of 1,127.9 total locum FTE). Rurality (IRR=1.250; 95%CI 1.095-1.428), inadequate CQC ratings (IRR=2.108; 95%CI 1.370-3.246) and single-handed practice (IRR=4.611; 95%CI 4.101-5.184), were strong predictors of locum use. There was substantial variation in locum use between regions.

CONCLUSION: GP locum use remained stable over time. Compared to other GPs, locums are younger male GPs, a substantial percentage of whom did not qualify in the UK, who serve underperforming practices in rural areas. This is likely to reflect recruitment or high turnover challenges in these practices/areas.

PMID:34990386 | DOI:10.3399/BJGP.2021.0311

Dis Colon Rectum. 2022 Feb 1;65(2):228-237. doi: 10.1097/DCR.0000000000002084.

ABSTRACT

BACKGROUND: Self-expanding metal stents as a bridge to surgery in acute malignant large-bowel obstruction has gained popularity. However, long-term oncologic outcomes have not been well established.

OBJECTIVE: To investigate long-term oncologic outcomes of patients undergoing curative resection after the placement of a colonic stent compared with emergency surgery for acute malignant large-bowel obstruction.

DESIGN: This is a retrospective study.

SETTING: All patients presenting at 3 tertiary care centers between April 2002 and December 2012 with a diagnosis of complete malignant large-bowel obstruction were reviewed. Patients with disease distal to the hepatic flexure were selected for analysis.

PATIENTS: One hundred twenty-two patients who underwent either emergency surgery or placement of a colonic stent with curative intent were included.

INTERVENTIONS: Patients receiving emergency surgery within 24 hours of presenting with obstructive symptoms, including those with failed stents, were included in the emergency surgery group. All patients with clinically successful stent deployment before surgery were included in the stent group.

MAIN OUTCOME MEASURES: Overall survival and disease-free survival were calculated using the Kaplan-Meier method.

RESULTS: Sixty-four patients underwent emergency surgery, and 58 patients underwent placement of a self-expanding metal stent. Groups were similar in terms of sex, tumor stage and grade, and Charlson and Charlson-Age Comorbidity Index scores. Patients in the surgery group were older than patients in the stent group. There were no differences in the number of lymph nodes harvested, positive nodes, rates of vascular and perineural invasion, or utilization of chemotherapy. Thirty-day mortality after resection was similar between groups (7.41% vs 4.41%; p > 0.05). Patients who underwent colonic stenting as a bridge to surgery had similar 10-year overall survival (40.5% vs 32.7%; p = 0.13) and 10-year disease-free survival (40.2% vs 33.8%; p = 0.26) compared with those who underwent emergency surgery. Similar results were seen on intention-to-treat analysis.

LIMITATIONS: This was a small retrospective study.

CONCLUSIONS: Stent insertion followed by oncologic resection is associated with similar overall survival and disease-free survival compared with emergency resection. Stent insertion as a bridge to surgery should be considered in patients presenting with malignant colorectal obstruction. See Video Abstract at http://links.lww.com/DCR/B714Los Stents Metálicos Autoexpandibles No Afectan Negativamente Los Resultados A Largo Plazo En La Obstrucción Maligna Aguda Del Colon: Un Análisis Retrospectivo.

ANTECEDENTES: Los stents metálicos autoexpandibles como puente a una cirugía en la obstrucción maligna aguda del colon han ganado popularidad. Sin embargo, no se han establecido bien los resultados oncológicos a largo plazo.

OBJETIVO: Investigar los resultados oncológicos a largo plazo de los pacientes sometidos a resección curativa después de la colocación de un stent colónico en comparación con la cirugía de urgencia para la obstrucción maligna aguda del colon.

DISEO: Estudio retrospectivo.

MBITO: Entre abril de 2002 y diciembre de 2012, se revisaron todos los pacientes que acudieron a tres centros de tercer nivel con un diagnóstico de obstrucción maligna completa del colon. Se seleccionaron para el análisis los pacientes con enfermedad distal al ángulo hepático.

PACIENTES: Se incluyeron 122 pacientes que fueron operados de urgencia o a una colocación de un stent colónico con intención curativa.

PROCEDIMIENTOS: Los pacientes que se sometieron a cirugía de urgencia dentro de las 24 horas posteriores a la presentación de síntomas obstructivos; se incluyeron aquellos con stents fallidos en el grupo de cirugía de urgencia. Todos los pacientes con colocación clínicamente exitosa del stent antes de la cirugía se incluyeron en el grupo de stent.

PRINCIPALES VARIABLES ANALIZADAS: La sobrevida global y la sobrevida libre de enfermedad se calcularon mediante el método de Kaplan-Meier.

RESULTADOS: Sesenta y cuatro pacientes fueron llevados a cirugía urgente y en 58 pacientes se colocó de un stent metálico autoexpandible. Los grupos fueron similares en relación a sexo, estadio y grado del tumor, puntuación de comorbilidad de Charlson y Charlson-Age. Los pacientes del grupo de cirugía eran mayores que los del grupo de stents. No hubo diferencias en el número de ganglios linfáticos recolectados, ganglios positivos, tasas de invasión vascular y perineural o utilización de quimioterapia. La mortalidad a los 30 días después de la resección fue similar entre los grupos (7,41% frente a 4,41%; p> 0,05). Los pacientes que se sometieron a la colocación de un stent colónico como puente a la cirugía tuvieron una sobrevida general a diez años similar (40,5% vs 32,7%; p = 0,13) y una sobrevida libre de enfermedad a diez años (40,2% vs 33,8%, respectivamente; p = 0,26) en comparación a los operados de urgencia. Se observaron resultados similares en el análisis por intención de tratamiento.

LIMITACIONES: Estudio retrospectivo reducido.

CONCLUSIONES: La utilización de un stent y posteriormente la resección oncológica se asocia a una sobrevida general y una sobrevida libre de enfermedad similar en comparación con la resección de urgencia. La utilización de un stent como puente a la cirugía debe considerarse en pacientes que presentan obstrucción colorrectal maligna. Consulte Video Resumen en http://links.lww.com/DCR/B714. (Traducción-Dr. Lisbeth Alarcon-Bernes).

PMID:34990424 | DOI:10.1097/DCR.0000000000002084

Acta Dermatovenerol Croat. 2021 Dec;29(3):121-126.

ABSTRACT

We aimed to investigate the relationship between single nucleotide polymorphism (SNP) in the promoter region of the 5-HT-R2C gene and stress-related disease psoriasis in the Turkish population. The putative association between the 5-HTR2C variant (rs6318 Cys23Ser allele) and patients with psoriasis was investigated. 100 patients with psoriasis and 100 age-sex matched, unrelated healthy subjects representing the control group were included in the study. The PCR-RFLP method was used for genotyping the 5-HTR2C variation. There was no statistically difference in terms of genotype distributions and allele frequencies between the control subjects and patients with psoriasis (P=0.360 and P=0.439, respectively). The comparison between the presence and absence of the 5-HTR2C gene rs6318 G allele within the determined clinical subsets resulted in a significant difference with regard to treatment methodology only when conventional therapy and one or more medical therapy was compared (P=0.021). This study is the first clinical study to investigate the association between 5-HTR2C polymorphism and psoriasis. The role of the 5-HTR2C gene should be examined with more parameters in a larger case series.

PMID:34990340

IEEE Trans Vis Comput Graph. 2022 Jan 6;PP. doi: 10.1109/TVCG.2022.3141040. Online ahead of print.

ABSTRACT

The machine learning (ML) life cycle involves a series of iterative steps, from the effective gathering and preparation of the dataincluding complex feature engineering processesto the presentation and improvement of results, with various algorithms to choose from in every step. Feature engineering in particular can be very beneficial for ML, leading to numerous improvements such as boosting the predictive results, decreasing computational times, reducing excessive noise, and increasing the transparency behind the decisions taken during the training. Despite that, while several visual analytics tools exist to monitor and control the different stages of the ML life cycle (especially those related to data and algorithms), feature engineering support remains inadequate. In this paper, we present FeatureEnVi, a visual analytics system specifically designed to assist with the feature engineering process. Our proposed system helps users to choose the most important feature, to transform the original features into powerful alternatives, and to experiment with different feature generation combinations. Additionally, data space slicing allows users to explore the impact of features on both local and global scales. FeatureEnVi utilizes multiple automatic feature selection techniques; furthermore, it visually guides users with statistical evidence about the influence of each feature (or subsets of features). The final outcome is the extraction of heavily engineered features, evaluated by multiple validation metrics. The usefulness and applicability of FeatureEnVi are demonstrated with two use cases and a case study. We also report feedback from interviews with two ML experts and a visualization researcher who assessed the effectiveness of our system.

PMID:34990365 | DOI:10.1109/TVCG.2022.3141040

Health Technol Assess. 2021 Dec;25(76):1-228. doi: 10.3310/hta25760.

ABSTRACT

BACKGROUND: The first histology-independent marketing authorisation in Europe was granted in 2019. This was the first time that a cancer treatment was approved based on a common biomarker rather than the location in the body at which the tumour originated. This research aims to explore the implications for National Institute for Health and Care Excellence appraisals.

METHODS: Targeted reviews were undertaken to determine the type of evidence that is likely to be available at the point of marketing authorisation and the analyses required to support National Institute for Health and Care Excellence appraisals. Several challenges were identified concerning the design and conduct of trials for histology-independent products, the greater levels of heterogeneity within the licensed population and the use of surrogate end points. We identified approaches to address these challenges by reviewing key statistical literature that focuses on the design and analysis of histology-independent trials and by undertaking a systematic review to evaluate the use of response end points as surrogate outcomes for survival end points. We developed a decision framework to help to inform approval and research policies for histology-independent products. The framework explored the uncertainties and risks associated with different approval policies, including the role of further data collection, pricing schemes and stratified decision-making.

RESULTS: We found that the potential for heterogeneity in treatment effects, across tumour types or other characteristics, is likely to be a central issue for National Institute for Health and Care Excellence appraisals. Bayesian hierarchical methods may serve as a useful vehicle to assess the level of heterogeneity across tumours and to estimate the pooled treatment effects for each tumour, which can inform whether or not the assumption of homogeneity is reasonable. Our review suggests that response end points may not be reliable surrogates for survival end points. However, a surrogate-based modelling approach, which captures all relevant uncertainty, may be preferable to the use of immature survival data. Several additional sources of heterogeneity were identified as presenting potential challenges to National Institute for Health and Care Excellence appraisal, including the cost of testing, baseline risk, quality of life and routine management costs. We concluded that a range of alternative approaches will be required to address different sources of heterogeneity to support National Institute for Health and Care Excellence appraisals. An exemplar case study was developed to illustrate the nature of the assessments that may be required.

CONCLUSIONS: Adequately designed and analysed basket studies that assess the homogeneity of outcomes and allow borrowing of information across baskets, where appropriate, are recommended. Where there is evidence of heterogeneity in treatment effects and estimates of cost-effectiveness, consideration should be given to optimised recommendations. Routine presentation of the scale of the consequences of heterogeneity and decision uncertainty may provide an important additional approach to the assessments specified in the current National Institute for Health and Care Excellence methods guide.

FURTHER RESEARCH: Further exploration of Bayesian hierarchical methods could help to inform decision-makers on whether or not there is sufficient evidence of homogeneity to support pooled analyses. Further research is also required to determine the appropriate basis for apportioning genomic testing costs where there are multiple targets and to address the challenges of uncontrolled Phase II studies, including the role and use of surrogate end points.

FUNDING: This project was funded by the National Institute for Health Research (NIHR) Evidence Synthesis programme and will be published in full in Health Technology Assessment; Vol. 25, No. 76. See the NIHR Journals Library website for further project information.

PMID:34990339 | DOI:10.3310/hta25760

J Clin Oncol. 2022 Jan 6:JCO2101422. doi: 10.1200/JCO.21.01422. Online ahead of print.

ABSTRACT

PURPOSE: To establish a patient-specific polygenic score derived from cytarabine (ara-C) pathway pharmacogenomic evaluation to personalize acute myeloid leukemia (AML) treatment.

MATERIALS AND METHODS: Single nucleotide polymorphisms (SNPs) in the ara-C-pathway genes were analyzed with outcome in patients from the multicenter-AML02 trial (N = 166). Multi-SNP predictor modeling was used to develop 10-SNP Ara-C_SNP score (ACS10) using top SNPs predictive of minimal residual disease and event-free survival (EFS) from the AML02-cohort and four SNPs previously associated with ara-C triphosphate levels in the AML97 trial. ACS10 was evaluated for association with outcomes in each clinical trial arms: the standard low-dose ara-C (LDAC, n = 91) and augmented high-dose ara-C (HDAC, n = 75) arms of AML02 and the standard Ara-C, daunorubicin and etoposide (ADE) (n = 465) and the augmented ADE + gemtuzumab ozogamicin (GO; n = 466) arms of AAML0531 trial.

RESULTS: In the standard LDAC-arm of AML02 cohort, the low-ACS10 score group (≤ 0) had significantly worse EFS (ACS10 low v high hazard ratio [HR] = 2.81; 95% CI, 1.45 to 5.43; P = .002) and overall survival (OS; HR = 2.98; 95% CI, 1.32 to 6.75; P = .009) compared with the high-ACS10 group (score > 0). These results were validated in the standard-ADE arm of AAML0531, with poor outcome in the low-ASC10 group compared with the high-ACS10 group (EFS: HR = 1.35, 95% CI, 1.04 to 1.75, P = .026; OS: HR = 1.64, 95% CI, 1.2 to 2.22, P = .002). Within the augmented arms (AML02-HDAC and AAML0531-ADE + GO), EFS and OS did not differ between low- and high-ACS10 score groups. In both cohorts, patients with low-ACS10 consistently showed a 10-percentage point improvement in 5-year EFS with augmented therapy (AML02-HDAC or AAML0531-ADE + GO arms) than with standard therapy (AML02-LDAC or AAML0531-ADE arms).

CONCLUSION: Patients with low-ACS10 score experienced significantly poor outcome when treated on standard regimen. Augmentation with either high-dose ara-C or GO addition improved outcome in low-ACS10 group. A polygenic ACS10 score can identify patients with unfavorable pharmacogenetic characteristics and offers a potential for an elective augmented therapy option.

PMID:34990262 | DOI:10.1200/JCO.21.01422

Br J Radiol. 2022 Jan 6:20210832. doi: 10.1259/bjr.20210832. Online ahead of print.

ABSTRACT

OBJECTIVE: Our single-centre retrospective study aimed to evaluate the relationship between magnetic resonance (MR)-directed ultrasound (MDUS) detectability and magnetic resonance imaging (MRI) findings of non-mass enhancement (NME) lesions, regarding the morphologic and enhancement features, the distance from the skin and nipple, and the presence of concomitant landmarks.

METHODS: A total of 350 MRI-detected NME lesions that were determined between January 2015 and May 2019 and subsequently underwent MDUS were analyzed. The MRI findings, biopsy results, and follow-up outcomes of lesions were recorded. The correlation between the MRI findings of the lesions and MDUS detectability was analyzed.

RESULTS: One hundred fourteen (32.6%) of the 350 lesions had a counterpart in the MDUS. Respectively, 66 (37.9%), 38 (43.2%) and 59 (38.3%) of the lesions detected in MDUS were larger than 20 mm in size, with a distance of less than 20 mm to the nipple and 15 mm to the skin. The lesion size and lesion distance to the nipple and skin were significantly associated with a US correlate (p < 0.05). The MDUS detection rate was significantly higher in NME lesions with MR findings including diffuse distribution (p < 0.001), clustered-ring enhancement pattern (p < 0.001), washout kinetic curve (p = 0.006), and MR-BIRADS category 5 (p < 0.001). Multivariate logistic regression showed that only the clustered-ring enhancement pattern was significantly associated with an MDUS correlation (p < 0.001).

CONCLUSION: Statistically significant correlations were found between the size, distance to the nipple and skin, distribution pattern, enhancement pattern and kinetic curve of the NME lesions on MRI and ultrasound detectability.

ADVANCES IN KNOWLEDGE: We found that clustered-ring enhancement patterns were significantly more frequent in MR-directed US detectable lesions.

PMID:34990263 | DOI:10.1259/bjr.20210832

Personal Disord. 2022 Jan 6. doi: 10.1037/per0000528. Online ahead of print.

ABSTRACT

Several psychiatric conditions (e.g., substance use, mood, and personality disorders) are characterized, in part, by greater delay discounting (DD)-a decision-making bias in the direction of preferring smaller, more immediate over larger, delayed rewards. Narcissistic personality disorder (NPD) is highly comorbid with substance use, mood, and other personality disorders, suggesting that DD may be a process underpinning risk for NPD as well. This meta-analysis examined associations between DD and theoretically distinct, clinically relevant dimensions of narcissism (i.e., grandiosity, entitlement, and vulnerability). Literature searches were conducted and articles were included if they were written in English, published in a peer-reviewed journal, contained measures of DD and narcissism and reported their association, and used an adult sample. Narcissism measures had to be systematically categorized according to clinically relevant dimensions (Grijalva et al., 2015; Wright & Edershile, 2018). Seven studies met inclusion criteria (N = 2,705). DD was positively associated with narcissism (r = .21; 95% confidence interval [.10, .32]), with this association being largely attributable to measures of trait grandiosity that were used in each study (r = .24; 95% confidence interval [.11, .37]). No studies included diagnostic NPD assessments. These findings provide empirical evidence that DD is related to trait narcissism and perhaps risk for NPD (e.g., grandiosity listed in Criterion B of the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, alternative model of personality disorders). Considering the positive evidence from this review, and the dearth of research examining DD in individuals with NPD, investigators studying NPD may consider incorporating DD measures in future studies to potentially inform clinical theory and novel adjunctive treatment options. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

PMID:34990195 | DOI:10.1037/per0000528

Plant Biol (Stuttg). 2022 Jan 6. doi: 10.1111/plb.13382. Online ahead of print.

ABSTRACT

Increases in environmental temperature are directly linked to the issue of climate change and are known to significantly disrupt plant growth and development. Studies of gene expression in plants commonly include RT-qPCR but the reliability of the method depends on the use of suitable reference genes for data normalization. Despite this, no reference genes have been validated specifically for experiments in Arabidopsis thaliana employing treatments with elevated temperature. Here, ten genes were selected for expression stability analysis based on the screening of available literature and microarray data from temperature-treated A. thaliana. Expression levels of candidate reference genes were measured in 12-day-old seedlings, rosette leaves and flower buds of 5-week-old A. thaliana plants exposed to five different temperatures (22°C, 27°C, 32°C, 37°C and 42°C) and their expression stabilities were assessed using four statistical algorithms (BestKeeper, geNorm, NormFinder and comparative ΔC_q method). This study provides reliable reference genes for use in A. thaliana RT-qPCR expression analyses employing elevated temperature treatments, namely OGIO and PUX7 in seedlings, UBC21 and PUX7 in leaves, TIP41 and UBC21 in buds, and TIP41 and UBC21 in all three tissues combined. Orthologues of these genes can be of potential use in less studied plants, especially agricultural species heavily affected by climate change.

PMID:34990067 | DOI:10.1111/plb.13382

J Exp Psychol Gen. 2022 Jan 6. doi: 10.1037/xge0001166. Online ahead of print.

ABSTRACT

The statistical relation between two events influences the perception of how one event relates to the presence or absence of another. Interestingly, the simultaneous absence of both events, just like their mutual occurrence, is relevant for describing their contingency. In three experiments, we explored the relevance of coabsent events by varying the duration and frequency of trials without stimuli. We used a rapid trial streaming procedure and found that the perceived association between events is enhanced with increasing frequency of coabsent events, unlike the duration of coabsent events, which had little effect. These findings suggest ways in which the benefits of trial spacing, during which both events are absent, could be obtained without increasing total training time. Centrally, this can be done by frequent repeating of shortened coabsent events, each marked by a trial contextual cue. We discuss four potential accounts of how coabsent experience might be processed contributing to this effect: (a) contingency sensitivity, (b) testing effect, (c) reduced associative interference by the context, and (d) reduced encoding interference. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

PMID:34990159 | DOI:10.1037/xge0001166