Category: Nevin Manimala

ANZ J Surg. 2021 Apr 1. doi: 10.1111/ans.16734. Online ahead of print.

ABSTRACT

BACKGROUND: Geographical remoteness and socioeconomic status (SES) are important factors affecting presentation stage and survival for colorectal cancer. A series of patients from a single institution in northern New South Wales was studied to determine if rural isolation or SES affected presentation and survival in patients undergoing resection.

METHODS: Consecutive colorectal cancer resections performed at Lismore Base Hospital from 2011 to 2019 were identified. Patient residential addresses were categorized by the Modified Monash Model (MMM), an Australian Government definition of rural isolation, and Socioeconomic Index for Areas (SEIFA) quintiles, an Australian Bureau of Statistics index of socioeconomic deprivation. Univariate and Cox regression survival analysis was performed on data from histopathology and clinical notes matched with survival data.

RESULTS: A total of 405 patients were included in MMM categories 3 (n = 207, 51.1%), 4 (n = 69, 17%) and 5 (n = 129, 31.9) corresponding to large, medium and small rural towns. MMM 3 was associated with emergency cases (25.6% versus 18.7%, P < 0.001), nodal disease (44.4% versus 38.4%, P = 0.018) and T3/4 tumours (82.1% versus 73.7%, P < 0.001) compared with isolated patients without difference in 5-year survival (P = 0.370). Disadvantaged SEIFA quintiles 1/2 demonstrated increased poor differentiation (23.0% versus 15.4%, P < 0.001) and vascular invasion (15.8% versus 9.1%, P < 0.001) with reduced 5-year survival (57.0% versus 70.4%, P = 0.039). Independent predictors of survival included age, emergency cases, group stage, lymphatic invasion and low lymph node yield.

CONCLUSION: A ‘rural reversal’ may be present for patients in northern New South Wales; however, SES and established clinicopathological factors are the strongest predictors of survival in our population.

PMID:33792127 | DOI:10.1111/ans.16734

HIV Med. 2021 Mar 31. doi: 10.1111/hiv.13095. Online ahead of print.

ABSTRACT

OBJECTIVES: Adolescents living with perinatal HIV infection (ALPHI) experience persistently high mortality rates, particularly in resource-limited settings. It is therefore clinically important for us to understand the therapeutic response, acquired HIV drug resistance (HIVDR) and associated factors among ALPHI, according to geographical location.

METHODS: A study was conducted among consenting ALPHI in two urban and two rural health facilities in the Centre Region of Cameroon. World Health Organization (WHO) clinical staging, self-reported adherence, HIVDR early warning indicators (EWIs), immunological status (CD4 count) and plasma viral load (VL) were assessed. For those experiencing virological failure (VF, VL ≥ 1000 copies/mL), HIVDR testing was performed and interpreted using the Stanford HIV Drug Resistance Database v.8.9-1.

RESULTS: Of the 270 participants, most were on nonnucleoside reverse transcriptase inhibitor (NNRTI)-based regimens (61.7% urban vs. 82.2% rural), and about one-third were poorly adherent (30.1% vs. 35.1%). Clinical failure rates (WHO-stage III/IV) in both settings were < 15%. In urban settings, the immunological failure (IF) rate (CD₄ < 250 cells/μL) was 15.8%, statistically associated with late adolescence, female gender and poor adherence. The VF rate was 34.2%, statistically associated with poor adherence and NNRTI-based antiretroviral therapy. In the rural context, the IF rate was 26.9% and the VF rate was 52.7%, both statistically associated with advanced clinical stages. HIVDR rate was over 90% in both settings. EWIs were delayed drug pick-up, drug stock-outs and suboptimal viral suppression.

CONCLUSIONS: Poor adherence, late adolescent age, female gender and advanced clinical staging worsen IF. The VF rate is high and consistent with the presence of HIVDR in both settings, driven by poor adherence, NNRTI-based regimen and advanced clinical staging.

PMID:33792134 | DOI:10.1111/hiv.13095

Oncologist. 2021 Mar 31. doi: 10.1002/onco.13770. Online ahead of print.

ABSTRACT

INTRODUCTION: Lenvatinib (Len) plus everolimus (Eve) is an approved therapy for metastatic renal cell carcinoma (mRCC) after first-line vascular endothelial growth factor receptor-tyrosine kinase inhibitors (VEGFR-TKI), but limited data exist on the efficacy of Len +/- Eve after progression on immune checkpoint inhibitors (ICI) and VEGFR-TKI.

METHODS: We retrospectively reviewed the records of patients with mRCC at our institution who were treated with Len +/- Eve after ICI and VEGFR-TKI. A blinded radiologist assessed objective response as defined by RECIST v1.1. Descriptive statistics and the Kaplan-Meier method were used.

RESULTS: 55 patients were included in the analysis. 81.8% had clear-cell histology (ccRCC) and 76.4% had IMDC intermediate-risk disease. Median number of prior therapies was 4 (range, 2-10); all patients had prior ICI and VEGFR-TKI, and 80% were previously treated with ICI and ≥2 VEGFR-TKI, including cabozantinib. One patient (1.8%) achieved a complete response and 11 patients (20.0%) achieved a partial response, for an overall response rate (ORR) of 21.8%; 35 patients (63.6%) achieved stable disease. In all patients, median progression-free survival (PFS) was 6.2 months (95% CI, 4.8-9.4) and median overall survival (OS) was 12.1 months (95% CI, 8.8-16.0). In patients with ccRCC, ORR was 24.4%, PFS was 7.1 months (95% CI, 5.0-10.5), and OS was 11.7 months (95% CI, 7.9-16.1). 50.9% of patients required dose reductions and 7.3% discontinued treatment because of toxicity.

CONCLUSIONS: Len +/- Eve demonstrated meaningful clinical activity and tolerability in heavily pre-treated patients with mRCC after disease progression with prior ICI and VEGFR-TKI.

PMID:33792094 | DOI:10.1002/onco.13770

ANZ J Surg. 2021 Apr 1. doi: 10.1111/ans.16743. Online ahead of print.

ABSTRACT

BACKGROUND: Supracondylar humerus fractures are common in children. Percutaneous pinning remains the mainstay in treatment; however, there is lack of consensus on the optimal configuration: lateral-only pinning or cross pinning. This study aims to investigate the differences in clinical and surgical outcomes between lateral-only and cross-pinning paediatric supracondylar humerus fractures.

METHODS: A systematic search was performed using Medline Ovid, Embase and Cochrane databases for relevant randomized control trials comparing lateral and cross pinning of paediatric supracondylar humerus fractures, reporting at least one of the following: rate of iatrogenic ulnar nerve injury, loss of reduction, infection, loss of Baumann’s angle and loss of carrying angle. Statistical analysis was performed using STATA 13.0.

RESULTS: Eleven suitable randomized control trials involving 900 patients were reviewed. Loss of reduction was more common with lateral pinning (relative risk 1.44, 95% confidence interval 1.04-2.00, P = 0.027). Iatrogenic ulnar nerve injury was less common in lateral pinning with treatment-based analysis (relative risk 0.36, 95% confidence interval 0.14-0.92, P = 0.032). There was no statistically significant difference in loss of carrying angle, loss of Baumann angle or rate of infection.

CONCLUSION: Cross pinning provides superior stability in the treatment of supracondylar humerus fractures in children; however, it carries greater risk of iatrogenic ulnar nerve injury.

PMID:33792121 | DOI:10.1111/ans.16743

Int J Health Plann Manage. 2021 Mar 31. doi: 10.1002/hpm.3166. Online ahead of print.

ABSTRACT

Government of India introduced National Rural Health Mission in 2005-now transformed into National Health Mission (NHM), to bring about architectural reforms in health sector. In this study, we evaluate the overall impact of NHM on infant mortality at national and state level. Annual data on infant mortality rate (IMR) from 1990 to 2016 were obtained from Sample Registration System bulletins. With reporting year 2009 considered as cut-off point, a two-step segmented time series regression analysis was conducted. Estimates of pre-slope, post-slope and change at the point of intervention were computed by applying auto-regressive integrated moving average (1, 0, 0) while adjusting for trend and auto correlation. We found that while IMR reduced from around 80 to 34 per 1000 live births at the national level from 1990 to 2016, the annual rate of reduction increased from 1.6 per 1000 live births before NHM to 2.2 per 1000 live births after NHM. This is estimated to have averted 248,212 infant deaths in India, between 2005 and 2017. The rate of decline in IMR accelerated in 13 out of 17 larger states, most significantly in Andhra Pradesh, Gujarat, Assam, Haryana, Punjab and Uttar Pradesh. NHM has thus been successful in accelerating the overall rate of reduction in IMR in India. There is still a need to identify the determinants of variations at state level. We recommend strengthening of NHM in terms of funding and implementation.

PMID:33792075 | DOI:10.1002/hpm.3166

J Hum Hypertens. 2021 Mar 31. doi: 10.1038/s41371-021-00502-x. Online ahead of print.

ABSTRACT

In Ghana, the management of hypertension in primary health care is a cost-effective way of addressing premature deaths from vascular disorders that include hypertension. There is little or no evidence of large-scale studies on the prevalence, risk, and knowledge/awareness of hypertension in students aged 12-22 years in Ghana. In a cross-sectional study, blood pressure, anthropometric indices, and knowledge/awareness assessment of students at second-cycle schools were recorded from 2018 to 2020 in three regions of Ghana. Multistage cluster sampling was used in selecting regions and the schools. Prevalence of prehypertension and hypertension was categorized by the Joint National Committee 7, where appropriate, chi-square, scatter plots, and correlations were used in showing associations. A total of 3165 students comprising 1776 (56.1%) females and 1389 (43.9%) males participated in this study within three regions of Ghana. The minimum age was 12 years and the maximum age was 22 years. The mean age was 17.21 with standard deviation (SD: 1.59) years. A 95% confidence interval was set for estimations and a P value < 0.05 was set as significant. The prevalence rate of overall hypertension was 19.91% and elevated (prehypertension) was 26.07%. Risk indicators such as weight, BMI, waist circumference, physical activity, and form of the diet were positively correlated with hypertension. Among Ghanaian students currently in second-cycle educational institutions, 19.91% were hypertensive and 26.07% were prehypertensive. This may indicate a probable high prevalence of hypertension in the future adult population if measures are not taken to curb the associated risks.

PMID:33790406 | DOI:10.1038/s41371-021-00502-x

J Hum Hypertens. 2021 Mar 31. doi: 10.1038/s41371-021-00485-9. Online ahead of print.

ABSTRACT

The majority of single-nucleotide polymorphism (SNP) association studies of salt sensitivity (SS) have focused on SNPs in protein-coding genes rather than on SNPs in noncoding RNAs. This study attempted to identify the association between whole blood microRNA (miRNA)-related SNPs and the risk of SS in a Han Chinese population. A case-control study of 762 individuals was performed. A modified Sullivan’s acute oral saline load and diuresis shrinkage test was used to assess SS. All SNPs were analysed by RT-PCR on a Sequenom Mass ARRAY Platform (Sequenom, San Diego, CA, USA). A genetic risk score (GRS) was used to evaluate the joint genetic effect. In total, 24 miRNA-related SNPs were genotyped, four of which (miR-1307-5p/rs11191676, miR-1307-5p/rs2292807, miR-145/rs41291957 and miR-4638-3p/rs6601178) were associated with both SS and salt sensitivity of blood pressure (SSBP) (p ≤ 0.05). MiR-382-5p/rs4906032 and miR-15b-5/rs10936201 were associated with SSBP. Weighted GRS showed that participants in the second, third and fourth quartiles had 1.760-fold (95% CI: 1.068-2.903), 2.450-fold (95% CI: 1.470-4.083) and 2.774-fold (95% CI: 1.680-4.582) increased risk of SS, respectively. Bioinformatics analysis indicated that these four SNP risk alleles may affect transcription factor binding and influence promoter activity. A total of six miRNA-related SNPs were found to be associated with SS or SSBP, and the presence of multiple risk alleles resulted in increased risk level.

PMID:33790405 | DOI:10.1038/s41371-021-00485-9

Sci Rep. 2021 Mar 31;11(1):7294. doi: 10.1038/s41598-021-86809-8.

ABSTRACT

Nasopharyngeal carcinoma (NPC) is a rare malignancy, with the unique geographical and ethnically characteristics of distribution. Gene chip and bioinformatics have been employed to reveal regulatory mechanisms in current functional genomics. However, a practical solution addressing the unresolved aspects of microarray data processing and analysis have been long pursuit. This study developed a new method to improve the accuracy of identifying key biomarkers, namely Unit Gamma Measurement (UGM), accounting for multiple hypotheses test statistics distribution, which could reduce the dependency problem. Three mRNA expression profile of NPC were selected to feed UGM. Differentially expressed genes (DEGs) were identified with UGM and hub genes were derived from them to explore their association with NPC using functional enrichment and pathway analysis. 47 potential DEGs were identified by UGM from the 3 selected datasets, and affluent in cysteine-type endopeptidase inhibitor activity, cilium movement, extracellular exosome etc. also participate in ECM-receptor interaction, chemical carcinogenesis, TNF signaling pathway, small cell lung cancer and mismatch repair pathway. Down-regulation of CAPS and WFDC2 can prolongation of the overall survival periods in the patients. ARMC4, SERPINB3, MUC4 etc. have a close relationship with NPC. The UGM is a practical method to identify NPC-associated genes and biomarkers.

PMID:33790390 | DOI:10.1038/s41598-021-86809-8

Sci Rep. 2021 Mar 31;11(1):7266. doi: 10.1038/s41598-021-86729-7.

ABSTRACT

Methotrexate (MTX) is a common first-line treatment for new-onset rheumatoid arthritis (RA). However, MTX is ineffective for 30-40% of patients and there is no way to know which patients might benefit. Here, we built statistical models based on serum lipid levels measured at two time-points (pre-treatment and following 4 weeks on-drug) to investigate if MTX response (by 6 months) could be predicted. Patients about to commence MTX treatment for the first time were selected from the Rheumatoid Arthritis Medication Study (RAMS). Patients were categorised as good or non-responders following 6 months on-drug using EULAR response criteria. Serum lipids were measured using ultra-performance liquid chromatography-mass spectrometry and supervised machine learning methods (including regularized regression, support vector machine and random forest) were used to predict EULAR response. Models including lipid levels were compared to models including clinical covariates alone. The best performing classifier including lipid levels (assessed at 4 weeks) was constructed using regularized regression (ROC AUC 0.61 ± 0.02). However, the clinical covariate based model outperformed the classifier including lipid levels when either pre- or on-treatment time-points were investigated (ROC AUC 0.68 ± 0.02). Pre- or early-treatment serum lipid profiles are unlikely to inform classification of MTX response by 6 months with performance adequate for use in RA clinical management.

PMID:33790392 | DOI:10.1038/s41598-021-86729-7

J Perinatol. 2021 Mar 31. doi: 10.1038/s41372-021-01006-9. Online ahead of print.

ABSTRACT

OBJECTIVE: To evaluate the optimal approaches to initial surgical management and the potential for prenatal ultrasound detection of patients with closing gastroschisis.

STUDY DESIGN: We performed a retrospective analysis of patients born with gastroschisis to determine clinical and surgical outcomes and the ability to determine prognosis by prenatal imaging. Data collected included operative findings and postoperative outcome, as well as prenatal imaging features from a subset of cases with and without closing gastroschisis. Statistical analyses were performed as appropriate.

RESULTS: We included 197 patients with gastroschisis. No statistical significance was seen in outcomes between closing gastroschisis patients undergoing resection versus intracorporeal parking (n = 18). Ultrasound review was performed on 33 of these patients, 11 with closing gastroschisis, and 22 without. Significantly more closing gastroschisis patients had imaging indicative of progressive defect narrowing and defect diameter ≤8 mm after 30 weeks of gestation versus non-closing patients (p = 0.002).

CONCLUSION: Parking of extruded bowel offers potential for intestinal remodeling. In addition, prenatal ultrasound may be useful in detection of closing gastroschisis in utero.

PMID:33790403 | DOI:10.1038/s41372-021-01006-9