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Nevin Manimala Statistics

The power of TOPMed imputation for the discovery of Latino-enriched rare variants associated with type 2 diabetes

Diabetologia. 2023 May 6. doi: 10.1007/s00125-023-05912-9. Online ahead of print.

ABSTRACT

AIMS/HYPOTHESIS: The Latino population has been systematically underrepresented in large-scale genetic analyses, and previous studies have relied on the imputation of ungenotyped variants based on the 1000 Genomes (1000G) imputation panel, which results in suboptimal capture of low-frequency or Latino-enriched variants. The National Heart, Lung, and Blood Institute (NHLBI) Trans-Omics for Precision Medicine (TOPMed) released the largest multi-ancestry genotype reference panel representing a unique opportunity to analyse rare genetic variations in the Latino population. We hypothesise that a more comprehensive analysis of low/rare variation using the TOPMed panel would improve our knowledge of the genetics of type 2 diabetes in the Latino population.

METHODS: We evaluated the TOPMed imputation performance using genotyping array and whole-exome sequence data in six Latino cohorts. To evaluate the ability of TOPMed imputation to increase the number of identified loci, we performed a Latino type 2 diabetes genome-wide association study (GWAS) meta-analysis in 8150 individuals with type 2 diabetes and 10,735 control individuals and replicated the results in six additional cohorts including whole-genome sequence data from the All of Us cohort.

RESULTS: Compared with imputation with 1000G, the TOPMed panel improved the identification of rare and low-frequency variants. We identified 26 genome-wide significant signals including a novel variant (minor allele frequency 1.7%; OR 1.37, p=3.4 × 10-9). A Latino-tailored polygenic score constructed from our data and GWAS data from East Asian and European populations improved the prediction accuracy in a Latino target dataset, explaining up to 7.6% of the type 2 diabetes risk variance.

CONCLUSIONS/INTERPRETATION: Our results demonstrate the utility of TOPMed imputation for identifying low-frequency variants in understudied populations, leading to the discovery of novel disease associations and the improvement of polygenic scores.

DATA AVAILABILITY: Full summary statistics are available through the Common Metabolic Diseases Knowledge Portal ( https://t2d.hugeamp.org/downloads.html ) and through the GWAS catalog ( https://www.ebi.ac.uk/gwas/ , accession ID: GCST90255648). Polygenic score (PS) weights for each ancestry are available via the PGS catalog ( https://www.pgscatalog.org , publication ID: PGP000445, scores IDs: PGS003443, PGS003444 and PGS003445).

PMID:37148359 | DOI:10.1007/s00125-023-05912-9

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Nevin Manimala Statistics

Physicochemical and histological analysis of an experimental endodontic repair material containing 45S5 bioactive glass

Biotechnol Lett. 2023 May 6. doi: 10.1007/s10529-023-03391-x. Online ahead of print.

ABSTRACT

This study aimed to evaluate the maximum compressive strength, the modulus of elasticity, pH variation, ionic release, radiopacity and biological response of an experimental endodontic repair cement based on 45S5 Bioglass®. An in vitro and in vivo study with an experimental endodontic repair cement containing 45S5 bioactive glass was conducted. There were three endodontic repair cement groups: 45S5 bioactive glass-based (BioG), zinc oxide-based (ZnO), and mineral trioxide aggregate (MTA). In vitro tests were used to evaluate their physicochemical properties: compressive strength, modulus of elasticity, radiopacity, pH variation, and the ionic release of Ca+ and PO4. An animal model was used to evaluate the bone tissue response to endodontic repair cement. Statistical analysis included the unpaired t-test, one-way ANOVA and Tukey’s test. BioG showed the lowest compressive strength and ZnO showed the highest radiopacity among the groups, respectively (p < 0.05). There were no significant differences in the modulus of elasticity among the groups. BioG and MTA maintained an alkaline pH during the 7 days of evaluation, both at pH 4 and in a pH 7 buffered solutions. PO4 was elevated in BioG, peaking at 7 days (p < 0.05). Histological analysis showed less intense inflammatory reactions and new bone formation in MTA. BioG showed inflammatory reactions that decreased over time. These findings suggest that the BioG experimental cement had good physicochemical characteristics and biocompatibility required for bioactive endodontic repair cement.

PMID:37148343 | DOI:10.1007/s10529-023-03391-x

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Nevin Manimala Statistics

Five-Factor Modified Frailty Index as a Predictor of Complications Following Total Ankle Arthroplasty

Foot Ankle Spec. 2023 May 6:19386400231169368. doi: 10.1177/19386400231169368. Online ahead of print.

ABSTRACT

INTRODUCTION: Ankle arthritis adversely affects patients’ function and quality of life. Treatment options for end-stage ankle arthritis include total ankle arthroplasty (TAA). A 5-item modified frailty index (mFI-5) has predicted adverse outcomes following multiple orthopaedic procedures; this study evaluated its suitability as a risk-stratification tool in patients undergoing TAA.

METHODS: The National Surgical Quality Improvement Program (NSQIP) database was retrospectively reviewed for patients undergoing TAA between 2011 and 2017. Bivariate and multivariate statistical analyses were performed to investigate frailty as a possible predictor of postoperative complications.

RESULTS: In total, 1035 patients were identified. When comparing patients with an mFI-5 score of 0 versus ≥2, overall complication rates significantly increased from 5.24% to 19.38%, 30-day readmission rate increased from 0.24% to 3.1%, adverse discharge rate increased from 3.81% to 15.5%, and wound complications increased from 0.24% to 1.55%. After multivariate analysis, mFI-5 score remained significantly associated with patients’ risk of developing any complication (P = .03) and 30-day readmission rate (P = .005).

CONCLUSIONS: Frailty is associated with adverse outcomes following TAA. The mFI-5 can help identify patients who are at an elevated risk of sustaining a complication, allowing for improved decision-making and perioperative care when considering TAA.

LEVELS OF EVIDENCE: III, Prognostic.

PMID:37148165 | DOI:10.1177/19386400231169368

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Nevin Manimala Statistics

Assessment of biological effect of nab-paclitaxel combined with gemcitabine, using contrast enhanced ultrasonography and elastography, in advanced pancreatic ductal carcinoma: A single-center pilot study

Endosc Ultrasound. 2023 Mar-Apr;12(2):273-276. doi: 10.4103/EUS-D-22-00040.

ABSTRACT

EUS associated with contrast-enhanced harmonic EUS (CH-EUS) and EUS elastography (EUS-E) are used in clinical practice to assess pancreatic tumor at the diagnosis. In case of pancreatic ductal adenocarcinoma (PDAC) with liver metastasis, nab-paclitaxel combined with gemcitabine is a first-line treatment option. We aimed to assess the modification of PDAC microenvironment induced by the combination of nab-paclitaxel with gemcitabine, by endoscopic ultrasonography techinics. This single center phase III study conducted between February 2015 and June 2016 included patients with pancreatic adenocarcinoma with mesurable liver metastasis and no prior cancer treatment fit for two cycles of nab-paclitaxel combined with gemcitabine. We aimed to perform EUS with CH-EUS and EUS-E of the pancreatic tumor, CT scan and contrast enhanced ultrasonogram (CE-US) of a reference liver metastasis, before and after the two cylces of chemotherapy. Primary end point was modification of vascularizaion of primary tumor and a reference liver metastasis. Secondary end points were modification of stromal content, safety profile of drug combination and tumor response rate. Sixteen patients were analyzed, but only 13 received two cycled of chemotherapy (CT) (toxicity [n = 1] or death [n = 2]). There was no statistical modification induced by CT concering vascularity of primary tumor (time to maximum intensity P = 0.24, value of maximum intensity P = 0.71, hypoechogenic aspect generated by injection of contrast enhancing agent), vascularity of a reference liver metastasis (time to maximum intensity P = 0.99, value of maximum intensity P = 0.71) and tumor elasticity (P = 0.22). Eleven patients had tumor response assessement, 6/11 (54%) had measurable disease response 4/11 (36%) with partial responses and 2/11 (18%) with stable disease. All other patients showed disease progression. No serious side effects occurred, 6/11 patients had a dose adjustment. We did not show significant modification of vascularity and elasticity but these results should be taken with caution because of important limitations.

PMID:37148140 | DOI:10.4103/EUS-D-22-00040

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Nevin Manimala Statistics

Mean quality of life of hypertensive and diabetic patients: A comparative study of patients in secondary and tertiary health facilities in Kaduna State, Nigeria

Niger Postgrad Med J. 2023 Apr-Jun;30(2):167-174. doi: 10.4103/npmj.npmj_5_23.

ABSTRACT

INTRODUCTION: Hypertension and diabetes have become major non-communicable diseases of public health importance globally, considering the magnitude of the diseases, the propensity to worsen the patients’ quality of life and the associated mortality. This study compared the health-related quality of life (HRQOL) of hypertensive and diabetic patients in both tertiary and secondary health facilities in Kaduna State, north-western Nigeria.

MATERIALS AND METHODS: This was a descriptive comparative cross-sectional study amongst 325 patients, of which 93 (28.6%) were from the tertiary and 232 (71.4%) were from the secondary facilities. All eligible respondents participated in this study. Data were analysed with SPSS version 25 and STATA SE 12, t-test for comparison of two means, Chi-square and multivariate analyses were performed with P < 0.05.

RESULTS: The mean age was 55.72 ± 13 years. Two-thirds, 197 (60.6%), were hypertensive only, 60 (18.5%) were diabetic only (18.5%) and 68 (20.9%) were hypertensive diabetic. For the hypertensive only at the tertiary facility, the mean scores for vitality (VT) (68.0 ± 5.97, P = 0.01), emotional well-being (EW) (77.33 ± 4.52, P = 0.0007) and bodily pain (BP), (74.17 ± 5.94, P = 0.05) were significantly higher for tertiary compared with those at secondary facilities. The mean HRQOL for the people with diabetes only at the tertiary facilities also showed statistically significant higher scores for VT (72.2 ± 61, P = 0.01), social functioning (72.2 ± 8.4, P = 0.02), EW (75.44 ± 4.9, P = 0.001) and BP (85.56 ± 7.7, P = 0.01) when compared with the secondary facilities.

CONCLUSION: Patients managed by specialists at the tertiary health facility had better HRQOL than those managed at the secondary health facilities. Continued medical education and the use of standard operating procedures are recommended for improved HRQOL.

PMID:37148121 | DOI:10.4103/npmj.npmj_5_23

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Nevin Manimala Statistics

Serum magnesium levels of term neonates with birth asphyxia and relationship to severity of asphyxia

Niger Postgrad Med J. 2023 Apr-Jun;30(2):161-166. doi: 10.4103/npmj.npmj_1_23.

ABSTRACT

BACKGROUND AND AIMS: Birth asphyxia is one of the three main causes of neonatal mortality in Nigeria. Hypomagnesaemia has been reported amongst severely asphyxiated babies. Despite this, the prevalence of hypomagnesaemia amongst newborns with birth asphyxia has not been well researched in Nigeria. This study set out to determine the prevalence of hypomagnesaemia in term neonates with birth asphyxia and the relationship (if any) between magnesium levels and the severity of birth asphyxia or encephalopathy.

METHODS: In this cross-sectional analytical study, the serum magnesium levels of consecutive cases of birth asphyxia were compared to that of gestational age-matched healthy term neonates. Babies with Apgar scores <7 in the 5th minute of life were recruited into the study. Blood samples were taken from each baby at birth and 48 h. Serum magnesium was measured using spectrophotometry.

RESULTS: Hypomagnesaemia was found in 36 (35.3%) babies with birth asphyxia and 14 (13.7%) healthy controls; this difference was statistically significant (χ2 = 18.098, P = 0.001), with an odds ratio of 3.4 (95% confidence interval = 1.7, 6.9). The median (interquartile range) levels of serum magnesium in babies with mild, moderate and severe asphyxia were 0.7 mmol/L (0.5-1.1), 0.7 mmol/L (0.4-0.9) and 0.7 mmol/L (0.5-1.0), respectively (P = 0.316), while those of babies with mild (stage 1), moderate (stage 2) and severe (stage 3) encephalopathy were 1.2 mmol/L (1.0-1.3), 0.7 mmol/L (0.5-0.8) and 0.8 mmol/L (0.6-1.0), respectively (P = 0.789).

CONCLUSION: This study has shown that hypomagnesaemia was more common in babies with birth asphyxia and there was no relationship between magnesium levels and the severity of asphyxia or encephalopathy.

PMID:37148120 | DOI:10.4103/npmj.npmj_1_23

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Nevin Manimala Statistics

Knowledge and perception of medication errors among health care workers in Ahmadu Bello University Teaching Hospital Zaria, Kaduna State, North-west Nigeria

Niger Postgrad Med J. 2023 Apr-Jun;30(2):150-155. doi: 10.4103/npmj.npmj_75_23.

ABSTRACT

INTRODUCTION: Medication errors (MEs) are important, often overlooked forms of medical error that are associated with morbidity and mortality in health care settings. Among health care workers, knowledge, attitude and perception may affect reporting of MEs.

AIM: The aim of this study was to determine the level of knowledge and perception of MEs among health care workers in Ahmadu Bello University Teaching Hospital, Zaria.

METHODOLOGY: A cross-sectional study was conducted among 138 health care workers selected randomly through a stratified sampling. Their responses were collected using pre-tested, self-administered questionnaires and analysed using the Statsitical Package for the Social Sciences. The numerical variables were summarised as means and standard deviations, whereas categorical variables were presented as frequencies and percentages. The Chi-square test was used to test for associations at P < 0.05.

RESULTS: All the respondents heard of MEs and up to 108 (78.3%) correctly defined them. While only 121 (87.7%) respondents had fair to good knowledge about MEs, all of them had good perception of them. Major types of MEs known by the respondents were knowledge-based errors (79.7%), rule-based errors (52.9%), action-based errors (67.4%) and memory-based errors (55.8%). The causes of MEs identified were communication problems (88.4%), poor organizational knowledge transfer (63.8%), heavy workload (80.4%) and not reading instructions carefully (63.0%). There was no statistically significant association between the level of knowledge on MEs and sociodemographic characteristics of the respondents.

CONCLUSION: Knowledge and perceptions of MEs were good among our respondents. Adequate mechanism (s) should be put in place to encourage the reporting of MEs whenever they occur to promote patient safety and improve health outcomes.

PMID:37148118 | DOI:10.4103/npmj.npmj_75_23

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Nevin Manimala Statistics

Clinical and microbiological profile of otomycosis in Lagos, Nigeria

Niger Postgrad Med J. 2023 Apr-Jun;30(2):132-136. doi: 10.4103/npmj.npmj_9_23.

ABSTRACT

INTRODUCTION: Otomycosis is a global disease, common in the world’s tropical and subtropical regions. The diagnosis is clinical, but mycological examination is required for its confirmation. There is a paucity of published data on otomycosis particularly the aetiologic agents in Nigeria. This study aims to fill in this gap by assessing the clinical presentations, risk factors and aetiologic agents of otomycosis in our setting.

METHODS: This was a prospective study of 126 clinically diagnosed patients and 30 controls. Mycological analysis of debris and swab samples from their external auditory canal was carried out.

RESULTS: One hundred and twenty-six patients were recruited, with 162 ear samples collected. There was mycological confirmation of otomycosis in 100 (79.4%) patients (subjects) and 127 (78.4%) specimens. The subjects’ age range was 1-80 years, 30.89 ± 21.15 mean age, and 29-year median age. The peak prevalent age of 1-10 years was statistically significant, P = 0.022. The common symptoms in the subjects were itching 86 (86%), ear blockage 84 (84%) and otalgia 73 (73%). Regular ear cleaning 67 (67.0%) was the most common risk factor. Noted aetiologic agents were Aspergillus species 81 (63.8%), Candida species 42 (33.1%) and Yeast 4 (3.1%). Aspergillus flavus (40/127; 31.5%) was the most common fungus isolated. Unilateral otomycosis 73 (73%) was more common than bilateral otomycosis 27 (27%).

CONCLUSION: Otomycosis is common in all ages, and is a commonly unilateral disease. Regular ear cleaning is the most common risk factor. A. flavus was the most common aetiologic agent in this study.

PMID:37148115 | DOI:10.4103/npmj.npmj_9_23

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Nevin Manimala Statistics

Tympanometry and endoscopic diagnosis of eustachian tube dysfunction in patients with chronic rhinosinusitis

Niger Postgrad Med J. 2023 Apr-Jun;30(2):126-131. doi: 10.4103/npmj.npmj_31_23.

ABSTRACT

BACKGROUND: This study assessed the eustachian tube (ET) function in adult patients with chronic rhinosinusitis (CRS) using tympanometry and nasal endoscope.

MATERIALS AND METHODS: This was a hospital-based cross-sectional study conducted for 9 months. All participants underwent endoscopic evaluation of the pharyngeal end of their ETs, and the middle ear function was assessed using tympanometry. Endoscopic findings were graded based on a validated mucosal inflammatory endoscopic grading scale. Statistical analysis was carried out using SPSS version 24.

RESULTS: A total of 102 CRS patients and age- and sex-matched controls were recruited. Tympanograms suggestive of eustachian tube dysfunction (ETD) types B and C were found among 7.8% and 12.8% of the right and left ears of the CRS groups, respectively. Mucosal inflammatory endoscopic grade that is diagnostic of ETD Grades 3 and 4 was found among 24.5% and 38.2% of the right and left ET of CRS cases, respectively.

CONCLUSION: CRS predisposes patients to anatomical and functional impairment of ET. The relationship between tympanometry and mucosal inflammatory endoscopic grading scale in detecting ETD among CRS patients showed a strong relationship. However, a combination of the two will improve the diagnosis of ETD by evaluating the ET function directly and indirectly.

PMID:37148114 | DOI:10.4103/npmj.npmj_31_23

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Nevin Manimala Statistics

Caregiving in a tertiary health institution in North Central Nigeria: Support types and financial burden

Niger Postgrad Med J. 2023 Apr-Jun;30(2):119-125. doi: 10.4103/npmj.npmj_15_23.

ABSTRACT

BACKGROUND: Caregivers play an important role in informal patient management. Identification of the support types and the financial challenges faced by caregivers will provide information on strategies to ease this burden. This study aimed to describe the support types and financial burden amongst caregivers in a tertiary hospital in North Central Nigeria.

METHODS: This was a cross-sectional study conducted amongst caregivers of inpatients in a tertiary hospital in North Central Nigeria. Data were collected using a pre-tested interviewer-administered questionnaire and were analysed using the Statistical Package for the Social Sciences package version 23. Results were reported in frequencies and proportions and presented in prose, tables and charts.

RESULTS: A total of 400 caregivers were recruited. The mean age was 38.32 ± 12.82 years and most (66.0%) were females. Caregivers supported their patients by running errands (96.3%) and 85.3% reported caregiving as stressful. The reported errands were purchase of medications (92.3%), supply of non-medical needs (63.3%), submission of laboratory samples and collection of results (52.3%) and service payment (47.5%). About two-thirds (63.2%) reported loss of income while caregiving and about half (50.8%) provided financial support to the patients.

CONCLUSION: This study suggests that majority of caregivers experience significant physical and financial burden while caregiving. This burden can be eased off by the simplification of payment and laboratory processes and employment of more staff to support patients admitted to the wards. The financial burden experienced by caregivers reinforces the need to encourage more Nigerians to enrol in a health insurance scheme.

PMID:37148113 | DOI:10.4103/npmj.npmj_15_23