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The alternative serotonin transporter promoter P2 impacts gene function in females with irritable bowel syndrome

J Cell Mol Med. 2021 Jun 24. doi: 10.1111/jcmm.16736. Online ahead of print.

ABSTRACT

Irritable bowel syndrome (IBS) is a gut-brain disorder in which symptoms are shaped by serotonin acting centrally and peripherally. The serotonin transporter gene SLC6A4 has been implicated in IBS pathophysiology, but the underlying genetic mechanisms remain unclear. We sequenced the alternative P2 promoter driving intestinal SLC6A4 expression and identified single nucleotide polymorphisms (SNPs) that were associated with IBS in a discovery sample. Identified SNPs built different haplotypes, and the tagging SNP rs2020938 seems to associate with constipation-predominant IBS (IBS-C) in females. rs2020938 validation was performed in 1978 additional IBS patients and 6,038 controls from eight countries. Meta-analysis on data from 2,175 IBS patients and 6,128 controls confirmed the association with female IBS-C. Expression analyses revealed that the P2 promoter drives SLC6A4 expression primarily in the small intestine. Gene reporter assays showed a functional impact of SNPs in the P2 region. In silico analysis of the polymorphic promoter indicated differential expression regulation. Further follow-up revealed that the major allele of the tagging SNP rs2020938 correlates with differential SLC6A4 expression in the jejunum and with stool consistency, indicating functional relevance. Our data consolidate rs2020938 as a functional SNP associated with IBS-C risk in females, underlining the relevance of SLC6A4 in IBS pathogenesis.

PMID:34165249 | DOI:10.1111/jcmm.16736

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Management of serious complications in intra-abdominal desmoid-type fibromatosis

Cancer Rep (Hoboken). 2021 Jun 24:e1411. doi: 10.1002/cnr2.1411. Online ahead of print.

ABSTRACT

BACKGROUND: Desmoid fibromatosis (DF) is a rare and locally infiltrative monoclonal fibroblastic proliferation arising from connective tissues, with lack of metastatic potential. About 10% of all DF cases are intra-abdominally sited. Complications in this site, due to the locally infiltrative nature of the disease, may be severe and potentially life threatening. However, data on incidence, management, and outcome of these complications are limited.

AIM: Data of patients with sporadic or FAP-related intra-abdominal DF treated at Istituto Nazionale dei Tumori (INT) in Milano from 2005 to 2020 who developed a serious complication during the course of their disease were retrospectively collected and analyzed with a descriptive statistics.

METHODS AND RESULTS: Out of 72 intra-abdominal DF, 8 cases were identified (M/F: 5/3, median age: 35 years, FAP-related/sporadic: 2/6): 3 with bowel obstruction, 5 with bowel perforation. In 4 cases the serious complication was the first evidence of disease; in the other 4 cases it occurred at a time interval from diagnosis in the range of 4-44 months (during an active surveillance program in one case and during chemotherapy in the other 3 cases). A surgical treatment was feasible and successful in 5 cases. In 3 surgically unmanageable patients, all progressing and experiencing acute complications while on chemotherapy, a non-surgical approach with intensive supportive treatment and with a prompt change of chemotherapy regimen was implemented, being successful in two, the other patient dying due to a concomitant progressive lymphoma thereafter.

CONCLUSION: In this series of intra-abdominal DF, the incidence of serious complications was 11%. Most patients were successfully treated with surgery. When surgery was deemed to be unfeasible, a conservative management with intensive supportive care and a careful choice of chemotherapy was adopted, ensuring a favorable outcome in most.

PMID:34165246 | DOI:10.1002/cnr2.1411

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Maternal serum 25-hydroxyvitamin D levels and infant atopic dermatitis: a prospective cohort study

Pediatr Allergy Immunol. 2021 Jun 23. doi: 10.1111/pai.13582. Online ahead of print.

ABSTRACT

BACKGROUND: Maternal vitamin D status during pregnancy has been linked with the risk of atopic dermatitis (AD) in children, while the results were inconsistent. The objective of this study was to assess the potential association.

METHODS: Serum 25-hydroxyvitamin D (25(OH)D) levels were measured in pregnant women from the birth cohort MKFOAD. Infant AD was diagnosed according to Williams’ criteria. Multivariate logistic regression model was used to examine the association of maternal serum 25(OH)D levels in the first, second and third trimester of gestation with the risk of infant AD at first year of age.

RESULTS: In total, 121 (26.5%) of 456 infants developed AD prior to 1 year of age. In general, higher maternal serum 25(OH)D levels throughout pregnancy were associated with increased risks of AD in infants prior to 1 year of age in multivariate logistic regression models, with borderline statistical significance in the first (per ln unit increase: adjusted OR = 1.93, 95% CI: 0.96, 3.88) and second (per ln unit increase: adjusted OR = 1.72, 95% CI: 0.93, 3.19) trimester. Multivariate logistic regression models using categorical variables of maternal 25(OH)D levels by tertiles showed similar results: infants born to mothers with serum 25(OH)D levels in the highest tertile had higher risk of AD than those with 25(OH)D in the lowest tertile.

CONCLUSIONS: The present study found some evidence supporting that higher maternal 25(OH)D levels during pregnancy increased the risk of infant AD. However, the clinical implication of the findings should be limited for those with blood levels over the recommendations.

PMID:34165218 | DOI:10.1111/pai.13582

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Association between early worsening of kidney function and poor outcomes in patients treated with renin angiotensin system inhibitors: A meta-analysis

Nephrology (Carlton). 2021 Jun 24. doi: 10.1111/nep.13915. Online ahead of print.

ABSTRACT

BACKGROUND: As renin angiotensin system inhibitors (RASi) are widely used in the clinic, early worsening of kidney function (EWKF) after RASi therapy deserves attention, as its clinical significance is unknown. The aim was to evaluate the relationship between EWKF and long-term outcomes including all-cause mortality, kidney and cardiovascular events, in all the patients treated with RASi.

METHODS: We searched PubMed, Embase and the Cochrane databases for controlled trials that compared the outcomes of patients with and without EWKF after RASi treatment. Our primary outcome was all-cause mortality, and secondary outcomes were kidney and cardiovascular events. We pooled data using a random effects model.

RESULTS: A total of 10 studies were enrolled, of which 8 were randomized trials (including 33 454 patients) and 2 were observational studies (including 148 144 patients). Of the 8 randomized trials, 4996 patients with type 2 diabetes, 19 118 with HF, and 9340 with atherosclerotic vascular disease and diabetes with end-organ damage. Both observational studies investigated all kinds of patients with initially RASi treatment. In patients with RASi, the EWKF group had a higher risk of all-cause mortality than the no-EWKF group in the randomized studies (n = 12 254; RR, 1.22; 95%CI, 1.04-1.42; P = 0.02) and in observational studies (n = 148 144; OR, 1.70; 95%CI, 1.43-2.01; P < 0.00001). In patients who experienced EWKF (n = 2246), no statistically significant difference was found between the efficacy of RASi and placebo in all-cause mortality (n = 1762; RR, 0.85; 95%CI, 0.68-1.06; P = 0.14).

CONCLUSION: RASi treatment led to an increased incidence of EWKF which was associated with poorer long-term outcomes. As the benefit of RAS blockade to patients with EWKF was limited, we suggest clinicians use RASi with caution when EWKF occurs.

PMID:34165226 | DOI:10.1111/nep.13915

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Prevalence and Associated Factors of Malnutrition in Under Five Children in a Rural Mountainous Area of Nepal: A Community Based Cross Sectional Study

Kathmandu Univ Med J (KUMJ). 2020 Oct.-Dec.;18(72):407-413.

ABSTRACT

Background Nutrition is believed to be very essential for socio economic development of the country and is an essential component of sustainable development goals. Malnutrition is a major public health problem in Nepal and is more common among under-five year children. Malnutrition among children is complex problem globally, affecting the physical, mental and social development. Objective To estimate the prevalence and explore the associated factors of malnutrition in study population. Method It was a community based cross-sectional study conducted among rural population of Nepal. Wards were selected by simple random sampling technique and household in each ward were selected by systemic random sampling. The mothers of 302 participants aged 12 to 59 months were interviewed for requisite information using pretested questionnaire and anthropometric measurements were taken using standard technique for each participant. Statistical Package for Social Sciences (SPSS) version 16.0 was used for data analysis. Result The prevalence of underweight, stunting and wasting was 36.8%, 37.5%, and 14.6% respectively. We found statistical significant association between underweight and children in lower age group, larger family size, lower level of mother’s education and illness in past one month. Factors that are significantly associated with stunting are children in lower age group, lower level of mother’s education and illness in past one month and wasting is significantly associated with children in lower age group. Conclusion This study showed the prevalence of malnutrition is high in study population. Factors associated with malnutrition were child’s age, family size, mother’s education and illness in past one month.

PMID:34165101

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Molecular mechanisms from insulin-mimetic effect of vitamin D: treatment alternative in Type 2 diabetes mellitus

Food Funct. 2021 Jun 24. doi: 10.1039/d0fo03230a. Online ahead of print.

ABSTRACT

Diabetes mellitus is a complex and multifactorial disease with a global prevalence that exceeds 425 million people. Type 2 diabetes mellitus (T2DM) is characterized by a state of insulin resistance, which leads to metabolic alterations that aggravate the state of health of people. Vitamin D deficiency appears to play an important role in the triggering mechanisms of insulin resistance. In this review, an analysis is made of the biochemical mechanisms associated with the insulin-mimetic effect of vitamin D, its supplementation being a possible nutritional strategy for the T2DM treatment. The current scientific evidence is extensive regarding the dose of vitamin D used for an insulin-mimetic effect. However, clinical trials and systematic reviews show statistical differences on glucose, insulin, and glycated hemoglobin levels of patients with T2DM, associated with activation mechanisms of transcription factors related to genes of the glucide metabolism and the insulin receptor, and the regulation of intracellular Ca2+ insulin concentrations. Likewise, an indirect mechanism associated with antioxidant and anti-inflammatory effects has been shown that also leads to sensitivity to the insulin receptor. The use of a specific dose of vitamin D could be an effective alternative in the T2DM treatment, which would reduce the risk of complications derived from hyperglycemia.

PMID:34165135 | DOI:10.1039/d0fo03230a

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Knowledge and Attitude Regarding Pubertal Changes among Secondary Level Students of Selected Schools of Dhulikhel Municipality

Kathmandu Univ Med J (KUMJ). 2020 Oct.-Dec.;18(72):386-390.

ABSTRACT

Background Adolescence is a transition phase of life during which a lot of pubertal changes occur. If not dealt properly, many mental and behavioral disturbances can result. Adolescents must have good knowledge and attitude regarding physical and psychosocial pubertal changes. Objective To assess the knowledge and attitude regarding pubertal changes among secondary level students of selected school of Dhulikhel Municipality. Method A quantitative, descriptive cross-sectional study was conducted among secondary level students of Dhulikhel Municipality. Study was conducted among students of grade 9 and 10 of four government and three private schools of municipality. After selection of seven schools, proportionate stratified random sampling technique was done followed by lottery method to select required number of students. Both descriptive statistics and inferential statistics were applied using Statistical Package for Social Science (SPSS) Version 25.0 for data analysis. Result The mean score of knowledge regarding pubertal changes was 26.2±2.9. Likewise, the mean attitude score regarding pubertal changes was 55.4±1.2. Knowledge regarding pubertal change was significantly higher among age group 15-17 years. Females had higher knowledge compared to males. Attitude related to pubertal change was significantly more in respondents who studied in government school. Conclusion Adolescents of Dhulikhel municipality schools had good knowledge and attitude about pubertal changes.

PMID:34165097

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The Prognostic Value of the Fracture Level in the Treatment of Displaced Supracondylar Humeral Fractures in Children

Kathmandu Univ Med J (KUMJ). 2020 Oct.-Dec.;18(72):391-395.

ABSTRACT

Background Supracondylar fractures are subclassified as high and low type depending on whether they are above or below the isthmus of the distal humerus and it play an important role in determining outcome. Objective To compare the clinical and radiological outcomes of patients with fractures above and below the distal humeral isthmus treated with closed reduction and percutaneous pinning. Method This is a prospective non-randomized analytical study of 40 patients with displaced extension type supracondylar fracture of distal humerus treated by closed reduction and percutaneous pinning. Radiological and functional outcomes was followed up to 6 months postoperatively. The significance of differences between means (baumann angle, carrying angle and time to recovery) were calculated using the independent t-test. Result Twenty-four (60%) patients were high type and 16 (40%) patients were low type. According to Flynn grading, there was no statistical significance between the high type and low type (p = 0.601). The time to recovery for the high type was 15.58 ± 2.95 weeks and for low type was 18.75 ± 2.18 weeks. Hence, the time to recovery for the low type was longer than high type and it was statistically significant (p = 0.001). Conclusion Low type supracondylar fractures require a longer period for the gain of elbow range of motion. However, in long term the prognosis of low type is comparable with that of high type fracture. Hence, the prognostic value of fracture level in the treatment of displaced supracondylar fractures is not statistically significant.

PMID:34165098

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Perception Regarding Care of Attempted Suicide Patients among Nursing Students in Kathmandu University School of Medical Sciences

Kathmandu Univ Med J (KUMJ). 2020 Oct.-Dec.;18(72):402-406.

ABSTRACT

Background Suicide is an act of deliberately killing oneself. It is a global health problem and is the second leading cause of death in 15 to 29 years. Thus, studying nursing students’ perception towards suicide attempters has paramount importance in understanding and addressing the existing gaps in healthcare delivery system. Objective To assess the nursing students’ perception towards attempted suicide and to find out the association between perception and selected variables. Method A descriptive, cross sectional design was carried out to assess the nursing students’ perception towards suicide attempters in Kathmandu University School of Medical Sciences. The respondents were 193 nursing students. A structured questionnaire was used in order to collect data. Descriptive statistics including frequency, percentage, mean and standard deviation were calculated to summarize the data and inferential statistics, Mann Whitney-U test was used for the association between perception and selected variables. Result A total 193 nursing students participated in this study. The scores between 1 and 2.4 were considered ‘positive’, ‘unsure’ or ‘uncertain’, between 2.5 and 3.4 and negative for 3.5 and above’ over all nurses showed relatively negative perception towards suicide attempters. According to results from eight domains of perception, those who did not attend the courses on psychiatry nursing presented higher score, which was found to have significant association with permissiveness, unpredictability and incomprehensibility. A younger nursing student shows significant association with incomprehensibility. Younger nursing student showed statistically significant association with duration of suicide process. Conclusion Nursing students are frequently encountered with attempted suicide patients. Therefore, they must be aware of their attitudes toward this group of patients as part of their professional and therapeutic role. Thus a nurse’s positive perception towards attempted suicide can play a key role in communicating and preventing a future suicide attempt.

PMID:34165100

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Risk Factors Associated with Ninety Day Readmission in Chronic Obstructive Pulmonary Disease Exacerbation at a Tertiary Care Hospital: A retrospective cohort study

Kathmandu Univ Med J (KUMJ). 2020 Oct.-Dec.;18(72):372-375.

ABSTRACT

Background Chronic obstructive pulmonary disease (COPD) exacerbation is a leading cause of frequent hospital admission. Globally, several studies have reported potential risk factors associated with COPD exacerbations which are largely unknown in Nepalese health care setting. Objective To identify the risk factors associated with hospital readmission within ninety days of discharge in acute COPD exacerbation. Method This is a hospital based retrospective cohort study conducted at Tribhuvan University Teaching Hospital. COPD patients admitted in respiratory ward from August 2019 to November 2019 were followed up till 90 days after discharge. Logistic regression analysis was performed at 95% Confidence Interval (CI) to identify risk factors for readmission in COPD exacerbation. Statistical analysis was performed using SPSS version 20.0. Result Of total 86 patients hospitalized for COPD, 42 (48.8%) had at least one subsequent readmission during post-discharge follow-up period of 90 days. Mean age of patients was 70.55±10.98 years. There were 45 (52.3%) males. Logistic regression analysis revealed preadmission domiciliary oxygen use (Odds Ratio (OR) 2.93; 95% CI 1.195- 7.202; p=0.019), admission in intensive care unit (ICU) (OR 3.060; 95% CI 1.145- 8.179; p=0.026), previous hospital admission for COPD exacerbation (OR 3.230; 95% CI 1.219-8.556; p=0.018), age (OR 0.946; 95% CI 0.905-0.988; p=0.012) and duration of hospital stay (OR 0.901; 95% CI 0.819-0.992; p=0.034) were independently associated with ninety day readmission in COPD patients. Conclusion Five clinical factors were found to be independently associated with COPD readmission in this study. Large multi-centre study at various health care levels is recommended to validate the potential risk factors in different populations and health care settings in Nepal.

PMID:34165094