Sphingolipids in Childhood Asthma and Obesity (SOAP Study): A Protocol of a Cross-Sectional Study.

Asthma and obesity are two of the most common chronic conditions in children and adolescents. There is increasing evidence that sphingolipid metabolism is altered in childhood asthma and is linked to airway hyperreactivity. Dysregulated sphingolipid metabolism is also reported in obesity. However, the functional link between sphingolipid metabolism, asthma, and obesity is not completely understood. This paper describes the protocol of an ongoing study on sphingolipids that aims to examine the pathophysiology of sphingolipids in childhood asthma and obesity. In addition, this study aims to explore the novel biomarkers through a comprehensive multi-omics approach including genomics, genome-wide DNA methylation, RNA-Seq, microRNA (miRNA) profiling, lipidomics, metabolomics, and cytokine profiling. This is a cross-sectional study aiming to recruit 440 children from different groups: children with asthma and normal weight (n = 100), asthma with overweight or obesity (n = 100), overweight or obesity (n = 100), normal weight (n = 70), and siblings of asthmatic children with normal weight, overweight, or obesity (n = 70). These participants will be recruited from the pediatric pulmonology, pediatric endocrinology, and general pediatric outpatient clinics at Sidra Medicine, Doha, Qatar. Information will be obtained from self-reported questionnaires on asthma, quality of life, food frequency (FFQ), and a 3-day food diary that are completed by the children and their parents. Clinical measurements will include anthropometry, blood pressure, biochemistry, bioelectrical impedance, and pulmonary function tests. Blood samples will be obtained for sphingolipid analysis, serine palmitoyltransferase (SPT) assay, whole-genome sequencing (WGS), genome-wide DNA methylation study, RNA-Seq, miRNA profiling, metabolomics, lipidomics, and cytokine analysis. Group comparisons of continuous outcome variables will be carried out by a one-way analysis of variance or the Kruskal-Wallis test using an appropriate pairwise multiple comparison test. The chi-squared test or a Fisher's exact test will be used to test the associations between categorical variables. Finally, multivariate analysis will be carried out to integrate the clinical data with multi-omics data. This study will help us to understand the role of dysregulated sphingolipid metabolism in obesity and asthma. In addition, the multi-omics data from the study will help to identify novel genetic and epigenetic signatures, inflammatory markers, and mechanistic pathways that link asthma and obesity in children. Furthermore, the integration of clinical and multi-omics data will help us to uncover the potential interactions between these diseases and to offer a new paradigm for the treatment of pediatric obesity-associated asthma.

Echocardiography protocol and cardiometabolic phenotyping in Indian birth cohorts-the IndEcho study.

Background: Asian Indians are at higher risk of cardiometabolic disease compared to other ethnic groups, and the age of onset is typically younger. Cardiac structure and function are poorly characterized in this ethnic group. In this study, we describe image-acquisition methods and the reproducibility of measurements and detailed echocardiography characteristics in two large Indian population-based cohorts (the New Delhi and Vellore Birth Cohorts) from India. Methods: The IndEcho study captured transthoracic echocardiographic measurements of cardiac structure and function from 2,322 men and women aged 43-50 years. M-mode measurements in the parasternal long axis (PLAX) and 2-dimensional (2D) short axis recordings at the mitral valve, mid-papillary and apical level were recorded. Apical 2D recordings of two- three- and four-chamber (2C, 3C and 4C) views and Doppler images (colour, pulsed and continuous) were recorded in cine-loop format. Left ventricular (LV) mass, LV hypertrophy, and indices of LV systolic and diastolic function were derived. Results: Echocardiographic measurements showed good/excellent technical reproducibility. Hetero-geneity across sites, sex and rural/urban differences in cardiac structure and function were observed. Overall, this cohort of South Asian Indians had smaller LV mass and normal systolic and diastolic function when compared with published data on other Asian Indians and the West, (LV mass indexed for body surface area: Delhi men: 68 g/m2, women 63.9; Vellore men: 65.8, women 61.6) but were within ethnic-specific reference ranges. The higher prevalence of obesity, diabetes and hypertension is reflected by the higher proportion of LV remodelling and lesser hypertrophy. Conclusions: Our study adds to scarce population-based echocardiographic data for mid-life Asian Indians. Compared to published literature on other ethnic groups, the Asian Indian heart is characterised by smaller cardiac dimensions and normal range systolic and diastolic function on a background of a high prevalence of hypertension, diabetes and cardiac disease at a relatively young age. This data will form the basis for further analyses of lifecourse, metabolic and body composition predictors of cardiac structure and function, and echocardiographic predictors of future mortality. ISRCTN registration number: 13432279.

Whole and cortical kidney volume predict 5-year post-nephrectomy eGFR in Indian living kidney donors.

AIM: To study the additional utility of pre-nephrectomy whole and cortical kidney volumes (WKV, CKV) in predicting long-term post-nephrectomy kidney function in Indian living kidney donors (LKDs). METHODS: This retrospective cohort study included all LKDs who underwent nephrectomy between 1 January 2006 and 31 December 2015 at our centre, had pre-nephrectomy height, weight and computed tomography (CT) angiography with arterial and nephrographic phase documented, and 5-year post-nephrectomy creatinine values measured. Correlation between body surface area (BSA) adjusted pre-nephrectomy total CKV, WKV and pre-nephrectomy CKD EPI eGFR; BSA-adjusted remnant pre-nephrectomy CKV (rCKV), WKV (rWKV) and 5-year post-nephrectomy CKD EPI creatinine eGFR (5yeGFRCr ); predictors of 5yeGFRCr < 70% of pre-nephrectomy CKD EPI creatinine eGFR (pre-eGFRCr ), and an equation to predict 5yeGFRCr from pre-nephrectomy variables were calculated. RESULTS: A total of 196 LKDs (74% female, mean age 41.7 ± 11.0 years) were included in the study. Total WKV showed higher correlation with pre-nephrectomy eGFR than CKV, the highest with CKD EPI cystatin eGFR. Remnant WKV showed higher correlation than rCKV with post-nephrectomy eGFRCr and this increased over time. Older age, lower rWKV or rCKV, higher BSA, and higher pre-eGFRCr identified LKDs with 5yeGFRCr < 70% of pre-eGFRCr , with rCKV identifying a higher proportion (4.5%) of such LKDs. A model including rWKV or rCKV predicted 5yeGFRCr better than one including age, gender, BSA and pre-eGFRCr alone. CONCLUSION: Inclusion of pre-nephrectomy remnant CKV and WKV into models for 5yeGFRCr and sub-optimal post-nephrectomy adaptation in Indian LKDs improves their accuracy. CKD EPI cystatin eGFR correlates better with functional renal mass.

Clinicopathological predictors of repeated recurrence in sinonasal inverted papilloma.

PURPOSE: To evaluate association between clinical and pathological findings and repeated recurrence in sinonasal inverted papilloma. METHODS: Retrospective cohort study conducted at a tertiary care teaching hospital included all patients operated for inverted papilloma from January 2010 to December 2019. Patients were categorized as primary and recurrent cases. Based on disease status at follow-up, they were subcategorized into 'primary with no recurrence' (PnR), 'primary with recurrence' (PwR), 'recurrent with no further recurrence' (RnR), and 'recurrent with further recurrence' (RwR) groups. Data including demography, clinical, endoscopic and pathological findings were collected and analyzed. RESULTS: Increased incidence of pale appearance of lesion in RnR group (p = 0.017), polypoidal appearance in primary group (p = 0.002) and fibrous appearance in the recurrent group (p = 0.002) were statistically significant. Predominant epithelium was combined respiratory and squamous epithelium in primary and recurrent groups and also in RnR group (p = 0.019), while it was squamous (p = 0.024) in RwR group. Epithelial hyperplasia was more common in primary and RnR groups. Oncocytic change, cystic dilatation, microabscess and squamous metaplasia were seen more in recurrent and RnR groups. Cytoplasmic glycogenation was more in recurrent and RwR groups. Stroma was predominantly edematous in all the groups. CONCLUSIONS: Patients with recurrence are younger and present earlier than those with primary disease. Fleshy appearance and pink/red colour of tumour, lining epithelium being squamous and cytoplasmic glycogenation could be considered as features predicting recurrence. Negative predictors of recurrence of IP include pale appearance of tumour, combined respiratory and squamous epithelium lining and squamous metaplasia.

Clinical and angiographic outcomes of Mycophenolate versus Methotrexate in South Asian patients of Takayasu arteritis: Results from an open-label, randomised controlled trial.

OBJECTIVE: To compare the clinical and angiographic responses of Mycophenolate Mofetil (MMF) versus Methotrexate (MTX) in Takayasu arteritis (TAK). METHODS: This was a open label, outcome assessor blinded trial. Adult patients of TAK with active disease were randomized 1:1 to MMF 1g twice daily or MTX 20 mg once weekly, by computer generated program. All patients were started on 0.5 mg/kg of steroids with a predetermined tapering protocol. Primary outcome was treatment response as defined by Indian Takayasu arteritis score at 9 months. Secondary end points included time to first failure and angiographic progression. RESULTS: A total of 52 patients (26 in each arm) were recruited. The rate of responders was 71.43% (15/21) in the MMF arm and 63.64% (14/22) in the MTX arm (p=0.58). The median time to 1st failure was 9 months (Range: 3-9) and 4.5 months (range: 3-9) in the MMF and MTX arm respectively (p=0.052). In both groups, 15 % of patients (n=3) had progressive disease in angiography. CONCLUSION: The results showed numerically better outcomes towards MMF, with a longer time to first failure than Methotrexate(9 months versus 4.5 months, p=0.052). No significant difference was seen in the angiographic outcomes.

Endometriosis and oocyte quality: an analysis of 13 614 donor oocyte recipient and autologous IVF cycles.

STUDY QUESTION: Does endometriosis affect live birth following donor oocyte recipient versus autologous IVF? SUMMARY ANSWER: There was no significant difference in the live birth rate (LBR) in women with endometriosis undergoing donor oocyte recipient cycles versus autologous IVF cycles. WHAT IS KNOWN ALREADY: For infertile women with endometriosis, IVF is often considered as a treatment option. Lower implantation and pregnancy rates have been observed following IVF in women with endometriosis. It has been debated whether the lower pregnancy rate is due to the effect on oocyte quality or the endometrium, thus affecting implantation. To delineate whether endometriosis affects oocyte quality or the endometrium, we planned a study, using a donor oocyte recipient model, where the recipients were women diagnosed with endometriosis and compared their outcomes with women who underwent autologous IVF, who had also been diagnosed with endometriosis. STUDY DESIGN SIZE DURATION: Human Fertilization and Embryology Authority (HFEA) anonymized data from 1996 to 2016 were analyzed. This comprised of a total of 758 donor oocyte recipients, where the recipients were women diagnosed with endometriosis, and 12 856 autologous IVF cycles where the women were diagnosed with endometriosis as the sole cause of infertility. PARTICIPANTS/MATERIALS SETTING METHODS: Data on all women with endometriosis undergoing donor oocyte recipient and autologous IVF cycles were analyzed to compare live birth outcomes. Logistic regression analysis was performed adjusting for number of previous IVF cycles, previous live birth, period of treatment, day of embryo transfer, number of embryos transferred and fresh or frozen embryo transfer cycle. MAIN RESULTS AND THE ROLE OF CHANCE: There was no significant difference in the LBR in women with endometriosis undergoing donor oocyte recipient fresh embryo transfer cycles compared to women undergoing autologous IVF fresh embryo transfer cycles (31.6% vs 31.0%; odds ratio (OR) 1.03, 99.5% CI 0.79-1.35). After adjusting for confounders, there was no significant difference in LBR in women with endometriosis undergoing donor oocyte recipient fresh embryo transfer cycles versus autologous fresh embryo transfer cycles (adjusted OR (aOR) 1.05, 99.5% CI 0.79-1.41).There was no significant difference in the LBR in women with endometriosis undergoing donor oocyte recipient frozen embryo transfer cycles compared to women undergoing autologous frozen embryo transfer cycles (19.6% vs 24.0%; OR 0.77, 99.5% CI 0.47-1.25). After adjusting for potential confounders, there was no significant difference in the LBR in women undergoing donor oocyte recipient frozen embryo transfer cycles compared with autologous frozen embryo transfer cycles (aOR 0.85, 99.5% CI 0.51-1.41). LIMITATIONS REASONS FOR CAUTION: Although the analysis was adjusted for potential confounders, there was no information on the extent and classification of endometriosis as well as oocyte number. Furthermore, adenomyosis is thought to co-exist in women with endometriosis and may have independent pathophysiological mechanisms affecting fertility, for which there was no information. WIDER IMPLICATIONS OF THE FINDINGS: The study shows no difference in LBR between donor oocyte recipient cycles in which all recipients had endometriosis compared to autologous IVF cycles in women with endometriosis. Therefore, this study finding suggests that there may be a minimal or no effect of oocyte quality on IVF outcomes in women with endometriosis. STUDY FUNDING/COMPETING INTERESTS: No funding was obtained. M.S.K. is an associate editor with Human Reproduction Open. He was not involved in the editorial or peer review process for the manuscript. TRIAL REGISTRATION NUMBER: N/A.

Effectiveness of music therapy as an adjuvant to conscious sedation in women undergoing transvaginal oocyte retrieval: A randomized controlled trial.

AIM: Assisted reproductive technique (ART) has emerged as the highest form of treatment for infertile couples. Transvaginal oocyte retrieval is currently performed under conscious sedation in most centers. Since it is a relatively painful procedure, a number of adjuvant therapies have been tried to improve pain relief during the procedure. Music therapy is a nonpharmacological technique that has been successfully used for pain relief in perioperative and chronic pain of malignancy. However, studies evaluating its usefulness in ART-related procedures are limited. We evaluated the effectiveness of music therapy as an adjuvant for pain relief during oocyte retrieval. METHODS: This was a randomized controlled trial conducted at a tertiary level teaching hospital in South India from September 2020 to March 2021. All women undergoing transvaginal oocyte retrieval were randomized to receive either music therapy along with conscious sedation (Group A) or conscious sedation alone (Group B). The primary outcome was postprocedure pain score assessed by the visual analog scale. Secondary outcomes included anxiety score. RESULTS: A total of 109 women were randomized into Group A (54 women) and Group B (55 women). The postprocedure pain score was comparable between the two study groups (6.0, interquartile range [IQR] 4 to 6 vs. 6.0, IQR 4 to 6; p = 0.69). However, anxiety levels were found to be significantly lower in women who were offered music therapy (3.0, IQR 1 to 5 vs. 4.0, IQR 3 to 6; p = 0.004). CONCLUSION: The use of music therapy as an adjuvant to conscious sedation was found to have no significant benefit in pain relief during oocyte retrieval.

Functional principal component analysis for identifying the child growth pattern using longitudinal birth cohort data.

BACKGROUND: Longitudinal studies are important to understand patterns of growth in children and limited in India. It is important to identify an approach for characterising growth trajectories to distinguish between children who have healthy growth and those growth is poor. Many statistical approaches are available to assess the longitudinal growth data and which are difficult to recognize the pattern. In this research study, we employed functional principal component analysis (FPCA) as a statistical method to find the pattern of growth data. The purpose of this study is to describe the longitudinal child growth trajectory pattern under 3 years of age using functional principal component method. METHODS: Children born between March 2002 and August 2003 (n = 290) were followed until their third birthday in three neighbouring slums in Vellore, South India. Field workers visited homes to collect details of morbidity twice a week. Height and weight were measured monthly from 1 month of age in a study-run clinic. Longitudinal child growth trajectory pattern were extracted using Functional Principal Component analysis using B-spline basis functions with smoothing parameters. Functional linear model was used to assess the factors association with the growth functions. RESULTS: We have obtained four FPCs explained by 86.5, 3.9, 3.1 and 2.2% of the variation respectively for the height functions. For height, 38% of the children's had poor growth trajectories. Similarly, three FPCs explained 76.2, 8.8, and 4.7% respectively for the weight functions and 44% of the children's had poor growth in their weight trajectories. Results show that gender, socio-economic status, parent's education, breast feeding, and gravida are associated and, influence the growth pattern in children. CONCLUSIONS: The FPC approach deals with subjects' dynamics of growth and not with specific values at given times. FPC could be a better alternate approach for both dimension reduction and pattern detection. FPC may be used to offer greater insight for classification.

Postchemotherapy tumor volume as a prognostic indicator in Wilms tumor: A single-center experience from South India.

BACKGROUND: Optimal risk stratification is the key to minimizing relapse and toxicity in children with Wilms tumor (WT). The study evaluated poor tumor volume response to chemotherapy as a risk factor that predicts relapse. PROCEDURE: Children with WT who were treated between 2005 and 2020 at the center were analyzed. Tumor volumes at the time of diagnosis and after preoperative chemotherapy were calculated from cross-sectional imaging. The International Society of Paediatric Oncology (SIOP)-WT-2001 protocol was used for treatment. The area under a receiver operating characteristic curve was estimated to ascertain the ability of tumor volume to predict relapse. RESULTS: Ninety-five patients with a median age of 40 months were included. A postchemotherapy tumor volume cutoff of 270 ml was ascertained to have the best predictive value for relapse. Patients with a tumor volume of <270 ml following preoperative chemotherapy had a better 3-year event-free survival (EFS) than those with a tumor volume of ≥270 ml (89.8% ± 4.0% vs. 57.4% ± 12.5%, p = .001). The data demonstrated that a tumor volume of ≥270 ml after chemotherapy was associated with an increased risk of relapse (hazard ratio [HR]: 5.3, p = .006). The EFS in patients with an epithelial or stromal type of histopathology was not affected by the tumor volume response (p = .437). Conversely, patients with other types of intermediate-risk histopathology who had a poor tumor volume response had an inferior survival (3-year EFS 51.4% ± 18.7%, p = .001). CONCLUSION: A postchemotherapy tumor volume cutoff of ≥270 ml emerged as a strong predictor of relapse in a low- and middle-income country (LMIC) center study of WT treated with the SIOP protocol.

Distinct opposing associations of upper and lower body fat depots with metabolic and cardiovascular disease risk markers.

BACKGROUND: To examine the associations of total and regional adiposity with metabolic and cardiovascular disease (CVD) risk markers. METHODS: This cross-sectional study included 1080 (53.8% men, aged 39-44 years) individuals from South India. Anthropometry (height, weight, waist and hip circumference), body composition assessment using dual-energy X-ray absorptiometry (DXA), blood pressure (BP), and plasma glucose, insulin and lipids were measured. Regression analysis was used to examine associations of standardized fat measurements with type 2 diabetes (T2D), insulin resistance (IR), hypertension and hypertriglyceridemia and continuous measurements of BP, glucose, insulin, HOMA-IR and lipids. Contour plots were constructed to visualize the differential effect of upper and lower fat depots. RESULTS: DXA-measured fat depots were positively associated with metabolic and CVD risk markers. After adjusting for fat mass index, upper body fat remained positively, while lower body fat was negatively associated with risk markers. A one standard deviation (SD) increase in android fat showed higher odds ratios (ORs) for T2D (6.59; 95% CI 3.17, 13.70), IR (4.68; 95% CI 2.31, 9.50), hypertension (2.57; 95% CI 1.56, 4.25) and hypertriglyceridemia (6.39; 95% CI 3.46, 11.90) in men. A 1 SD increase in leg fat showed a protective effect with ORs for T2D (0.42; 95% CI 0.24, 0.74), IR (0.31; 95% CI 0.17, 0.57) and hypertriglyceridemia (0.61; 95% CI 0.38, 0.98). The magnitude of the effect was greater with DXA-measured fat compared with anthropometry. CONCLUSION: At any level of total body fat, upper and lower body fat depots demonstrate opposite risk associations with metabolic and CVD risk markers in Asian Indians.

Satisfaction and genital perception after orchiectomy for prostate cancer: does the technique matter? A randomized trial.

OBJECTIVES: Bilateral extracapsular or total orchiectomy (BEO) for prostate cancer is presumed to have psychological consequences after the surgery due to perception of an empty scrotum. Bilateral subcapsular orchiectomy (BSO) was designed to preserve perception of palpable testes. We compared the patients' satisfaction and genital perception following BEO and BSO. MATERIALS AND METHODS: Prostate cancer patients eligible for androgen deprivation therapy who opted for orchiectomy were enrolled in prospective randomized study. Patients with bleeding disorder or uncorrected coagulopathy, poor performance score, and psychiatric problems were excluded. Outlook to life and own health in-general, overall satisfaction to the procedure and genital perception was evaluated using modified Fugl-Meyer questionnaire (FMQ) which was administered before and after 3 months of the surgery. Patients were randomized to BEO and BSO groups at the time of surgery using block randomization. Primary outcome was to compare the genital perception of testicular loss and patients' satisfaction to BSO and BEO. Secondary outcomes included testosterone and PSA control, operative time, and complications. RESULTS: Total 35 patients were enrolled in each group which was comparable. There was no difference in PSA control at 3 months. Mean operative time and blood loss were significantly lesser in BEO group. FMQ score at 3 months did not show significant difference. Majority of the patients in both groups were satisfied with procedure and the aesthetic value of scrotum after surgery. However, 84% in BSO group did not feel that testes were removed on self-examination, as compared to 28% in BEO group. Majority patients in both groups did not report physical or psychological discomfort from change in scrotal content. CONCLUSIONS: Results showed that patients' satisfaction and genital perception following BSO and BEO were similar. Feeling of remaining intrascrotal contents after BSO did not had added psychological advantage in terms of perception of genitalia.

POSEIDON classification and the proposed treatment options for groups 1 and 2: time to revisit? A retrospective analysis of 1425 ART cycles.

STUDY QUESTION: Do live birth outcomes differ when Patient-Oriented Strategy Encompassing IndividualizeD Oocyte Number (POSEIDON) stratified groups are compared with women with good prognosis (non-POSEIDON group) undergoing ART? SUMMARY ANSWER: The current study showed no significant difference in the live birth rates (LBRs) per embryo transfer between POSEIDON groups 1 and 2 when compared with women in the non-POSEIDON group undergoing ART. WHAT IS KNOWN ALREADY: Recently, there has been a lot of focus on the POSEIDON classification for low prognosis women undergoing ART and various management options have been advocated. For POSEIDON groups 1 and 2, low starting dose and gonadotrophin receptor polymorphism have been suggested as possible reasons for a hyporesponse, and increasing the starting gonadotrophin dose, the addition of recombinant LH and dual stimulation have been suggested as treatment options. Most of these treatment options are hypothetical in nature and need validation. STUDY DESIGN SIZE DURATION: In the current cohort study, a total of 1425 cycles were analyzed retrospectively following a single cycle fresh embryo transfer. The study period was from January 2013 to June 2018. PARTICIPANTS/MATERIALS SETTING METHODS: Women undergoing ART at a tertiary level infertility clinic were included. Clinical and treatment-related details were obtained from the hospital's electronic medical records. The ART outcomes in a non-POSEIDON group (women with an adequate ovarian reserve and/or optimal ovarian response i.e. >9 oocytes retrieved in the previous ART cycle) and a low prognosis group stratified by POSEIDON criteria were compared. We also examined the effectiveness of the modifications made in the current ART treatment protocols among women with an adequate ovarian reserve who had a history of poor/suboptimal response (POSEIDON 1 and 2). MAIN RESULTS AND THE ROLE OF CHANCE: There was no statistically significant difference in the LBR per embryo transfer in POSEIDON group 1 (32/109, 29%) and group 2 (17/58, 29%) when compared with the non-POSEIDON group (340/1041, 33%) (adjusted odds ratio (aOR) 0.69; 95% CI 0.37-1.27 and aOR 0.93, 95% CI 0.43-1.97, respectively), while significantly lower LBR were observed in POSEIDON groups 3 (17/97, 17.5%) and 4 (12/120, 10%) (aOR 0.49; 95% CI 0.28-0.89 and aOR 0.38, 95% CI 0.19-0.74, respectively). The gonadotrophin dose alone was increased in one-quarter of the cycles and in another 27% the dose was increased along with the protocol change among POSEIDON group 1. In POSEIDON group 2, a change in the dose alone and in combination with protocol change was performed in 5 and 41% of cycles, respectively. LIMITATIONS REASONS FOR CAUTION: A limitation of our study is the retrospective nature of the study with an inherent risk of unknown confounders influencing the outcomes. Other limitations are the lack of cumulative live birth data and the relatively small sample within POSEIDON group 2, which could lead to a type II error. WIDER IMPLICATIONS OF THE FINDINGS: The current study showed no significant difference in the LBR between the POSEIDON groups 1 and 2 when compared with the non-POSEIDON group of women, while groups 3 and 4 had significantly lower LBR. The simple gonadotrophin/protocol changes in groups 1 and 2 resulted in LBRs comparable to women with good prognosis. These findings call for revisiting the proposed treatment strategies for POSEIDON groups 1 and 2. STUDY FUNDING/COMPETING INTERESTS: No funding was obtained. There are no competing interests to declare.

Role of Hysterosalpingography in Diagnosing Tubal Blockage - A Prospective Diagnostic Study.

BACKGROUND: Women with abnormal hysterosalpingography (HSG) are anxious regarding the presence of tubal pathology. It is important to know the predictive value of HSG and the need for subsequent laparoscopy following an abnormal report. In the era of assisted reproductive technology, the role of invasive testing such as diagnostic laparoscopy is being increasingly questioned due to its invasiveness and associated risks. There is a need to explore the positive predictive value (PPV) of HSG in detecting bilateral tubal block in our population as PPV changes with the prevalence of disease. AIM: The aim of this study was to evaluate the diagnostic accuracy of HSG in identifying tubal blockage in subfertile women. SETTING AND DESIGN: This was a prospective diagnostic study conducted in the department of reproductive medicine and surgery in a university-level hospital. MATERIALS AND METHODS: The study included 199 subfertile women who had undergone HSG earlier and were planned for laparoscopy from April 2017 to January 2021. Findings of HSG and laparoscopy were compared with HSG as index test and laparoscopy as reference test, and the outcomes analysed were PPV of HSG for a bilateral tubal block, bilateral hydrosalpinx, abnormal HSG (unilateral or bilateral tubal block) and agreement between HSG and diagnostic laparoscopy in detecting normal and abnormal findings. STATISTICAL ANALYSIS: Kappa statistics, Stuart-Maxwell tests of marginal homogeneity and prevalence-adjusted bias-adjusted kappa (PABAK) statistics were used. RESULTS: The PPV for a bilateral block with HSG was 20.9% (95% CI: 13.7-29.7). The PPV of HSG for bilateral hydrosalpinx was 50.0% (95% CI: 6.8-93.2). PABAK was estimated to be 0.42 (95% CI: 0.30-0.55), suggestive of moderate agreement between the tests. Findings of laparoscopy in women with at least one patent tube in HSG showed that in 12.3% of cases, the management was likely to change due to the operative findings. CONCLUSION: The current study showed low PPV for bilateral tubal block diagnosed with HSG which translates into a need for further confirmation by laparoscopy. In one out of every eight women with at least one patent tube on HSG, performing laparoscopy changed the management.

Combination of methotrexate and sulfasalazine is an efficacious option for axial spondyloarthritis in a resource-limited, real-world clinical setting: a prospective cohort study.

OBJECTIVE: Evaluation of response to combination conventional synthetic DMARD (csDMARD) therapy with methotrexate (MTX) and sulfasalazine (SSZ) in active axial spondyloarthritis (axSpA) patients without peripheral arthritis (group 1) as compared to active axSpA with peripheral arthritis (group 2), who are economically constrained for biologicals. METHODS: A prospective, observational, single-centre, cohort study on 150 consecutive active axSpA patients who were already initiated on the above mentioned combination csDMARD therapy and satisfying the other pre-defined eligibility criteria, was conducted between July 2016 and July 2017 using ASAS20 response as primary outcome measure at 3 and 6 months post treatment. RESULTS: ASAS20 response at 3 months was achieved in 31/58 (53.4%) and in 24/36 (66.6%) in groups 1 and 2, respectively (p = 0.2); at 6 months, these figures were 45/76 (59.2%) and 28/44 (63.6%), respectively (p = 0.6). Similarly, there was significant reduction in mean ASAS NSAID index from 29.6 to 14 over 6 months from baseline (p = 0.001), and it was similar in both groups. Using BASDAI ≥ 4 to define active disease, a 34% reduction in requirement of biologicals was also observed. CONCLUSION: In resource-limited population, treatment with combination of methotrexate and sulphasalazine over a period of 6 months is equally efficacious in patients with active axSpA with and without peripheral arthritis, as evidenced by improved ASAS20 response rates, reduction in NSAID use and fewer patients switching to biologicals. Key Points • Combination of MTX+SSZ was efficacious and safe in active axSpA patients who had economic hardships to use biologicals. • This benefit in axSpA patients was similar between those without any peripheral arthritis and those with. • MTX+SSZ combination therapy also demonstrated NSAID sparing action. • Combination of MTX and SSZ prevented escalation to biological therapy as per a BASDAI score driven policy.

Female causes of infertility are associated with higher risk of preterm birth and low birth weight: analysis of 117 401 singleton live births following IVF.

STUDY QUESTION: Does the cause of infertility affect the perinatal outcomes preterm birth (PTB) and low birth weight (LBW) following IVF treatment? SUMMARY ANSWER: The risk of PTB and LBW was higher with female causes of infertility-ovulatory disorders, tubal disorders and endometriosis-compared to unexplained infertility but the absolute increase in risk was low. WHAT IS KNOWN ALREADY: Infertility is associated with an increased risk of adverse perinatal outcomes. Risk of adverse perinatal outcomes is also higher following ART compared to spontaneous conceptions. Infertility can result from female and/or male factors or is unexplained when the cause cannot be delineated by standard investigations. Given that infertility and ART are contributory to the adverse perinatal outcomes, it is a matter of interest to delineate if the specific cause of infertility influences perinatal outcomes following IVF treatment. STUDY DESIGN, SIZE, DURATION: Anonymous data were obtained from the Human Fertilization and Embryology Authority (HFEA). The HFEA has collected data prospectively on all ART cycles performed in the UK since 1991. Data from 1991 to 2016 comprising a total of 117 401 singleton live births following IVF with or without ICSI (IVF ± ICSI) for sole causes of infertility were analysed for PTB and LBW. Cycles having more than one cause of infertility and/or multiple births were excluded. PARTICIPANTS/MATERIALS, SETTING, METHODS: Data on all women undergoing stimulated IVF ± ICSI treatment cycles were analysed to compare perinatal outcomes of PTB and LBW among singleton live births based on the cause of infertility (ovulatory disorders, tubal disorders, endometriosis, male factor, unexplained). Logistic regression analysis was performed, adjusting for female age category, period of treatment, previous live births, IVF or ICSI, number of embryos transferred and fresh or frozen embryo transfer cycles. MAIN RESULTS AND THE ROLE OF CHANCE: Compared to unexplained infertility, the risk of PTB was significantly higher with ovulatory disorders (adjusted odds ratio (aOR) 1.31, 99.5% CI 1.17 to 1.46); tubal disorders (aOR 1.25, 99.5% CI 1.14 to 1.38) and endometriosis (aOR 1.17, 99.5% CI 1.01 to 1.35). There was no significant difference in the risk of PTB with male factor causes compared to unexplained infertility (aOR 1.01, 99.5% CI 0.93, 1.10). The risk of LBW was significantly higher with ovulatory disorders (aOR 1. 29, 99.5% CI 1.16 to 1.44) and tubal disorders (aOR 1.12, 99.5% CI 1.02 to 1.23) and there was no increase in the risk of LBW with endometriosis (aOR 1.11, 99.5% CI 0.96 to 1.30) and male factor causes (aOR 0.94, 99.5% CI 0.87, 1.03), compared to unexplained infertility. LIMITATIONS, REASONS FOR CAUTION: Although the analysis was adjusted for several important confounders, there was no information on the medical history of women during pregnancy to allow adjustment. The limitations with observational data would apply to this study, including residual confounding. WIDER IMPLICATIONS OF THE FINDINGS: This is the largest study to address the causes of infertility affecting perinatal outcomes of PTB and LBW. The information is important for the management of pregnancies and the underlying reasons for the associations observed need to be further understood. STUDY FUNDING/COMPETING INTEREST(S): No funding was obtained. There are no competing interests to declare. TRIAL REGISTRATION NUMBER: N/A.

Prevalence, incidence and predictors of cardiovascular risk factors: longitudinal data from rural and urban South India and comparison with global data.

INTRODUCTION: India has high mortality rates from cardiovascular disease (CVD). Understanding the trends and identifying modifiable determinants of CVD risk factors will guide preventive strategies and policy making. RESEARCH DESIGN AND METHODS: CVD risk factors (obesity, central obesity, and type 2 diabetes (T2D), hypertension, hypercholesterolemia and hypertriglyceridemia) prevalence and incidence were estimated in 962 (male 519) non-migrant adults from Vellore, South India, studied in: (1) 1998-2002 (mean age 28.2 years) and (2) 2013-2014 (mean age 41.7 years). Prevalence was compared with the Non-Communicable Disease Risk Collaboration (global) data. Incidence was compared with another Indian cohort from New Delhi Birth Cohort (NDBC). Regression analysis was used to test baseline predictors of incident CVD risk factors. RESULTS: The prevalence at 28 and 42 years was 17% (95% CI 14% to 19%) and 51% (95% CI 48% to 55%) for overweight/obesity, 19% (95% CI 17% to 22%) and 59% (95% CI 56% to 62%) for central obesity, 3% (95% CI 2% to 4%) and 16% (95% CI 14% to 19%) for T2D, 2% (95% CI 1% to 3%) and 19% (95% CI 17% to 22%) for hypertension and 15% (95% CI 13% to 18%) and 30% (95% CI 27% to 33%) for hypertriglyceridemia. The prevalence of T2D at baseline and follow-up and hypertension at follow-up was comparable with or exceeded that in high-income countries despite lower obesity rates. The incidence of most risk factors was lower in Vellore than in the NDBC. Waist circumference strongly predicted incident T2D, hypertension and hypertriglyceridemia. CONCLUSIONS: A high prevalence of CVD risk factors was evident at a young age among Indians compared with high and upper middle income countries, with rural rates catching up with urban estimates. Adiposity predicted higher incident CVD risk, but the prevalence of hypertension and T2D was higher given a relatively low obesity prevalence. Preventive efforts should target both rural and urban India and should start young.

Tamsulosin and placebo vs tamsulosin and tadalafil in male lower urinary tract symptoms: a double-blinded, randomised controlled trial.

OBJECTIVE: To compare the efficacy and safety of tamsulosin vs the combination of tamsulosin and tadalafil in male lower urinary tract symptoms (LUTS). PATIENTS AND METHODS: This was a double-blinded, parallel-arm randomised controlled trial. Men aged >45 years with moderate LUTS and a maximum urinary flow rate (Qmax ) of 5-15 mL/s were included. One arm received 0.4 mg tamsulosin only (Group-A), while the second received 5 mg tadalafil with tamsulosin (Group-B). The primary outcome was the International Prostate Symptom Score (IPSS). Secondary outcomes were IPSS quality of life (QoL) score, five-item version of the International Index of Erectile Function (IIEF-5) score, Qmax , and post-void residual urine (PVR). Block randomisation was used. Placebo was used for blinding and allocation concealment. Intention-to-treat analysis was used for outcome measures. RESULTS: Of the 183 men screened, 140 were randomised (71 in Group-A, 69 in Group-B); 116 (82.85%) (61 in Group-A, 55 in Group-B) completed the study. Baseline characteristics were comparable. The improvements in the IPSS, IPSS QoL score, IIEF score and Qmax were -1.69 (95% confidence interval [CI] -1.4 to -2.0), -0.70 (95% CI -0.60 to -0.80), 3.8 (95% CI 3.4-4.2) and 1.8 mL/s (95% CI 1.1-2.4) respectively, in favour of the combination group. The difference in PVR was not significant. There were no serious adverse events (AEs). The dropout rate due to AEs was 2.85%. Myalgia (five patients) was the commonest AE in the combination group. CONCLUSION: The combination of tamsulosin and tadalafil produced significantly better improvements in LUTS, QoL, erectile function and Qmax compared to monotherapy with tamsulosin, without an increase in AEs.

Cross-Sectional Study of Dermatoscopic Findings in Relation to Activity in Vitiligo: BPLeFoSK Criteria for Stability.

BACKGROUND: Stability in vitiligo is an important concept in guiding patient management and a vital prerequisite before vitiligo surgery. Disease activity of vitiligo based on patient's history is imprecise. It is practically impossible to perform biopsy from all lesions of vitiligo to ascertain stability. Dermatoscopy can be used to examine all clinical lesions in a patient of vitiligo. There is a need to validate many reported dermatoscopic findings for universal use. AIMS: To analyze the significance of dermatoscopic findings in the activity of vitiligo and to devise a cutoff score for stable vitiligo. MATERIALS AND METHODS: Dermatoscopic examination was performed in 85 patients clinically diagnosed with vitiligo. Six dermatoscopic parameters, namely, border, pigment network, perilesional hyperpigmentation, perifollicular pigmentation, satellite lesions, and micro-Koebner phenomenon (acronym: BPLeFoSK) were evaluated against Wood's lamp findings as standard. Chi-square test was used to test association between categorical variables. Cutoff values for stability for these six parameters were plotted in receiver operating curve. RESULTS: A total of 131 vitiligo lesions were analyzed with dermatoscopy. Absence of satellite lesions and absence of micro-Koebner phenomenon were the most sensitive parameters (96.7% and 100%, respectively). Sharp border and absent or reticulate pigment network within the vitiligo patch were the most specific findings (100% and 91.5%, respectively). CONCLUSION: A cutoff score of more than or equal to 1.5 using the "BPLeFoSK criteria" indicates stability in the vitiligo lesion.

Temporal trends in the incidence and demographics of cancers, communicable diseases, and non-communicable diseases in Saudi Arabia over the last decade.

OBJECTIVES: To describe the trends in the incidence rates of 5 most common cancers, communicable diseases, and non-communicable diseases in Saudi Arabia over the last decade.  Methods: The incidence rates of cancers (2001-2014), communicable diseases (2003-2016), and non-communicable diseases (1990-2017) were retrieved, classified, and analyzed retrospectively during November 2017, based on data available with the Ministry of Health and were analyzed at the Imam Abdulrahman Bin Faisal University in Dammam, Kingdom of Saudi Arabia. Results: Age-standardized incidence rate (ASR) (per 100,000 population) of breast cancer among women increased dramatically from 11.8 in 2001 to 22.7 in 2014, indicating a 92.4% increase over the decade. Colorectal cancer incidence was the highest among men, and its ASR per 100,000 population increased from 5.0 to 10.6 in men and from 5.0 to 8.2 in women. Among communicable diseases, incidences of hepatitis B, measles, chickenpox, and brucellosis decreased while dengue fever increased. An alarming increase was observed in the incidence rate of non-communicable diseases namely, obesity, diabetes, and hypertension. Conclusion: The incidence rate of non-communicable diseases increased over the decade and was associated with increased mortality and disability, reduced quality of life, and increased health-care costs, indicating an urgent need to establish prevention and control programs. The rising trend in the incidence of cancers may also become a health care issue in Saudi Arabia in the coming years.

Risk Factors for Acquiring Scrub Typhus among the Adults.

BACKGROUND: Behavioral and geographical factors may play a role in the acquisition of scrub typhus infection. In this prospective case-control study, we studied the factors associated with infection. PATIENTS AND METHODS: Consecutive adult patients admitted with scrub typhus infection over 10 months were recruited. For every case, a geographical control from the same area and a gender-matched clinical control admitted with acute febrile illness were enrolled. The risk factors, which included sanitation, environment, activity, and protective measures, were compared between cases and controls using univariable and multivariable conditional logistic regression analysis and expressed as odds ratio (OR) with 95% confidence interval (CI). RESULTS: The study cohort (n = 225; 132 female) aged 44 ± 17 years comprised of 75 cases and 150 controls from mid to low socioeconomic background. When compared with clinical controls, on univariable conditional regression analysis, cases were more likely to be involved in farming or gardening and less likely to have a toilet within the house. On multivariate regression analysis, only involvement in farming or gardening was associated with infection (OR: 4.2, 95% CI: 1.5-11.5). When compared with geographical controls, on univariable conditional regression analysis, cases were less likely to change undergarments or clothes before sleeping (OR: 3.5, 95% CI: 1.3-9.5) and more likely to have rodents in their house (OR: 2.5, 95% CI: 1-6.4) and rest on grass/mud without a mat (OR: 2.4, 95% CI: 1.1-5.3). On multivariate regression analysis, not changing undergarments or clothes tended to be associated with infection (OR: 2.7, 95% CI: 0.98-7.3). CONCLUSION: Certain behavioral factors predisposed our cohort to develop scrub typhus infection. Lifestyle changes may reduce the burden of scrub typhus in South India.