Plasma-based circulating cell-free tumor DNA (ctDNA) genomic profiling by next-generation sequencing (NGS)is an emerging diagnostic tool for pancreatic cancer (PC). The impact of detected genomic alterations and variant allele fraction (VAF) in tumor response to systemic treatments and outcomes is under investigation.Patients with advanced PC who had ctDNA profiled at time of initial diagnosis were retrospectively evaluated. We considered the somatic alteration with the highest VAF as the dominant clone allele frequency (DCAF). ctDNA NGS results were related to clinical demographics, progression-free survival (PFS) and overall survival (OS).KRAS was associated with disease progression to systemic treatments , worse median PFS (p < 0.001) and worse median OS (p = 0.002). TP53 was associated with worse median PFS (p = 0.02) and worse median OS (p = 0.001). The median DCAF was 0.45% (range 0-55%). DCAF >0.45% was associated with worse median PFS (p<0.0001) and median OS (p=0.0003). Patients that achieved clearance of KRAS had better PFS (p=0.047), while patients that achieved clearance of TP53 had better PFS (p=0.0056) and OS (p=0.037).A total of 104 patients were evaluated. Somatic alterations were detected in 84.6% of the patients. Patients with ≥ 2 detectable genomic alterations had worse median PFS (p < 0.001) and worse median OS (p = 0.001). Initial detection of ctDNA in advanced PC can identify somatic alterations that may help predict clinical outcomes. The dynamics of ctDNA are prognostic of outcomes and should be evaluated in prospective studies. Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer-related deaths in the United States, with 60,430 estimated new cases and 48,220 expected related deaths in 2021  in these tumors is proving to be important and impactful in the management of disease –7. Tissue tumors –11. Furte tumors . Furthere tumors .KRAS and other mutations in ctDNA pre-operatively and post-operatively was related to worse recurrence-free survival and overall survival, with recurrence observed in all patients with detectable ctDNA post-surgery (KRAS detected by ctDNA are associated with worse specific disease outcomes (Liquid biopsies are non-invasive tests that can perform comprehensive genomic profiling from a blood sample. NGS of plasma-derived circulating cell-free tumor DNA (ctDNA) is being investigated as a potential tool for diagnosis and prognosis, and as alternative for tumor tissue in the identification of potential actionable biomarkers –18. ctDN-surgery . In advaoutcomes , 24–27. From December 2014 through October 2019, patients with PDAC underwent liquid biopsy testing using a clinically available assay . Two 10mL blood samples were obtained from patients cared for at Mayo Clinic in Florida and Arizona. In this study we evaluated 104 patients that had blood collected for ctDNA analysis at diagnosis of advanced disease. The data analysis from this patient cohort was reviewed and approved by the Mayo Clinic institutional review board.All samples were shipped to Guardant Health, Inc., Redwood City, California as part of routine clinical care. After centrifugation of whole blood, 5 ng – 30 ng of cell -free DNA isolated from plasma was processed for digital NGS. The variant allele fraction (VAF) was calculated as the proportion of ctDNA harboring the variant in a background of wild type cell-free DNA (cfDNA). The assay demonstrated analytical sensitivity and specificity of 100% for single nucleotide variants >0.25% allele fraction , 29. BioVariant allele frequency (VAF) is a measurement of the percent of DNA fragments that harbor a somatic mutation (ctDNA) divided by the wild-type sequence derived from cell-free DNA (cfDNA). The dominant clone allele frequency (DCAF) is defined as the somatic alteration(s) detected in the sample with highest VAF, suggesting clonal alterations.Continuous variables were compared between groups by Wilcoxon rank sum test, and Fisher Exact test was conducted for categorical data comparisons. The relationship between alteration types, such as mutation and amplification targetable status was evaluated using Spearman’s rank correlation. The analysis was conducted in 104 patients with baseline ctDNA results available prior to initiation of systemic therapy to determine the association of somatic alterations and disease stage . Kaplan-Meier analysis was used to estimate progression-free survival (PFS) and overall survival (OS) based on stage or the absence/presence of somatic alterations. Patients without a progression/death event were considered censored at the date of last known follow-up in addition, Cox regression models were evaluated in a univariate and multivariable fashion. P values <0.05 were considered statistically significant. All computations were carried out in SAS version 9.3 and R version 3.6.2.–A total of 104 patients were included in this study, 39 with stage III  and 65 with stage IV (metastatic disease[MPC]). Demographic data are summarized in A total of 23 patients had blood collected for NGS at diagnosis of advanced disease and upon disease progression to first line SOC therapy.via liquid biopsy had initial liver metastasis compared to 40% of patients without any detected alterations (p <0.001) . Interestingly, 83.1% of patients with somatic alterations detected Ninety-one percent of MPC had at least one genetic alteration (n=59) compared to 74% of patients with LAPC . Seventy five percent of MPC patients had at least 2 alterations (n=49) compared to 36% with LAPC . The median number of detectable somatic alterations was 3 in MPC compared to 1 in LAPC.KRAS mutations were detected in 73.8% of MPC compared to 43.6% of LAPC (p=0.002). Approximately 66% of patients with MPC harbored 1 KRAS mutation and 7.7% harbored 2 KRAS mutations, compared to 43.6% and 0% for those with LAPC (p=0.004). Additionally, 85% of patients with MPC who harbored a KRAS mutation experienced the liver as the primary site of metastasis compared to 62% of patients without KRAS mutations (p=0.03). TP53 mutations were also detected more frequently in patients with metastases, detected in 69% of patients with MPC compared to 43.6% with LAPC (p=0.01) . Other gene alterations with significant differences include SMAD, which was present in 13.8% of MPC compared to 0% of LAPC (p=0.02) . Of the non-responders, 66.7% had one KRAS mutation while 5% had at least 2 mutations in KRAS. In patients who responded to therapy, those numbers decreased to 37% and 3.7% respectively (p=0.22).Of the 63 patients who did not respond to treatment, 71.4% harbored a via liquid biopsy compared to 6.2 months (95% CI: 5.4 - 8.0) in those with somatic alterations detected  compared to 5.5 months (95% CI: 4.6 - 6.9) in those with metastatic disease (p<0.0001). PFS significantly increased with a median of 15.3 months (95% CI: 10.1 – Not estimated) in patients with no somatic alterations detected p=0.005, Figure 1CCND2 mutations had a significantly reduced median PFS of 3.7 months (95% CI: 2.4 - 8.2) compared to 8.2 months in those without a mutation in CCND2 (95% CI: 6.3 – 11.0). Those with KRAS mutations also experienced a statistically significant reduction, with median PFS of 5.8 (95% CI: 4.6 - 6.7) for KRAS mutant as compared to 12.9 months (95% CI: 10.1 – 22.0) for KRAS not being detected. The reduction in median PFS was more pronounced when analyzing the number of mutations, as those with two or more KRAS mutations had a median PFS of 3.7 months (95% CI: 3.68 – Not estimated) compared to 5.9 months with 1 alteration (95% CI: 4.8 - 6.9) and 12.9 months with no KRAS alteration detected (95% CI: 10.1 – 22.0). In patients with TP53 mutations, median PFS was also significantly reduced to 5.9 months (95% CI: 4.8 - 7.9) compared to 10.9 months for patients without TP53 mutations (95% CI: 9.2 – 22.0) (Patients with  – 22.0) Figure 1KRAS mutation had median OS of 11.5 months (95% CI: 8.21 - 14.8) and 26.3 months (95% CI: 21.67 – Not estimated) respectively. Similarly, those with and without TP53 mutations had median OS of 13.5 months (95% CI: 9.06 - 21.7) and 24.2 months (95% CI: 14.02 – Not estimated)  of 11.5 months (range 8.11 - 21.1 months) compared to 24.2 months (95% CI: 14.38 – Not estimated) in patients with ≤ 1 alteration. This association was preserved when separately analyzing patients with MPC, as those with ≥2 alterations had a median OS of 9.82 months (95% CI: 7.03 - 16.6) compared to 13.89 months (95% CI: 7.78 – Not estimated) in patients with ≤1 alteration. This was also noted in LAPC, with median OS of 24.9 months (95% CI: 40.8 – Not estimated) for patients with ≥2 alterations and 40.8 months (95% CI: 13.5 – Not estimated) for patients with ≤1 alteration. Patients with and without a timated) Figure 2TP53 and/or KRAS alterations at baseline. Patients with clearance at any timepoint of TP53 (3/18)17% and/or KRAS (6/18) 33% achieved improved PFS . Clearance of KRAS in ctDNA after first line SOC trended towards improved OS (p=0.059), while clearance of TP53 significantly improves OS (p=0.047), though in a small sample size. Interestingly, if a patient is found to have a mutation in TP53 or KRAS upon disease progression, (12/23) 50% acquired TP53 or KRAS mutations on progression; (10/23) 43.5% patients acquired TP53, (8/23) 35% patients acquired KRAS mutations (some patients acquired both mutations), PFS is not significantly impacted  samples harbored impacted Figure 3KRAS mutations (p=0.52).All 104 patients were included in the VAF analysis. The median dominant clone allele frequency (DCAF) was 0.45% (range 0-55%). The presence of DCAF >0.45% was associated with worse median PFS  and inferior median overall survival (11.5 vs 26.3 months) when compared to KRAS non-detected patients. Our observation, combined by findings from other groups, corroborates the hypothesis that detection of ctDNA mutated KRAS at diagnosis of advanced pancreatic cancer is correlated with reduced time-to-progression and overall survival or KRAS 33% (6/18) mutations after chemotherapy treatment was associated with improved PFS , and this observation is corroborated by other groups and highlights additional clinical utility of ctDNA in PDAC  compared to LAPC (43.6%). Furthermore, median progression-free survival  and median overall survival  was also significantly reduced in patients with TP53 mutations in ctDNA. Considering that the most frequently mutated genes were KRAS and TP53, as expected, a higher median PFS was observed in those patients who had no somatic alterations detected in ctDNA compared to those with alterations (15.27 versus 6.24 months), and this remained consistent for patients with zero or no genetic alterations detected in ctDNA compared to those with at least 2 alterations . This result highlights that ctDNA and detection of KRAS and TP53 could be used as a stratification tool to guide prospective studies in advanced PDAC.In PDAC, alterations in utations , 30, 42.otherapy , 44. In SMAD4 are detected in about 20-30% of patients with PDAC  compared to LAPC (0%). Larger cohorts evaluating SMAD4 detection by ctDNA at diagnosis and between treatments would be necessary to address the real impact of this biomarker as monitoring strategy or prognostic factor. CCND2 (cyclin D2) regulates CDK kinases, forms a complex with CDK4 and CDK6, and possesses multiple functions necessary for cell cycle G1/S transition ].In tissue samples, somatic alterations in ith PDAC . Mutatioc cancer . Althougansition . Genomicarcinoma  and coloarcinoma  and CCNDc cancer . AlthougLastly, in this study we evaluated variant allelic frequencies. Variant allele frequency changes between treatments and is related to outcomes in pancreatic cancer , 25. In KRAS or TP53 were not detected, there is a chance that a mutation was present but below the limit of detection for the ctDNA assay. For patients who had no alterations detected by liquid biopsy, tumor shed may have been suppressed by therapy, the patient may have indolent of slow-growing disease or low disease burden, or the tumor is shedding very low amounts of ctDNA below the level of detection of the assay. Patients who had higher numbers of genomic alterations detected were related to worse PFS and OS. It would be necessary to address KRAS and TP53 to fully understand the impact of specific mutations identified and whether they contributed a distinct impact on clinical outcomes. In multivariate analysis detection of specific genetic mutations did not translate in worse overall survival, metastatic disease and DCAF>0.45% remained associated with inferior PFS and OS. It has been already shown and discussed that KRAS, TP53, and SMAD4 are the main genetic findings in pancreatic cancer and considering that most patients will have these genomic alterations it would be necessary bigger samples of patients to identify impact of the absence of these mutations in outcomes. Considering the findings, VAF could serve as a stratification factor for advanced pancreatic cancer with detectable somatic mutations in ctDNA.There are several limitations in this study. The timing of ctDNA analysis was not consistent across all patients and it would be necessary to evaluate ctDNA prospectively at diagnosis and between chemotherapy treatments in larger cohorts to fully understand the prognostic and predictive utility of the platform. Also, in patients where This study suggests that evaluation of ctDNA at diagnosis of advanced PDAC is a prognostic tool that may be applicable to clinical practice. This evaluation may be incorporated for deciding therapeutic strategies, designing, and enrolling patients onto clinical trials, and as an alternative genotyping assay in cases where tumor tissue samples are scarce or hardly obtainable. Perhaps a more important and impactful application would be utilizing the changes in ctDNA to guide early switch in systemic therapy, both in the neoadjuvant setting and MPC.The original contributions presented in the study are included in the article/The studies involving human participants were reviewed and approved by IRB Mayo Clinic Arizona. Written informed consent for participation was not required for this study in accordance with the national legislation and the institutional requirements.GB and PU has written the manuscript and created the tables, review, assisted in the design, and final approval of the manuscript. PR, AK, HK, JY, YF, UM, MS, DA, IC, LD, HD, JS, MB, KM, and TB-S assisted in the design, review, and final approval of the manuscript. TB-S assisted in project administration and conceptualization. All authors contributed to the article and approved the submitted version.The Mayo Clinic Hepatobiliary SPORE (P50CA 210964) funded the statistical analysis for this project.Authors YF, LD and HD were employed by company Guardant Health, Inc.The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


There are no published studies on the use of QRISK-3 in people with ID. This project aimed to understand the use of QRISK-3 in an ID clinic and to quantify individual CVD risks to recommend appropriate management options.The prevalence of cardiovascular diseases (CVD) in people with intellectual disability (ID) is around 14%, higher than the general population. However, CVD risk assessments are not consistently performed. Given the high risk of premature deaths in people with ID, it is important to identify preventable risk factors and follow evidence-based interventions. QRISK-3 is a validated risk-stratification tool, which calculates the 10-year risk of developing a heart attack or stroke  defined as schizophrenia, bipolar disorder and other psychotic illnesses. QRISK-3 ≥ 10% was defined as elevated risk in accordance with NICE guidelines. Patients who had a high QRISK-3 score were advised to contact their GP.Of 143 patients, 73 (51.0%) had a mild ID and the remaining had a moderate to severe ID. The mean age was 43.3 years, 53.1% were male. Overall, 28 (19.6%) participants had an elevated CVD risk, of whom 16 (57.1%) were not on statins, which is the recommended treatment. The mean QRISK-3 score was 6.31 (standard deviation [SD] 8.95), and the relative risk is 3.50 (SD 7.13). The proportion of QRISK-3 ≥ 10% and mean score were not significantly different in those with SMI, but those with SMI were more likely to be prescribed statins than those without . Statins were given to 24 (16.8%) participants, of whom 12 (50%) had elevated CVD risk. 89% had a blood pressure recording within the past 5 years, 87% had height and 88% had weight recorded. 73% had lipid serology results recorded.Elevated CVD risk was common in this ID study population, and more than half with elevated QRISK-3 were not on the medical treatment recommended by national guidelines. QRISK-3 could feasibly be implemented in the outpatient setting. Increased routine CVD risk assessment and management should be considered as another measure to reduce morbidity and mortality.


Rapid weight loss (RWL) is commonly practiced in combat sports. Both magnitude and methods used to induce RWL are largely similar among combat sports, but currently, there is no data on RWL methodology used by sambo athletes. Therefore, the aim of this study was to determine RWL procedures sambo athletes apply to lose weight rapidly.The sample consisted of 199 participants, of which 132 males and 67 females who participated in the World Sambo Championship 2020 held in Novi Sad, Serbia. Each participant received RWL questionnaire that was available in multiple languages, and every participant was instructed how to fill it out.Almost 87% of sambo participants declared to have intentionally cut their weight prior to the competition, whereby 5.27 kg (SD: ±7.57) was lost. Gradual dieting, sauna use and skipping meals were the most dominant methods used to reduce weight prior to competition while more extreme methods of RWL such as the use of laxatives, diuretics, diet pills and vomiting were also implemented but by much smaller fragment of the participants involved.Findings from our study largely match with previously conducted RWL studies in terms of prevalence, magnitude and methods used by combat sport athletes, especially in judo and wrestling. Knowing the hazardous consequences of RWL, alternative methods of sustainable weight loss should be considered. Prior to 1940s the Committee of Sports of Union of Soviet Socialist Republics declared sambo to be the official combat sport of the Soviet Union .Elite athletes are always aiming for a peak performance throughout the year. Sambo athletes are no different. Besides maintaining excellent physical shape and technical skills , 4, sambHowever, so far, no data has been obtained on RWL methods in sambo athletes. Therefore, the aim of this study was to identify the methodology and magnitude of RWL used by sambo athletes with a particular emphasis on sex-based differences.To determine methods of RWL used by sambo athletes, we adopted RWL questionnaire developed by Artioli et al. . The queThe sample consisted of 199 participants, of which 132 males (66.3%) and 67 females (33.7%). The mean age of the sample was 21.70 years (SD: ±5.22) for females and 23.16 years (SD: ±6.08) for males. The average height was 1.64 m (SD: ±0.09) for females and 1.75 m (SD: ±0.10) for males, while the average weight was 64.58 kg (SD: ±14.90) for females and 75.22 (SD: ±17.78) for males.Participants from 20 countries took part in the study: Ukraine (20.1%), France (15.6%), Serbia (12.1%), Russia (11.1%), Moldavia (10.6%), Spain (7.5%), Uzbekistan (7.0%), Cameroon (3.0%), Bulgaria (2.5%), Kyrgyzstan (2.0%), Colombia (1.5%), Belarus (1.0%), Belgium (1.0%), Croatia (1.0%), Italy (1.0%), USA (1.0%), Lithuania (0.5%), Mexico (0.5%), South Africa (0.5%) and Tajikistan (0.5%).The study was conducted according to the Helsinki declaration and ethical approval was obtained from ethics committee of University of Novi Sad, Serbia (Ref. No. 46–06-02/2020–1). All sambo athletes gave written informed consent upon agreement to participate. Since 30 participants were minor (younger than 18), written consent was obtained from their national team coach as their legal guardian during the championship.Obtained data were analyzed using SPSS statistical software (ver. 23.0). Descriptive statistics were first calculated on all the variables involved, including height, weight, athletic experience, RWL frequency, RWL methodology, and influence in weight-cutting practices. Gender differences regarding the amount of weight loss and regain were evaluated through t-test, while differences in RWL techniques and influences were calculated through the Wilcoxon Rank Sum test. The significance level was set at α = 0.05.n = 173) of sambo participants declared to have intentionally cut their weight prior to the competition. In addition, athletes reported performing their first RWL at age 15.77 (SD: ±3.54). The sample declared to cut around 5.27 kg (SD: ±7.57) of body weight on average and usually started doing so 11.87 (SD: ±9.51) days before the competition (Table The average sambo experience of the participants was 11.37 years (SD: ±6.44). Most participants declared to have won at least one medal at international level (74.4%). The 86.9% . Females started before males to cut weight prior to competition  and tended to regain less weight than their male counterparts   was gradual dieting (80.5%), followed by sauna (75.9%), skipping meals (70.7%), training with plastic suits (63.8%), not ingesting fluids 62.1%), training in a heated room (60.9%), increased exercise (58.0%), fasting (44.8%) and spitting (44.8%). Less common methods adopted were the use of laxatives (16.1%), diuretics (13.2%), diet pills (10.9%) and vomiting (9.8%) . Physicians and dietitians were not influential for most athletes  Table . WilcoxoThe aim of this study was to determine the methods sambo athletes use to induce RWL. Acquired data shows that gradual dieting, sauna use and skipping meals were the most common methods used to reduce weight prior to competition in both males and females. However, more extreme methods of RWL such as the use of laxatives, diuretics, diet pills and vomiting were not frequently used. The latter is especially worrisome not strictly because diuretics are prohibited by the World Anti-Doping Agency  and are Our study showed that coaches were the most important figure influencing sambo athletes to pursue RWL. Berkovich et al.  found idComing from a perspective that prioritizes athlete’s health and safety, it is important to outline that RWL practice is not without consequences. Existing literature eloquently describes RWL-induced physical and psychological consequences, which can range from acute to chronic , with reThe current study comes with two main limitations: first, it has only an explorative purpose, therefore no causal inference has been done on the collected data. Moreover, questions about RWL could be sensitive to social desirability, thus participants could have been biased in their answers, even though we ensured that the questionnaire was totally anonymous.Nevertheless, the study covers a topic that has never been addressed previously in sambo athletes and it was administered in people from more than 20 nations from all over the world. Since the majority of sambo athletes did not consult physician or dietitian about RWL, the results of the current study pertain primarily to coaches who should upgrade their knowledge about the risks of adopting RWL techniques, whereby athletes’ health will be the utmost priority.Nearly 87% of sambo athletes reported to have intentionally cut their weight prior to the competition, whereby 5.27 kg (SD: ±7.57) was lost. Gradual dieting, sauna use and skipping meals were the most dominant methods used to reduce weight prior to competition. Overall, males tended to lose more weight during RWL and regained more weight after RWL when compared to females. Findings from current study are consistent with results depicted in previously conducted RWL studies in terms of prevalence, magnitude and methods used by combat sport athletes, especially in judo and wrestling. Knowing the hazardous consequences of RWL, alternative methods of sustainable weight loss should be considered.


Clinical effectiveness and safety data of pazopanib in patients with advanced or mRCC in real-world setting from Asia Pacific, North Africa, and Middle East countries are lacking.PARACHUTE is a phase IV, prospective, non-interventional, observational study. Primary endpoint was the proportion of patients remaining progression free at 12 months. Secondary endpoints were ORR, PFS, safety and tolerability, and relative dose intensity (RDI).Overall, 190 patients with a median age of 61 years (range: 22.0–96.0) were included. Most patients were Asian (70%), clear-cell type RCC was the most common (81%), with a favourable (9%), intermediate (47%), poor (10%), and unknown (34%) MSKCC risk score. At the end of the observational period, 78 patients completed the observational period and 112 discontinued the study; 60% of patients had the starting dose at 800 mg. Median RDI was 82%, with 52% of patients receiving < 85%. Of the 145 evaluable patients, 56 (39%) remained progression free at 12 months, and the median PFS was 10 months (95% CI: 8.48–11.83). 19% of patients (21/109) were long-term responders (on pazopanib for ≥18 months). The best response per RECIST 1.1 was CR/PR in 24%, stable disease in 44%, and PD in 31%. Most frequent (> 10%) TEAEs related to pazopanib included diarrhoea (30%), palmar-plantar erythrodysesthesia syndrome (15%), and hypertension (14%).Results of the PARACHUTE study support the use of pazopanib in patients with advanced or mRCC who are naive to VEGF-TKI therapy. The safety profile is consistent with that previously reported by pivotal and real-world evidence studies. Pazopanib is an orally bioavailable adenosine triphosphate–competitive tyrosine kinase inhibitor (TKI) of vascular endothelial growth factor receptors (VEGFR) 1, 2, and 3), platelet-derived growth factor receptors (α and β), and c-Kit ) than among patients aged ≥65 years (6.8 months [95% CI: 4.2–9.9]). The median time to progression was longer for the intermediate categories  than for the poor categories . Median not reached in favourable group and median time to progression in unknown risk categories was comparable with the overall patients  Fig. Among the 127 patients with available RECIST data, the most commonly reported best objective response by EOS was stable disease (56 patients [44.1%]), followed by progressive disease , PR (27 patients [21.3%]), and CR (4 [3.1%] patients). The ORR (CR + PR) for the overall population was 24.4%. The disease control rate  was 68.5%. For patients with measurable disease, the ORR was 25.7% and DCR was 67.3% (Table 1.5%), PRPatients in the < 65 years age group were more likely to achieve CR or PR as best response (27.5%) than patients in the ≥65 years age group (19.1%). Among patients with MSKCC and IMDC risk data available at baseline, the highest proportion of patients who achieved CR or PR as best response was the favourable group  in the IMDC risk group)  patients had received prior treatment for RCC before switching to pazopanib. The most frequent prior treatment was interferon (12 of 15 patients [80.0%]); all other types of prior treatments were received by 1 patient (6.7%) each. Disease progression was the most common reason reported for switching to pazopanib (11 patients [73.3%])  received treatment after discontinuing pazopanib. The most common (≥10.0%) treatments were nivolumab (21 patients [40.4%]), axitinib (13 patients [25.0%]), everolimus (13 patients [25.0%]), and sunitinib (9 patients [17.3%]). Disease progression was the most common reason reported for switching from pazopanib (45 patients [86.5%]) followed by AEs (7 patients [13.5%]) (Table The starting dose of pazopanib was 800 mg (full dose) in 63.2% of patients, 600 mg in 22.1%, and 400 mg in 14.7%. Overall, 5.8% of the patients receiving 400 mg/day and 3.2% receiving 600 mg/day of pazopanib had a dose increase, while 10.5% of patients receiving 800 mg/day and 2.1% receiving 600 mg/day had a dose decrease. From the initial prescription of pazopanib, the overall mean (standard deviation [SD]) exposure to pazopanib was 10.1 (6.79) months.The mean (SD) overall RDI was 79.4% (21.04), which was close to the median RDI of 81.9%. The minimum RDI was 32.5% and maximum was 100%. A total of 120 patients 63.2%) had a reduced RDI (< 100%), of whom 99 (52.1%) had an RDI of < 85%. A higher proportion of patients achieving CR or PR (32.7%) and a lower proportion of patients with PD (23.6%) were seen with a mean RDI of ≥85% vs a mean RDI of < 85% . In patients who attained CR or PR, the overall mean (SD) RDI was 83.1% (19.4). The mean (SD) RDI in patients with an RDI of < 85% was 63.7% (12.8), and in patients with an RDI of ≥85%, the mean (SD) RDI was 98.2% (3.4). Patients with a mean RDI of ≥85% were less likely to experience an AE (76.9%) or a serious AE  than patients who had a mean RDI of < 85%   received pazopanib for ≥18 months and 21 remained progression-free at 18 months, with a proportion of 0.19 .Overall, 167 patients (87.9%) experienced at least one treatment-emergent AE (TEAE) during the study period, of whom 138 (72.6%) experienced at least one TEAE related to pazopanib. The most common (≥ 15%) TEAEs were diarrhoea (31.1%) and hypertension (15.3%). A total of 65 patients (34.2%) experienced at least one SAE, of whom 13 (6.8%) experienced at least 1 SAE related to pazopanib. Of the 65 patients, 38 (20.0%) died owing to an SAE; three patients (1.6%) died owing to a treatment-related SAE. A total of 36 (18.9%) patients discontinued study treatment owing to a TEAE, of whom 11 (10.9%) discontinued owing to a TEAE related to pazopanib. A total of 77 (40.5%) patients required treatment interruptions or dose adjustments due to a TEAE, of whom 64 (33.7%) required treatment interruptions or dose adjustments due to a TEAE related to pazopanib. TEAEs related to pazopanib are summarised in Table n = 1 each).A total of 57 patients (30.0%) died during the study. The most common cause of death was disease progression (31 patients [16.3%]), followed by death from unknown causes (8 patients [4.2%]). Three deaths were suspected to be related to pazopanib, including deaths from cerebrovascular stroke, cytomegaloviral pneumonia, and sepsis  in this study is comparable to the PFS noted in the pivotal study and real-world studies reported so far , 11, 12.Median PFS for patients with unknown risk group is (months) is comparable with the median PFS of overall population. The proportion of patients remaining progression free for 18 months or longer while on pazopanib in this study was similar to that reported in a long-term response study of sunitinib  .At the time of start of the PARACHUTE study, pazopanib was considered as one of the standard-of-care first-line therapies for RCC in most countries . The recA considerable proportion of patients (37%) started pazopanib at a reduced dose, with all patients being Asian. One potential explanation for this high percentage could be that most patients (70%) recruited in the study were Asian. Patients receiving a higher mean RDI showed better chances of achieving objective response, indicating a correlation between RDI and treatment outcomes. In contrast to the notion that higher RDI is associated with higher toxicity, patients in the high RDI group reported a better safety profile with fewer AEs and SAEs. Though the performance status was not recorded in this study, it is possible that the physically fit patients might have received higher doses and reported fewer AEs as compared to the lower dose intensity in less fit patients and resulting higher toxicity. The other less likely reason could be that patients on a full dose had a response that might have improved symptoms related to the disease.With no new or unexpected AEs reported, the safety profile observed in this study is consistent with that seen in the pivotal and real-world evidence studies –17. The This study was subject to some limitations, mainly the observational nature and non-interventional design of the study and lack of a control group or tests of hypothesis. However, the non-interventional nature of the study is best suited to obtain real-world data. The representative number of patients observed and the full safety reporting were assets of this study and minimised its limitations. Limitations such as information and selection bias and limitations of feasibility were expected to be similar to those of other multicentre, prospective non-interventional trials.The PARACHUTE study represents the real-world evaluation of the effectiveness and safety of pazopanib in patients with advanced or metastatic RCC who are naive to VEGFR-TKI therapy in countries across Asia Pacific, North Africa, and Middle East regions. The results support the use of pazopanib in routine clinical practice and confirm the favourable safety profile of pazopanib consistent with the previously reported safety profile in pivotal and real-world evidence-based studies.


A subset of monomicrobial BCs (n = 560) were analyzed in parallel with a Sepsityper® Kit  and compared with the rapid BACpro® II kit. In addition, this kit was also compared with two different in-house methods. Overall, 80.0% of the monomicrobial isolates  were correctly identified by the rapid BACpro® II kit at the species level (92.3% of the Gram negative and 72.4% of the Gram positive bacteria). The comparison with the Sepsityper® Kit showed that the rapid BACpro® II kit generated higher rates of correct species-level identification for all categories (p > 0.0001), except for yeasts identified with score values > 1.7. It also proved superior to the ammonium chloride method (p > 0.0001), but the differential centrifugation method allowed for higher rates of correct identification for Gram negative bacteria (p > 0.1). The percentage of accurate species-level identification of Gram positive bacteria was particularly noteworthy in comparison with other commercial and in-house methods.The identification of microorganisms directly from blood cultures using MALDI-TOF MS has been shown to be the most impacting application of this methodology. In this study, a novel commercial method was evaluated in four clinical microbiology laboratories. Positive blood culture samples ( The rapid identification of microorganisms causing bloodstream infections (BSI) is one of the most impactful applications of Matrix Assisted Laser Desorption/Ionization-Time of Flight Mass Spectrometry (MALDI-TOF MS) in clinical microbiology ,2. This Different pre-processing methods have been developed for the successful identification of microorganisms directly from positive BCs using MALDI-TOF MS. Most of these focus on isolating the microorganisms present in BCs from blood cells and other contaminants by using either a differential centrifugation method  or by em® Kit  is a CE-IVD labeled and FDA approved kit that is widely used, and numerous studies have reported successful direct identification by using this kit [® MS Blood Culture Kit  is another commercial kit and is currently RUO labeled [Commercial kits have been manufactured for the improved lysis of blood cells, and subsequent recovery of the microorganisms present in positive BCs, facilitating the standardization and implementation of this task in the routine of the clinical microbiology laboratory. The Sepsityperthis kit ,15,16,17this kit ,14. The  labeled . High ra labeled . However® II  is a relatively new CE-IVD labeled kit, which utilizes a polyallylamine-polystyrene copolymer for the efficient isolation of microorganisms [® II  was conducted in four clinical microbiology labs. The performance of this commercial kit was compared with the Sepsityper® Kit and with two in-house methods: differential centrifugation and lysis of blood cells with ammonium chloride  was carried out in four research centers: the Microbiology Department from Complejo Hospitalario Universitario A Coruña—CHUAC—, the Department of Microbiology at Oslo University Hospital—OUH—, the Institute of Microbiology from the University Hospital of Lausanne—CHUV— and the Clinical Microbiology and Infectious Diseases Department from the Gregorio Marañón University Hospital—HGM—. In each laboratory, 200 consecutive positive BCs (from 200 (CHUAC), 200 (OUH), 200 (HGM) and 201 (CHUV) patients) were collected between January and June 2019. Aerobic and anaerobic BC bottles  were incubated at 35 °C for up to 5 days in the BACTEC™ FX incubation system (Becton Dickinson). When the bottles flagged positive, Gram staining was performed, and a small amount of broth was cultured on suitable agar media and further incubated at 35 °C overnight. Growth on agar media and the subsequent identification by MALDI-TOF MS was considered as a gold standard. In parallel, the evaluation of the rapid BACpro® II kit was carried out.The evaluation of the rapid BACpro® II kit (Nittobo Ltd.) was compared with that of the Sepsityper® Kit  at three centers  At one center (CHUV), the rapid BACpro® II kit was compared with an in-house processing method [n = 201). In addition, the HGM laboratory also compared the rapid BACpro® II kit with their in-house differential centrifugation method (n = 200) [The performance of the rapid BACprog method  which emg. After the supernatant was thoroughly removed, the pellet was resuspended in 800 μL of deionized water and transferred to another tube containing a mixture of 200 μL of cationic polymer and 200 μL of reaction buffer. The mixture was vortexed and centrifuged at 2000–5000× g for 1 min. The supernatant was then removed again, and the pellet was resuspended in 800 μL of 70% ethanol. After complete resuspension of the pellet by pipetting it up and down, the sample was centrifuged again in the above-mentioned conditions, and the pellet was submitted to a protein extraction step with 30 μL of formic acid 70% and the same amount of acetonitrile. After another centrifugation step, 1–2 μL of supernatant was deposited on the MALDI target plate, allowed to dry and covered with 1 μL of HCCA matrix, which was prepared according to the manufacturer instructions .Bacterial pellets from positive BCs were processed following the manufacturer’s instructions. Briefly, 1 mL of broth was mixed with 500 μL of lysis buffer, and the mixture was centrifuged for 3 min at 2000–5000× Sample preparation of bacterial pellets was performed according to the instructions of the manufacturer . The method consisted of mixing 1ml of BC broth with 200 μL of lysis buffer. The mix was centrifuged for 2 min at 13,000 rpm. The pellet was washed with 1ml of washing buffer and centrifuged for 1 min at 13,000 rpm. The supernatant was removed and the pellet submitted to protein extraction with formic acid and acetonitrile. As explained above, 1–2 μL of supernatant was transferred onto the MALDI target plate and covered with 1 μL of HCCA matrix.g for 10 min at room temperature. The supernatant containing lysed blood-cells was discarded, and the pellet was suspended in 1 mL of ammonium chloride . A second centrifugation step at 140× g for 10 min was applied and the supernatant discarded. The final pellet was suspended in 0.2 mL of deionized water and 1–2 μL was transferred to the MALDI target plate and, once dry, covered with formic acid and, subsequently, with HCCA matrix.Ammonium chloride erythrocyte-lysing procedure was applied as previously described . Five mlg) for 10 min. The supernatant was then collected in four 1.5-mL tubes and centrifuged again at maximal speed  for 1 min. The pellets from the four tubes were collected in one tube and washed with 1 ml deionized water. After another centrifugation step under the same conditions, the supernatant was discarded and the pellet spotted directly onto the MALDI target plate. The spots were allowed to dry at room temperature and then covered with 1 μL of formic acid. Once dried, HCCA matrix was added [From each BC, 8 mL of broth was transferred to a 15 mL tube and centrifuged at low speed  containing 7331 reference spectra. FlexControl 3.3 and Maldi Biotyper 3.0 software  were applied to acquire the spectra and for the identification of the isolates with the standard Biotyper module, respectively. The Bacterial Test Standard  was used for calibration purposes. The identification was performed in duplicates, and the highest score from each pair was recorded.In this study, score values ≥2.0 and ≥1.7 were established as the cut-off value for species- and genus-level identification, respectively. Isolates identified with score values below 1.6 were considered only when the first three identifications provided by MALDI-TOF MS were consistent, either at the species- or the genus level. Otherwise, the identification was considered “not reliable”. Agreement at species- and genus level between the methods tested and the gold standard (identification from isolated colonies) was also analyzed.® II kit using the McNemar test for paired samples with two tails. The validity values were calculated with a 95% confidence interval (CI) following an exact binomial distribution.The sensitivity values for each pre-processing method and 95% confidence intervals were also calculated. They were compared with the sensitivity of the rapid BACpro® II kit. In 761 BCs , only one species was present (n = 13), no growth was recorded after 24 h incubation on agar plates, despite flagging positive in their BACTEC systems. The Gram staining of these BCs were reviewed and considered as inconclusive in 13/13 cases. Therefore, these BCs were considered as false positives and removed from the study.During the study period, 801 consecutive, positive BCs were collected in the four participating laboratories, and microorganisms present in these cultures were identified by MALDI-TOF MS after sample pre-processing using the rapid BACpro present , while i present . In the ® II kit in the four participating laboratories allowed for an overall 80.0%  correct identification rate at the species level  of the pathogens present in the monomicrobial BCs  with the Sepsityper® Kit. A similar number of BCs was identified at the genus level using both kits  compared to 15.2% for the Sepsityper® Kit –85/560; 95% CI 15.1 to 15.3). The rate of unreliable identifications was higher with the Sepsityper® Kit  vs. 15.5%−87/560; 95% CI 15.5 to 15.5)  for the Sepsityper® Kit). Interestingly, differences were observed in the number of unreliable identifications  for the rapid BACpro® II kit compared to 10.8%  for the Sepsityper® Kit). Regarding Gram positives, the rate of species-level identifications yielded by the rapid BACpro® II kit was higher  than the Sepsityper® Kit , and the number of BCs with score values below 1.7 was reduced . The proportion of yeasts identified at the genus level, however, was higher using the Sepsityper® Kit ) than the rapid BACpro® II ) and the number of unreliable isolates was lower  vs. 53.4% ), although species-level identification was achieved more often with the rapid BACpro® II kit ) than the Sepsityper® Kit )  and the genus-level .A subset of 560 monomicrobial BCs were analyzed at CHUAC, HGM and OUH  with botaluation . Overallto 15.5) . Gram ne2–62.8)) . Overall® II kit and in 22/27 cases with the Sepsityper® Kit, with scores between 1.75 and 2.45. In two cases, both pathogens present in the same BC could be identified using the rapid BACpro® II kit (Staphylococcus epidermidis plus Staphylococcus capitis and Klebsiella pneumoniae plus Staphylococcus haemolyticus) and in a different case with the Sepsityper® Kit (Staphylococcus aureus plus Enterococcus faecium). Finally, both kits failed to identify all microorganisms from the same BC in two cases (Capnocytophaga sputigena plus Fusobacterium nucleatum and S. aureus plus Streptococcus mitis), and the Sepsityper® Kit also failed in two more cases where two microorganisms were present  vs. 39.8% (80/201); p < 0.01) (® II kit was higher for both the Gram negatives (96.7% (88/91) vs. 53.8% (49/91)) and Gram positives (83.6% (87/104) vs. 26.9% (28/104)). In the first case, the application of the commercial kit allowed for the identification of 97.4% (75/77) of the microorganisms from the Enterobacteriaceae family and 100% (5/5) of the Pseudomonas, compared to 61.0% (47/77) and 0% (0/5) when the in-house method was applied. In the case of the Gram positives, the ammonium chloride method allowed for 40.0% (8/20) of the species-level identification of S. aureus compared to 100% (20/20) using the rapid BACpro® II kit  of the Gram negatives and 38.5% (40/104) of the Gram positives were identified by MALDI-TOF MS with score values ≤ 1.7, whilst the use of the rapid BACpro® II kit reduced the number of non-reliable identifications to 1.1% (1/91) of the Gram negatives and 2.9% (3/104) of the Gram positives (The performance of the rapid BACproll lysis  in a hea < 0.01) . The rat® II kit . The samositives . Likewis® II kit was also compared with the differential centrifugation method in the HGM laboratory  correct species-level assignment compared to the 61.6% (109/177) obtained by using the in-house kit   vs. 50.0% (2/4)). Conversely, successful species-level identification was obtained for several Gram positives using the rapid BACpro® II kit, especially for S. aureus (91.7% (11/12) vs. 25.0% (3/12)) and Enterococci (91.7% (11/12) vs. 75.0% (9/12)), which added to the global superiority of the commercial kit for the identification of Gram positives at the species level (58.0% (51/88) vs. 44.3% (39/88)), despite its lower rates of correct identifications at this level for Streptococci (36.7% (11/30) vs. 46.7% (14/30)). Finally, the percentage of yeast correctly identified by the rapid BACpro® II kit was also lower (12.5% (1/8) vs. 25.0% (2/8)), but the differential centrifugation method yielded a higher rate of unreliable identified isolates (75.0% −6/8 vs. 62.5% −5/8).The performance of the rapid BACproboratory . Overall CI 95%) . Differe® II kit allowed for the identification of at least one microorganism in 22/23 cases with score values between 1.75 and 2.55, while the differential centrifugation method provided the identification of one microorganism in 20/23 cases, with score values ranging between 1.45 and 2.45. Moreover, the commercial kit allowed for the identification of both pathogens in two cases  and the in-house method in one case .Of the polymicrobial BCs, 23 cases were included in this head-to-head comparison. The rapid BACpro® Kit [® MS Blood Culture Kit [® II kit [® II contains a polyallylamine-polystyrene copolymer for the recovery of microorganisms present in BCs. Bacterial isolates have been shown to adhere to positively charged polymers, forming macroscopic aggregates that can be easily recovered by centrifugation [With the advent of MALDI-TOF MS for the rapid identification of microorganisms, several pre-processing methods have been developed for the direct identification of pathogens present in BCs which encompass different in-house methods ,6,7,11 a® Kit ,15,16 anture Kit , which a® II kit ,23. The fugation .® Kit has been extensively evaluated and successful, accurate identifications at the species level of over 80.0% have been reported [® II has been reported by only a few groups as single center studies [® II kit yielded an overall 87.4% correct species-level identification  using the standard module of the Biotyper system . This rate increased to 94.4% when the specific Sepsityper module for Sepsityper Kit  was applied. Gram positives were accurately identified at the species level in 91.5% of the cases using the Sepsityper module [The Sepsityperreported ,16,17,21 studies ,23. Tsuc studies  analyzed® II kit. We identified 80.0% of the isolates correctly at the species level with score values ≥2.0, and 94.4% correctly at the genus level with score values ≥1.7. The remaining isolates (n = 42) could be reliably identified despite the lower scores. These results agree with those obtained by Tsuchida et al. (2018) and Kayin et al. (2019). The Enterococci (97.3%) and S. aureus (94.7%) were correctly identified with scores ≥2.0 more often than other Gram positives such as Streptococci (66.3%) and coagulase negative Staphylococci (59.5%). Regarding the Gram negatives, 92.3% of the isolates were correctly identified at species level with score values ≥2.0, and 38.1% of the yeasts were unreliably identified even when applying score values <1.7 as the cut-off. Nevertheless, only 42.9% of the 21 yeast samples were accurately identified with score values ≥2.0, and 38.1% of them were unreliably identified even when applying score values <1.7 as the cut-off. While the study by Yonezawa et al. [C. albicans and C. parasilosis, it has been difficult to judge the rapid BACpro® II’s performance on yeast due to the low abundance of clinical samples [® II kit, which was also reported as a challenge for the Sepsityper Kit [In our study, 761 monomicrobial BCs were analyzed in four laboratories using the rapid BACproa et al.  showed h samples ,23. The  samples , likely  samples . With a yper Kit .® II and Sepsityper® Kit in a head-to-head comparison. High rates of Gram negatives were correctly identified by both kits: 90.5% with the rapid BACpro® II kit and 85.8% with Sepsityper® Kit . The rate of correct species assigned was higher than 90% for E. coli, K. pneumoniae and other Enterobacteriaceae using both kits, as previously observed [P. aeruginosa isolates were identified with score values ≥2.0 using the rapid BACpro® II kit compared to 70.0% with the Sepsityper® Kit. Higher differences were observed for Gram positive bacteria: 68.7% with the rapid BACpro® II kit  and 59.7% with the Sepsityper® Kit. Within this group, major differences were observed in the identification of coagulase-negative Staphylococci ) and Enterococci ). Errors in the identification of coagulase negative bacteria present in BC pellets have been reported [A subset of 560 BCs was analyzed with the rapid BACproobserved . However® II kit. The method containing a lysis step with ammonium chloride showed lower accuracy than the rapid BACpro® II kit when applied to the different microbial pellets. Species-level identifications for the rapid BACpro® II and the ammonium chloride method were, respectively, 89.0% and 39.8% for the overall, 96.7% and 53.8% for Gram negatives, 83.6% and 26.9% for Gram positives and 66.7% and 50.0% for the yeast. The rates of identification by the ammonium chloride method in this study were lower than those previously obtained by the same research group  [® II kit (58.0%) than the in-house method (44.3%), but the in-house method gave more correct identification of Gram negatives (83.9%) than the rapid BACpro® II (81.5%).The performance of two in-house pre-processing methods were also compared with the rapid BACpro® II kit and once (3.7%) with the Sepsityper® Kit. These rates are lower than those reported by Scohy et al. (2018), who identified two pathogens in 36.8% of the cases by applying the specific Sepsityper module from the Compass IVD software  [® II kit performance coupled to the Sepsityper module is desired.Among the 27 polymicrobial BCs, we could identify both pathogens twice (7.4%) with the rapid BACproltonics) . The com® II kit proved less efficient for the identification of yeasts, it allowed for a high rate of correct identifications of Gram negative and Gram positive bacteria. The results obtained were consistent in the four laboratories where the kit was tested, showing a reduced number of unreliable identifications and a high rate of Gram positive bacteria reliably identified at the species level. Hands-on time was calculated as 30 to 40 min for 1 to 10 BCs, which enables the implementation of this methodology in the laboratory routine in a standardized way. Moreover, the kit is manufactured independently from the mass spectrometry systems, which provides flexibility to the MALDI-TOF MS user regarding the optimized use of available reagents and represents a good alternative to the limited number of available commercial kits. In addition, we confirmed the robustness of the MALDI-TOF MS approach, since we observed no discordant results, even when applying different pellet preparation methods.In summary, although the evaluated rapid BACpro


Optimum glycemic control is necessary to reduce and even prevent the risk of micro- and macrovascular complications of type 1 diabetes mellitus (T1DM). The main aim of this study was to assess the prevalence of T1DM patients with adequate glycemic control in 4 Arabian Gulf countries.This study was a multicenter, observational, cross-sectional disease registry. Data were collected from adult T1DM patients who were treated with insulin within 6 months prior to the study visit.P < 0.001) and absence of a family history of diabetes (P = 0.002).Out of 241 patients whose data were eligible for primary endpoint analysis, 27.4% had adequate glycemic control (HbA1c < 7%). The patients’ age ranged from 18 to 64 years, and 53% were males. The mean (SD) duration of diabetes was 14.6 (9) years and the mean HbA1c was 8.11 (1.8) %. At the time of T1DM diagnosis, mean HbA1c was 10.7 (2.17) %. About 98% of the patients were normotensive and the lipid profile of patients was found to be optimal. The main variables associated with adequate glycemic control were low HbA1c at diagnosis (We found that the glycemic control of T1DM adult patients in Kuwait, UAE, Oman and Bahrain is suboptimal. More efforts are necessary to pinpoint the causes of inadequate control in this population.The online version contains supplementary material available at 10.1186/s12902-022-00946-3. Type 1 Diabetes Mellitus (T1DM) is a chronic autoimmune disease characterized by immune-mediated destruction of insulin-producing beta cells of the pancreas; its main precipitating factors are genetic susceptibility and environmental insults .In the Middle East and North Africa (MENA) region, nearly 12.8% of the adult population aged 20 to 79 years old (corresponding to nearly 55 million people) were living with diabetes in 2019. According to the International Diabetes Federation (IDF), this prevalence is predicted to increase by a staggering 96.5% to reach 16.7% (or 108 million people) in 2045 . Anders Insulin from an outside source is indispensable for the survival of T1DM patients . As a reThe most recent standards of medical care in diabetes put forward by the American Diabetes Association (ADA) in 2017 recommended an HbA1c goal less than 7% in non-pregnant adults with diabetes . HoweverCompared to the extensive work conducted on Type 2 Diabetes Mellitus (T2DM), T1DM has gained less attention; especially in developing countries . This stAlready-diagnosed T1DM patients of both genders who were 18 years or older  and who were being treated with insulin within 6 months prior to the study visit were eligible for inclusion. All patients signed an informed consent form prior to any study procedures. Patients with any other type of diabetes , pregnant and breast-feeding women, or patients who were concurrently participating in other clinical trials were excluded.This was a multicenter, cross-sectional, non-interventional disease registry. Thirteen centers  participated in the study. In the UAE, the centers were Rashid hospital, Aster Jubilee clinic, American Hospital, and Emirates Hospital. In Kuwait, the centers were Tiba Hospital, Dasman Diabetes Institute, Mubarak Al Kabeer Hospital, and Al-Naeem primary healthcare center. The centers in Bahrain were Salmaniya Medical Complex (SMC), Royal Bahrain Hospital, and Ahmed Ali Kanoo Public Health center. The centers in Oman were Sultan Qaboos University Hospital (SQUH), and Bakra primary healthcare center. All participating centers managed T1DM patients through endocrinologists and primary care physicians. Centers were selected for the study through convenience sampling. Due to the observational nature of this study, no assessments were mandated; data were only collected following routine clinical practice, and data requested for this study were determined based on medical practice in the participating countries. Data about socio-demographics and medical history  were collected. Data on prior and current insulin regimens, concomitant medications, and glycemic control were also recorded. Final database extraction was done on the 21st of February 2019. History and type of hypoglycemic events and access to patient’s education, − as per the physicians’ opinion- were collected. Physical examination was performed for all patients and vital signs were recorded.The primary objective of this study was assessing the prevalence of adequate glycemic control (HbA1c < 7%) in adult patients with T1DM in Arabian Gulf countries , Bahrain and Oman). The secondary objectives were describing the clinical profile of these patients, their insulin regimens and diabetes medications, complications and comorbidities related to T1DM, and frequency and types of hypoglycemic episodes in the 2 months prior to the study. In addition, we aimed to identify the nature of insurance coverage and to observe the patients’ access to educational programs on diabetes.The number of patients included must allow estimation with a sufficient precision to assess the prevalence of glycemic control in these patients. Referring to previous studies performed in the gulf region, controlled glycemic level was achieved in 9.5% of patients diagnosed with T1DM. The minimal size was calculated using the following simple formula based on the estimation of an observed percentage of 10% with two-sided 95% Confidence Intervals (CIs):Where N = sample size, Z = Z statistic for a level of confidence (1.96 for a given 95% CI), P = expected proportion, and D = precision.According to the given formula, at least 216 T1DM patients were required to estimate an observed percentage of 10% with an absolute precision of 4% and a 95% CI. Assuming that 15% of participating subjects would not be evaluable for the primary analysis due to missing values or unfulfilled inclusion/exclusion criteria; a minimum of 254 patients should be enrolled. Moreover with 254 patients, we were able to estimate with a precision rate ≤ 10% all other proportions allowing to describe the profile of patients living with T1D in Gulf countries.All data summaries were based on a single analysis set that included all eligible patients enrolled in the study. In general, data were summarized using frequency and percentages for categorical variables with their 95% CI. Mean, median, standard deviation (SD), range, and 95% CI were used for continuous variables. All statistical tests were performed using two-tailed tests at a 5% level of significance. For any comparative analyses, Chi-square was used for all categorical variables, while T-test/ ANOVA test was used for continuous variables. Missing data or unknown responses were not counted in the percentages.A total of 264 patients with T1DM were enrolled in this study; three patients were excluded and 261 were eligible for descriptive analysis. Of these, 20 patients lacked data on HbA1c values, resulting in a total of 241 patients being eligible for primary analysis. Figure The mean age (SD) of enrolled patients was 31.6 (9.4) years. The highest proportion of patients were from Kuwait (37.9%) and the least were from Oman (6.9%). The proportion of males was slightly higher than females (52.9% vs 47.1%). The highest level of attained education was graduate/post-graduate education at ~ 67%. The majority of patients (~ 96%) lived in urban areas and nearly 58% were full-time employed. Health insurance was provided to ~ 76% of the study population. Of these, nearly 57% had public health insurance. In addition, the most commonly prescribed concomitant medications were lipid-lowering drugs; all of which were statins. Detailed information on the characteristics of enrolled patients is in Table We found that 27.4% (66 out of 241 patients) had adequate glycemic control. They were mainly from the UAE (44%), followed by Kuwait (30%), Bahrain (18%), and lastly Oman (8%).During the 2 months preceding our study, five patients (1.9%) had severe hypoglycemia; two of which required hospitalization  followed by ketonuria (39%); while the least common were C-peptide test (1.2%) and glucose urine test (0.4%).At diagnosis, most patients (nearly 98%) had normal blood pressure. The same proportion were not being prescribed any concomitant medications. The mean lipid profile was optimal. Mean HbA1C (SD) at diagnosis was high; 10.7 (2.17) %.Detailed data on the clinical picture of T1DM at diagnosis are presented in Table At the study visit, the majority (92 to 93%) were on basal-bolus insulin, while only 4.9% were on premix insulin. Basal insulin was mostly long-acting insulin analog , while prandial insulin was mostly rapid-acting insulin analog . In terms of off-label prescriptions for T1DM, metformin was the most commonly prescribed  compared to other antihyperglycemic medications. Further data on therapies received for T1DM at the study visit are in Table Out of 241 patients, 130 patients (54%) previously participated in a diabetes educational program. These were largely conducted in hospital-based diabetes centers (87.7%) and were mainly delivered by certified diabetes educators (77.7%) and dieticians/nutritionists (71.5%). The main focus of these programs was on the correct use of medications (90%), on increasing awareness of the benefit of diet and exercise (85.4%), increasing skills on self-management (83.8%), increasing knowledge on the nature of diabetes (79.2%), and on the recognition and management of hypoglycemia (71.5%).Out of 241 patients, 110 (45.6%) had comorbidities. The most commonly reported were hyperlipidemia (51.9%), hypertension (28.5%), hypothyroidism (15.5%), and obesity (13.6%). Diabetes complications were mainly diabetic retinopathy and neuropathy (each in 18.2% of patients), in addition to diabetic nephropathy (16.3%).To find out the factors that could potentially be associated with better glycemic control, we analyzed several characteristics among patients with adequate glycemic control (HbA1c < 7%) and inadequate glycemic control (HbA1c ≥ 7%).P = 0.046], had significantly lower body mass index (BMI) , significantly higher rate of probable symptomatic hypoglycemia in the 2 months prior to the study , and significantly lower HbA1c at the time of T1DM diagnosis ; compared to patients with inadequate glycemic control. Table Patients with adequate glycemic control were significantly older , similar systolic [124.5 (17.3) vs 121.2 (14.4) mmHg] and diastolic blood pressure [73.3 (10.2) vs 73.8 (9.4) mmHg], higher total serum cholesterol [199.6 (36.5) vs 126.8 (34.8) mg/dL] and higher level of triglycerides [101.3 (100.6) vs 97.4 (36.3)] , had lower BMI [22.4 (3.1) vs 26.2 (5.0) Kg/m (36.3)] .Surprisingly, some patients in our study received other diabetes drugs  besides their insulin regimen. Although none of these medications is approved for use in T1DM, these were all prescribed “off-label”. The notion of adjunctive therapy in T1DM has been circulating in clinical practice for quite some time. Adjunctive therapies are usually used to reduce insulin dose requirements, contribute to more HbA1c reduction, and cause weight loss ; we specGiven that about 2.2% of our patients were neither on prandial nor premix insulin, it is worth mentioning that a small percentage of patients enrolled in this study could have been affected by latent autoimmune diabetes in adults (LADA). It is possible that they may have been registered as T1DM because they were positive for glutamic acid decarboxylase antibodies (GADA), but – due to their preserved beta cell function – did not necessarily require treatment with multiple daily insulin injections . AccordiAccording to the recent position statement by the ADA, nearly 30% of T1DM in children and adolescents presents as diabetic ketoacidosis (DKA). However, DKA was employed in the diagnosis of only 8.7% of our study population. In our study, the most commonly used method for confirming diagnosis of T1DM was the random blood sugar test. The position statement also pointed out that the female to male ratio in children and adolescents with T1DM is usually 1:1; much similar to ours (it should be noted that our study did not include children but included adolescents and adults) .Although several studies found a higher prevalence of dyslipidemia in children and adolescents with T1DM compared to controls , 27, theBased on multivariate regression analysis, the main variables associated with adequate glycemic control in our study were low HbA1c at the time of diagnosis and absence of a family history of diabetes. A recent retrospective Jordanian study found that younger age, dietary compliance, receiving insulin at school, high grades in school, and the presence of direct mother care; were all associated with better metabolic control in T1DM Jordanian children .Given that 96.2% of our study population resided in urban settings and 59.4% were employed, our results should not necessarily represent people with T1DM who are unemployed or those who live in rural areas. Given also that people who live in rural areas often face difficulties in accessing optimal healthcare and in adhering to the standard of diabetes care , 22, it We believe that there are some obstacles opposing the uptake of educational programs (i.e. leading to poor attendance) in the region. Further studies are needed to determine whether these obstacles stem from clinicians not referring their patients to the programs or from patients not complying. Findings of such studies would be crucial to improve attendance in our hospitals.The main strength of our study lies in the amount of data collected from T1DM patients in the participating centers. However, a few limitations exist. The exact names of insulin analogs and the duration and nature of diabetes educational programs were not recorded. In addition, the degree of adherence to insulin regimens and the QoL of patients were not assessed.The current study showed that the glycemic control of T1DM patients in Kuwait, Oman, UAE and Bahrain is still sub-optimal. Further studies are warranted to identify possible causes.Additional file 1: Supplementary Table 1. Multivariate Logistic regression analysis for predictors of adequate glycemic control (HbA1c of < 7%) in T1DM.


Preoperative and postoperative PSQI scores correlated with SF-36, SST, ASES and Constant scores at each follow-up. Preoperative and one-month postoperative OSS correlated with the PSQI score. Using the Friedman test, we found an overall improvement in all score analyses (p < 0.001). The results prove that after rotator cuff repair, sleep disturbances improve three to six months after surgery improving the quality of life of these patients.Sleep disturbances are very common in patients with rotator cuff injury. Improvement of sleep quality in these patients can be considered a significant factor for healing in conjunction with surgery. The primary objective of this prospective study was to evaluate changes in sleep quality after surgery in patients with rotator cuff repair by analyzing the PSQI  score. The secondary aim was to evaluate the improvement in quality of life in terms of functional limitations and shoulder pain after surgery. Fifty-eight patients with rotator cuff tears treated by arthroscopic surgery were included. All the patients completed the PSQI, the 36-Item Short Form Survey (SF-36), the Simple Shoulder Test (SST), the American Shoulder and Elbow Surgeons Shoulder Score (ASES), the Oxford Shoulder Score (OSS) and the Constant-Murley Score (Constant) before and at one, three and six months after surgery. Overall improvement in all the scores analyzed ( Rotator cuff injury is the cause of approximately 70% of all outpatient visits for shoulder pain. Rotator cuff tear is found in 20% to 54% of people between the ages of 60 and 80 . This inSleep disturbances are among the most frequent health disorders with a prevalence of 15% to 20% in the general adult population . In rotaTherefore, the improvement of sleep quality in patients with rotator cuff tear can be considered a significant factor for healing in conjunction with surgery ,6. DespiThe primary objective of this paper was to evaluate changes in sleep quality after surgery in patients with rotator cuff arthroscopic repair by analysing the PSQI  score. The secondary aim was to evaluate improvement in the quality of life in terms of functional limitations and shoulder pain after surgery.This article was written in accordance with the STROBE  guidelines to improve the quality of reporting of this observational study. Shoulder surgeries were performed in 104 patients of the Department of Orthopedic and Traumatological Surgery of our University Hospital. This prospective study included patients with rotator cuff tear undergoing rotator cuff arthroscopic repair (RCR). The tears were assessed by preoperative magnetic resonance imaging (MRI) and clinical examination by two orthopedic surgeons specializing in shoulder arthroscopy. Only patients with Goutallier grade 2  and PattThe PSQI is a 19-question survey used to measure through self-assessment the quality of sleep in patients . It is uThe study participants completed the PSQI , the 36-p-values of < 0.05 were considered statistically significant.All the data were analyzed using IBM SPSS Statistics for Windows, Version 26.0. . To assess data normality, the Shapiro–Wilk test was used. Since the data did not respect the normality distribution, baseline and postoperative follow-up scores were compared using the Friedman test and the Wilcoxon signed-rank test. The numerical data were expressed with the means and standard deviations. Correlation analysis using the Spearman’s rho coefficient was performed between the PSQI score and SF-36, SST, ASES, OSS and Constant scores at each follow-up. Two-tailed An a priori power analysis was conducted using G*Power 3.1. With an alpha level of 0.05, minimum power established at 0.80 and a medium effect size of 0.491 , 35 partThis study included a total of 58 patients  with an average age of 63.4 ± 13 years (ranging between 18 and 87 years).p < 0.001), SF-36 (p < 0.001), SST (p < 0.001), ASES (p < 0.001), OSS (p < 0.001) and Constant scores (p < 0.001) in the patients who underwent arthroscopic repair  (The mean PSQI score decreased from 7.19 ± 3.91 before surgery to 3.81 ± 3.32 at six months after surgery (< 0.001) .p < 0.001) (The mean SF-36 score increased from 58.15 ± 17.35 before surgery to 78.75 ± 14.9 at six months after surgery (< 0.001) .p < 0.001) (The mean SST score increased from 3.41 ± 2.73 before surgery to 8.62 ± 2.65 at six months after surgery (< 0.001) .p < 0.001) (The mean ASES increased from 43.94 ± 20.4 before surgery to 84.95 ± 13.27 at six months after surgery (< 0.001) .p < 0.001) (The mean OSS increased from 36.09 ± 10.96 before surgery to 53.60 ± 5.79 at six months after surgery (< 0.001) .p < 0.001) (The mean Constant score increased from 41.6 ± 15.58 before surgery to 64.59 ± 9.85 at six months after surgery (< 0.001) .p = 0.098 and p = 0.533, respectively)  .Preoperative and postoperative PSQI scores correlated with SF-36, SST, ASES and Constant scores at each follow-up timepoint, while they correlated with the OSS only at one-month postoperatively . At eachThe present study assessed different dimensions of sleep quality using a validated and reliable assessment tool, the PSQI, in a sample of 58 consecutive patients undergoing rotator cuff tear repair surgery. The results showed that sleep quality and quality of life increased with surgery, while functional limitations and the pain decreased. In the preoperative period, poor sleep quality was reported in all the patients included with the mean PSQI value of 7.19. In general, the PSQI progressively improved across the various follow-up timepoints, reaching the best value at the last follow-up timepoint.Horneff et al.  reportedAustin et al.  analysedMaestroni et al.  reportedOther studies state how common nocturnal shoulder pain is present in patients with a rotator cuff tear. In particular, Khazzam et al.  describeWerner et al.  investigGumina et al.  differenThe second aim of this study was to assess the quality of life improvement after surgery. Patients reported an improvement in functionality, pain and performance in daily living activities starting from three months after surgery. The improvements remained stable during six months of follow-up.A limitation of this study is lack of a control group treated conservatively and the lack of follow-up longer than six months. Patients included in this study reported only Goutallier grade 2 and Patte stage 2 lesions. The results of this study were related to these types of lesions; therefore, it was not possible to define precise results in other types of RCTs. The severity of the patient’s condition affects the outcome; therefore, further randomized controlled studies including other types of lesions are required to confirm our results. The strength of this study is due to the poor evidence in the literature on the correlation between sleep quality improvement and surgery. This study aimed to reinforce the scientific evidence regarding the hypothesis that sleep disturbances were common in patients with rotator cuff tears and sleep quality improved after surgical repair.The results of this study support the hypothesis that after rotator cuff repair, sleep disturbances improve three to six months after surgery improving the quality of life of this patient population. Future randomized controlled trials with longer follow-up aimed to assess sleep quality in the rotator cuff tear population treated conservatively and surgically are required.


Background: The purpose of this study was to investigate the prevalence of depressive symptom and the factors associated with this condition among urban, semi-urban and rural adolescents in the Dhaka district of Bangladesh.Methods: A cross sectional study using two stage cluster sampling procedure was performed. A self-administered questionnaire was conveyed to 2,355 adolescents from nine secondary schools of Dhaka district of Bangladesh. Of the respondents, 2,313 completed the nine item Patient Health Questionnaire (PHQ-9). Besides, sociodemographic information, self-reported body image as well as modification of Leisure Time Exercise Questionnaire (LTEQ) and WHO Global PA Questionnaire (GPAQ) were used to determine the sociodemographic and lifestyle factors associated with depressive symptom among adolescents.Results: A total of 30.1% adolescents were found to be suffering from moderate to severely severe depressive symptom. Females (60.8%) were found suffering significantly more than males (39.2%). Sociodemographic factors, for example, residential setting and family size were found significantly associated with depressive symptom among adolescents. Adjusted estimate of logistic regression shows that physical inactivity , >2 h/day screen time , sleep dissatisfaction , and underweight body image perception  were significantly associated with depressive symptom among adolescents.Conclusions: Among urban, semi-urban and rural school adolescents in Dhaka, Bangladesh, depressive symptom is quite prevalent. To lessen the spread of depressive symptom among Bangladeshi adolescents, urgent steps should therefore be taken. Adolescence is a period of life preceded by childhood and followed by adulthood and is usually considered to be between the ages of 10 and 19. During this time an individual undergoes major physical, mental, and behavioral changes . In addiWith more than 264 million people affected, depressive disorder is a widespread public health concern worldwide . In spitDepressive disorder is a significant adolescent psychiatric illness that can also affect an adolescent's social functioning, family relationships and academic performance . These iAbout thirty six million adolescents live in Bangladesh, making up 22% of the population . HoweverThis cross-sectional study was conducted between January 2019, and February 2020 in three different areas—urban, semi-urban, and rural . In thisInitially all the secondary schools of the urban, semi-urban and rural areas were listed and it was found that the number of secondary schools in Dhanmondi, Savar and Dhamrai were 16, 14, and 16 respectively. Three schools were purposefully chosen from each region, taking into account the diverse socio-economic context of the participants and their accessibility to the research team. The study population in this study consisted of adolescents of grades 8–10 (12–17 y), since grades 6–10 are considered secondary education at schools in Bangladesh. Following a two-stage cluster sampling technique with a 10% non-response rate, a sample of 2,355 was calculated for this study. Two stage cluster sampling technique was used in this study since the study population were from diverse clusters of different socioeconomic backgrounds, and collecting data from all units inside the clusters was not only expensive but also time-consuming. Prior to field data collection, the research team collected a student list of all the enrolled students of grades 8, 9, and 10 from the respective school authorities. After that, with the approval of the headmasters/principals of the schools as well as the teachers of respective classes, the research team went to classrooms and explained the rationale and aim of the study to the students. Students were also told that they would need to seek permission from their parents for taking part in the study. With informed consent of their own as well as of their parents, 2,313 students completed the survey questionnaire (98% response rate) in the classroom under the direction of the lead researcher. A teacher and a member of the study team were both present in the classroom to track the progress of the survey and to answer any questions or to resolve any complaints of the participants. Students who did not consent to take part in the study engaged in activities of their choice during that time. The respondents of this study can be considered representative of the whole adolescent population in the urban, semi-urban and rural areas in Bangladesh, since the urban, semi-urban and rural settings of the country share the same demographic and socio-economic conditions.To measure the level of depressive symptom of the participants, this study used a validated Bangla version of the nine-item Patient Health Questionnaire (PHQ-9) corresponding to the diagnostic criteria of symptoms for major depressive disorders as stated in the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition . The PHQThe participants were asked how often they experienced each of the depressive symptom, with four response options: 0 = not at all, 1 = several days, 2 = more than half the days and 3 = nearly every day over the last 14 days. The response options were also treated as a continuous ordinal measure. Hence, the range of scores for the PHQ-9 was 0–27. The cut-off points for the categorization of depressive symptom were as follows: 0–4 = normal, where no depressive symptom appeared, hence no depression treatment was required; 5–9 = mild depressive symptom, where psychological support and educational counseling were required; 10–14 = moderate depressive symptom, where clinical judgement about treatment was needed based on the subject's duration of symptom; 15–19 = moderately severe depressive symptom, where a combination of treatment with drugs and therapy was needed; and ≥20 = severely severe depressive symptom, where urgent specialized treatment with drugs and therapy was required.During data collection and analysis, the respondents who were found to be suffering from moderate to severely severe depressive symptom, were contacted through school authority by the research team for taking treatment from registered psychiatrists/ psychologists/ psychotherapists.Data on sex, age, grade in school, birth order, parent's educational level, number of family members and residential setting were collected from the adolescents.Physical activity (PA), screen based sedentary behavior (SBSB) and sleeping status were considered for determining lifestyle factors of the adolescents. Three different PA levels were incorporated in the questionnaire: low-level PA , moderate PA  and vigorous PA  . Regardi2 test were used. Logistic regression models were used to detect any association of study variables with the outcome variables. In regression analysis, data were adjusted for various factors and were reported for the adjusted odds ratios (AORs) with 95% CIs. The level of significance was set at p < 0.05. χ2 test and logistic regression have been conducted considering depressive symptom as the dependant variable, while socio-demographic variables  and lifestyle variables  were considered as independent variables. The Statistical Package for the Social Sciences software for Windows, version 22.0  was used to analyse all data.Data were analyzed using descriptive statistics as well as inferential statistics. To identify any significant relationships between the study variables, test statistics such as the χThe prevalence and severity of depressive symptom among the participants are shown in 2 = 33.72; p < 0.001). This study found a significant  relationship between respondents' age and depressive symptom. The 15-year-old students (34.1%) were suffering from depressive symptom more than any other age groups, and they were followed by the age groups of 14 years (27.3%), 16 years (19.1%), and 13 years (13.2%). School adolescents of class 9 were found to have more depressive symptom (45.4%) than those of other classes, with 29.3% of the class 8 respondents and 25.3% of class 10 respondents having depressive symptom. Again, student's grade was found to be statistically significant  with depressive symptom. Of the students who reported to have depressive symptom, their father's level of educational qualification was reported to be graduation or above by 57.7%, secondary or higher secondary by 30.3% and primary by 12%. Again, of the students who were found to have depressive symptom, their mother's level of education was reported to be secondary and higher secondary by 46.4%, graduation or above by 37.7% and primary education by 16.0%. Analysis shows that students' family size was significantly  associated with depressive symptom. The students who had ≤4 family members were suffering more from depressive symptom (58.8%) than students having ≥5 family members (41.2%). In terms of residential area, among the total students who were found to have depressive symptom, 43.7% were from urban, 34.9% from semi-urban and 21.4% from rural areas, and this result is statistically significant .2 = 25.84; p < 0.001) relationship was found between involvement in PA and depressive symptom. Besides, 36.3% of the respondents who were not involved in regular PA had depressive symptom, while 26.2% who were involved in regular PA were also found to have depressive symptom, and there is a significant  relationship between this variable and depressive symptom. Again, 34% of the respondents who did PA <30 min per day were found to have depressive symptom; in contrast, 23.1% of the respondents who did PA 30–60 min per day as well as 24.2% of the respondents who did PA more than 60 min per day also reported to be suffering from depressive symptom. The relationship between duration of the daily PA and depressive symptom was found to be statistically significant . Furthermore, 44.9% of the respondents who reported doing PA in the evening had depressive symptom. On the other hand, 26.2% doing PA early in the morning and 22.5% doing PA in the late afternoon had depressive symptom. PA time was found to have a statistically significant  association with depressive symptom.2 = 17.76; p < 0.001) relationship with depressive symptom. Similarly, in this study, 37.5% of the respondents with a reported daily screen time of >2 h per day as well as 24.5% with a daily screen time of ≤2 h per day were found to have depressive symptom. The duration of daily SBSB had a significant  statistical relationship with depressive symptom. In addition, 48.4% respondents who had dissatisfaction about their daily sleep reported having depressive symptom, while 20.7% respondents who were satisfied with their daily sleep also reported suffering from depressive symptom, and there was a statistically significant  link between sleep satisfaction and depressive symptom. Besides, sleep duration was also found to be statistically significant  with depressive symptom. Of the respondents who reported a long sleep duration (>9 h/day), 38.5% reported suffering from depressive symptom. Again, 34.2% of the respondents with a short sleep duration (<7 h/day) and 26.2% with an ideal sleep duration (7–9 h/day) also reported suffering from depressive symptom.Regarding the SBSB, 33.3% of the respondents who stated using social media  were found having depressive symptom, while 25.0% of them who were not using any type of social media also reported to be suffering from depressive symptom. Using social media had a significant statistical  more likely to be suffering from depressive symptom than male. Besides, in adjusted estimates-1 and adjusted estimates-2, it was found that female students had 1.9 (95% CI: 1.57–2.29) times and 1.67 (95% CI: 1.34–2.04) times higher risks of suffering from depressive symptom than males, respectively. Students of class 10 had 1.63 times (95% CI: 1.28–2.07) higher risks of suffering from depressive symptom than class 8 students in the unadjusted estimates. In adjusted estimates 1 and 2, compared to class 8 students, class 10 students were, respectively, at 1.26 times (95% CI: 0.91–1.75) and 1.44 times (95% CI: 1.16–1.80) higher risks of suffering from depressive symptom. Statistically significant higher odds ratio  for depressive symptom was found among students of class 9 than among class 8 students in the unadjusted estimate. In adjusted estimates 1 and 2, it was found that class 9 students were, respectively, 1.35 times (95% CI: 1.06–1.73) and 1.40 times (95% CI: 1.08–1.82) more likely to be suffering from depressive symptom than class 8 students. In reference to respondents aged <15 years, respondents aged ≥15 years had 1.39 times (95% CI: 1.09–1.78) more risks of suffering from depressive symptom in adjusted estimate-1 and 1.35 times (95% CI: 1.11–1.64) more risks in adjusted estimate-2. Besides, respondents of this age group were found to be 1.57 times (95% CI: 1.31–1.88) more likely to be suffering from depressive symptom than others in the unadjusted estimate. With regard to residence, the unadjusted estimate shows that urban students were 2.29 times (95% CI: 1.82–2.88) more likely to be suffering from depressive symptom than rural students, while semi-urban students were 1.93 times (95% CI: 1.52–2.44) more likely to be suffering from depressive symptom than their rural counterparts. In adjusted estimate-1, urban students had 2.45 times (95% CI: 1.94–3.10) greater risks of suffering from depressive symptom than rural students, while for semi-urban students the risk was 1.88 times (95% CI: 1.47–2.40) higher than those for rural ones. Urban students and semi-urban students were, respectively, 1.42 times (95% CI: 1.10–1.83) and 1.39 times (95% CI: 1.08–1.79) more likely to be suffering from depressive symptom than rural students, as indicated in adjusted estimate 2.In case of lifestyle variables, the unadjusted estimate shows that students who were not involved in PA were 1.60 times (95% CI: 1.33–1.92) more likely to be suffering from depressive symptom than those who were involved in PA, and same is the case with the variable—irregularity in PA. In adjusted estimate-1, it was found that the risk of depressive symptom was 1.52 times (95% CI: 1.25–1.84) higher in those not involved in PA than those involved in PA, and 1.53 times (95% CI: 1.26–1.85) higher in those irregular in PA than those who reported doing PA regularly. Again, adjusted estimate-2 shows that the students not involved in PA had 1.44 times (95% CI: 1.14–1.84) greater risks of depressive symptom than those involved in PA, and students who were irregular in PA had 1.43 times (95% CI: 1.12–1.82) greater risks of depressive symptom than those regular in PA. Students who were inactive or involved in low PA were 1.67 times (95% CI: 1.38–2.03) more likely to be suffering from depressive symptom than those involved in moderate to vigorous PA in the unadjusted estimate. In adjusted estimates 1 and 2, the students with inactivity or low PA were 1.44 times (95% CI: 1.17–1.77) and 1.60 times (95% CI: 1.30–1.96) more likely to have depressive symptom than those with moderate to vigorous PA. In addition, the risk of depressive symptom was 1.50 times (95% CI: 1.24–1.80) higher in students using social media than those not using any social media. Again, in the adjusted estimates, those who used social media were, respectively, 1.50 times (95% CI: 1.23–1.83) and 1.16 times (95% CI: 0.91–1.46) more likely to be suffering from depressive symptom than those who reported no use of social media. In the unadjusted estimate, a significantly higher odds ratio  was found for depressive symptom among students with a daily screen time of >2 h than those with a lower screen time. Adjusted estimate-1 shows that students with a screen time of >2 h were 1.74 times (95% CI: 1.44–2.11) more likely to suffer from depressive symptom than those with a lower screen time, while in adjusted estimate-2, they were 1.68 times (95% CI: 1.39–2.03) more likely to be suffering from depressive symptom than those with a lower screen time.In the unadjusted estimates, students with dissatisfaction about sleep were 3.60 times (95% CI: 2.98–4.33) more likely to suffer from depressive symptom than those who were satisfied with their daily sleep. Adjusted estimates show that daily sleep dissatisfaction was, respectively, 3.14 times (95% CI: 2.58–3.82) and 3.23 times (95% CI: 2.64–3.96) more likely to cause depressive symptom among students, compared to those satisfied with daily sleep. In reference to ideal sleep duration (7–9 h/day), students who reported short (<7 h/day) and long (>9 h/day) sleep duration had 1.47 times (95% CI: 1.22–1.77) and 1.76 times (95% CI: 1.23–1.53) higher risks of depressive symptom, respectively, in the unadjusted estimate. In adjusted estimate-1, students with a short sleep duration had 1.30 times (95% CI: 1.07–1.58) and students with a long sleep duration had 1.77 times (95% CI: 1.22–2.57) greater risks of depressive symptom than those with an ideal sleep duration. Besides, adjusted estimate-2 shows that students who reported long sleep duration had 1.47 times (95% CI: 0.99–2.17) greater risks of depressive symptom than those who reported an ideal sleep duration.The unadjusted estimate shows that the students who reported body image dissatisfaction were 2.64 times (95% CI: 2.18–3.18) more likely to suffer from depressive symptom than those satisfied with their body image. However, adjusted estimate-1 shows that body image dissatisfaction was responsible for 2.40 times (95% CI: 1.98–2.92) higher risks of developing depressive symptom in students. In adjusted estimate 2, it was found that body image dissatisfaction was highly correlated with perceived weight category, and for this it was removed from there. Furthermore, in the unadjusted estimate, overweight/obese and underweight students were 2.52 times (95% CI: 2.02–3.13) and 2.86 times (95% CI: 2.14–3.82) more likely to be suffering from depressive symptom, respectively, than the students with normal body weight. Besides, adjusted estimate-1 shows that underweight and overweight/obese students were 2.78 times (95% CI: 2.05–3.74) and 2.19 times (95% CI: 1.75–2.75) more likely to suffer from depressive symptom, respectively, than those with normal body weight, where as adjusted estimate-2 shows that overweight/obese and underweight students had 2.14 times (95% CI: 1.70–2.70) and 2.30 times (95% CI: 1.70–3.13) greater risks of depressive symptom, respectively, than those with normal body weight.This study indicates that the prevalence of moderate to severe depressive symptom among urban, semi-urban and rural school adolescents of the Dhaka district in Bangladesh is 30.1%. This prevalence is lower than that (36.6%) reported in the pilot study conducted upon the same population in urban and semi-urban areas in 2018 . Again, Different factors played a role in the high prevalence of adolescent depression in these studies. For example, in the Iranian study various academic factors  along with residential setting were responsible for the high prevalence . In the In this study, numerous socio-demographic as well as lifestyle variables are found to be responsible for the high prevalence of depressive symptom among school adolescents of Dhaka district, Bangladesh. The findings of this study demonstrated that 60.8% of the female participants were found to have depressive symptom, and as the regression analysis showed, female adolescents were 1.70 times more likely to be suffering from depressive symptom than their male counterparts. This finding is consistent with the findings of the pilot study where 42.9% female adolescents reported depression with the OR of 2.18 . BesidesThe current study revealed that 33.3% of students who reported to use social media  were found to be suffering from depressive symptom, and the regression analysis showed that social media use was significantly (OR: 1.50) associated with depressive symptom. This social media use leads to increase in daily SBSB of adolescents. This study found that adolescents with SBSB of >2 h per day had 1.85 times higher risks of suffering from depressive symptom. Social media use also affects the sleep habit of adolescents. In this study, those who were dissatisfied with their daily sleep were 3.60 times more likely to suffer from depressive symptom than those satisfied with their daily sleep. Vidal et al.  in theirNotwithstanding the gravity of this public health issue, very few studies have been conducted upon adolescent mental health in Bangladesh. These studies were conducted either in urban or rural settings, not in urban, semi-urban and rural area simultaneously. To the best of our knowledge, this is the first study to explore depressive symptom among urban, semi-urban and rural adolescents of Bangladesh. Spanning over a period of 1 year, this study followed a pilot study conducted upon urban and semi-urban adolescents of the study area . TherefoThis study has its limitations as well. This cross sectional study collected data at one point of time and the participants represent a small segment of the adolescents of the Dhaka district, which is why the findings of this study cannot be generalized for other districts of the country and instead should be used with caution. Besides, the participants' self-reported information involves the risk of recall bias. Therefore, large-scale longitudinal studies need to be conducted on the same cohort covering the entire Dhaka district to advance generalizable findings that would feed into policy formulation initiatives in Bangladesh.The findings of this study revealed that a substantial number of Bangladeshi adolescents are experiencing depressive symptom and different socio-demographic  and lifestyle-related factors  play active roles as contributing factors behind this phenomenon. With a severe dearth in evidence, these findings are crucial to stress the importance of conducting longitudinal research to explore issues related to adolescents' mental health and well-being in the country. These findings might help to design low intensity psychosocial interventions for this particular subgroup of the population. Moreover, these findings might be utilized in formulating appropriate adolescent friendly policies for the betterment of the mental health condition of the future generations of Bangladesh.The original contributions presented in the study are included in the article/supplementary material, further inquiries can be directed to the corresponding authors.The studies involving human participants were reviewed and approved by Institutional Review Board, Jahangirnagar University . Besides, all participants read, understood and signed a written consent form at the time of survey data collection. Written informed consent to participate in this study was provided by the participants' legal guardian/next of kin.AA: conceptualization, methodology, investigation, data curation, formal analysis, writing—original draft, writing—review and editing, and validation. SH: conceptualization, investigation, data curation, writing—review and editing, and validation. MH and MU: writing—review and editing and validation. SA: writing—original draft and validation. MS: conceptualization, supervision, writing—review and editing, and validation. All authors contributed to the article and approved the submitted version.This study was funded by Ministry of Science and Technology of the People's Republic of Bangladesh (NST 2019-20/MSc).MH was employed by company Jeeon Bangladesh Ltd. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.