The increasing complexity of academia, with its demanding working conditions and uncertain career opportunities, may affect the mental health of academics and potentially lead to mental health problems. The aim of this study is to determine the prevalence of depressive and anxiety symptoms in the academic population of the University of Udine and to compare symptoms in senior and younger academics and administrative staff.A cross-sectional survey was conducted between June and December 2020, involving academic and administrative staff in all departments. The prevalence of depressive and anxiety symptoms was assessed using the PHQ-9 and GAD-7 tools. The relationship between mental health outcomes and job role was analyzed using nonparametric tests and ordinal logistic regression.A total of 366 individuals participated: 109 junior academics, 146 senior and 111 administrative staff. The proportion of women was 55.7% and the mean age was 47.9 years. The prevalence of depressive and anxiety symptoms in the studied population was 25.7% (95% IC 21.5–30.4) and 22.7% (95% IC 18.7–27.2) respectively, with junior academics having the higher prevalence of both symptoms. Univariate models suggest a higher risk for anxiety symptoms OR 1.89 (1.13–3.17) for women.The prevalence of depressive symptoms is higher in our academic community than in the general population, especially among junior academics. These findings may reflect the impact of uncertain career and challenging environment on the mental health of young academics. Universities should provide more support to young academics so that they can contribute effectively and healthily to the advancement of research. The academic profession is in some ways atypical: professionals are intrinsically motivated and in most cases experience high levels of job satisfaction, but they can suffer from high levels of external pressure, leading to psychological problems . RecentlDespite these conditions, there is still a lack of knowledge about the current burden of mental illness in the academic community. Recent studies looking at anxiety and depressive symptoms in medical students and physicians during their residency program found a prevalence of mental health problems ranging from 20.9 to 43.2% –21. Thesburnout and improve psychosocial functioning. For this reason, we decided to investigate the presence and extent of anxiety and depressive symptoms among academic professionals at the University of Udine . The aims of our study are to 1) determine the prevalence of anxiety and depressive symptoms; 2) compare the prevalence between senior, junior and administrative staff; 3) determine the demographic characteristics of those with higher prevalence.An accurate assessment of the prevalence of anxiety and depressive symptoms representative of possible mental disorders in academics is the first step in providing prevention and support strategies for university members to prevent Between June and December 2020, we conducted a cross-sectional study (UN-SAD: Symptoms of Anxiety and Depression within the UNiversity community) at the University of Udine, a university in northeastern Italy with approximately 15,000 students.The study included all academic and administrative staff of all academic departments  except visiting professors.Data were collected using an anonymous online survey with 69 questions. Invitations to participate were sent to institutional email addresses with a request to complete the survey; reminders were sent shortly before the deadline. Participant consent was implied by completion of the questionnaire.The survey included questions on sociodemographic characteristics  and two validated tests of psychological assessment: the Patient Health Questionnaire–9 (PHQ-9)  for deprThe sample size for each group  was calculated with a confidence level of 95% and a precision of 7%. Based on our hypothesis of different prevalence of depression and anxiety symptoms in the three groups , the calculated sample size was at least 86, 101, and 62 respondents for each group, respectively. The procedures performed in this study with human participants conformed to ethical standards, the 1964 Declaration of Helsinki and its subsequent amendments, or comparable ethical standards. The study was approved by the Institutional Review Board of the University of Udine, Italy.https://www.r-project.org/. [Last accessed on 2021 Oct 05]].Data were reported as frequencies and percentages for categorical variables and as means and standard deviations for continuous variables. Results were presented as both categorical  and dichotomous variables, with PHQ-9 and GAD-7 scores ≥ 10 showing high sensitivity and specificity, respectively, for detecting a diagnosis of the respective disorder compared with diagnostic tests –29. Chi-A total of 1,550 participants were eligible . Of them, 366 participated in the survey, for a response rate of 23.6% (366/1550). Of these, 146 (39.9%) were senior academics, 109 (29.8%) were junior academics and 111 (30.3%) were administrative staff. In the groups of junior academics and administrative staff, most respondents were female , while the senior academics group was predominantly male . The mean age of all respondents was 47.9 ± 12.0 years, with a lower age for junior academics (33.2 ± 6.4 years). The most represented departments were Basic Sciences and Engineering  and Humanities . The full list of sociodemographic variables is shown in Table p < 0.001). Table The prevalence of depressive and anxiety symptoms in the studied population was 25.7% (95% IC 21.5–30.4) and 22.7% (95% IC 18.7–27.2), respectively (dichotomous scoring criteria). Junior academics reported higher rates of depressive (39.4%) and anxiety (33.0%) symptoms than senior academics (depressive symptoms 14.4% and anxiety symptoms 15.1%) and administrative staff (depressive symptoms 27.0% and anxiety symptoms 22.5%), using dichotomous scoring criteria. Moreover, the severity of both mental disorders was higher in junior academics than in the other two groups  3.86 (2.12–7.14) and 2.77 (1.52–5.13), respectively, compared with senior academics; similar results, although less severe, were found for administrative staff, who reported a higher frequency of depressive symptoms 2.20 (1.18–4.15) and anxiety symptoms 1.64 (0.86–3.12) compared with senior academics. In our population, female sex was associated with a significantly higher risk for anxiety symptoms OR 1.89 (1.13-3.17), whereas no statistically significant differences were found for depressive symptoms OR 1.48 (0.91–2.39).p = 0.33), but the overall risk for depression decreased with age OR 0.43 (0.21–0.88). For anxiety symptoms, the risk was higher among junior academics OR 2.12 (0.92–5.28) and among administrative staff OR 1.30 (0.70–2.55) than among senior academics. The risk for anxiety symptoms was significantly higher in women than in men (OR 1.85 (1.07–3.19)), while there was no significant association with age (p = 0.54). No significant differences were found in any of the multivariate models with respect to years of work experience, commuting distance, educational profile, marital status, or university department, so these results were not presented. The results of the multivariate model are presented in Table Univariate regression confirmed that administrative staff also had a higher risk for depressive symptoms OR 2.20 (1.18–4.15), but not for anxiety symptoms OR 1.64 0.86–3.12). However, when both sex and age were taken into account (with mean age as the cutoff), the significance of the role association decreased with a relative risk for depressive symptoms of 1.92 for junior academics (0.86–4.41) and 1.91 (0.99–3.71) for administrative staff. This model for depressive symptoms showed no difference with respect to sex  underpins the findings of this study, which may be useful in the implementation of prevention and support strategies by the university. Finally, the overall response rate was satisfactory and the different academic groups were homogeneously represented. To improve knowledge and awareness of the burden of mental illness among academics, this study would need to be expanded on a national scale.High external pressure, commonly referred to as the “publish or perish” aphorism, may play an important role in the mental health of academics. The higher prevalence of depressive and anxiety symptoms among junior academics may be an impact of career uncertainty and experiences in the demanding academic environment on the mental health of the younger ones. Because mental health problems are in turn associated with poor academic outcomes and productivity , 49 as w


Primary central nervous system lymphoma (PCNSL) is a rare malignancy. Standard of care is upfront high-dose methotrexate (HD-MTX) chemotherapy, while cranial radiation is more commonly used in the salvage setting. In this retrospective study, we aimed to investigate the safety and efficacy of salvage cranial radiation in PCNSL. PCNSL patients who received upfront HD-MTX chemotherapy and salvage cranial radiation after treatment failure between 1995 and 2018 were selected. Radiological response to cranial radiation was assessed as per Response Assessment in Neuro-Oncology Criteria. Twenty one patients were selected (median age 59.9 years), with median follow-up of 19.9 months. Fourteen patients (66.7%) received a boost to the gross tumour volume (GTV). Four patients (19.0%) sustained grade ≥2 treatment-related neurotoxicity post-completion of cranial radiation. Of the 19 patients who had requisite MRI with gadolinium imaging available for Response Assessment in Neuro-Oncology (RANO) criteria assessment, 47.4% achieved complete response, 47.4% achieved partial response, and 5.3% of patients exhibited stable disease. Higher dose to the whole brain (>30 Gy) was associated with higher rate of complete response (63.6%) than lower dose , while boost dose to the gross disease was also associated with higher rate of complete response (61.5%) compared with no boost dose (33.3%). Median overall survival was 20.0 months. PCNSL patients who relapsed following upfront chemotherapy showed a high rate of response to salvage cranial radiation, especially in those receiving greater than 30 Gy to the whole brain and boost to gross disease.  Primary central nervous system lymphoma (PCNSL) accounts for 3% of primary central nervous system (CNS) tumours and is a challenging malignancy to treat . Early wInstitution Review Board approval was obtained prior to commencement of the study. A retrospective study was conducted on patients with pathologic diagnosis of PCNSL, who were found to have treatment failure following chemotherapy, and were offered cranial radiation therapy (WBRT with or without boost) between 1995–2018. Upfront HD-MTX chemotherapy was administered according to hospital protocol. In general, induction cycles were administered every 14 days until complete response followed by consolidation treatments every 14 days for two cycles. Serial MR imaging was used to assess response. Following completion of HD-MTX chemotherapy, eligible patients were considered for consolidative autologous stem cell transplant. The main endpoints were response to cranial radiation, overall survival, and neurotoxicity. Response to cranial radiation was determined by considering best response on magnetic resonance imaging (MRI) with gadolinium contrast administration as per Response Assessment in Neuro-Oncology (RANO) Criteria .CR was a® SPSS Statistics 27.0 . Survival was analyzed with the Kaplan–Meier methods. OS was defined as time interval between completion of radiation therapy and death from any cause, and progression-free survival (PFS) was defined as time interval between completion of radiation therapy and either disease progression or death from any cause, whichever occurred first.Statistical analysis was performed using IBMA total of 220 patients with CNS lymphoma were identified in our database. Eighty-eight of these patients had a pathologically confirmed diagnosis of primary CNS lymphoma, who were assessed by both Hematologic Oncology and Radiation Oncology. Of these, 47 patients were excluded as they did not receive upfront HD-MTX chemotherapy . Forty-one patients were treated with upfront HD-MTX chemotherapy. Eighteen of these patients were excluded as they were not referred for consideration of salvage radiation therapy . This left a total of 23 consecutive patients with pathologic diagnosis of PCNSL who had relapsed or progressed after chemotherapy who were offered salvage cranial radiation therapy. Of these 23 patients, 21 chose to proceed with radiation therapy . All patCranial radiation therapy consisted of WBRT with or without a boost. WBRT was planned with opposed lateral beams encompassing the cranium and extending inferiorly to the level of the C2 vertebra, encompassing the entire cranial meninges. Implementation of a boost was accomplished with the addition of conformal beams, and MRI fusion to aid target delineation. The average age at time of cranial radiation was 59.9 years (range 37.3 to 72.3 years). The median time from PCNSL diagnosis to first fraction of cranial radiation was 4.5 months (range 1.7 to 47.8 months). Patient performance status was not consistently documented at time of radiation oncology consultation. Of the 21 patients treated with cranial radiation, 14 received a boost to the gross tumour volume (GTV) via involved field radiation therapy. For patients who received a boost, the median whole brain dose was 34.5 Gy (range 30 Gy to 45 Gy), and the median localized boost dose to the GTV was 10 Gy (range 5 Gy to 24 Gy). For patients who did not receive a boost, the median whole brain dose was 30Gy (range 20 Gy to 45 Gy). For all patients, the median fraction size was 2 Gy, as was the most common fraction size (range 1.70 Gy to 4 Gy). In our cohort, 60% of patients ≤60 received a WBRT >30 Gy compared to 54.5% of patients over age 60. Patients over the age of 60 made up 50% of patients who received a WBRT dose >30 Gy, and 55.5% of patients who received a WBRT dose ≤30 Gy. Furthermore, 50% of patients ≤60 received a boost, while 81.8% of patients >60 received a boost. Patients over age 60 made up 64.3% of patients receiving a boost, and 40% of patients not receiving a boost.Considering the number of lesions, 16.7% of patients with solitary brain lesions received a WBRT dose >30 Gy, compared with 73.3% of patients with multiple foci of disease. Furthermore, 91.7% of patients who received a WBRT dose >30 Gy had multifocal disease compared with just 44.4% of patients who received a WBRT dose <30 Gy, while 50% of patients with solitary brain lesions and 50% of patients with multiple lesions received a boost. With respect to maximum tumour size, 58.3% of patients with maximum tumour size ≤3 cm received a WBRT dose >30 Gy compared to 55.6% of patients with lesions >3 cm. In addition, patients with tumour size >3 cm made up 41.7% of patients who received a WBRT dose >30 Gy compared with 44.4% of patients with WBRT dose ≤30 Gy. Furthermore, 50% of patients with smaller index lesions received a boost to gross disease, whereas 88.9% of patients with larger index lesions received a boost. Furthermore, patients with larger lesions made up 57.1% of those who received a boost to gross disease, compared with just 14.2% of patients who did not receive a boost.With respect to deep structure involvement, 41.7% of patients without deep structure involvement received a WBRT dose >30 Gy, compared with 77.8% of patients without deep structure involvement. In addition, 58.3% of patients who received WBRT dose >30 Gy had deep structure involvement, while 22.2% of patients who received WBRT ≤30 Gy had deep structure involvement. In addition, 50% of patients without deep structure involvement received a boost, compared with 88.9% of patients with deep structure involvement. Additionally, 57.1% of patients who received a boost to gross disease had deep structure involvement, while the rate of deep structure involvement among patients who did not receive a boost was just 14.3%.All patients completed their courses of prescribed radiation and were maintained on oral corticosteroids for the duration of their radiation treatment, with a trial of taper shortly following completion of cranial radiation therapy, as per protocol.Of the 21 patients who completed cranial radiation therapy, 19 had the requisite pre- and post- treatment MRI with gadolinium contrast administration which formed the basis for RANO criteria assessment. Two other patients had pre-treatment MRI with gadolinium enhancement, but post-treatment imaging in the form of computed tomography (CT) head with contrast. For the 19 patients with requisite imaging, the best radiologic response was recorded for each patient following completion of cranial radiation therapy. Nine patients (47.4%) attained a CR, and an additional 9 patients (47.4%) attained a PR for a total response rate of 94.8% . One patOf the 19 cranial radiation patients analyzed by RANO criteria, a total of 7 (36.8%) were prior responders to up-front chemotherapy . Of these 7 responders to chemotherapy, all 7 (100%) were found to be subsequent responders to cranial radiation therapy, with 5 patients (71.4%) achieving CR following cranial radiation. Of the 12 patients who were non-responders to chemotherapy, 11 (91.7%) responded to cranial radiation therapy, with 4 (36.4%) achieving CR following cranial radiation therapy. Of the 11 patients who received a WBRT dose >30 Gy, 10 (90.9%) were responders, with 3 (27.3%) achieving PR and 7 (63.6%) achieving a CR. One patient (9.1%) exhibited stable disease. All 8 patients who received a WBRT dose ≤30 Gy were found to be responders, with 5 (62.5%) achieving PR and 3 (37.5%) achieving CR. Of the 13 patients who received a boost to gross disease, 12 (92.3%) were responders, with 4 (30.1%) achieving PR, and 8 (61.5%) achieving CR. One patient (7.7%) had stable disease. All 6 patients who did not receive a boost were found to be responders, with 4 (66.7%) achieving PR and 2 (33.3%) achieving CR. At time of analysis, 16 of the 21 patients who underwent cranial radiation therapy had died. Of the deceased, 14 patients died from PCNSL, while one patient died from a stroke with brain imaging negative for recurrence 7 days prior to death, and another patient died of end-stage renal disease and no evidence of clinical relapse. Median OS from the completion of radiation therapy was 20.0 months (range 0.9 months to 143.6 months), while median progression-free survival (PFS) was 14.1 months (range 0.9 months to 111.4 months) Median OS was 29.5 months (range 0.9 to 143.6 months) for 12 patients receiving WBRT >30 Gy, and 18.1 months (range 5.7 to 71.1 months) for 9 patients receiving WBRT ≤30 Gy. Median OS was 22.9 months (range 0.9 to 143.6 months) for 14 patients receiving boost, and 20.0 months (range 5.7 to 71.8 months) for 7 patients without a boost. Median OS for the 10 patients ≤60 years old was 24.2 months (range 2.7 to 143.6 months), compared to 15.3 months (range 0.9 to 69.8 months) among the 11 patients >60 years old . In our cohort, two patients who relapsed after up-front HD-MTX were offered salvage WBRT and declined. The first patient lived 0.6 months, and the second patient lived 1.2 months after relapse.Four patients (19.0%) sustained confirmed or probable neurotoxicity secondary to radiation treatment, diagnosed at 14, 15, 18 and 59 months post-completion of cranial radiation therapy. The first confirmed case relates to a patient who presented 15 months post-WBRT with gait changes and cognitive decline indicative of subcortical pathology. The repeat MRI did not show any evidence of disease recurrence, but there was evidence of treatment-related white matter disease. The second definite case relates to a patient who similarly presented with gait instability and confusion nearly five years post-RT. Repeat MRI was negative for disease recurrence, but white matter changes consistent with radiation treatment were appreciated. The two cases of probable treatment-related neurotoxicity involve symptomatic patients with repeat imaging showing mixed evidence of disease progression and treatment-related white matter changes. Specifically, the first patient presented 18 months post-WBRT with cognitive decline. Repeat brain imaging revealed evidence of disease progression, but also white matter changes related to radiation treatment. The second patient similarly presented with fatigue and confusion 14 months post-WBRT, with imaging showing treatment-related white matter changes and disease progression.All cases of neurotoxicity were observed in patients who received both a whole brain dose >30 Gy and a boost. Of patients ≤age 60, one patient (10%) sustained neurotoxicity, while 3 patients (27.3%) >age 60 sustained neurotoxicity. Our results suggest that salvage cranial radiation therapy is an effective and relatively safe treatment option for patients with PCNSL who experience disease progression or relapse following upfront HD-MTX chemotherapy. The median OS measured from time of diagnosis was 30.3 months in our cohort, which is similar to previous trials where patients were treated with upfront combination HD-MTX plus WBRT, where OS ranged from 25–33 months ,9,17. ThIn our cohort, patients over 60 accounted for 55.5% of the patients receiving ≤30Gy and 50% of patients receiving >30 Gy. While these proportions are not dissimilar given our modest cohort size, we can not rule out the possibility that response or survival outcomes were affected by selection bias, as younger patients were more likely to receive higher WBRT dose. Interestingly, patients over 60 were more likely to be prescribed a boost compared to younger patients ≤60 , and patients over 60 made up the majority of the patients receiving a boost (64.3%) compared with just 40% of the patients not receiving a boost. Increasing age is a negative prognostic factor, and it is interesting to note that in our cohort, survival and response outcomes were slightly better among patients who received a boost, despite there being a higher proportion of older patients in this group ,21.In our cohort we found that patients with multifocal disease were more likely to receive a WBRT >30 Gy (73.3%) compared with patients with solitary lesions (16.7%). The rates of boost implementation was not found to differ based on lesion number, with 50% of patients with solitary lesions and 50% of patients with multiple lesions prescribed a boost. Prior studies have failed to demonstrate that the number of brain lesions in patients with PCNSL is an independent prognostic factor for survival or response ,21,22. TOur data shows that 58.3% of patients with maximum tumour size ≤3 cm received WRBT >30 Gy compared to 55.6% of patients with maximum tumour size <3 cm. These rates are not markedly different given the small size of our cohort. Larger maximum tumour size was associated with increased rates of boost utilization, however, with 88.9% of patients with tumor size >3 cm receiving a boost, compared to 50% of patients with tumour size ≤3 cm. There is conflicting evidence in the literature regarding size of the primary tumour as a prognostic factor ,23,24. WIn our cohort, patients with deep structure involvement were more likely to receive a WBRT dose >30 Gy, compared with no deep structure involvement . Similarly, patients with deep structure involvement were more likely to receive a boost . Deep structure involvement is a known negative prognostic factor ,25,26. IThe overall cranial radiation therapy response rate in our cohort was robust at 94.8% (47.4% CR and 47.4% PR) which is consistent with previously reported retrospective series ,18. In oOur results suggest that higher WBRT dose and the implementation of a boost to gross disease may be associated with increased response rates. Patients receiving a WBRT dose >30 Gy had a CR rate of 63.6% compared to 37.5% among patients who received ≤30 Gy, while patients who received a GTV boost exhibited a CR rate of 61.5%, compared to 33.3% for patients who did not receive a boost. Similarly, our data suggests that increased WBRT dose was associated with improved OS, as patients who received a WBRT dose >30Gy had a median OS of 29.5 months, compared to median OS of 18.1 months for those receiving ≤30 Gy. Median OS was 22.9 months for patients who received a boost to gross disease, and 20.0 months for patients who did not receive a boost. There was also evidence that higher WBRT dose and the use of a boost were associated with increased rates of treatment-related neurotoxicity. In total, there were four confirmed or probable cases of radiation induced neurotoxicity diagnosed at 14, 15, 18, and 59 months post-completion of RT, all of whom received WBRT dose of at least 30 Gy and a boost to gross disease. There were no cases of neurotoxicity among patients receiving a WBRT dose ≤30 Gy, or in patients who did not receive a boost. Taken together, one interpretation of this result is that higher whole-brain dose and the use of a boost may be associated with a higher risk of neurotoxicity. However, patients receiving higher doses with boost may also be living long enough to sustain neurotoxicity secondary to their radiation treatment, as these patients also exhibited improved OS in our cohort. The observed neurotoxicity rate in our series is 19% is similar to a prior series where WBRT was used in the salvage setting, which reported a neurotoxicity rate of 15% ,8,18 witAs our study is limited by the lack of a control group, we can not definitely state that cranial radiation therapy was responsible for the observed improvement in OS advantage. This study is also limited by modest cohort size, lack of consistent documentation of patient performance status and steroid requirement throughout treatment duration and follow up, and the single center nature of this study. In our cohort, we found that patients with multifocal disease were more likely to be prescribed WBRT dose >30 Gy, while patients with maximum tumour size >3cm were more likely to receive both WBRT dose >30 Gy and a boost to gross disease. The impacts of lesion number and size as independent prognostic factors have not yet been established. As such, our report is limited by the potential impact that these prescribing disparities may have had on our outcomes .Our results provide additional evidence that cranial radiation is an effective and relatively safe treatment for PCNSL among patients who relapse following HD-MTX chemotherapy. Practitioners need to employ a balanced approach when deciding on treatment, as higher WBRT dose and the implementation of a boost were associated with improved response rates and survival outcomes, but were also associated with increased rates of neurotoxicity, particularly in the elderly. Continued work should focus on validating these results with larger cohorts, ideally across multiple centers.


Sub-Saharan Africa is predicted to have the steepest increase in the prevalence of diabetes in the next 25 years. The latest Mozambican population-based STEPS survey (STEPS 2005) estimated a 2.9% prevalence of diabetes in the adult population aged 25-64 years. We aimed to assess the change in prevalence, awareness, and management of diabetes in the national STEPS survey from 2014/2015 compared to 2005.We conducted an observational, quantitative, cross-sectional study following the WHO STEPS surveillance methodology in urban and rural settings, targeting the adult population of Mozambique in 2015. We collected sociodemographic data, anthropometric, and 12 hour fasting glucose blood samples in a sample of 1321 adults. The analysis consisted of descriptive measures of the prevalence of impaired fasting glucose (IFG), diabetes and related risk factors by age group, sex, and urban/rural residence and compared the findings to those of the 2005 survey results.The prevalence of IFG and diabetes was 4.8% (95CI: 3.6-6.3) and 7.4% (95CI: 5.5-10.0), respectively. These prevalence of IFG and diabetes did not differ significantly between women and men. The prevalence of diabetes in participants classified with overweight/obesity [10.6% (95CI: 7.5-14.6)] and with central obesity (waist hip ratio) [11.0% (95CI: 7.4-16.1)] was almost double the prevalence of their leaner counterparts, [6.3% ] and [5.2% (95CI: 3.2-8.6)], respectively. Diabetes prevalence increased with age. There were 50% more people with diabetes in urban areas than in rural. Only 10% of people with diabetes were aware of their disease, and only 44% of those taking oral glucose-lowering drugs. The prevalence of IFG over time [2.0% (95CI: 1.1-3.5) vs 4.8% (95CI: 3.6-6.3)] and diabetes [2.9% (95CI: 2.0-4.2) vs 7.4% (95CI: 5.5-10.0)] were more than twofold higher in 2014/2015 than in 2005. However, awareness of disease and being on medication decreased by 3% and by 50%, respectively. Though this was not statistically significant.While the prevalence of diabetes in Mozambique has increased from 2005 to 2015, awareness and medication use have declined considerably. There is an urgent need to improve the capacity of primary health care and communities to detect, manage and prevent the occurrence of NCDs and their risk factors.The online version contains supplementary material available at 10.1186/s12889-022-14595-7. Non-communicable diseases (NCDs) account for about 71% of all deaths recorded globally every year .Factors such as rapid urbanization, an ageing population, smoking, harmful alcohol consumption, physical inactivity, and the adoption of unhealthy diets have been implicated in the increasing burden of NCDs in LMIC, affecting the most disadvantaged subgroups , 4. The Mozambique’s official data sources indicate that risk factors for NCDs have been increasing and mainly affect the younger population and are, therefore, implicated in early disability and mortality from NCD in the country . FurtherThis report describes the changes in type 2 diabetes prevalence and the cascade of care over a ten year period (2005-2015). As part of a community-based epidemiological survey for chronic diseases risk factors surveillance in Mozambique in 2015, we conducted a cross-sectional study to assess the prevalence of diabetes, impaired fasting glucose (IFG) and related risk factors, and examine the cascade of care for diabetes in the adult Mozambican population.We conducted a cross-sectional study following the World Health Organization (WHO) STEPS surveillance methodology in urban and rural settings, targeting the adult population of Mozambique in 2015.This study was conducted in Mozambique, located on the Eastern Coast of Africa, with a mainly subsistence agricultural-based economy and one of the lowest reported gross domestic products globally . A natioParticipants were selected through a complex sampling design in three stages. The first stage included the selection of 120 primary sampling units , with probability proportional to the number of households, stratified according to province and urban-rural areas. The second stage included the random selection of one enumeration area  within each PSU, corresponding to a total of 120 clusters. The third stage comprised an update of the list of households in each enumeration area selected, followed by random and systematic selection of 24 households. Within each selected household, all dwellers aged 15 to 64 years were listed and a maximum of two were selected, one aged 15 to 44 years and one aged 45-64 years, whenever available. When there was more than one household member in each of these age-groups, only one per group was randomly selected, using a Kish selection grid. A total of 3277 subjects were invited and 3119 agreed to participate (participation rate: 95.2%)  normoglycaemic if they had a FBG < 5.6 mmol/l; 2) having impaired fasting glucose (IFG) if their FBG ≥ 5.6 mmol/l and < 6.1 mmol/l; and 3) as diabetic if their FBG ≥ 6.1 mmol/l or if they were being treated with insulin and/or oral glucose lowering drugs .Instituto Nacional de Estatística, INE) in Maputo, between February and April 2016. The team used an interactive software for microcomputers Census and Survey Processing System (CSPRO) for data entry. We employed double data entry to allow an interactive verification process of the variable ranges, detection of inconsistencies, and quality control of the internal data flow.Detailed sociodemographic information, measurements and laboratory results were recorded using paper-based data collection tools and then computerized centrally at the National Institute of Statistics  to account for the sample’s complex design  and to obtain Mozambique’s national adult population representativeness. We estimated variances through the first-order Taylor series linearization and reported 95% confidence intervals (95CI). Given that a substantial fraction (39.4%) of the sample did not fulfil the fasting requirement, the imputation of FBG was performed using a multiple chain equation (MICE). Miri et al. recommended that MICE was conducted in the Box-Cox transformed continuous variables FBG, BMI, height, hip length and waist lengths  vs. 41.2 [SD 11.4]); lived mostly in urban areas (52% vs. 41%); and were leaner  vs. 80.4 cm (SD 12.6); male mean waist circumference 74.9 cm (SD 9.4) vs. 78.5 cm (SD 10.5). A sensitivity analysis using the imputation of fasting blood glycemia (FBG) through MICE did not show significant differences in the results of diabetes and IFG point estimates and confidence intervals compared to a complete case analysis (Supplementary Tables S(Table ). Age, rural-urban distribution, and educational level, reported in our survey, were similar to that which has been reported in official national numbers, however the female to male sex difference was wider (20% vs 4%) in our population.Of subjects with complete data, the majority were women (60%), lived mainly in rural settings (68%), and were between the ages of 25 and 54 years (83%). Most had a low level of education, with < 20% having pursued more than a primary education (5th grade) Table . Age, ruThe prevalence of IFG and diabetes was 4.8% 95% CI: 3.6-6.3%) and 7.4% (95% CI: 5.5-10.0%), respectively. There were only slight differences in IFG prevalence across the assessed characteristics. The highest was between women and men, with women having nearly twofold higher prevalence than men [5.9% (95% CI: 4.3-8.0) vs 3.2% (95% CI: 2.0-4.9)]. The prevalence of diabetes differed across all characteristics assessed, although the CIs often overlapped. Overall, diabetes prevalence increases with age. The prevalence was almost twofold higher in the 45-64 age group  than in the 25-44 age group . Prevalence was higher in men  than in women  and in urban  than in rural  residents. There were also differences within subgroups; in the urban but not rural setting, there was a notable increase in prevalence with age, with a 10% difference between 25 and 44 and 45-64 groups  compared to only 2% in the rural setting [5.4% (95% CI: 3.3-8.8) vs 7.3% (95% CI: 4.3-12.1)]; likewise, females living in an urban setting aged 45-64 had a twofold higher prevalence compared to the 25-44 age group. Participants with formal education, primary level and above, had a higher prevalence than those with no education. Within the group with formal education, but not the group without formal education, differences were again noticeable between age groups; the older age group (45-65) had a twofold higher prevalence of diabetes than those in the 25-44 age group. The analysis also shows an increasing diabetes prevalence among men and women with overweight/obesity and central obesity (waist to height ratio) with age. Men and women with overweight/obesity aged 45-65 had a twofold higher prevalence of diabetes than those aged 25-44 [14.3% (95% CI: 9.5-20.8) vs 7.2% (95% CI: 3.9-12.9)], and participants with central obesity (WHtR ≥0.6) aged 45-65 had a sixfold higher prevalence of diabetes than those aged 25-44 [16.6% (95% CI: 9.6-27.1) vs 2.8%(95% CI: 0.8-8.9)]. (Table .6-6.3% ap = 0.057) higher diabetes prevalence than women, however, this effect loses statistical significance with adjusted estimates. Otherwise, findings show a statistically significant increase in diabetes prevalence with age, up to twice as high in the 55-64 year age group compared to the 25-34 age group   of study participants classified as diabetics were aware of their diagnosis and among these, less than half, 44% (95% CI: 12.1- 81.8) were taking glucose-lowering medicines. Additionally, approximately 80% (95% CI: 47.8 – 94.8) of participants also reported using non-pharmacological measures such as dietary changes (100%), exercise (48.2%), and weight loss (40%). Only a third of those who were aware of their diabetes status prior to the survey  were controlled (had measurements below the WHO definition of diabetes used in this study).The study samples of 2005 and 2015 were comparable in terms of sex, area of residence distribution, and level of education, however there were some differences in the age group distribution. For example, there was a 6% decrease in the 25-34 age group and a 4% increase in the 55-64 age group, which resulted in a two-year increase in the mean age of the 2015 survey participants, from 39.4 (2005) to 41.4 years (2015). Although mean BMI [p = 0.001) from 2 to 4.8%. This increase in the prevalence resulted from the combination of a 4% (p = 0.000) increase in women, a 4.9% (p = 0.001) increase in the urban residents, and a 5.1% (p = 0.003) and 5.8% (p = 0.123) increase in the population with overweight/obesity and central obesity, respectively.The IFG prevalence more than doubled between 2005 and 2015 , with a threefold increase in men (p = 0.021), people living in rural areas (p = 0.001) and with primary level education (p = 0.001) and a twofold increase in women (p = 0.002) and people living in urban areas (p = 0.058). No difference was observed concerning obesity levels. In addition, diabetes prevalence in men increased approximately twofold compared to women and with the number of years of education. For all sub-groups of analysis, the prevalence of diabetes has increased with age, Supplementary Fig. As seen in Table n p = 0.01, peopleThe proportion of people aware of their diabetes status has decreased by 3%, and about 50% of those who were aware were taking glucose-lowering drugs in 2015 compared to 2005 . HoweverRoughly 7% of adults aged 25 to 64 years had type 2 diabetes in Mozambique in 2015. This is more than twofold higher than the reported prevalence in 2005. Despite women having more risk factors, men were more affected by type 2 diabetes . LikewisThe rise in prevalence found in this study is not limited to Mozambique in the SSA region. Other studies measured diabetes prevalence over time and reported rising results, albeit in smaller proportions. For example, a STEPS survey conducted in Zambia in 2008 and 2017 reported a rise from 4.0%  to 6.2% Participants aged 45-64 years showed a statistically significant higher type 2 diabetes prevalence than that found for the 25-44 years age group. This finding is in keeping with the growing trend in type 2 diabetes observed in other settings , 27.The rising diabetes prevalence found in this study may be attributed to some drivers. One of the most remarkable was overweight and obesity. Total obesity measured by the BMI ≥ 25 was present in 30% of the study sample and 48% of participants with diabetes (data not shown). However, a steep increase in diabetes prevalence was observed in the subgroup of people with BMI < 25. A similar finding was reported in Malawi by Price and colleagues  and contParticipants living in urban areas were 50% more likely to have diabetes than those in rural areas. In another study using the same data , this waWhile not statistically significant, diabetes prevalence was almost 60% higher in men than in women, which is consistent with the global figures for diabetes sex-distribution .Review of the diabetes care cascade in our sample has revealed that 90% of participants were unaware of their diabetes status, with less than half of those who were aware taking glucose-lowering drugs. Among those taking medication, only one third reported having their diabetes controlled. Mozambique’s is not unique in this sense. These figures are in keeping with an analysis of 12 SSA countries conducted by Atun and colleagues . They foThis study had a number of limitations. Only 60% of the total population sampled complied with the 12-hour fasting requirement. Our sample population was older, had a higher proportion reporting being from rural areas, and had overall larger waist circumferences. This may have biased our findings, potentially resulting in an overestimation of the burden of risk factors and disease associated with increasing age and central obesity on the one hand and an underestimation of the disease prevalence associated with an urban residence. These aspects can lead to an underestimation of the actual disease burden in our total sample. A further limitation was our use of capillary blood samples and POC glucose meters rather than laboratory blood glucose estimations to determine the level of blood glucose . StudiesThe increase in prevalence of type 2 diabetes as reported here is concerning. Despite, Mozambique’s prioritization of NCDs in several national policy documents , programThe rising prevalence of diabetes and the population’s low rates of awareness about their disease and its subsequent management are concerning. This calls for urgent adaptation of health service delivery, mainly at the primary health care level, to improve diabetes detection and management and to promote community-based initiatives to improve diabetes related health education and prevention.Additional file 1.Additional file 2.


Objectives: To estimate the frequency of intradialytic hypertension (IDH) in our centre as per the definition suggested by Kidney Disease: Improving Global Outcomes (KDIGO).Methods: A cross-sectional study was conducted at the dialysis department of The Kidney Centre Post Graduate Training Institute (PGTI) Karachi, Pakistan from August 2021 to October 2021 among 263 end-stage kidney disease (ESKD) patients on maintenance hemodialysis (MHD) aged ≥ 18 years of both genders. The study outcome was the frequency of IDH as per the latest KDIGO suggested definition i.e., systolic blood pressure (SBP) rise of > 10 mm Hg from pre- to post-dialysis within the hypertensive range in at least four out of six consecutive dialysis treatments. Frequencies (%) and mean (±SD) were calculated for categorical and continuous variables respectively, using SPSS version 21 .Results: Among 263 patients, the mean age was 51.02 (±14.1) years and 56.3% were males. Around 30.8% of patients were dialysis-dependent for 1.1 to three years. The most common comorbidity was hypertension (88.6%). Standard dialysate calcium of 3mEq/l was received by 91.6% of study participants. About 78.7% of patients were using antihypertensive(s), out of which 85.5% were compliant and 37.6% were using a single antihypertensive. The most common antihypertensive in use was beta-blockers (78.3%). Around 16% of patients were found to have IDH. Age of the patients was significantly associated with IDH (p=0.038). The majority of the patients with IDH were those who were taking anti-hypertension medications as compared to the patients who were not taking them (p <0.004). Interdialytic weight gain was not a significant predictor for IDH.Conclusion: The frequency of IDH was 16% according to the latest suggested KDIGO definition. This is much lower than regional and global estimates according to earlier definitions. There is a dire need to establish a standardized definition of IDH in guidelines to diagnose, manage and compare data. Also, the association of IDH with fluid overload is not found in our study which emphasizes the need to evaluate other causative factors.  Among all comorbidities, hypertension (HTN) is almost universally present in end-stage kidney disease (ESKD) patients on maintenance hemodialysis (MHD). The reason for such high prevalence is a combination of different pathophysiological mechanisms, including renin-angiotensin-aldosterone system, endothelial dysfunction, arterial stiffness, and increased sympathetic nervous system activity . AnotherThe most challenging part of the management of ESKD patients is the frequent BP change that occurs in between and during hemodialysis treatment. The BP abnormalities during dialysis treatment include intradialytic hypotension and intradialytic hypertension (IDH). Up till now, there is no consensus on the definition of IDH. Arbitrary clinical definitions include BP rise of any degree during the second or third intradialytic hour, systolic blood pressure (SBP) rise >15 mm Hg within or immediately post-dialysis, SBP rise >10 mm Hg from pre- to post-dialysis or rising intradialytic BP that is unresponsive to volume removal . The KidThe proposed pathophysiology of IDH involves extracellular volume overload and peripheral vasoconstriction . ExtraceThe frequency of IDH has shown variability over time and across countries due to the involvement of multiple risk factors, as studied by Park et al. . ResearcDue to a lack of consensus on the definition of IDH, the current data available on the frequency of IDH is based on different definitions. This brings difficulty in comparing data, assessment of risk factors, and making newer strategies for its management. Intradialytic hypertension carries an exceedingly high risk of morbidity and mortality ,14; therStudy design, setting, and participantsA hospital-based cross-sectional study was carried out at the dialysis department of The Kidney Centre Post Graduate Training Institute (TKC PGTI) from August 2021 to October 2021. A non-probability consecutive sampling technique was used. The total number of registered patients at the dialysis hall was 419 out of which 270 fulfilled our inclusion and exclusion criteria. All patients 18 years of age and above, irrespective of gender, on maintenance hemodialysis thrice weekly for more than three months, with apparently stable dry weight were included in our study. Patients on maintenance hemodialysis for less than three months and whose dry weight was currently being adjusted were excluded. Sample size estimationThe sample size calculation was done using the Open Epi Version 3.01 and came out to be 254 based on the frequency of intradialytic hypertension i.e. 34.5% , consideProcedureInformed written consent in English/Urdu was taken from eligible candidates. A total of 13 dialysis sessions for each patient were studied. Statistical analysisData was entered and analyzed on IBM SPSS version 26 . Cleaning and coding of the data were done prior to analysis. Continuous data like age, BP, and weight were expressed in Mean±Std, while the frequency with percentage was calculated for categorical data like gender and comorbid. The normality of continuous variables was checked by the Shapiro-Wilk test. To observe any mean difference between pre- and post-hemodialysis BP and weight of the same patients paired t-test was applied in normally distributed data, while the Wilcoxon sign rank test was used on skewed parameters. To see any mean difference between the two groups, the student t-test or Mann-Whitney U test was applied according to the normality of the data. Association between the variables was accessed by Chi-square or Fisher exact test as appropriate. The significant variables of univariate analysis were kept in the multivariable binary logistic regression model and an odds ratio with a 95% confidence interval was obtained. A p-value of ≤0.05 was considered significant. Ethical considerationThe Kidney Centre Ethical Review Committee provided ethical approval for the study (Reference No. 112-NEPH-122020).Of around 419 patients registered at TKC PGTI Dialysis Hall, 32 expired during the study period, 13 transferred to another facility and three patients underwent a transplant. Of the remaining 371 patients, 270 fulfilled our inclusion criteria. Two hundred sixty-three patients agreed to participate with a response rate of 97%. Out of 263 patients, 148 (56.3%) were male while 115 (43.7%) were female. The mean age was 51.02 ± 14.1 years, median was 51 years with a minimum of 20 and a maximum of 90 years. The most prevalent comorbidity was HTN  in our patients followed by DM . The majority  were dialysis dependent between 1.1 to three years followed by 67 (25.5%) being on dialysis between 5.1 to 10 years. The most common access for dialysis was arteriovenous fistula (AVF) in 253 (96.2%) patients. Arteriovenous graft (AVG) was found in five (1.9%) patients and another five (1.9%) had a tunneled catheter with the most common site being subclavian in three patients. Dialysate calcium of 3mEq/L was received by 241 (91.6%) of the study participants, while the remaining had dialysate calcium of 2mEq/L  patients were taking anti-HTN medications and among them, 78 (37.6%) were on one drug while only 14 (6.8%) were using four drugs to control their BP. When we observed the type of anti-HTN drugs, we noted that the majority of the patients were taking beta-blockers  from which 112 (69.1%) were using dialyzable, while 50 (30.9%) were on a non-dialyzable beta-blocker  Table . The meaThe overall prevalence of intradialytic hypertension was 16% among our participants in the study and we noted that the age of the patients was significantly associated with intradialytic hypertension (p=0.038). We observed that the mean age was higher in patients who had intradialytic HTN as compared to the patients who did not have it (55.3±14.3 v/s 50.2±14 years respectively). On the other hand, gender and all comorbid conditions were equally distributed in both groups of patients (p>0.05) (Table The majority of the patients with IDH were those who were taking anti-HTN medications as compared to the patients who were not taking them (p<0.004). On the contrary, the difference in mean of pre- and post-dialytic weight gain was higher in patients without intradialytic HTN than the patients with it (1.8±0.7 v/s 1.7±1.3 respectively) Table .We made a multivariate predictive model for the IDH by adding all significant predictors of univariate analysis and found that average intradialytic weight gain became insignificant in this model, while age and use of anti-HTN medications remained the significant predictors for IDH. We perceived that a one-year increase in age can cause a 3% increase in intradialytic HTN (odds ratio 1.03 CI 1.006-1.06 p=0.018). Similarly, the patients who were taking one anti-HTN drug had a 5.5 times more chance to develop intradialytic HTN as compared to the patients who were not taking any medication (odds ratio 5.5 CI 1.2-25.7 p=0.031). Same as the patients who were using three anti-HTN were 15.8 times more prone to intradialytic HTN than no use of medication (odds ratio 15.8 CI 3.2-76.9 p=0.001) . Studies have shown a consistent association of IDH with old age and multiple comorbidities . The majOur study reported that 91.6% of patients received dialysate calcium 3mEq/L and only 8.4% received dialysate calcium 2mEq/L. Most patients at our facility have low calcium and high parathyroid hormone, therefore, dialysate calcium is kept at 3mEq/L to prevent hyperparathyroidism. This rationale has been supported by KDIGO CKD-MBD guidelines of 2017 which advocate the use of 2.5-3mEq/L dialysate calcium to lower serum phosphorus and maintain serum calcium .Antihypertensive medications were used by 78.7% of patients, out of which 85.5% of the patients were compliant with antihypertensive(s). Compliance was checked by interviewing the patients. This method of checking compliance may have recall and response bias. It was not possible to check their pharmacy record as many of them bought medicines from outside our facility. Single or dual antihypertensive agents were prescribed to 37.6% and 36.2% of patients respectively. 19.3% and 6.8% of patients were prescribed three and four types of antihypertensive agents which has depicted a serious effort to control persistently elevated intradialytic hypertension. Beta-blockers were the most used antihypertensive medication in 78.3% of patients, followed by calcium channel blockers prescribed to 65.2% of patients. Vasodilators and angiotensin receptor blockers were prescribed to 26.1% and 16.4% of patients, respectively. Very few patients were using alpha-blocker and angiotensin-converting enzyme inhibitors, 3.4% and 1.9% respectively. No recommendations are available for any specific antihypertensive medication class due to the heterogeneity of patient characteristics and lack of comparative evidence. Medication selection should be based on cardiovascular indications, patient characteristics, and side effect profile of drugs [Out of 162 patients on beta-blockers, 69.1% were on dialyzable beta-blockers like metoprolol, atenolol and bisoprolol while 30.9% were on non-dialyzable drugs like carvedilol, propranolol and nebivolol. In contrast to earlier research  our studFlythe et al. suggested that the use of long-acting and once-daily medication with relatively stable intradialytic blood pressure might help improve adherence and reduce the pill burden . The admAmong patients with IDH, 30.8% were dialysis dependent for 1.1 to three years while 25.5% were dialysis dependent for 5.1 to 10 years. Earlier studies have shown an association between IDH with shorter dialysis duration . A multiOur study possesses strengths in highlighting the importance of standard criteria to diagnose IDH and gathering important facts that will add value to existing literature. A few limitations of our study are that it is a single-centre study, therefore our findings lack generalizability. Since this was a cross-sectional study the temporal association could not be explored. The method of checking compliance may have recall and response bias.In conclusion, the frequency of IDH in our study according to the latest KDIGO definition is much lower than frequencies calculated from earlier definitions. Various definitions to label IDH can lead to variation in the estimation resulting in diverse approaches in IDH case management. With a high risk of morbidity and mortality in association with IDH, there is an imminent need to reach a unified consensus on the definition of IDH and the establishment of best practice guidelines accordingly. The association of fluid overload with IDH was also not found in this study which suggests the need for evaluation of other etiological factors.


External carotid artery originated superior thyroid artery are frequently documented in classical anatomical, surgical and radiological textbooks. Knowledge of anatomical variations, proper identification of superior thyroid arteries is very important to avoid major complications during and after neck surgeries. The aim of the study is to find out the prevalence of right superior thyroid artery originating from right external carotid artery in cadavers of a Medical College in Nepal.A descriptive cross-sectional study was carried out at the department of anatomy in Universal College of Medical Sciences, Bhairahawa, Nepal from October 2020 to January 2021 after ethical clearance from the same institution . Variations in origin of superior thyroid arteries were observed, recorded and photographed. Convenient sampling method was used. Data was analyzed using Microsoft Excel 2016. Point estimate at 90% Confidence Interval was calculated along with frequency and percentage.Out of 30 right superior thyroid arteries of 30 cadavers, 27 (90%) at 90% Confidence Interval (80.22-96.44) originates from right external carotid artery.In our study we observed that almost nine tenths of right superior thyroid arteries originated from the right external carotid artery which was relatively high in comparison to other studies. Thus, Extensive knowledge of variations in origin of superior thyroid artery is important for surgeons prior to various interventional surgeries. Ethical approval was taken from Institutional Review Board of Universal college of Medical Sciences and Teaching Hospital, Bhairahawa, Rupandehi, Nepal .The sample size (n) was calculated as,2 × p × q / e2n = Z2 × 0.9 × (1 - 0.9) / (0.1)2  = (1.645)  = 25Where,n = required sample sizeZ = 1.67 at 90% Confidence Interval (CI)p = 90%, prevalence from previous studyq = 1-pe = margin of error, 10%Our calculated sample size was 25.However,total thirty formalin embalmed cadavers of the department of anatomy were dissected exposing thyroid gland. Convenient sampling method was used. The cadavers who had any pathological lesions in neck region, cause of death were trauma to neck/chest was excluded for study. Variations in external carotid artery originated superior thyroid arteries was observed, recorded and photographed. All the collected data were entered into Microsoft Excel 2016. Point estimate at 90% Confidence Interval was calculated along with frequency and percentage.Out of 30 right superior thyroid arteries of 30 cadavers, 27 (90%) at 90% Confidence Interval (80.22-96.44) originates from right external carotid arteries .Additionally, when we observed the sex distribution in origin of right superior thyroid artery it was 20 (90.90%) from right external carotid artery from 22 male cadavers and 7 (87.50%) from right external carotid artery from eight female cadavers .Out of thirty right superior thyroid artery of 30 cadavers, 2 (3.33%) right superior thyroid artery have their origin other than external carotid artery. One (1.67%) right superior thyroid artery originate from carotid bifurcation .8Ranjit Sreedharan did a study in Kasturba medical college, Manipal and stated that 88.33% of STA originated from the ECA, 8.33% from the carotid bifurcation and 3.33% from common carotid artery which was quite similar to our study.10 This was related from our study where STA arise from ECA in 90.0% from right side, carotid bifurcation 6.66% from right side, common carotid artery 3.3% from right side.In another study conducted by Dhindsa et al. and Shivaleela et al., STA arise from ECA in 66.67% in right side and 76.21% in left side, from common carotid bifurcation in 31.81% in right side, 21.43% in left side and from common carotid artery in 1.51% in right side, 2.38% in left side respectively.7An digital subtraction angiographic study was done by pankaj gupta et al in 14 patients where 71.5% STA was originated from ECA in right side.11 Mean while Kevin Ongeti did a study in 46 cadaver in kenya in which he reported that superior thyroid artery arises 80% from external carotid artery, 13% from common carotid artery and 6.5 % from linguo-facial trunk of the cadavers.12In contrast to this MA Dessie did a study in 42 cadavers in ethopia that reported superior thyroid artery arises from the external carotid artery in 44.2%, carotid bifurcation in 27.9% and common carotid artery in 26.7%.13 Similarly in another computer tomography study by Mario Herrera-Nunez, 50.7% of the STA was originated from ECA, 20.40% was originated from carotid body and 17.1% originated from common carotid artery respectively.14Kaan esen did a computer tomography study in 640 Japanese population and reported the right and left STA arose from the ECA in 64.5% and 39.7% patients, from the bifurcation of the common carotid artery in 20.5% and 23.1% patients, and from the common carotid artery in 14.1% and 35.3% patients, respectively.15Bergam reported that STA arise from the common carotid in 18% of cases, the point of division of the common carotid in 36%, or from the external carotid in 36% of cases.16In our study, right STA originated more consistently from right ECA in male cadavers as compared to the female cadavers (90.9% vs 87.5%) which was similar to the finding a study by Toni, et al.Since the current study was carried out in 30 cadavers of a tertiary centre, the result of this study may not be generalized. However, study of similar type can be done in a large sample so that the actual findings can be generalized.The present study provided data of right ECA originated right STA which was high in our study as in comparison to previous other studies. These Variations plays an immense importance prior to planning of head and neck surgery.Thus, we recommend surgeons to have an extensive knowledge of variations prior to surgical innervations.


Bipolar disorder (BD) is a chronic, recurring illness that can lead to serious disruptions in functioning.To evaluate functionning in this population and to explore the relationship with socio-demographic and clinical features of BD.This is a descriptive and analytical cross-sectional study including patients with BD (DSM V) in euthymia, followed on an ambulatory basis to the Mood Disorders Unit of the Psychiatry A Department at Hedi Chaker Hospital University of Sfax between January and April 2019. Patients were considered euthymic if they scored less than 7 on the Young Mania (YMRS) rating scale and less than 8 on the Hamilton Depression scale (HDRS-17). The Short Function Evaluation Test  was used to evaluate functionning. Global functional impairment is defined by a total FAST score>11.We recruited 62 patients with a mean age of 45.65 years (SD=13.3) and a sex ratio of 1.13. 88.7% of patients were followed for BD I and 11.3% for BD II. The mean age of onset was 29.37 years (SD=11.6). The mean numbers of manic and depressive episodes were respectively 3.73 (SD=3.8) and 2.48 (SD=2.9). The mean FAST score was 28.97 (SD=15). Overall impairment was observed in 85.5% of patients. Impaired functionning was significantly more frequent in patients with a history of surgery (p=0.046), in those with a higher number of depressive episodes (p<0.001) and in subjects with partial remission (p=0.01).Thus, the treatment should target not only the improvement of symptoms but also the reduction of the incapacity of patients.


Particulate matter  and (t = 5.77 p ≤ 0.05), respectively. Cooking outdoors was associated with a 0.112 increase in the PM2.5 concentrations in the cooking area . Cooking with moderately polluting fuel was associated with a 0.718 increase in CO concentrations  in the living area.The majority  of the households used charcoal for cooking. More than half  cooked outdoors. Cooking areas had significantly higher PM2.5 and CO during the cooking time. Cooking with charcoal resulted in higher CO in the living area. Furthermore, cooking outdoors did not have a protective effect against PM2.5, and ambient PM2.5 exceeded the WHO Air quality limits. Interventions to improve the indoor air quality in informal settlements should promote a switch to cleaner cooking energy and improvement in the ambient air quality.The cooking and the living areas had high concentrations of PMThe online version contains supplementary material available at 10.1186/s12889-022-14015-w. Globally, indoor air pollution (IAP) was responsible for 3.8 million death in 2018 . The pub2), particulate matter (PM) and CO . More than half  had attained post-primary education  of the respondents used charcoal as the main type of fuel, while less than 1% used LPG or electricity  of the households did not have a window close to the main entrance door. However, adequate cooking area ventilation was observed for 60% (225/374) of the households  of the respondents stored fuel indoors, and 37% (137/374) stored the fuel in a separate building outside the house. However, only 64% 236/368) reported that the biomass fuel was protected from rainwater, while 157/368 (43%) were found using damp biomass fuel .During the cooking time, the mean PM2.5 and CO of 176.13 µg/m3 and 46.86 ppm, respectively (Table 2.5 (162.58 µg/m3) and CO (44.37 ppm). Cooking with all fuel types showed high concentrations of PM2.5 and CO in this informal settlement’s cooking and living areas   and 0.934  decrement in PM2.5 respectively  in the living room  was associated with a higher CO concentration in the living area. Incomplete combustion of charcoal in the traditional cookstoves may have resulted from the accumulation of CO, especially in the poorly ventilated living spaces. Other studies have shown an association between charcoal combustion and increased indoor CO , 55. Exp2.5. Most households cooked outside to avoid getting smoke inside their houses as they lacked space designated for cooking in their single or double-roomed structures. Cooking outdoors results in the dispersal of airborne particles away from the cooking area by ambient air currents. However, ambient PM2.5 particles that were observed may also have contributed to the PM2.5 in the outdoor cooking areas. Cooking location is an identified factor that influences the average concentrations of smoke in the cooking areas [2.5.Cooking outdoors was associated with a 0.112 unit increase in PMng areas , 59. For2.5, using less or moderately polluting cooking fuel resulted in lower PM2.5 concentrations (less polluting cooking fuel ˂ moderately polluting cooking fuel). When using traditional cookstoves, incomplete combustion of solid biomass fuels occurs due to difficulty in mixing of the solid fuel and air during burning, unlike for LPG (gas) and kerosene (liquid), leading to the release of a significant proportion of products of incomplete combustion PM2.5 [2.5 concentration with the type of cooking fuel is similar to a study conducted in rural Malawi that assessed the effect of cooking location and type of cooking fuel on the level of PM2.5 [2.5 in the cooking area, emphasising the need to promote cleaner cooking energy.Although cooking outdoors in this informal urban settlement was associated with higher PMon PM2.5 , 60. Theof PM2.5 . Using l2.5 and CO concentrations of the cooking and living areas for most households in this informal urban settlement. The cooking period presented the most eminent danger as fuel sources are actively burning with the highest expected concentration of incomplete combustion products of PM2.5 and CO.This study determined the cooking time PM2.5 and CO during the cooking time. Cooking with charcoal resulted in higher CO in the living area. Furthermore, cooking outdoors did not have a protective effect against PM2.5, and ambient PM2.5 exceeded the WHO Air quality limits. This was due to the predominant usage of charcoal for cooking fuel coupled with the congestion of households, abundant fuel filling stations and poor ambient air quality, which impact the indoor air quality in this community. Interventions to improve the indoor air quality in informal settlements need to promote a switch to cleaner cooking energy for all households in the neighbourhood for the benefit of reduction in indoor PM2.5 and CO concentrations to be realised.The cooking and the living areas had high concentrations of PMAdditional file 1.


The diagnosis of cervical intraepithelial neoplasia during pregnancy poses a great challenge to the treating clinician and the patient. According to the current guidelines, watchful waiting during pregnancy can be justified. Only in cases of invasion, immediate treatment may be indicated. However, few data are available on the management of cervical dysplasia during pregnancy. Further research is important for counselling affected women.Data of pregnant patients with suspected cervical dysplasia who presented to the University Women’s Hospital Tübingen between 2008 and 2018 were evaluated retrospectively. Colposcopic, cytologic, and histologic assessment was performed for diagnosis. Data on remission, persistence and progression of disease based on histologic and cytologic assessment and the mode of delivery were correlated.142 patients were enrolled. Cytology at first presentation was PAPIII (-p/-g) in 7.0%, PAPIIID (IIID1/IIID2) in 38.7%, PAPIVa (-p/-g) in 50.0%, PAPIVb (-p) in 2.8%, and PAPV (-p) in 1.4%. All cases with suspected invasion were recorded at the initial presentation. Complete histological or cytological remission was observed in 24.4%, partial remission in 10.4%, persistence in 56.3%, and progression in 8.9%. In two cases (1.5%) progression to squamous cell carcinoma occurred.Watchful waiting for cervical intraepithelial neoplasia during pregnancy seems to be sufficient and oncologically safe. It is important to exclude invasion during pregnancy, to perform frequent colposcopic, cytologic and histologic examinations and to ensure a postpartum follow-up examination to initiate the treatment of high-grade lesions. Spontaneous delivery seems to be safe in patients with cervical dysplasia, Caesarean section is not indicated. The management of pregnant women with abnormal cytological findings is a challenge for the attending physicians. On the one hand, maternal health must be preserved, and invasive lesions must be excluded; on the other hand, the unborn child should not be exposed to any avoidable risks. Cervical intraepithelial neoplasia (CIN) is particularly common in women aged 20–34 years , 2. The In pregnancy, incidences of CIN are reported to be between 1.3 per 1000  and 7 peCIN 1 and CIN 2 have a high spontaneous regression rate, CIN 3 shows progression in 12% of cases . PersistThe management of abnormal cytology findings in pregnant women is almost the same as recommended in non-pregnant women. Endocervical curettage is contraindicated in all cases . PregnanColposcopy is an important tool for evaluating cervical dysplasia in pregnancy. The transformation zone is usually visible in pregnancy. Enlargement of the cervix and local oedema may occur during pregnancy due to hormonal influences. Inflammation as well as increased vascularization and high vulnerability of the epithelium may complicate the differentiation from invasive processes , 16. TheThe aim of this work is to further assess the course of dysplasia during pregnancy, to generate data especially on remission, persistence, and progression of CIN and to facilitate the counselling of affected women. In addition, diagnostics in pregnancy and postpartum as well as possible effects of the mode of delivery on the probability of remission will be investigated.This is a retrospective, monocentric data analysis. Ethics approval was obtained by the ethics review board of the University Hospital Tübingen. In accordance with the ethics approval, obtaining informed consent from the patients was not required. All data were analysed anonymously. The data were taken retrospectively from the medical record; there was no patient contact during the study.Pregnant patients who presented to the dysplasia clinic at the University Women’s Hospital Tübingen with suspected cervical dysplasia between January 2008 and December 2018 were included in the study. Data on general medical history and current pregnancy, cytologic, colposcopic, and histologic findings, as well as information on HPV status and therapies performed were obtained from the medical record. In case of abnormal colposcopy and cytology, colposcopy-guided biopsies were taken preferably in the 16–20th week of pregnancy. Endocervical curettage was never performed. Usually, follow-up appointments with repeated Pap smear and colposcopy were made every 8–10 weeks. Further biopsies were taken only in cases of suspected invasion. Postpartum consultation took place 6–8 weeks after delivery. Classification of cytologic findings was performed according to Munich Nomenclature II  until Ju® Excel® for Windows was used for data processing and IBM SPSS Statistics®, version 26 for Windows was used for statistical analysis. Ordinal logistic regression analysis was performed to determine the impact of delivery mode and parity on the postpartum outcome.MicrosoftOf 229 patients assessed, 142 patients could be included in the further analysis. 87 patients were excluded from further analysis due to missing follow-up examinations or discontinuation of pregnancy.. 77 (54.2%) of patients showed histologic CIN 2 + at initial presentation. Colposcopic abnormalities were detected in 130 (91.5%) patients, including minor changes in 43 (30.3%) and major changes in 85 (59.9%) cases Table At initial presentation, ten (7.0%) patients were found to have PAPIII, 55 (38.7%) PAPIIID, 71 (50.0%) PAPIVa, four (2.8%) PAPIVb, and two (1.4%) PAPV Table 1n = 141), concordance was found in 105 (74.5%) cases. In 19 (13.5%) patients, minor changes were found with cytological PAPIIID2 or PAPIVa and in five (3.5%) patients colposcopy was inconspicuous although cytological PAPIIID or PAPIVa was reported. Of 85 patients with colposcopic major changes at initial presentation, 80 (94.1%) had a cytologic result of the categories PAPIIID, PAPIIID2, PAPIVa, or PAPIVb. Of 75 patients with histologic CIN 2, CIN 3, or adenocarcinoma in situ (ACIS), 62 (82.7%) showed major changes, eleven (14.7%) showed minor changes, one (1.3%) had an inconspicuous colposcopy and in one patient (1.3%), suspected invasion was reported.In 98 (69.0%) cases, the external and internal cytology findings at initial presentation were in agreement; in 29 (20.4%) patients, external cytology was of higher grade and in 14 (9.9%), it was of lower grade than internal cytology. The respective higher-grade finding was used for further evaluation. When comparing cytology and colposcopy at initial presentation (A T1 transformation zone was described in 105 (74.5%), T2 in 21 (14.9%), and T3 in 14 (9.9%) patients. In one case, the transformation zone was not definable because of invasive carcinoma.n = 77), PAPIIID + was found.Cytology and histology at initial presentation corresponded exactly in 64 (56.1%) cases, the lesion was cytologically underestimated in 11 (9.6%), and cytologically overinterpreted in 34 (29.8%). In 75 (97.4%) women with histologically confirmed CIN 2 + (Postpartum therapy of the diagnosed lesion was performed in 84 (60.4%) patients. LEEP excision was performed in 81 (58.3%) and laser vaporization in three 2.2%) patients. Therapy was performed after colposcopic and, if necessary, cytologic and histologic assessment. In 67 (82.7%) cases, the excidate showed CIN 2 + Table .2% patien = 35), we observed remission in 13 (37.1%) cases, persistence in 19 (54.3%) and progression to CIN 3 in three (8.6%) women. In patients with CIN 2 (n = 17), we observed remission in six (35.3%), persistence in four (23.5%) and progression to CIN 3 in seven (41.2%) cases. A change between CIN 1 and CIN 2 occurred in one case, respectively, and was considered persistence. Of 78 patients with CIN 3, remission occurred in twelve (15.4%) cases, partial remission to CIN 1/2 occurred in 14 (17.9%) cases, in 50 (64.1%) patients, lesions persisted postpartum, and progression to invasive carcinoma was observed in two (2.6%) cases Fig. 1.Of 135 patients, remission of the lesion occurred in 33 (24.4%) patients, partial remission from CIN 3 to CIN 1/2 in 14 (10.4%), and persistence of the lesion in 76 (56.3%) patients. Progression was observed in twelve (8.9%) patients, including invasive carcinoma in two cases (1.5%). In patients with CIN 1  were confirmed. Colposcopy and cytology were performed regularly during pregnancy and there was no suspicion of invasion at any time. The patient presented 9 weeks postpartum. At this time, evidence of invasive carcinoma was noted during colposcopy, cytology revealed PAPIVa-p, and histology revealed CIN 2 and CIN 3. Therapy was immediately initiated, and excision 12 weeks postpartum revealed a squamous cell carcinoma of the cervix . Large conization with endocervical curettage was performed. Despite dysplasia-free resection margins, hysterectomy was recommended due to an increased risk of recurrence of the grade 3 carcinoma. After individual consultation, the patient still desired a fertility-preserving procedure. No residual primary tumor and no lymph node or distant metastases were found in the positron emission tomography–magnetic resonance imaging (PET-MRI). After the pelvic sentinel lymph node procedure, a bilateral laparoscopic pelvic lymphonodectomy was performed. A bone marrow examination was performed to detect tumor cells. There was no evidence of lymph node or distant metastasis here either. The patient was then advised to undergo a hysterectomy after the completion of family planning. To date, the patient is recurrence-free.Another patient presented with PAPIVa (Munich Nomenclature II) in the 22nd week of pregnancy. Very difficult examination conditions existed due to severe obesity. Biopsies were taken under anesthesia during the Caesarean section, and CIN 2 was confirmed. Despite the urgent recommendation, the patient presented again only eight months postpartum. Here, a squamous cell carcinoma  was diagnosed during excision. No further data are available on this patient.In three patients, invasive carcinoma was diagnosed at the time of initial presentation. These patients were individually counselled and treated. In all cases, the lesion was detected by cytology, colposcopy, and histology at initial presentation.One patient was diagnosed with FIGO stage IIA squamous cell carcinoma of the cervix  in the 16th week of gestation. After individual consultation, a Wertheim’s procedure with sectio parva, without adnexectomy and radical pelvic and para-aortic lymphonodectomy were performed. The patient then underwent postoperative radiochemotherapy. To date, the patient is free of recurrence regarding the diagnosed and treated cervical carcinoma.Another patient presented at 7 + 1 weeks of gestation with PAPV (Munich Nomenclature II) and suspected adenocarcinoma of the cervix. Colposcopy revealed suspicion of invasion; in the biopsies at initial presentation, the invasion could not be excluded. Based on these findings, a LEEP excision was performed in the 9th week of gestation, and a re-excision with total cervical occlusion and cerclage were performed without complications in the 13th week of gestation. There was no evidence of invasion. To quickly establish the final diagnosis and not to delay further treatment, labor was induced in the 39th week of gestation. 12 weeks postpartum, laparoscopic total hysterectomy with bilateral salpingectomy was performed. The histologic specimen showed ACIS of the cervix of 8 mm ectoendocervical length, resection margins were free or tumor. There was no evidence of an invasive tumor growth. To date, the patient is free of recurrence.One patient was diagnosed with FIGO stage IIB squamous cell carcinoma in the 24th week of pregnancy. Colposcopy showed evidence of invasion and PAPV-p was diagnosed in cytology. Induction of fetal lung maturation was performed. After individual counseling, neoadjuvant chemotherapy with carboplatin and paclitaxel was started under close fetal monitoring. However, the tumor did not regress, so a cesarean section was performed in the 32nd week of gestation. The child showed postpartum complications like perinatal acidosis, infant respiratory distress syndrome, hyperbilirubinemia, anemia, apnea of prematurity and feeding problems which were attributed to prematurity but not to the mother's neoadjuvant chemotherapy. To date, the child has not shown any complications caused by the maternal treatment. Postpartum, the maternal tumor was found to be inoperable. The final staging revealed a squamous cell carcinoma of the cervix, grading: G2, TNM: pT3b, pN1, M1, FIGO III C. Radiochemotherapy was started. In the further course, distant metastasis became apparent and palliative chemotherapy was initiated. Due to the worsening of the general condition, the patient was transferred to an external hospital for palliative care.Information on the high-risk HPV status was available in 64 (45.1%) patients. Among them, 54 (84.4%) patients were high-risk HPV positive and ten (15.6%) were high-risk HPV negative. Two of the HPV-negative patients presented with PAPIII and showed a postpartum remission. One patient presented with PAPIIID, and CIN 1 was found in the postpartum biopsy. Two patients were diagnosed with CIN 2. There was postpartum progression to CIN 3 and total remission in one case, respectively. CIN 3 was diagnosed in five patients. In three cases the lesion persisted postpartum and in two cases remission occurred.R2 = 0.102). For vaginal delivery compared with Caesarean section, the probability of evolution towards remission appeared to be significantly increased . No significant effect could be determined for parity .Vaginal delivery was performed in 86 (60.6%) patients, Caesarean section in 42 (29.6%), and no data were available in 14 (9.9%) cases. In no case, the presence of CIN was the reason for performing a Caesarean section. The influence of the delivery mode on the postpartum outcome regarding remission, partial remission, persistence and progression was determined using ordinal logistic regression. Factors used were parity (primiparous or multiparous) and mode of delivery , persistence in 54.3% (n = 19) and progression to CIN 3 in 8.6% (n = 3). Previous publications report varying remission rates of 35.9–69%, progression to invasive carcinoma is not described [3. In patients with CIN 2 or PAPIIID2, we observed remission in 35.3% (n = 6), persistence in 23.5% (n = 4) and progression to CIN 3 in 41.2% (n = 7). Hong et al. report a lower rate of total remission and progression [3. In patients with CIN 3, remission of the lesion was observed in 15.4%, partial remission to CIN 1 or CIN 2 in 17.9%, persistence of the lesion postpartum in 64.1%, and progression to invasive carcinoma in 2.6%. Microinvasive squamous cell carcinoma (pT1a1) was diagnosed in one case and macroinvasive squamous cell carcinoma (pT1b1) in another. The literature provides widely varying data regarding regression, persistence, and progression of CIN 3 lesions. Hong et al. report similar persistence and progression rates and more total remission. Squamous cell carcinoma was found in stage pT1a1 in two cases and stage pT1b1 in one case [4. The course of CIN during pregnancy has been reported differently. On the one hand, this may be due to differences in the study populations regarding size and age as well as diagnostics performed during pregnancy, and on the other hand, it must be noted that all studies are retrospective analyses with rather small cohorts. Despite the varying results of different studies, it can be stated that progression to invasive carcinoma of CIN in pregnancy is rare. A wait-and-see approach can therefore be justified. Postpartum follow-up and, if necessary, treatment of the lesion are essential.Overall, of 135 patients, remission of the respective lesion was observed in 24.4%, partial remission from CIN 3 to CIN 1 and CIN 2 in 10.4%, persistence of the lesion in 56.3% and progression in 8.9%, including progression to invasive carcinoma in 1.5%. Remission, persistence and progression rates of previous publications are summarized in Tables 4escribed –29 Tablegression . Yost etgression  Table 3.one case . Paraskeone case . In contone case . There aone case , Fader eone case . Similarone case  Table 4.In one case, progression to macro invasive squamous cell carcinoma was observed. In this case, the progression cannot be explained by delayed postpartum presentation or missed follow-up examinations. There was no colposcopic, cytologic, or histologic suspicion of invasion in the patient at any time during pregnancy. 9 weeks postpartum, colposcopic signs of invasion were noted, and cytology and histology revealed PAPIVa-p with CIN 2 and CIN 3. Therapy was immediately initiated. A squamous cell carcinoma of the cervix, pT1b1, G3 was diagnosed in the excidate. To assess whether, knowing the squamous cell carcinoma diagnosed later, the evaluation of the biopsies and the images of the colposcopic examinations during pregnancy would have been different, they were re-evaluated in this study. Again, there was no suspicion of malignancy. The cause of progression can only be speculated. Immunosuppressed women are at increased risk for developing CIN 3 + . CombineIn another case, progression to invasive carcinoma was observed. In this case , despite the urgent recommendation, the patient presented for follow-up only eight months postpartum. This case also highlights the importance of early postpartum presentation and treatment of high-grade dysplasia. In this case, the progression can be explained by the failure to attend check-ups and the resulting delay in treatment.In three cases, an invasive carcinoma was suspected at initial presentation. In all these cases, the lesion could be detected in all three examination methods. Invasive carcinoma in pregnancy requires acute treatment and a waiting approach cannot be justified in all cases. Examinations during pregnancy should be performed by experienced clinicians , 18. AftIn one case, a FIGO stage IIA squamous cell carcinoma of the cervix was diagnosed at the 16th week of gestation. The current German guideline recommends that if cervical carcinoma is diagnosed at FIGO stage IB and IIA before the 16th week of gestation, termination of pregnancy should be performed and therapy should be started . This apIn one case, suspicion of invasion could not be excluded in a patient with ACIS in the 8th week of pregnancy. Therefore, LEEP excision during pregnancy was recommended. In the case of ACIS, the indication for excision should be made generously because it is often not possible to exclude invasion with certainty . In the The treatment of pregnant women with invasive carcinomas is a major challenge for all parties involved. It is important that decisions regarding therapy and pregnancy are always made by a specialized and interdisciplinary team. The diagnosis of cervical carcinoma in pregnancy is rare. The management of an invasive carcinoma is always an individual decision, considering the current guidelines but also the wishes and needs of the patients concerned , 37.High-risk HPV status was only available for 45.1% of patients. Due to the new screening for cervical cancer in Germany which started in 2020, we expect more information on the high-risk HPV status in the future, especially in patients aged 35 and older . High-riIn this study, the presence of cervical dysplasia has never been the reason for performing a Caesarean section. The influence of the mode of delivery on the likelihood of postpartum remission is controversial. Some authors report increased rates of regression of CIN in women after vaginal delivery , 39, wheIn summary, not treating diagnosed CIN during pregnancy seems to be safe for mother and child. Close monitoring by cytology, colposcopy and histology should be performed by experienced examiners during pregnancy. In order not to delay treatment, especially of high-grade lesions, a postpartum presentation around 6 weeks after delivery is essential. Therapy in case of diagnosed CIN does not seem necessary during pregnancy. In the case of CIN, spontaneous delivery is safe, there is no indication for a Caesarean section.


Lack of a dementia severity measure in administrative claims data is a major barrier in Alzheimer’s Disease and Related Dementias (ADRD) research using such data sources. A claims-based frailty index  is a validated measure of frailty that can be calculated from administrative claims data and is correlated with functional status. We conducted a cross-sectional study to examine whether CFI can be a claims-based measure to differentiate dementia severity in 814 participants with ADRD with linked to Medicare claims in the National Health and Aging Trends Study (NHATS). We estimated the Functional Assessment Staging Test (FAST) scale  using NHATS variables and calculated CFI from Medicare claims in the prior 12 months. The prevalence of FAST stage 5 or higher was 244 . The C-statistic of CFI to identify FAST stage 5 or higher was 0.78 [95% CI:0.73–0.82], with a CFI cut-point of 0.3 achieving the maximum sensitivity 72.5% and specificity 67.5%. The equipercentile linking procedure showed that CFI scores of 0.30, 0.35, and 0.40 corresponded to FAST stages 4, 5, and 6, respectively. Our results support the utility of a CFI as a proxy of dementia severity in administrative claims data.