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Background: Basal cell carcinoma (BCC) is the most frequently diagnosed malignancy worldwide and an ever increasing annual incidence is observed. However, nationwide registries of BCCs are very rare, and often extrapolation of the data has been necessary to estimate the absolute number of diagnoses. As of September 2016, all histopathologically confirmed BCCs are registered in the Netherlands, due to developments in automatic notification and import in the Netherlands Cancer Registry. This offers the unique possibility to assess the nationwide population-based incidence of first and multiple BCCs. Objectives: To assess the nationwide incidence and trends of first and multiple BCCs in the Netherlands and to predict incidence rates up to 2029. Methods: All patients with histopathologically confirmed BCC between 2001 and 2019 were selected from the population-based Netherlands Cancer Registry. Age-standardized incidence rates were calculated and trends were analysed with use of the estimated annual percentage change. Prediction of BCC incidence rates up to 2029 was based on a regression model. Results: In total, 601 806 patients were diagnosed with a first BCC over the period 2001–2019. The age-standardized incidence rates for both men and women with a first BCC increased over these years, from 157 to 304 and from 124 to 274 per 100 000 person-years, respectively. For male and female patients aged 30–39 years, decreases in annual incidences of −3·6% and −3·0%, respectively, were found in recent years. For patients aged 50 years or older an ever increasing trend was found. One-quarter of the patients with a first primary BCC developed one or more subsequent BCCs within 3 years. Increases in incidence of 30·4% (male) and 25·3% (female) are expected in the next 10 years. Conclusions: BCC incidence has doubled over the past two decades. Trends have seemed to stabilize in recent years for patients aged < 50 years. This might be a first sign of a decreasing trend. The incidence continues to rise in patients aged 50 years and older. In the next decade a further increase in BCC incidence is expected.

Objective To assess concordance among criteria for inactive disease (ID) and low disease activity (LDA) in juvenile idiopathic arthritis (JIA) and to seek factors driving discordance. Methods The frequency of fulfillment of existing criteria was evaluated in information on 10,186 patients extracted from 3 cross-sectional data sets. Patients were divided up according to the functional phenotypes of oligoarthritis and polyarthritis. Concordance between criteria was examined using weighted Venn diagrams. The role of each individual component in explaining discordance between criteria was assessed by calculating the absolute number and percentage of instances in which the component was responsible for discrepancy between definitions. Results Criteria for ID were met by 28.6–41.1% of patients with oligoarthritis and by 24.0–33.4% of patients with polyarthritis. Criteria for LDA were met by 44.8–62.4% of patients with oligoarthritis and by 44.6–50.4% of patients with polyarthritis. There was a 57.9–62.3% overlap between criteria for ID and a 67.9–85% overlap between criteria for LDA. Parent and physician global assessments and acute-phase reactants were responsible for the majority of instances of discordance among criteria for ID (8.7–15.5%, 10.0–12.3%, and 10.8–17.3%, respectively). Conclusion We found fair concordance between criteria for ID and LDA in JIA, with the main drivers of discordance for ID being physician and parent global assessments and acute-phase reactants. This observation highlights the need for further studies aimed to evaluate the impact of subjective physician and parent perception of disease remission and of laboratory measures of inflammatory activity on the definition of ID.

Literature suggests that adolescents may not accurately report sexual activity to their providers, impeding risk-based screening efforts for gonorrhea and chlamydia (GC/CT). We assessed the effect of a clinic-based universal GC/CT screening initiative on GC/CT screening frequency and detection of GC/CT infections among adolescents (boys and girls ≥13 years) and the association between positive GC/CT and documented sexual activity.We conducted a pre-post analysis of a primary care clinic affiliated with an academic institution. The electronic medical record was queried to extract all adolescent well and acute encounters for the 12 months preimplementation and postimplementation of universal GC/CT screening in January 2015.Eight hundred fifty-six encounters from 752 unique adolescents were included. Screening increased postimplementation (23.3% vs 61.4%, P0.001) of universal screening. Although there were similar rates of documented sexual activity preimplementation and postimplementation (14.6% vs 16.0%), a larger proportion of unknown sexual activity was documented (10.5% vs 23.7%, P0.001). Provider-level factors were the most frequent reasons for not screening. The absolute number of GC/CT cases increased, although the proportion of cases out of all eligible adolescents remained similar as more testing was completed (chlamydia, 5 of 752 vs 12 of 752; P = 0.09; gonorrhea, 0 of 752 vs 1 of 752; P = 0.32). Nearly half of positive chlamydia infections postimplementation appeared in adolescents who reported no sexual activity.Universal screening in a primary care clinic increased screening and detection of cases of gonorrhea and chlamydia, including in adolescents who did not report sexual activity.

lt;bgt;Background and Objective:lt;/bgt; COVID-19 is a fast-spreading worldwide pandemic caused by SARS-CoV-2. The World Health Organization recommended wearing face masks. Masks have become an urgent necessity throughout the pandemic, the study's goal was to track the impact of wearing masks on immunological responses.lt;bgt;Materials and Methods:lt;/bgt; This study was conducted on 40 healthy people who were working in health care at Nineveh Governorate Hospitals from September-December, 2020. They wore face masks at work for more than 8 months for an average of 6 hrs a day. The control sample included 40 healthy individuals, who wore masks for very short periods. All samples underwent immunological and physiological tests to research the effects of wearing masks for extended periods within these parameters.lt;bgt;Results:lt;/bgt; The results showed a significant decrease in total White Blood Count and the absolute number of neutrophils, lymphocytes, monocytes and phagocytic activity. However, there was a significant increase in the absolute number of eosinophils in participants compared with the control. The results also suggested there were no significant differences in IgE, haemoglobin concentration and blood Olt;subgt;2lt;/subgt;saturation in participants who wore masks for more than 6 hrs compared to the control group. The results showed a significant increase in pulse rate in participants who wore masks for more than 6 hrs compared to the control group. The results also showed a strong correlation coefficient between the time of wearing masks and some immunological, haematological parameters.lt;bgt;Conclusion:lt;/bgt; Wearing masks for long periods alters immunological parameters that initiate the immune response, making the body weaker in its resistance to infectious agents.

lt;bgt;Background and Objective:lt;/bgt; A well-established treatment for childhood epilepsy, the Ketogenic Diet (KD) is increasingly gaining acceptance as a preventative tool for obesity. The current study aims to compare the effects of a ketogenic diet on some of the immunological parameters among obese individuals and contrast them with non-obese individuals. This includes finding the absolute numbers of white blood cells and estimating the efficacy of phagocytic cells and serum IgA concentration.lt;bgt;Materials and Methods:lt;/bgt; Twenty healthy persons were chosen for the study, with an age range between 18-45 years, a weight range before the ketogenic diet of 80-115 kg and after the ketogenic diet 60-80 kg with a height range between 155-180 cm during a period between 8-16 weeks. Their daily food was composed of high fats (80%), moderate protein (15%) and small amounts of carbohydrates (5%). The control sample included twenty healthy subjects, their food consisted of different types of food carbohydrates (75-80%), proteins (10%) and fats (10%).lt;bgt;Results:lt;/bgt; The results showed a significant increase in the White Blood Cells (WBC) count in KD individuals. Additionally, no significant difference was noticed in the absolute number of neutrophils and lymphocytes. Conversely, a significant increase in the absolute number of monocytes was observed. Moreover, the study showed a significant decrease in IgA concentration in KD individuals compared with control.lt;bgt;Conclusion:lt;/bgt; In the ketogenic system users indicated a rise in the number of monocytes and a decrease in the concentration of IgA. This provides a strong sign that autoimmune disorders are emerging.

OBJECTIVE: To describe the epidemiological trends and characteristics of extrapulmonary tuberculosis (EPTB) in Galicia, Spain, from 2000 to 2019.METHODS: This was a retrospective cohort study based on data from the Galician TB information system.RESULTS: Of the total number of TB cases (n = 15,871), 5,428 (34.2%) had EPTB. The absolute number of cases and incidence of EPTB decreased dramatically (from 480 cases and 17.8 cases/100,000 in 2000, to 172 and 6.4 cases/100,000 in 2019, respectively), with a mean annual decrease of respectively 64% and 4.7% for absolute cases and incidence rates. The risk for EPTB was higher in men than in women (RR 3.86, 95% CI 3.66–4.07). The most frequent age group was 15–44 years (2,234 patients, 41.2%); overall reductions per age group were 82% (0–14 years), 75% (15–44 years), 44% (45–64 years) and 63% (≥65 years), with statistically significant differences. The most frequently locations were the pleura (1,916 cases; 35.3%) and the lymph nodes (1,504; 27.7%).CONCLUSION: The incidence of EPTB in Galicia has decreased significantly in the last 20 years. The epidemiological characteristics have not changed, except for the number of patients with risk factors. This improvement of EPTB epidemiological trends coincides with the implementation of the programme for the prevention and control of TB, which suggests that it has been very effective in the control of the EPTB.

Introduction: We evaluated the impact of public health measures on paediatric emergency department attendances during the COVID-19 and severe acute respiratory syndrome (SARS) outbreaks in Singapore. Methods: Between 1 January 2020 and 31 July 2020, we retrospectively reviewed paediatric emergency department attendances and admissions in a tertiary paediatric hospital in Singapore before and after a national lockdown to combat the spread of COVID-19 in Singapore. Hospital attendances and admissions were compared with data from a corresponding period in 2019 (1 January 2019 to 31 July 2019), as well as during and after the SARS outbreak (1 January 2003 to 31 December 2004). Results: Compared with a corresponding non-outbreak period, emergency department attendances decreased in line with nationwide public health measures during the COVID-19 and SARS outbreaks (2020 and 2003 respectively), before increasing gradually following lifting of restrictions, albeit not to recorded levels before these outbreaks. During the COVID-19 outbreak, mean daily attendances decreased by 40%, from 458 per day in January–July 2019, to 274 per day in January–July 2020. The absolute number of hospital inpatient admissions decreased by 37% from January–July 2019 (19,629) to January–July 2020 (12,304). The proportion of emergency department attendances requiring admission remained similar: 20% in January–July 2019 and 21% in January–July 2020. Conclusion: Nationwide public health measures in Singapore have had an impact on paediatric emergency department attendances and hospital inpatient admissions. Data from this study could inform planning and resource allocation for emergency departments in Singapore and internationally. Keywords: COVID-19, paediatric emergency department, public health measures, SARS

Contains fulltext : 235444.pdf (Publisher’s version ) (Open Access) PURPOSE: Compare patients treated for Retinopathy of Prematurity (ROP) in two consecutive periods. METHODS: Retrospective inventory of anonymized neonatal and ophthalmological data of all patients treated for ROP from 2010 to 2017 in the Netherlands, subdivided in period (P)1: 1-1-2010 to 31-3-2013 and P2: 1-4-2013 to 31-12-2016. Treatment characteristics, adherence to early treatment for ROP (ETROP) criteria, outcome of treatment and changes in neonatal parameters and policy of care were compared. RESULTS: Overall 196 infants were included, 57 infants (113 eyes) in P1 and 139 (275 eyes) in P2, indicating a 2.1-fold increase in ROP treatment. No differences were found in mean gestational age (GA) (25.9 ± 1.7 versus 26.0 ± 1.7 weeks, p = 0.711), mean birth weight (791 ± 311 versus 764 ± 204 grams, p = 0.967) and other neonatal risk factors for ROP. In P2, the number of premature infants born

The restrictive measures adopted by the Italian Government during the COVID-19 outbreak caused dramatic changes in routine public health care. Surprisingly, emergency activity also registered a reduction in frequency.This multicentre retrospective study aims to investigate eventual changes in ENT surgical emergencies in a highly populated area of southern Italy during the COVID-19 pandemic. Data concerning the period between the February 1 and the May 31, 2020 were collected from the main three hospitals in the district and compared with the same period of 2019.A substantial reduction was found in the number of ENT emergency interventions in 2020 compared to the same period of 2019, particularly in the main lockdown phase and in the tertiary referral centre.The reduction in the absolute number of emergency ENT interventions can be only partially explained by social distancing and home confinement. We have reason to believe that some of these patients may have not sought medical support due to fear of nosocomial SARS-CoV2 infection. This study could represent a trigger for further implementation of health system responses to emergencies in a period of transition that is likely to last for a prolonged period of time.Le urgenze chirurgiche otorinolaringoiatriche durante l’epidemia di COVID-19.Le misure restrittive adottate in Italia durante la pandemia di COVID-19 hanno determinato uno stravolgimento delle attività medico chirurgiche. Inaspettatamente, anche le prestazioni urgenti hanno registrato una riduzione.Abbiamo retrospettivamente confrontato le urgenze chirurgiche ORL eseguite nei tre principali ospedali della Provincia di Bari nel periodo compreso tra il 1° febbraio e il 31 maggio del 2020 con quelle dello stesso periodo del 2019.È stata riscontrata una importante riduzione nel numero di interventi nel 2020 rispetto all’anno precedente, in particolare nella fase del lockdown vero e proprio e nel centro di riferimento terziario.La riduzione del numero di urgenze chirurgiche ORL può essere solo parzialmente spiegata dal distanziamento sociale e dal confinamento domiciliare imposti dalle misure restrittive. Abbiamo motivo di credere che alcuni pazienti potrebbero aver evitato l’assistenza medica per paura di contrarre l’infezione nosocomiale da SARS-CoV2. Questo primo studio potrebbe avviare un processo di implementazione del sistema di risposta alle urgenze ORL che sarebbe auspicabile in un periodo di transizione potenzialmente duraturo.

Topic This article presents an overview of the burden of peripheral intravenous catheter infections and current evidence-based recommendations for prevention. Clinical Relevance Peripheral intravenous catheters are ubiquitous in most health care settings, fostering an acceptance of the peripheral intravenous catheter as benign and inevitable. This device, however, is far from benign, with reported failure rates as high as 90% from complications such as infection and phlebitis. Although reported rates of bloodstream infection related to peripheral intravenous catheters are much lower than those attributed to central venous catheters, the exponentially higher use of peripheral intravenous catheters indicates that the absolute number of peripheral venous catheter–related bloodstream infections is likely as high as and may surpass the number of central venous catheter–related bloodstream infections, with significant associated morbidity and mortality. Purpose of Paper Sustained improvements in outcomes related to peripheral intravenous catheters will depend on recognition of the root causes of failure and increased commitment to practice patterns consistent with infusion therapy standards of practice, effective education about peripheral intravenous catheters, accurate documentation of all aspects of peripheral intravenous catheter management, and consistent surveillance of patient outcomes related to peripheral intravenous catheters. Content Covered This article reviews the significant burden of peripheral intravenous catheter infections, barriers to effective peripheral intravenous catheter management, and current evidence-based recommendations to prevent this source of patient harm.

Objective. The aim of this study was to characterize the subsets of circulating CD56+ NK cells in pSS patients and their potential value in the diagnosis and/or prediction of prognosis in patients with pSS. Methods. We included 52 pSS patients fulfilling the 2002 AECG criteria or 2012 ACR criteria and 20 age- and gender-matched healthy volunteers. The frequency and absolute number of NK cells and CD56 NK cell subsets in peripheral blood samples were detected by flow cytometry. Other laboratory parameters such as the IgG level and complement protein levels were extracted from the clinical system. Results. Both the frequency and the absolute number of peripheral blood NK cells were reduced in pSS patients compared to healthy controls. The proportion of CD56bright NK cell subset was increased, and the proportion of CD56dim NK cell subset was decreased among NK cells, resulting in the ratio of CD56bright NK to CD56dim NK which was significantly elevated in pSS patients. ROC analysis indicated that the AUC of CD56bright NK/CD56dim NK ratio was 0.838, and the best diagnostic cut-off point was 0.0487 for pSS patients. Furthermore, this CD56bright NK/CD56dim NK ratio was positively correlated with the IgG level and negatively correlated with the complement protein C3 and C4 levels. More importantly, the CD56bright/CD56dim NK ratio was either slightly increased or not changed in other autoimmune diseases such as SLE and IgG4-related disease. Conclusion. Our findings suggest that the ratio of blood CD56bright NK to CD56dim NK might have a diagnostic value relatively specific for pSS.

Contains fulltext : 220534.pdf (Publisher’s version ) (Open Access) We performed a retrospective cohort study in the Dutch patient population to identify active substances with a relatively high number of adverse drug reactions (ADRs) potentially related to drug switching. For this, we analyzed drug switches and reported ADRs related to switching between June 1, 2009, and December 31, 2016, for a selection of 20 active substances. We also compared pharmacovigilance analyses based on the absolute, switch-corrected, and user-corrected numbers of ADRs. In total, 1,348 reported ADRs and over 23.8 million drug switches were obtained from the National Health Care Institute in The Netherlands and from Lareb, which is The Netherlands Pharmacovigilance Centre. There was no correlation between the number of ADRs and the number of switches, but, on average, we found 5.7 reported ADRs per 100,000 switches. The number was relatively high for rivastigmine, levothyroxine, methylphenidate, and salbutamol, with 74.9, 50.9, 47.6, and 26.1 ADRs per 100,000 switches, respectively. When comparing analyses using the absolute number and the switch-corrected number of ADRs, we demonstrate that different active substances would be identified as having a relatively high number of ADRs, and different time periods of increased numbers of ADRs would be observed. We also demonstrate similar results when using the user-corrected number of ADRs instead of the switch-corrected number of ADRs, allowing for a more feasible approach in pharmacovigilance practice. This study demonstrates that pharmacovigilance analyses of switch-related ADRs leads to different results when the number of reported ADRs is corrected for the actual number of drug switches.

ObjectiveThis study systematically reviews the data extracted from the Global Burden of Disease Study and sets out to assess the age-specific and sex-specific mortality and disability attributable to different forms of tobacco from 1990 to 2017, for Nepal.DesignThis cross-sectional study extracted data from the Institute for Health Metrics and Evaluation’s Global Burden of Disease database, then was quantitatively analysed to show the trends and patterns of prevalence of tobacco use, deaths and disability-adjusted life-years (DALYs) attributable to tobacco use from different diseases from the year 1990 to 2017 in Nepal.SettingNepal.ResultsIn between 1990 and 2015, the age-standardised prevalence of daily tobacco smoking decreased by 33% in males, 48% in females and 28% in both. By 2017, the age-standardised mortality rate and DALYs attributable to tobacco use, including any form, decreased by 34% and 41%, respectively, with tobacco smoking having the most contribution. However, the absolute number of deaths and DALYs increased by 39% and 3%, respectively. An increasing rate of deaths and DALYs attributable to tobacco was noted with an increase in age. Non-communicable diseases were responsible for most deaths and disabilities attributable to tobacco use.ConclusionThe prevalence of smoking along with the age-standardised mortality rate and DALYs shows a decreasing trend. However, attention should be made to implement a strong plan to control all forms of tobacco including secondhand exposure.

Hematopoietic stem cells (HSCs) are a rare population of cells that reside mainly in the bone marrow and are capable of generating and fulfilling the entire hematopoietic system upon differentiation. Thirty-six healthy donors, attending the HSCT center to donate their bone marrow, were categorized according to their age into child (0–12 years), adolescence (13–18 years), and adult (19–59 years) groups, and gender into male and female groups. Then, the absolute number of HSCs and mature immune cells in their harvested bone marrow was investigated. Here, we report that the absolute cell number can vary considerably based on the age of the healthy donor, and the number of both HSCs and immune cells declines with advancing age. The gender of the donor (male or female) did not have any impact on the number of the HSCs and immune cells in the bone marrow. In conclusion, since the number of HSCs plays a pivotal role in the clinical outcome of allogeneic HSC transplantations, identifying a younger donor regardless the gender is critical.

Measurement of long-term functional and anatomical outcomes in the same animal is considered a powerful strategy for correlating structure with function. In a neonatal animal model of hypoxic-ischemic brain injury that is relevant to cerebral palsy, long-term functional deficits on the staircase test and long-term anatomical deficits in the absolute number of medium-spiny projection neurons in the caudate-putamen were reported in different animals due to logistical constraints. Here, we investigated if these functional and anatomical measures were correlated when measured in the same animals. The medium-spiny projection neurons were investigated because (1) they comprise the vast majority (>97%) of all neurons in the caudate-putamen and (2) motor deficits observed during staircase testing are likely to involve these striatal medium-spiny projection neurons through their connections. We found that long-term skilled forepaw capability on the staircase test was correlated with the absolute number of DARPP-32-positive medium-spiny projection neurons in the caudate-putamen. Specifically, deficits in skilled forepaw ability for the number of sugar pellets eaten and retrieved, and for the maximum staircase level reached, were significantly correlated with a lower absolute neuronal number. We also found that skilled forepaw ability on the staircase test was not correlated with the neuronal density (i.e., number per unit volume) of DARPP-32-positive medium-spiny projection neurons. Since neuronal density is an indirect measure of neuronal survival that is used in the literature, and absolute neuronal number is a direct measure, the results also highlight the scientific value of measuring absolute neuronal number. Anat Rec, 302:2040-2048, 2019. © 2019 American Association for Anatomy.

Introduction we examined the consequences of applying the new EWGSOP2 algorithm for sarcopenia screening instead of the former EWGSOP algorithm (EWGSOP1) in geriatric inpatients. Methods the dataset of our formerly published Sarcopenia in Geriatric Elderly (SAGE) study includes 144 geriatric inpatients (86 women, 58 men, mean age 80.7±5.6 years) with measurements of gait speed, handgrip strength and appendicular muscle mass by dual x-ray absorptiometry (DXA). We analysed the agreement between EWGSOP and EWGSOP2 algorithms in identifying patients as sarcopenic/non-sarcopenic. Differences in the distribution sarcopenic vs. non-sarcopenic were assessed by Chi²-test. Results sarcopenia prevalence according to EWGSOP1 (41 (27.7%)) was significantly higher than with EWGSOP2 (26(18.1%), p Discussion there is a substantial mismatch in sarcopenia case finding according to EWGSOP1 and EWGSOP2. The overall prevalence and the number of men diagnosed with sarcopenia are significantly lower in EWGSOP2. While the absolute number of women identified as sarcopenic remains relatively constant, the overlap of individual cases between the two definitions is low.

Between 2005 and 2015, 138,165 hematopoietic stem cell transplantation (HSCT) were reported in 18 countries/regions in the Asia-Pacific region. In this report, we describe current trends in HSCT throughout the Asia-Pacific region and differences among nations in this region and various global registries. Since 2008, more than 10,000 HSCTs have been recorded each year by the Asia-Pacific Blood and Marrow Transplantation Group Data Center. Between 2005 and 2015, the greatest increase in the number of HSCTs was observed in Vietnam. Allogeneic HSCT was performed more frequently than autologous HSCT, and a majority of cases involved related donors. Regarding allogeneic HSCT, the use of cord blood has remained steady, especially in Japan, and the number of cases involving related HLA non-identical donors has increased rapidly, particularly in China. The incidence of hemoglobinopathy, a main indication for allogeneic HSCT in India, China, Iran, and Pakistan, increased nearly six-fold over the last decade. Among the 18 participating countries/regions, the transplant rate per population varied widely according to the absolute number of HSCTs and the national/regional population size. We believe that this report will not only benefit the AP region but will also provide information about HSCT to other regions worldwide.

The association between the preoperative absolute neutrophil count (NC), lymphocyte count (LC), and monocyte count (MC) in the peripheral blood and the prognosis of gastric cancer (GC) patients has not been investigated widely. We enrolled 445 patients who underwent surgery for GC between January, 2005 and April, 2013 to analyze the correlations among NC, LC, and MC and their prognoses. Based on cut-off values calculated by ROC analysis, patients were sub grouped as having: NC ≥ 4477 (NCHigh), NC

The neuronal microtubule cytoskeleton underlies the polarization and proper functioning of neurons, amongst others by providing tracks for motor proteins that drive intracellular transport. Different subsets of neuronal microtubules, varying in composition, stability, and motor preference, are known to exist, but the high density of microtubules has so far precluded mapping their relative abundance and three-dimensional organization. Here, we use different super-resolution techniques (STED, Expansion Microscopy) to explore the nanoscale organization of the neuronal microtubule network in rat hippocampal neurons. This revealed that in dendrites acetylated microtubules are enriched in the core of the dendritic shaft, while tyrosinated microtubules are enriched near the plasma membrane, thus forming a shell around the acetylated microtubules. Moreover, using a novel analysis pipeline we quantified the absolute number of acetylated and tyrosinated microtubules within dendrites and found that they account for 65–75% and ~20–30% of all microtubules, respectively, leaving only few microtubules that do not fall in either category. Because these different microtubule subtypes facilitate different motor proteins, these novel insights help to understand the spatial regulation of intracellular transport., eLife digest Cells in the body need to control the position of the molecules and other components inside them. To do this, they use a system of proteins that work a bit like a road network. The ‘roads’ are tubular structures known as microtubules, while ‘vehicles’ are transporters, called motor proteins, that ‘walk’ along the microtubules. Microtubule networks are important in all cells, but especially in neurons, which can grow very large. These cells have tree-like branches called dendrites that receive messages from other neurons. Dendrites contain different types of microtubules with many chemical modifications. These modifications consist of specific molecules or ‘groups’ becoming attached to or removed from the microtubules to change their properties – for example, microtubules can be ‘acetylated’ or ‘detyrosinated’. Motor proteins prefer different kinds of microtubules, and so understanding transport inside cells involves creating a precise roadmap showing how many of each type of microtubule exist and where they go. Using different super-resolution microscopy techniques, Katrukha et al. created maps of the microtubules in rat neurons. These show that acetylated microtubules form a core in the centre of the dendrites, while tyrosinated microtubules (which did not undergo detyrosination) line the cell membrane of the dendrites. Katrukha et al. then used the maps to determine that acetylated microtubules account for 65 to 70% of all microtubules, while tyrosinated microtubules make up 20 to 30%. This means that most microtubules fall into these two categories. The work by Katrukha et al. provides one of the first quantitative estimates of the relative amount of acetylated and tyrosinated microtubules, starting to shed light on how cells control their transport network. This could ultimately allow researchers to explore how transport changes in health and disease.

Background We aimed to describe the epidemiology of catheter-related bloodstream infections (CRBSIs) in onco-hematological neutropenic patients during a 25-year study period, to evaluate the risk factors for Gram-negative bacilli (GNB) CRBSI, as well as rates of inappropriate empirical antibiotic treatments (IEAT) and mortality. Materials/Methods All consecutive episodes of CRBSIs were prospectively collected (1994–2018). Changing epidemiology was evaluated comparing five-year time spans. A multivariate regression model was built to evaluate risk factors for GNB CRBSIs. Results 482 monomicrobial CRBSIs were documented. The proportion of CRBSIs among all BSIs decreased over time from 41.2% to 15.8% (pP. aeruginosa increased and comprised up to 40% of all GNB. Independent factors related with GNB-CRBSIs were: longer duration of in-situ catheter (OR 1.007; 95%CI 1.004–1.011), older age (OR 1.016; 95%CI 1.001–1.033), prior antibiotic treatment with penicillins (OR 2.716; 95%CI 1.306–5.403), and current antibiotic treatment with glycopeptides (OR 1.931; 95%CI 1.001–3.306). IEATs were administered to 30.7% of patients, with the highest percentage among MDR P. aeruginosa (76.9%) and S. maltophillia (92.9%). Mortality rate was greater among GNB than GPC-CRBSI (14.4% vs 5.4%; p = 0.002), with mortality increasing over time (from 4.5% to 11.2%; p = 0.003). Conclusion A significant shift towards GNB-CRBSIs was observed. Secondarily, and coinciding with an increasing number of GNB-MDR infections, mortality increased over time.

PURPOSE To assess the changing diversity of faculty in specific clinical and basic science departments, stratified by sex and underrepresented in medicine (URM) status, at all Liaison Committee on Medical Education (LCME)-accredited medical schools. METHOD In this retrospective, cross-sectional, observational study, the authors used data from the Association of American Medical Colleges Faculty Roster (data pulled in October 2019) to identify trends in clinical department faculty and in basic science department faculty by sex and URM status. They included full-time faculty at all LCME-accredited medical schools from 1979 to 2018. They compared the proportions of faculty across separate departments according to sex and URM status, and they used 2-independent-sample t test and simple linear regressions for statistical comparisons. RESULTS The number of full-time faculty increased from 49,909 in 1979 to 175,326 in 2018. The largest increase occurred in clinical departments, where the number of faculty increased from 38,726 to 155,677 (a fourfold increase). The number of faculty in basic science departments increased from 11,183 to 19,649 (a 1.8-fold increase). The proportions of faculty who were non-URM females (compared with non-URM males, URM females, and URM males) increased the most-from 14.4% (5,595 of 38,726) to 37.6% (58,478 of 155,677) for clinical departments, and from 14.9% (1,669 of 11,183) to 33.0% (6,485 of 19,649) for basic science departments. Growth was steady but slow among URM faculty, especially for Black males; the absolute number of male URM faculty remained low in both basic science and clinical departments. The proportions of females and URM faculty were highest in the departments of obstetrics and gynecology, pediatrics, and family medicine. CONCLUSIONS The substantial increase in faculty, especially in clinical departments, has led to greater diversity, but mostly among non-URM females. The rise of URM male and URM female faculty has been minimal.

Objective: to evaluate the influence of acetylsalicylic acid (ASA) on cell proliferation after partial hepatectomy in rats. Methods: 40 male Wistar rats were separated into four groups of ten rats each. Groups 1 and 2 (controls): undergoing 30% partial hepatectomy and, after one day (group 1) and seven days (group 2), to euthanasia; daily administration of 0.9% saline solution (1mL per 200g of body weight). Groups 3 and 4 (experimental): undergoing 30% partial hepatectomy and, after one day (group 3) and seven days (group 4), to euthanasia; daily administration of ASA (40mg/mL, 1mL per 200g of body weight). The absolute number of cells stained with PCNA was counted in photomicrographs, in five fields, and it was calculated the mean of positive cells per animal and per group. Results: the final mean of PCNA+ cells per group was: in group 1, 17.57 ± 6.77; in group 2, 19.31 ± 5.30; in group 3, 27.46 ± 11.55; and, in group 4, 12.40 ± 5.23. There was no significant difference at the two evaluation times in the control group (p=0.491), but there was in the experimental group (p=0.020), with a lower number of PCNA+ cells on the seventh day. The comparison between the two groups, on the first day, showed more PCNA+ cells in the livers of the animals that received ASA (p=0.047), and on the seventh day the number was lower in the experimental group (p=0.007). Conclusion: ASA induced greater hepatocyte proliferation. RESUMO Objetivo: avaliar a influência do ácido acetilsalicílico (AAS) na proliferação celular após hepatectomia parcial em ratos. Métodos: 40 ratos Wistar machos foram separados em quatro grupos com dez ratos cada. Grupos 1 e 2 (controles): submetidos à hepatectomia parcial de 30% e, após um (grupo 1) e sete dias (grupo 2), à eutanásia; administração diária de solução fisiológica 0,9% (1mL por 200g de peso). Grupos 3 e 4 (experimentos): submetidos à hepatectomia parcial de 30% e, após um (grupo 3) e sete dias (grupo 4), à eutanásia; administração diária de AAS (40mg/mL, 1mL por 200g de peso). Realizou-se a contagem do número absoluto de células coradas com PCNA em fotomicrografias, em cinco campos e cálculo da média de células positivas por animal e por grupo. Resultados: A média final de células PCNA+ por grupo foi: no grupo 1, de 17,57 ± 6,77; no grupo 2 de 19,31 ± 5,30; no grupo 3, de 27,46 ± 11,55; e, no grupo 4, de 12,40 ± 5,23. Não houve diferença significante nos dois tempos de avaliação no grupo controle (p=0,491), mas houve no grupo experimento (p=0,020), observando-se menor número de células PCNA+ no sétimo dia. A comparação entre os dois grupos, no primeiro dia, mostrou mais células PCNA+ nos fígados dos animais que receberam AAS (p=0,047), e no sétimo dia o número foi menor no grupo experimento (p=0,007). Conclusão: O AAS induziu maior proliferação hepatocitária.

SUMMARY OBJECTIVES: To describe the incidence by gender and region, lethality, and costs associated with the treatment of femoral fractures in the elderly (≥ 60 years) hospitalized in the Unified Health System (SUS) of Brasil between 2008 and 2018. METHODS: This is a cross-sectional, descriptive, retrospective study of hospitalizations of elderly people due to femoral fractures by analyzing secondary data obtained from the SUS Hospital Information System (SIH/SUS) between 2008 and 2018; for calculation of epidemiological coefficients, we used information from demographic censuses (2000 and 2010) of the Brazilian Geography and Statistics Institute (IBGE). RESULTS: A total of 478,274 hospitalizations were recorded in the period; the incidence was 1.7 times higher in females (overall average of 274.91/100,000 for women and 161/100,000 for men). The Southeast region had the highest absolute number of hospitalizations and the South region presented the highest annual overall average incidence (224.02/100,000). The average annual cost for SUS for the treatment of femoral fractures in the elderly was R$ 99,718,574.30. CONCLUSIONS: In the evaluated period (2008-2018), femoral fractures in the elderly had a high incidence (478,274 hospitalizations; 224.02 cases/100,000 elderly), a predominance of females (1.7F/1.0M), a higher absolute number of hospitalizations in the Southeast region and a higher incidence in the South region; the lethality was high (an increase of 17.46%; overall mean coefficient of 4.99%/year); and the costs for the SUS were huge (an increase of 126.24%; average annual expenditure of R$ 99,718,574.30). RESUMO OBJETIVOS: Descrever a incidência por gênero e região, a letalidade e os custos associados ao tratamento de fraturas do fêmur em idosos (≥ 60 anos) internados no Sistema Único de Saúde (SUS) do Brasil entre 2008 e 2018. MÉTODOS: Estudo transversal, descritivo e retrospectivo das internações de idosos por fraturas do fêmur mediante análise dos dados secundários obtidos do Sistema de Informações Hospitalares do SUS (SIH/SUS) entre 2008 e 2018; para cálculo dos coeficientes epidemiológicos, utilizamos informações dos censos demográficos (2000 e 2010) do Instituto Brasileiro de Geografia e Estatística (IBGE). RESULTADOS: Foram registradas 478.274 mil internações no período. A incidência foi 1,7 vezes maior no gênero feminino (média geral de 274,91/100.000 para mulheres e 161/100.000 para homens). A região sudeste obteve maior número absoluto de internações e na região sul apresentou a maior incidência média geral anual (224,02/100.000). O custo médio anual do SUS para o tratamento das fraturas de fêmur em idosos foi de R$ 99.718.574,30. CONCLUSÕES: No período avaliado (2008-2018), as fraturas do fêmur em idosos apresentaram alta incidência (478.274 mil internações; 224,02 casos/100.000 idosos), predomínio do gênero feminino (1,7F/1,0M), maior número absoluto de internações na região sudeste e maior incidência na região sul; a letalidade foi elevada (aumento de 17,46%; média geral do coeficiente de 4,99%/ano); e, os custos para o SUS foram vultuosos (aumento de 126,24%, média anual de gastos de R$ 99.718.574,30).

PURPOSE Both bone-scan and cross-sectional imaging are indicated in the staging of high-risk prostate cancer (PCa). However, 68Ga-prostate-specific membrane antigen (PSMA)-PET/computed tomography (CT) has proven to be an excellent tracer for detection of skeletal metastases. The aim of this study was to assess if adding skeletal imaging (with 18F-Fluoride-PET/CT) to 68-Ga-PSMA-PET/CT had any impact on high-risk PCa staging. METHOD Fifty treatment-naive, histopathologically proven, high-risk (European Association of Urology) PCa patients underwent both 68-Ga-PSMA-PET/CT and 18F-Fluoride-PET/CT for staging. RESULTS Fluoride-PET/CT detected significantly a higher number of skeletal metastases/patient than PSMA-PET/CT (median 4.5/patient vs 3.0; Wilcoxan-signed-rank-test, P = 0.060) and there was a significantly higher proportion of only Fluoride-avid than only PSMA-avid lesions (McNemar-test P < 0.001). No significant advantage was seen in patient-wise metrics. Most lesions missed by PSMA-PET/CT were in flat bones (25/33). serum prostate specific antigen (S.PSA) showed positive correlation with both, the number of lesions [r(PSMA)-0.555 (P = 0.006) and r(Fluoride)-0.622 (P = 0.001)] as well as tumor to background ratio (TBR) [[r-0.706 (P < 0.001) and 0.516 (P = 0.010)]. Median TBR was significantly higher in PSMA-PET/CT (22.77 vs 16.30; P < 0.001). All three patients with only Fluoride-avid lesions (also not identified in bone-scan) showed biochemical response with additional therapy. CONCLUSION Though, Fluoride-PET/CT detected a higher absolute number of lesions than PSMA-PET/CT, no significant advantage was seen in patient-wise metrics. Fluoride-PET/CT added second-line management in only 3/50 patients, which could have been reduced to 1/50, with more sensitive evaluation of flat bones in PSMA-PET-CT. Therefore, additional skeletal imaging is not needed with 68-Ga-PSMA-PET/CT in initial staging of high-risk PCa.

Introduction:Colombia is the fourth largest country in South America. It is an upper middle-income country with an estimated population of 49.2 million people, and road traffic collisions (RTCs) are the second most common cause of traumatic death. The United Nations (UN) proclaimed 2011 to 2020 as the “Decade of Action for Road Safety.” In this context, the government of Colombia established the National Road Safety Plan (PNSV) for the period 2011-2021, aiming to reduce RTC-related deaths by 26%. Some road safety laws (RSLs) were implemented before the PNSV, but their impact on deaths and injuries is still not known.Study Objective:The aim of this study was to evaluate whether these RSLs have had a long-term effect on road safety in the country.Methods:Data on RTC casualties, deaths, and injuries from January 1, 2001 through December 31, 2017 were collated from official Colombian governmental publications. Three different periods were considered for analysis: 2001-2010 to evaluate the Transit Code; 2011-2017 to evaluate the PNSV; and 2001-2017 to evaluate a composite of the full study period. Analyses of trends in deaths and injuries were related to dates of new RSLs.Results:A total of 102,723 deaths (12.7%) and 707,778 injuries (87.3%) were reported from 2001 through 2017. The Transit Code period (2001-2010) showed a 10.1% decline in deaths, 16.6% decline in injuries, and rates per 100,000 inhabitants and per 10,000 registered vehicles also declined. During the period of the PNSV (2011-2017), there was an increase in the number of deaths by 16.6%, injuries decreased by 1.7%, and death rates per 100,000 inhabitants also increased. During the total study period, a 12.4% reduction in the total number of casualties was achieved, and death and injury rates per 100,000 inhabitants decreased by 12.4% and 27.5%, respectively.Discussion:Despite the introduction of the PNSV, RTCs remain the second most common cause of preventable death in Colombia. Overall, while the absolute number of RTCs and deaths has been increasing, the rate of RTCs per 10,000 registered vehicles has been decreasing. This suggests that although the goals of the PNSV may not be realized, some of the laws emanating from it may be having a beneficial effect. Further study is required over a protracted period to determine the longer-term impact of these initiatives.

Aim This study examined the prevalence and clinical significance of the sapovirus infection in children with acute gastroenteritis before and after the introduction of the rotavirus vaccination in Finland in 2009. Methods We collected 1437 stool samples from children under 16 years during three prospective hospital-based surveillance studies of acute gastroenteritis at Tampere University Hospital, Finland. The children were seen in the emergency department (47%) or admitted to the ward (53%). Sapovirus findings from 2006 to 2008 (n = 759), before national immunisation, were compared to 2009-2011 (n = 330) and 2012-2014 (n = 348), after the national programme was launched. Results The overall incidence of the sapovirus was 3.3%. It was present in 1.4% of acute gastroenteritis cases in 2006-2008 and 5.5% in the post-vaccination years, but the absolute number did not increase. Sapoviruses mainly occurred in the winter and spring, but did not follow the prevalence of the norovirus or rotavirus. Sapovirus GI.1 and GII.1 were the most common genotypes, but the predominant strain was different each season. Many sapovirus lineages appeared during multiple seasons and reappeared later. Conclusion The sapovirus was uncommonly and sporadically detected in children seen in the hospital for acute gastroenteritis, and its relative role increased after national immunisation was introduced.

OBJECTIVES Central perivenulitis can occur in association with T-cell-mediated rejection and can sometimes require strong immunosuppressant therapy as refractory rejection. Furthermore, patients with central perivenulitis are more likely to have subsequent episodes of T-cell-mediated rejection and develop chronic rejection than those without central perivenulitis. We retrospectively analyzed clinical data of pediatric patients with episodes of T-cell-mediated rejection according to severity of central perivenulitis and monitored HLA-DR-positive CD8-positive T cells and recent thymic emigrants during treatment for T-cell-mediated rejection. MATERIALS AND METHODS We identified biopsy-proven T-cell-mediated rejection in 50 liver transplant recipients (45 with living-related donors, 5 with deceased donors) between September 2014 and August 2018. Lymphocyte subsets in peripheral blood samples were analyzed. RESULTS Of 50 pediatric patients, 30 were boys and 20 were girls (median age at transplant of 1.1 y; interquartile range, 0.6-6.2 y). Central perivenulitis was found in 46 patients (92%), which was mild in 13, moderate in 16, and severe in 17. Antithymocyte globulin was more frequently administered to patients with severe central perivenulitis than others (P < .05). Patients with antithymocyte globulin treatment were less likely to have subsequent episodes of T-cell-mediated rejection than those without this treatment (P < .05). The absolute number of CD8-positive HLA-DR-positive T cells in patients during treatment was significantly higher than in control patients (P < .05). The absolute number of recent thymic emigrants in patients with active infection was significantly lower than in patients without infection (P < .05). CONCLUSIONS Our results suggest the efficacy and safety of antithymocyte globulin for treating T-cell-mediated rejection with severe central perivenulitis in pediatric liver transplant recipients and suggest that antithymocyte globulin can prevent subsequent episodes of T-cell-mediated rejection. Analyzing lymphocyte subsets during treatment for rejection may help highlight viable therapeutic strategies for achieving a good outcome.

Background Malignant melanoma (MM) causes the highest absolute number of deaths among skin cancers. An up‐to‐date analysis of international MM mortality trends is required for assessing the burden of disease, and may support the assessment of the effectiveness of new diagnostic, therapeutic and preventative strategies. Objectives To report MM mortality trends between 1985 and 2015 using the World Health Organization (WHO) Mortality Database. Materials and methods We used country‐level MM mortality data from the WHO Mortality Database for all countries with high usability death registration data. Mortality trends were described using Joinpoint regression modelling. Results Thirty‐one countries met the inclusion criteria. All countries, except the Czech Republic, demonstrated increased age‐standardized death rates (ASDRs) in males over the observation period. More countries exhibited decreased or stable MM mortality in females. The median mortality rate for 2013–2015 was 2·57 deaths per 100 000 for males and 1·55 per 100 000 for females. Australia and Norway had the highest ASDRs for males (5·72 per 100 000 and 4·55 per 100 000, respectively). Norway and Slovenia had the highest ASDRs for females (3·02 per 100 000 and 2·58 per 100 000, respectively). MM mortality was greater for males than females in all countries, with sex disparity increasing across the period. Disparity in mortality between older and younger cohorts in several countries was also found. Conclusions An overall increase in MM mortality over the past 30 years was observed. However, there was notable variation in mortality trends between countries, as well as between males and females, and between different age groups. What is already known about this topic? Malignant melanoma (MM) has the highest mortality among skin cancers. The majority of MM cases can be attributed to known, modifiable risk factors. The incidence of MM is reported to have increased over past decades in many regions, but recent signs of stabilization and decline in MM incidence and mortality have also been reported in some regions. What does this study add? MM mortality trends across a large number of different populations over the past 30 years were studied. An overall increase in MM mortality was observed. All countries except one demonstrated increased age‐standardized death rates in males, while more countries exhibited decreased or stable MM mortality in females. MM mortality was greater in males than in females in all countries, with sex disparity increasing across the period.

Background Approximately 70% of the global burden of dengue disease occurs on the Asian continent, where many large urban centres provide optimal environments for sustained endemic transmission and periodic epidemic cycles. Jakarta, the capital of Indonesia, is a densely populated megacity with hyperendemic dengue transmission. Characterization of the spatiotemporal distribution of dengue transmission intensity is of key importance for optimal implementation of novel control and prevention programmes, including vaccination. In this paper we use mathematical models to provide the first detailed description of spatial and temporal variability in dengue transmission intensity in Jakarta. Methodology/Principal findings We applied catalytic models in a Bayesian framework to age-stratified dengue case notification data to estimate dengue force of infection and reporting probabilities in 42 subdistricts of Jakarta. The model was fitted to yearly and average annual data covering a 10-year period between 2008 and 2017. We estimated a long-term average annual transmission intensity of 0.130 (95%CrI: 0.129–0.131) per year in Jakarta province, ranging from 0.090 (95%CrI: 0.077–0.103) to 0.164 (95%CrI: 0.153–0.174) across subdistricts. Annual average transmission intensity in Jakarta province during the 10-year period ranged from 0.012 (95%CrI: 0.011–0.013) in 2017 to 0.124 (95%CrI: 0.121–0.128) in 2016. Conclusions/Significance While the absolute number of dengue case notifications cannot be relied upon as a measure of endemicity, the age-distribution of reported dengue cases provides valuable insights into the underlying nature of transmission. Our estimates from yearly and average annual case notification data represent the first detailed estimates of dengue transmission intensity in Jakarta’s subdistricts. These will be important to consider when assessing the population-level impact and cost-effectiveness of potential control and prevention programmes in Jakarta province, such as the controlled release of Wolbachia-carrying mosquitoes and vaccination., Author summary Characterization of the spatiotemporal distribution of dengue transmission intensity, a key measure of population infection risk, can inform the optimal use and deployment of control and prevention programmes. Jakarta, the capital of Indonesia, is a large urban centre with hyperendemic dengue transmission. We fitted catalytic models to age-stratified dengue surveillance data reported in Jakarta’s subdistricts from 2008 to 2017. We estimated a long-term average annual transmission intensity of 0.130 (95%CrI: 0.129–0.131) per year in Jakarta province, which varied across subdistricts from 0.090 (95%CrI: 0.077–0.103) per year in Sawah Besar to 0.164 (95%CrI: 0.153–0.174) per year in Pasar Rebo. We observed significant spatiotemporal variation and clustering of transmission intensity in Jakarta. Our estimates obtained from the analysis of yearly and cumulative case-notification data reported between 2008 and 2017 represent the first detailed estimates of average dengue transmission intensity, which will be key to assess the potential impact of future control and prevention programmes in Jakarta province.

Purpose To estimate the minimum number of cells required to obtain reliable data in a specular microscope, which could possibly represent the real clinical condition of the corneal endothelium. Methods A cross-sectional study of 122 eyes of 61 individuals submitted to noncontact specular microscope was conducted. Data generated by the manufacturer's software were uploaded to specific statistical software for sampling relative error calculation. When relative error was above 5%, new images were acquired and more cells counted until the desired relative error was reached. Data analyzed in this study for the desired relative error were number of cells marked by the examiner for each eye (marked cells), number of cells used for data analysis (analyzed cells), endothelial area used for analysis, sampling error, and absolute number of images used for each eye. Results The average number of marked cells required to obtain a relative sampling error of less than 5% was 425.2 ± 102.2 cells. The average number of analyzed cells used by the specular microscope to generate the data was 247.4 ± 51.6 cells. The average endothelial area of the analyzed cells was 0.43 ± 0.08 mm. The mean sampling error was 3.7% ± 0.6%, and an average of 2.95 ± 0.74 images was needed to obtain a relative sampling error of less than 5%. Conclusions We conclude that, theoretically, a minimum of 425.2 cells from 2.95 images must be marked to obtain reliable results, which could possibly represent the real endothelial clinical condition of the whole cornea.

Introduction and objectives PCSK9 inhibitors (PCSK9i) are safe and effective lipid-lowering drugs . Their main limitation is their high cost. The aim of this study was to estimate the number of patients eligible for treatment with PCSK9i according to distinct published criteria. Methods Data were obtained from the Information System for the Development of Research in Primary Care. Included patients were equal to or older than 18 years and had at least 1 low-density lipoprotein cholesterol measurement recorded between 2006 and 2014 (n = 2 500 907). An indication for treatment with PCSK9i was assigned according to the following guidelines: National Health System, Spanish Society of Arteriosclerosis , Spanish Society of Cardiology, National Institute for Health and Care Excellence, and the European Society of Cardiology/European Atherosclerosis Society Task Force. Lipid-lowering treatment was defined as optimized if it reduced low-density lipoprotein levels by ≥ 50% and adherence was > 80%. Results Among the Spanish population aged 18 years or older, the number of possible candidates to receive PCSK9i in an optimal lipid-lowering treatment scenario ranged from 0.1% to 1.7%, depending on the guideline considered. The subgroup of patients with the highest proportion of potential candidates consisted of patients with familial hypercholesterolemia , and the subgroup with the highest absolute number consisted of patients in secondary cardiovascular prevention. Conclusions The number of candidates to receive PCSK9i in conditions of real-world clinical practice is high and varies widely depending on the recommendations of distinct scientific societies.

Presentation of epidemiological information about the absolute number of suicides has been used occasionally to increase awareness of the suicide phenomenon. This study investigated the effectiveness of absolute quantitative messages versus relative messages. An example of relative messages would be comparing the number of suicide deaths with the number of deaths by car accidents. Participants were randomly presented with absolute or relative messages regarding suicide. They were then requested to indicate the degree of severity they attributed to the suicide phenomenon, being the level to which they view the phenomenon as sufficiently important to mandate national intervention and resource allocation. Relative messages proved more effective than absolute ones in yielding greater perceived severity of suicide. Increasing public and policymakers’ awareness of the suicide phenomenon could be aided by presenting information in relative terms.

Background: The World Health Organization (WHO) and the Global Burden of Disease (GBD) study at the Institute for Health Metrics and Evaluation (IHME) periodically provide global estimates of tuberculosis (TB) mortality. We compared the 2015 WHO and GBD TB mortality estimates and explored which factors might drive the differences. Methods: We extracted the number of estimated TB-attributable deaths, disaggregated by age, HIV status, sex and country from publicly available WHO and GBD datasets for the year 2015. We ‘standardized’ differences between sources by adjusting each country’s difference in absolute number of deaths by the average number of deaths estimated by both sources. Results: For 195 countries with estimates from both institutions, WHO estimated 1 768 482 deaths attributable to TB, whereas GBD estimated 1 322 916 deaths, a difference of 445 566 deaths or 29% of the average of the two estimates. The countries with the largest absolute differences in deaths were Nigeria (216 621), Bangladesh (49 863) and Tanzania (38 272). The standardized difference was not associated with HIV prevalence, prevalence of multidrug resistance or global region, but did show correlation with the case detection rate as estimated by WHO [r ¼ 0.37, 95% confidence interval (CI): 049; 0.24] or, inversely, with case detection rate based on GBD data (r ¼ 0.44, 95% CI: 0.31; 0.54). Countries with a recent national prevalence survey had higher standardized differences (higher estimates by WHO) than those without (P ¼ 0.006). After exclusion of countries with recent prevalence surveys, the overall correlation between both estimates was r ¼ 0.991. Conclusions: A few countries account for the large global discrepancy in TB mortality estimates. The differences are due to the methodological approaches used by WHO and GBD. The use and interpretation of prevalence survey data and case detection rates seem to play a role in the observed differences.

Background The accuracy of CD4 T cell monitoring by the recently developed flow cytometry-based CD4 T cell counting Muse™ Auto CD4/CD4% Assay analyzer (EMD Millipore Corporation, Merck Life Sciences, KGaA, Darmstadt, Germany) was evaluated in trained lay providers against laboratory technicians. Methods After 2 days of training on the Muse™ Auto CD4/CD4% analyzer, EDTA-blood samples from 6 HIV-positive and 4 HIV-negative individuals were used for CD4 T cell counting in triplicate in parallel by 12 trained lay providers as compared to 10 lab technicians. Results Mean number of CD4 T cells in absolute number was 829 ± 380 cells/μl by lay providers and 794 ± 409 cells/μl by technicians (P > 0.05); and in percentage 36.2 ± 14.8%CD4 by lay providers and 36.1 ± 15.0%CD4 by laboratory technician (P > 0.05). The unweighted linear regression and Passing-Bablok regression analyses on CD4 T cell results expressed in absolute count revealed moderate correlation between CD4 T cell counts obtained by lay providers and lab technicians. The mean absolute bias measured by Bland–Altman analysis between CD4 T cell/μl obtained by lay providers and lab technicians was −3.41 cells/μl. Intra-assay coefficient of variance (CV) of Muse™ Auto CD4/CD4% in absolute number was 10.1% by lay providers and 8.5% by lab technicians (P > 0.05), and in percentage 5.5% by lay providers and 4.4% by lab technicians (P > 0.05). The inter-assay CV of Muse™ Auto CD4/CD4% in absolute number was 13.4% by lay providers and 10.3% by lab technicians (P > 0.05), and in percentage 7.8% by lay providers and 6.9% by lab technicians (P > 0.05). Conclusions The study demonstrates the feasibility of CD4 T cell counting using the alternative flow cytometer Muse™ Auto CD4/CD4% analyzer by trained lay providers and therefore the practical possibility of decentralization CD4 T cell counting to health community centers.

Background France is among the countries showing fastest growth of thyroid cancer (TC) incidence and highest incidence rates in Europe. This study aimed to clarify the temporal and geographical variations of TC in France and to quantify the impact of overdiagnosis. Methods We obtained TC incidence data in 1986–2015, and mortality data in 1976–2015, for eight French departments covering 8% of the national population, and calculated the age-standardised rates (ASR). We estimated the average annual percent changes (AAPC) of TC incidence, overall and by department and histological subtype. Numbers and proportions of TC cases attributable to overdiagnosis were estimated by department and period, based on the comparison between the shape of the age-specific curves with that observed prior to changes in diagnostic practice. Results During 1986–2015, there were 13,557 TC cases aged 15–84 years. Large variations of TC incidence were observed across departments, with the highest ASR and the fastest increase in Isere. Papillary subtype accounted for 82.8% of the cases, and presented an AAPC of 7.0% and 7.6% in women and men, respectively. Anaplastic TC incidence decreased annually 3.0% in women and 0.8% in men. Mortality rates declined consistently for all departments. The absolute number (and proportion) of TC cases attributable to overdiagnosis grew from 1074 (66%) in 1986–1995 to 3830 (72%) in 2006–2015 in women, and varied substantially across departments. Conclusions Overdiagnosis plays an important role in the temporal and regional variations of TC incidence in France. Monitoring the time trends and regulating the regional healthcare practice are needed to reduce its impact.

Aspirin could reduce the risk of cancer metastasis. Circulating tumor cells (CTCs) are a key factor of cancer metastasis, but no evidence has revealed how aspirin affects CTCs and its epithelial–mesenchymal transition (EMT). Here, we conducted a clinical trial to investigate how aspirin affects CTCs in metastatic colorectal cancer (MCC) and breast cancer patients (MBC). The trial is retrospective registered at clinicaltrials.gov (NCT02602938). The eligible patients are given 100 mg aspirin q.d. for 8 weeks, and CTCs are evaluated at baseline, 4 and 8 weeks for absolute number, phenotype (epithelial type, E+, mesenchymal type, M+, and biophenotypic type, B+), and vimentin expression. Data on 21 MCC and 19 MBC patients are analyzed, and it revealed that the CTC numbers decreased with aspirin treatment in MCC (p

To elucidate the current treatment strategies of LRS in German-speaking Europe. Little is known about the treatment of large renal stones (LRS > 3 cm) in daily urological practice. LRS therapy can be, however, challenging and hazardous. A 39 item web-based survey was performed among urologists listed by the German, Austrian and Swiss Associations of Urology, addressing professionals treating LRS “on their own” and working in a German-speaking country. Uniparametric descriptions indicated as absolute numbers and percentages without p values, simple linear associations and bubble plots without arithmetic means or bar charts with standard deviation between targeted parameters and percentages were used. 266 of the 6586 responding urologists claimed to treat urinary stones on a regular basis. The majority of them were male (90.2%) and over 50 years old (42.9%). Most stones are treated in non-university hospitals (69.5%). 81.9% of all the institutions treat more than 150 cases/y. Open surgery is still performed in 45.5% of the centres, laparoscopy in 32%. Percutaneous nephrolithotomy (PNL) is the primary treatment option. Antimicrobial strategies vary considerably. Serious complications seem to be rare. However, quite a few responders reported treatment-related deaths. The main limitation is the absolute number of urologists performing LRS treatment, which is unknown. The German-speaking urologist treating LRS is a male and over 50. Although he performs PNL primarily, he is not averse to open surgery and SWL. He applies guidelines and employs modern equipment. Only antimicrobial strategies are out of line with the international standards.

BACKGROUND AND OBJECTIVES The integration of a restrictive packed red blood cells (PRBC) transfusion strategy into daily clinical practice presents a challenge. This study describes the effect of an intervention including educational presentations and computerized alerts on PRBC utilization at a tertiary hospital. MATERIALS AND METHODS During December 2014, lectures describing recommended PRBC transfusion indications were presented to all non-intensive care departments. Starting from January 2015, an alert was added to the electronic drug ordering system recommending transfusions at a haemoglobin (Hb) level

BACKGROUND AND PURPOSE: Previous studies have suggested that the central vein sign and iron rims are specific features of MS lesions. Using 3T SWI, we aimed to compare the frequency of lesions with central veins and iron rims in patients with clinically isolated syndrome and MS-mimicking disorders and test their diagnostic value in predicting conversion from clinically isolated syndrome to MS. MATERIALS AND METHODS: For each patient, we calculated the number of brain lesions with central veins and iron rims. We then identified a simple rule involving an absolute number of lesions with central veins and iron rims to predict conversion from clinically isolated syndrome to MS. Additionally, we tested the diagnostic performance of central veins and iron rims when combined with evidence of dissemination in space. RESULTS: We included 112 patients with clinically isolated syndrome and 35 patients with MS-mimicking conditions. At follow-up, 94 patients with clinically isolated syndrome developed MS according to the 2017 McDonald criteria. Patients with clinically isolated syndrome had a median of 2 central veins (range, 0–19), while the non-MS group had a median of 1 central vein (range, 0–6). Fifty-six percent of patients who developed MS had ≥1 iron rim, and none of the patients without MS had iron rims. The sensitivity and specificity of finding ≥3 central veins and/or ≥1 iron rim were 70% and 86%, respectively. In combination with evidence of dissemination in space, the 2 imaging markers had higher specificity than dissemination in space and positive findings of oligoclonal bands currently used to support the diagnosis of MS. CONCLUSIONS: A single 3T SWI scan offers valuable diagnostic information, which has the potential to prevent MS misdiagnosis.

Made available in DSpace on 2020-12-12T01:52:38Z (GMT). No. of bitstreams: 0 Previous issue date: 2020-05-01 Hallux valgus surgery (HVS) is one of the most common orthopedic procedures, often occurring in older adults. Guidelines provide inconsistent recommendations about venous thromboembolism (VTE) prophylaxis after HVS and data are scarce regarding VTE presentation and outcomes in this population. We reported the clinical characteristics and outcomes of VTE following HVS among patients enrolled in Registro Informatizado Enfermedad TromboEmbolica (RIETE), a prospective multicenter VTE registry. We compared the findings with those of other patients in RIETE. Consecutive patients with VTE post HVS were included in the study. Baseline characteristics, administration of VTE prophylaxis prior to diagnosis, presenting symptoms and signs, risk factors for VTE, and 90-day outcomes including recurrent VTE, major bleeding and death were determined. A total of 54 patients with VTE post HVS were identified in RIETE [median age: 64 (interquartile range 56–71) years; 85.2% female] and were compared with 74,111 VTE patients who had not undergone HVS. Among those with VTE post HVS, 63.0% had received VTE prophylaxis, in contrast to 35.6% in the rest of the RIETE cohort. Simplified Pulmonary Embolism Severity Index was zero in 66.7% of the patients with pulmonary embolism post HVS and 33.3% of other RIETE patients (P = 0.011). Compared with other VTE patients, use of estrogens was higher in HVS group (13.0% vs 5.4%, P = 0.01). All patients with VTE post HVS (100%) and most of other VTE patients (99.6%) were treated with anticoagulation, most commonly with low-molecular weight heparins. In contrast to the rest of the patients in RIETE, the absolute number of all fatal and non-fatal outcomes at 90 days was zero in the post HVS group (i.e. no deaths, no recurrence of VTE, and no major bleeding). In a large registry of patients with VTE, all patients with VTE post HVS underwent anticoagulation. These patients had much better outcomes than the rest of VTE patients, with no deaths, recurrences or major bleeding events at 90-day follow-up. Aged & Extended Care Services Central Adelaide Local Health Network The Queen Elizabeth Hospital, 28 Woodville Road, Woodville South Adelaide Geriatrics Training and Research With Aged Care (GTRAC) Centre School of Medicine Faculty of Health and Medical Science University of Adelaide Division of Medical Subspecialties Lyell McEwin Hospital Fireman Vascular Center Massachusetts General Hospital Department of Pneumonology Hospital Universitario Araba Department of Internal Medicine Hospital General Virgen de La Luz Department of Internal Medicine Hospital Reina Sofía Department of Internal Medicine Hospital Comarcal de Axarquía Department of Internal Medicine Hospital Italiano de Buenos Aires Department of Internal Medicine – Pulmonary Division Botucatu Medical School São Paulo State University (UNESP) Division of Cardiology Department of Medicine Columbia University Medical Center/New York-Presbyterian Hospital Yale/YNHH Center for Outcomes Research & Evaluation Cardiovascular Research Foundation (CRF) Hospital Universitari Germans Trias I Pujol Universidad Católica de Murcia Department of Internal Medicine – Pulmonary Division Botucatu Medical School São Paulo State University (UNESP)

Background Fall-induced traumatic brain injuries (TBI) of elderly adults are a major public health concern. Methods We determined the current trends in the absolute number and incidence (per 100,000 persons) of severe fall-induced TBI among 80-year-old or older Finns by taking into account all persons who were admitted to Finnish hospitals for primary treatment of such injury between 1970 and 2017. Results The total number of hospitalized older Finns with a fall-induced TBI increased considerably between the years 1970 and 2017, from 60 (women) and 25 (men) in 1970 to 1622 (women) and 991 (men) in 2017. The age-adjusted incidence of TBI (per 100,000 persons) also showed a clear increase from 1970 to 2017: from 167.9 to 800.4 in women (377% increase), and from 176.8 to 927.3 in men (424% increase). If this trend in the age-adjusted incidence of hospital-treated TBI continues, and the size of the 80-year-old or older Finnish population increases as predicted (from 0.29 million in 2017 to 0.49 million in 2030), the number of these severe injuries among 80-year-old or older Finns will be approximately 1.8 times higher in 2030 (4811 injuries) compared with 2613 injuries in 2017. Conclusions The number and age-adjusted incidence of fall-induced hospital-treated TBI among elderly Finns increased considerably between 1970 and 2017. Wide-scale fall and injury prevention measures are urgently needed, because further aging of the population is likely to worsen the problem in the near future.

Background Older adults are more prone to develop adverse drug reactions (ADRs) since they exhibit numerous risk factors. The first aim was to analyse the number of spontaneous ADR reports regarding older adults (> 65) in the ADR database of the German Federal Institute for Drugs and Medical Devices (BfArM) and to set them in relation to i) the number of ADR reports concerning younger adults (19–65), and ii) the number of inhabitants and assumed drug-exposed inhabitants. The second aim was to analyse, if reported characteristics occurred more often in older vs. younger adults. Methods All spontaneous ADR reports involving older or younger adults within the period 01/01/2000–10/31/2017 were identified in the ADR database. Ratios concerning the number of ADR reports/number of inhabitants and ADR reports/drug-exposed inhabitants were calculated. The reports for older (n = 69,914) and younger adults (n = 111,463) were compared using descriptive and inferential statistics. Results The absolute number of ADR reports involving older adults increased from 1615 (2000) up to 5367 ADR reports (2016). The age groups 76–84 and 70–79 had the highest number of ADR reports with 25 ADR reports per 100,000 inhabitants and 27 ADR reports per 100,000 assumed drug-exposed inhabitants. For both ratios, the number of reports was higher for males (26 and 28 ADR reports) than for females (24 and 26 ADR reports). Fatal outcome was reported almost three times more often in older vs. younger adults. Six out of ten drug substances most frequently suspected were antithrombotics (vs. 1/10 in younger adults). For some drug substances (e.g. rivaroxaban) the ADRs reported most frequently differed between older (epistaxis) and younger adults (menorrhagia). Conclusions There is a need to further investigate ADRs in older adults since they occurred more frequently in older vs. younger adults and will likely increase in future. Physicians should be aware of different ADRs being attributed to the same drug substances which may be more prominent in older adults. Regular monitoring of older adults taking antithrombotics is recommended.

AIMS The aim of this study was to analyse the real-world national data on parallel utilisation of transcatheter (TAVR) and surgical (SAVR) aortic valve replacement. METHODS AND RESULTS We queried an all-payer, administrative United States in-patient database to identify all AVR hospitalisations in patients aged ≥18 years from January 2012 to December 2016 and examined the temporal changes in the number of AVR procedures and in-hospital mortality. A total of 463,675 AVRs were performed - 363,275 (78.4%) SAVR and 100,400 (21.6%) TAVR. AVR linearly increased (from 78,985 in 2012 to 103,415 in 2016; +30.9%; ptrend

Background The aim of this study is to quantify the burden caused by viral hepatitis in China from 1990 to 2016. Methods Data from the GBD 2016 study were extracted to calculate incidence, prevalence and disability-adjusted life years (DALYs). Trends in DALYs were assessed in 33 provinces/regions. Results From 1990 to 2016, the total incidence of hepatitis decreased by 88.5%. However, the prevalence of hepatitis (counts in thousands), increased by 37.6% from 153,856 (95% UI: 136,047-172,319) in 1990 to 211,721 (95% UI: 179,776-240,981) in 2016, with age-standardized prevalence rates changing slightly. The number and age-standardized rates of prevalence increased by 35.9 and 1.6% for hepatitis B, respectively, and by 81.8 and 30.4% for hepatitis C. Guangxi, Guangdong and Hainan had the highest age-standardized prevalence rates (≥16,500 per 100,000). Tibet, Qinghai and Gansu had the highest age-standardized DALYs rates (≥40 per 100,000). The largest absolute number of DALYs was observed in the 15–49 year age group in 2016. The highest rate of DALYs occurred in males aged 50–69 years and in females aged ≧70 years. Conclusion The incidence and DALYs of viral hepatitis decreased dramatically from 1990 to 2016. However, the prevalence still remains at a high level, which may result in heavy burdens in the future.

New HIV infections among adolescents continues to be a large public health burden in sub-Saharan Africa, with few adolescents accessing HIV testing and counseling (HTC) services. We evaluated the effect of a peer referral program among adolescents in Kisumu county, Kenya in accessing HTC. Female adolescents aged 15 to 19years were recruited from three health clinics in Kisumu County. They, in turn, recruited their peers for HTC by handing out referral cards. Referrals would then recruit their peers and this peer-referral repeated for approximately 5months. The 252 female index seeds showed a relatively higher-risk profile for HIV compared to the 792 referral participants. The referral system yielded an increased proportion of first-time adolescent testers from 13.1% among index seeds to 42.7% among the second wave of referrals. However, the peer referral system ultimately did not increase the absolute number of adolescents Queryaccessing HTC. Future strategies should consider these findings to better target those with undiagnosed HIV infection.

Background: Nigeria, the most populous country in Africa, has reported relatively high levels of alcohol misuse, yet limited resources to guide effective population-wide response. There is a need to integrate existing empirical information in order to increase the power and precision of estimating epidemiological evidence necessary for informing policies and developing prevention programs.\ud \ud Objectives: We aimed to estimate nationwide and zonal prevalence of harmful use of alcohol in Nigeria to inform public health policy and planning.\ud \ud Methods: Epidemiologic reports on alcohol use in Nigeria from 1990 through 2018 were systematically searched and abstracted. We employed random-effects meta-analysis and meta-regression model to determine the number of harmful alcohol users.\ud \ud Results: 35 studies (n = 37,576 Nigerians) were identified. Pooled crude prevalence of harmful use of alcohol was 34.3% (95% CI: 28.6–40.1); twice as high among men (43.9%, 31.1–56.8) compared to women (23.9%, 16.4–31.4). Harmful alcohol use was higher in rural settings (40.1%, 24.2–56.1) compared to urban settings (31.2%, 22.9–39.6). The number of harmful alcohol users aged ≥15 years increased from 24 to 34 million from 1995 to 2015. However, actual age-adjusted prevalence of harmful use of alcohol in Nigeria decreased from 38.5% to 32.6% over the twenty-year period.\ud \ud Conclusions: While the prevalence of the total population that drinks harmfully appears to be dropping, absolute number of individuals that would be classified as harmful drinkers is increasing. This finding highlights the complexity of identifying and advocating for substance abuse policies in rapidly changing demographic settings common in Africa, Asia, and other developing countries.

Introduction Flat urothelial lesions fall into one of four diagnostic categories including urothelial carcinoma in-situ (CIS). There is morphologic overlap between the categories leading to immunohistochemistry (IHC) utilization in difficult cases. The purpose of this study was to examine the frequency, variation and utility of IHC use in bladder biopsy specimens over a 17 year period. Methods A search of “CD44”, “p53”, and “CK20” keywords was conducted from the pathology files (1/1/2003 to 12/31/2017) on bladder biopsy specimens at our institution. Atypical (AUS), dysplastic (UD) and CIS rates were calculated. Results A total of 4597 cases were identified. IHC was performed on 345 specimens (7.5%, 345/4597). For cases without IHC (H&E only), the AUS rate was 4.8% (206/4252), UD rate was 9.4% (399/4252), and the CIS rate was 8.4% (359/4252). For IHC cases, the AUS rate was 5.2% (18/345), the UD rate was 8.1% (28/345), and the CIS rate was 11.3% (39/345). There was no statistical difference between the H&E only or IHC rates ( p > 0.05). The absolute number IHC orders per year increased until 2011 (60 cases) but drastically declined over the last five years (5 total cases in 2017). The CIS rates have remained relatively constant. Conclusion We found the AUS, UD and CIS rates were similar regardless of IHC use. Our institution was an early adopter of IHC and it quickly fell out of favor. We agree with the ISUP in that IHC has limited clinical utility for flat urothelial lesions and morphology remains the gold standard.

Background Prescription drug suicide merits study to guide the development of strategies to reduce suicide risk. We examined prescription drug suicide specifically in non-abusers of prescription drugs; this is a relatively unexplored subject. Methods Six-year data on prescription drug suicide in non-abusers were extracted from the records of the Department of Forensic Medicine at the All India Institute of Medical Sciences, New Delhi. These records contained information obtained from the scene of the suicide, from interviews with relatives of the deceased, and from forensic toxicological analyses at two laboratories. Results There were 27 (8%) cases of prescription drug suicide in non-abusers out of 338 cases of suicidal poisoning. The mean age of this sample was 26 years. The sample was 74% male. Nearly half of the cases (44%) were students. A combination of dextropropoxyphene with dicyclomine, with or without paracetamol, was used by 41% of cases. Overdose was achieved through the ingestion of 10–40 (median, 30) tablets or by the injection of 2–3 (median, 2) vials of medication. In 52% of cases, it appeared that the drugs had been procured over the counter. Conclusions It is reassuring that the absolute number of prescription drug suicides in non-abusers was small; the findings, however, are important because they could serve as a baseline for assessing time trends in future studies. For the present, we suggest that prescription drugs of potential abuse, especially those containing opioids and antispasmodics, should be prescribed and dispensed judiciously, especially to youth.

SETTING The Cameroonian National Tuberculosis Programme. OBJECTIVES To assess case surveillance data for the 9-year period between January 2006 and December 2014. DESIGN Retrospective descriptive analysis of tuberculosis (TB) case finding in Cameroon using routine surveillance data. Data on sociodemographic characteristics, disease category, clinical and laboratory variables, and geographic regions were analysed. RESULTS The absolute number of TB cases (all forms) notified increased from 24 878 in 2006 to 26 517 in 2014; however, the population-adjusted annual case notification rate (CNR) of TB (all forms) as well as that of new smear-positive pulmonary TB cases decreased significantly, from 139 to 121 (P < 0.001) and from 77 to 70/100 000 population (P < 0.02), respectively. The human immunodeficiency virus (HIV) infection rate reported among all TB cases (39% in 2014) remained stable from 2009. The male-to-female ratio also remained stable, with a slight shift towards older age. There was a CNR gradient from the north to the south that appears to be related to HIV infection rates, population density and access to health services. CONCLUSIONS TB CNRs in Cameroon for the 2006-2014 period show a slow but steady decrease, and there are indications that the trend reflects incidence. However, there is evidence to suggest that TB transmission is still ongoing.

The second phase of Healthy Japan 21 seeks to increase disability-free life expectancy (DFLE) more than life expectancy (LE) between 2013 and 2022. In the face of the rising incidence of disability, the feasibility of achieving this goal remains unclear. We examine changes in DFLE at birth between 2000 and 2010 across 47 prefectures, with particular attention given to changes in the absolute number of years and in the proportion of disability-free life years. Although LE increased across all prefectures, there is a variation in DFLE. While the number of disability-free life years increased in many parts of the country, some prefectures had decreases in DFLE. Downturns become particularly evident when DFLE is interpreted in relative terms. The proportion of life spent without disability declined in the majority of prefectures. Results from subnational level analyses suggest that the rate of increase in DFLE lagged behind that in LE across Japanese prefectures during the past decade. More policy attention should be devoted to health-promotion initiatives at the prefecture level to achieve the nationwide health agenda.