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ObjectivesTo describe the global trends of pulmonary nontuberculous mycobacteria (NTM) infection and disease.MethodsA systematic review of studies including culture-based NTM data over time. Studies reporting on pulmonary NTM infection and/or disease were included. Information on the use of guideline-based criteria for disease were collected, in which, infection is defined as the absence of symptoms and radiological findings compatible with NTM pulmonary disease. The trends of change for incidence/prevalence were evaluated using linear regressions, and the corresponding pooled estimates were calculated.ResultsMost studies reported increasing pulmonary NTM infection (82.1%) and disease (66.7%) trends. The overall annual rate of change for NTM infection and disease per 100,000 persons/year was 4.0% (95% confidence interval [CI]: 3.2-4.8) and 4.1% (95% CI: 3.2-5.0), respectively. For absolute numbers of NTM infection and disease, the overall annual change was 2.0 (95% CI: 1.6-2.3) and 0.5 (95% CI: 0.3-0.7), respectively. An increasing trend was also seen for Mycobacterium avium complex infection (n = 15/19, 78.9%) and disease (n = 10/12, 83.9%) and for Mycobacterium abscessus complex (n = 15/23, 65.2%) infection (n = 11/17, 64.7%) but less so for disease (n = 2/8, 25.0%).ConclusionOur data indicate an overall increase in NTM worldwide for both infection and disease. The explanation to this phenomenon warrants further investigation. Objectives: To describe the global trends of pulmonary nontuberculous mycobacteria (NTM) infection and disease.Methods: A systematic review of studies including culture-based NTM data over time. Studies reporting on pulmonary NTM infection and/or disease were included. Information on the use of guideline-based criteria for disease were collected, in which, infection is defined as the absence of symptoms and radiological findings compatible with NTM pulmonary disease. The trends of change for incidence/prevalence were evaluated using linear regressions, and the corresponding pooled estimates were calculated.Results: Most studies reported increasing pulmonary NTM infection (82.1%) and disease (66.7%) trends. The overall annual rate of change for NTM infection and disease per 10 0,000 persons/year was 4.0% (95% confidence interval [CI]: 3.2-4.8) and 4.1% (95% CI: 3.2-5.0), respectively. For absolute numbers of NTM infection and disease, the overall annual change was 2.0 (95% CI: 1.6-2.3) and 0.5 (95% CI: 0.3-0.7), respectively. An increasing trend was also seen for Mycobacterium avium complex infection (n = 15/19, 78.9%) and disease (n = 10/12, 83.9%) and for Mycobacterium abscessus complex (n = 15/23, 65.2%) infection (n = 11/17, 64.7%) but less so for disease (n = 2/8, 25.0%).Conclusion: Our data indicate an overall increase in NTM worldwide for both infection and disease. The explanation to this phenomenon warrants further investigation.(c) 2022 The Author(s). Published by Elsevier Ltd on behalf of International Society for Infectious Diseases. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)

Purpose To design a model based on the three pillars of new institutional theory (NIT), that facilitates cross-country comparison of labor participation (LP) of people with chronic diseases. This model should support getting a comprehensive overview of factors representing country differences, understanding these differences and should support estimating cross-country transferability of policies and interventions in the context of Work Disability Prevention. Methods Based on NIT, a draft model was designed by means of (1) a literature review of empirical studies; (2) theoretical books and articles; (3) a focus group with six expert researchers. This draft model was (4) adapted in the context of academic education. Literature was searched on Web of Science and EBSCO host. Feedback on (use of) the model was received from the focus group, four different academic courses at 28 occasions and two international conferences. Results The cross-country comparison model for labor participation (CCC model for LP) of persons with chronic diseases is proposed consisting of five factors: (1) Legislation; (2) Norms & values in practice; (3) Culture; (4) Organization of WDP in practice; (5) Labor market characteristics. Within these factors and based on (in)direct empirical evidence, subfactors are distinguished. The feedback received led to renaming (sub) factors, improved visual representation and a tool for estimating transferability. Conclusions The CCC model for LP of persons with chronic diseases allows for a comprehensive understanding of country differences and cross-country transferability of policies and interventions. The CCC model can be used for other populations when population-specific subfactors are included.

Objective To determine whether high-flow nasal cannula oxygen (HFNCO) provided enhanced respiratory support in bronchiolitis than low-flow oxygen (LFO). Methods We conducted a prospective, randomized controlled trial in children between 1 and 24 months diagnosed with moderate-to-severe bronchiolitis requiring oxygen therapy. Participants received LFO via face mask (6-10 L/min) or HFNCO (2 L/kg/min). Primary outcomes were the time that heart rate (HR) and respiratory rate (RR) return to their normal range for age and the time that baseline clinical respiratory score (CRS) regress to a lower severity score. Secondary outcomes were changes in HR, RR, and CRS over time, length of stay (LOS), duration of oxygen requirement, treatment failure, and adverse event (AE). Results Eighty-seven children were enrolled (48 in LFO; 39 in HFNCO). The time that HR and RR baseline values reached their normal range for age was shorter in HFNCO therapy (2.0 h [1.0-4.0] vs. 12.0 h [2.0-24.0], and 4.0 h [2.0-12.0] vs. 24.0 h [4.0-48.0], respectively; p < 0.001); additionally, the improvement in CRS emerged more quickly in children treated with HFNCO (2.0 h [1.0-4.0] vs. 4.0 h [2.0-24.0]; p = 0.003). While the duration of oxygen requirement (19.0 h [4.0-30.0] vs. 29.5 h [14.0-45.7]; p = 0.009) and treatment failure (3% vs. 21%) was statistically lower in children who received HFNCO, there were no differences in LOS and AE between groups. Conclusion HFNCO may provide enhanced respiratory support with a notable improvement in HR, RR, and CRS than LFO. Comprehensive studies are needed to assess the clinical efficacy of HFNCO therapy., Ege University Research Foundation [17-2.1/18], Ege University Research Foundation, Grant/Award Number: 17-2.1/18

Purpose: To evaluate patient-reported sexual outcomes after chemoradiation therapy and image-guided adaptive brachytherapy for locally advanced cervical cancer in the observational, prospective, multicenter EMBRACE-I study. Methods and Materials: Sexual outcomes were assessed prospectively with the European Organization for Research and Treatment of Cancer Qualify of Life Questionnaire (EORTC-QLQ-CX24) at baseline and follow-up. Crude incidence and prevalence rates of sexual activity, vaginal functioning problems (dryness, shortening, tightening, pain during intercourse), and sexual enjoyment were evaluated. Associations between pain during intercourse and vaginal functioning problems or sexual enjoyment were calculated, pooling observations over all follow-ups (Spearman correlation coefficient). In patients who were frequently sexually active (≥50% of follow-ups), the effects of regular hormonal replacement therapy (HRT) on vaginal functioning problems were evaluated (Pearson χ 2). Results: The analysis involved 1045 patients with a median follow-up of 50 months. Sexual activity was reported by 22% of patients at baseline and by 40% to 47% of patients during follow-up (prevalence rates). Vaginal functioning problems in follow-up were dryness (18%-21%), shortening (15%-22%), tightening (16%-22%), pain during intercourse (9%-21%), and compromised enjoyment (37%-47%). Pain during intercourse was significantly associated with vaginal tightening (r = 0.544), shortening (r = 0.532), and dryness (r = 0.408) and negatively correlated with sexual enjoyment (r = –0.407). Regular HRT was associated with significantly less vaginal dryness (P = .015), shortening (P = .024), pain during intercourse (P = .003), and borderline higher sexual enjoyment (P = .062). Conclusions: Vaginal functioning problems are associated with pain and compromised sexual enjoyment. Further effort is required for the primary prevention of vaginal morbidity with dose optimization and adaptation. Secondary prevention strategies, including HRT for vaginal and sexual health after radiation therapy in locally advanced cervical cancer, should be considered and sexual rehabilitation programs should be developed further.

BACKGROUND AND AIMS: Increased fatty acid (FA) flux from adipose tissue to the liver contributes to the development of NAFLD. Because free FAs are key lipotoxic triggers accelerating disease progression, inhibiting adipose triglyceride lipase (ATGL)/patatin-like phospholipase domain containing 2 (PNPLA2), the main enzyme driving lipolysis, may attenuate steatohepatitis. APPROACH AND RESULTS: Hepatocyte-specific ATGL knockout (ATGL LKO) mice were challenged with methionine-choline-deficient (MCD) or high-fat high-carbohydrate (HFHC) diet. Serum biochemistry, hepatic lipid content and liver histology were assessed. Mechanistically, hepatic gene and protein expression of lipid metabolism, inflammation, fibrosis, apoptosis, and endoplasmic reticulum (ER) stress markers were investigated. DNA binding activity for peroxisome proliferator-activated receptor (PPAR) α and PPARδ was measured. After short hairpin RNA-mediated ATGL knockdown, HepG2 cells were treated with lipopolysaccharide (LPS) or oleic acid:palmitic acid 2:1 (OP21) to explore the direct role of ATGL in inflammation in vitro. On MCD and HFHC challenge, ATGL LKO mice showed reduced PPARα and increased PPARδ DNA binding activity when compared with challenged wild-type (WT) mice. Despite histologically and biochemically pronounced hepatic steatosis, dietary-challenged ATGL LKO mice showed lower hepatic inflammation, reflected by the reduced number of Galectin3/MAC-2 and myeloperoxidase-positive cells and low mRNA expression levels of inflammatory markers (such as IL-1β and F4/80) when compared with WT mice. In line with this, protein levels of the ER stress markers protein kinase R-like endoplasmic reticulum kinase and inositol-requiring enzyme 1α were reduced in ATGL LKO mice fed with MCD diet. Accordingly, pretreatment of LPS-treated HepG2 cells with the PPARδ agonist GW0742 suppressed mRNA expression of inflammatory markers. Additionally, ATGL knockdown in HepG2 cells attenuated LPS/OP21-induced expression of proinflammatory cytokines and chemokines such as chemokine (C-X-C motif) ligand 5, chemokine (C-C motif) ligand (Ccl) 2, and Ccl5. CONCLUSIONS: Low hepatic lipolysis and increased PPARδ activity in ATGL/PNPLA2 deficiency may counteract hepatic inflammation and ER stress despite increased steatosis. Therefore, lowering hepatocyte lipolysis through ATGL inhibition represents a promising therapeutic strategy for the treatment of steatohepatitis. ispartof: HEPATOLOGY vol:75 issue:1 pages:125-139 ispartof: location:United States status: published

Rates of survival with functional recovery for both in-hospital and out-of-hospital cardiac arrest are notably low. Extracorporeal cardiopulmonary resuscitation (ECPR) is emerging as a modality to improve prognosis by augmenting perfusion to vital end-organs by utilizing extracorporeal membrane oxygenation (ECMO) during conventional CPR and stabilizing the patient for interventions aimed at reversing the aetiology of the arrest. Implementing this emergent procedure requires a substantial investment in resources, and even the most successful ECPR programs may nonetheless burden healthcare systems, clinicians, patients, and their families with unsalvageable patients supported by extracorporeal devices. Non-randomized and observational studies have repeatedly shown an association between ECPR and improved survival, versus conventional CPR, for in-hospital cardiac arrest in select patient populations. Recently, randomized controlled trials suggest benefit for ECPR over standard resuscitation, as well as the feasibility of performing such trials, in out-of-hospital cardiac arrest within highly coordinated healthcare delivery systems. Application of these data to clinical practice should be done cautiously, with outcomes likely to vary by the setting and system within which ECPR is initiated. ECPR introduces important ethical challenges, including whether it should be considered an extension of CPR, at what point it becomes sustained organ replacement therapy, and how to approach patients unable to recover or be bridged to heart replacement therapy. The economic impact of ECPR varies by health system, and has the potential to outstrip resources if used indiscriminately. Ideally, studies should include economic evaluations to inform health care systems about the cost-benefits of this therapy.

IntroductionHospital admissions in many countries fell dramatically at the onset of the COVID-19 pandemic. Less is known about how care patterns differed by patient groups. We sought to determine whether areas with higher levels of socioeconomic deprivation or larger ethnic minority populations saw larger falls in emergency and planned admissions in England.MethodsWe conducted a national observational study of hospital care in the English National Health Service (NHS) in 2019–2020. Weekly volumes of elective (planned) and emergency admissions in 2020 compared with 2019 were calculated for each census area. Multiple linear regression analysis was used to estimate the reductions in volumes for areas in different quintiles of socioeconomic deprivation and ethnic minority populations after controlling for national time trends and local area composition.ResultsBetween March and December 2020, there were 35.5% (3.0 million) fewer elective admissions and 22.0% (1.2 million) fewer emergency admissions with a non-COVID-19 primary diagnosis than in 2019. Areas with the largest share of ethnic minority populations experienced a 36.7% (95% CI 24.1% to 49.3%) larger reduction in non-primary COVID-19 emergency admissions compared with those with the smallest. The most deprived areas experienced a 10.1% (95% CI 2.6% to 17.7%) smaller reduction in non-COVID-19 emergency admissions compared with the least deprived. These patterns are not explained by differential prevalence of COVID-19 cases by area.ConclusionsEven in a healthcare system founded on the principle of equal access for equal need, the impact of COVID-19 on NHS hospital care for non-COVID patients has not been spread evenly by ethnicity and deprivation in England. While we cannot conclusively determine the mechanisms behind these differences, they risk exacerbating prepandemic health inequalities.

Publisher Copyright: © 2021 The Authors. Influenza and Other Respiratory Viruses published by John Wiley & Sons Ltd. Background: The clinical significance of respiratory syncytial virus (RSV) among adults remains underinvestigated. We compared the characteristics and population-based attack rates of RSV and influenza hospitalizations. Methods: During 2018–2020, we recruited hospitalized adults with respiratory infection to our prospective substudy at a tertiary care hospital in Finland and compared the characteristics of RSV and influenza patients. In our retrospective substudy, we calculated the attack rates of all RSV and influenza hospitalizations among adults in the same geographic area during 2016–2020. Results: Of the 537 prospective substudy patients, 31 (6%) had RSV, and 106 (20%) had influenza. Duration of hospitalization, need for intensive care or outcome did not differ significantly between RSV and influenza patients. RSV was more often missed or its diagnosis omitted from medical record (13% vs. 1%, p = 0.016 and 52% vs. 85%, p < 0.001). In the retrospective substudy, the mean attack rates of RSV, influenza A, and influenza B hospitalizations rose with age from 4.1 (range by season 1.9–5.9), 15.4 (12.3–23.3), and 4.7 (0.5–16.2) per 100,000 persons among 18- to 64-year-olds to 58.3 (19.3–117.6), 204.1 (31.0–345.0), and 60.4 (0.0–231.0) per 100,000 persons among 65+-year-olds and varied considerably between seasons. Discussion: While the attack rates of influenza hospitalizations were higher compared with RSV, RSV and influenza hospitalizations were similar in severity. Missing or underreporting of RSV infections may lead to underestimating its disease burden. Both RSV and influenza caused a substantial amount of hospitalizations among the elderly, stressing the need for more effective interventions.

Listeriosis is an infective complication that primarily affects pregnant women, patients at extremes of age or those with weakened immune systems. Ingestion of food contaminated with Listeria monocytogenes is the most common source of infection, causing self-limiting illness in immunocompetent hosts but associated with invasive infection and high mortality in high-risk patient groups. Milder illness presents as gastroenteritis with fever, diarrhoea, nausea and vomiting common in the 7 days post exposure. Invasive infection, characterised by bacteraemia and encephalitis, can develop in high-risk patients. Fetal loss is a major complication of listeriosis during pregnancy. Penicillin-based therapy (high dose penicillin or amoxicillin) in combination with gentamicin is advised for invasive infection; co-trimoxazole may be considered for patients intolerant to penicillin. Vulnerable individuals, notably pregnant women, should be counseled on appropriate preventative strategies including avoiding foods commonly contaminated with L. monocytogenes, such as soft ripened cheeses, pate, cooked chilled meats, unpasteurised milk, and ready to eat poultry unless thoroughly cooked.

Varicella-zoster virus (VZV) infection of neuronal cells and the activation of cell-intrinsic antiviral responses upon infection are still poorly understood mainly due to the scarcity of suitable human in vitro models that are available to study VZV. We developed a compartmentalized human-induced pluripotent stem cell (hiPSC)-derived neuronal culture model that allows axonal VZV infection of the neurons, thereby mimicking the natural route of infection. Using this model, we showed that hiPSC-neurons do not mount an effective interferon-mediated antiviral response following VZV infection. Indeed, in contrast to infection with Sendai virus, VZV infection of the hiPSC-neurons does not result in the upregulation of interferon-stimulated genes (ISGs) that have direct antiviral functions. Furthermore, the hiPSC-neurons do not produce interferon-α (IFNα), a major cytokine that is involved in the innate antiviral response, even upon its stimulation with strong synthetic inducers. In contrast, we showed that exogenous IFNα effectively limits VZV spread in the neuronal cell body compartment and demonstrated that ISGs are efficiently upregulated in these VZV-infected neuronal cultures that are treated with IFNα. Thus, whereas the cultured hiPSC neurons seem to be poor IFNα producers, they are good IFNα responders. This could suggest an important role for other cells such as satellite glial cells or macrophages to produce IFNα for VZV infection control. ispartof: VIRUSES-BASEL vol:14 issue:11 ispartof: location:Switzerland status: published

Background Bone fractures are a global public health issue; however, to date, no comprehensive study of their incidence and burden has been done. We aimed to measure the global, regional, and national incidence, prevalence, and years lived with disability (YLDs) of fractures from 1990 to 2019. Methods Using the framework of the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019, we compared numbers and age-standardised rates of global incidence, prevalence, and YLDs of fractures across the 21 GBD regions and 204 countries and territories, by age, sex, and year, from 1990 to 2019. We report estimates with 95% uncertainty intervals (UIs). Findings Globally, in 2019, there were 178 million (95% UI 162-196) new fractures (an increase of 33.4% [30.1-37.0] since 1990), 455 million (428-484) prevalent cases of acute or long-term symptoms of a fracture (an increase of 70.1% [67.5-72.5] since 1990), and 25.8 million (17.8-35.8) YLDs (an increase of 65.3% [62.4-68.0] since 1990). The age-standardised rates of fractures in 2019 were 2296.2 incident cases (2091.1-2529.5) per 100 000 population (a decrease of 9.6% [8.1-11.1] since 1990), 5614.3 prevalent cases (5286.1-5977.5) per 100 000 population (a decrease of 6.7% [5.7-7.6] since 1990), and 319.0 YLDs (220.1-442.5) per 100 000 population (a decrease of 8.4% [7.2-9.5] since 1990). Lower leg fractures of the patella, tibia or fibula, or ankle were the most common and burdensome fracture in 2019, with an age-standardised incidence rate of 419.9 cases (345.8-512.0) per 100 000 population and an age-standardised rate of YLDs of 190.4 (125.0-276.9) per 100 000 population. In 2019, age-specific rates of fracture incidence were highest in the oldest age groups, with, for instance, 15 381.5 incident cases (11 245.3-20 651.9) per 100 000 population in those aged 95 years and older. Interpretation The global age-standardised rates of incidence, prevalence, and YLDs for fractures decreased slightly from 1990 to 2019, but the absolute counts increased substantially. Older people have a particularly high risk of fractures, and more widespread injury-prevention efforts and access to screening and treatment of osteoporosis for older individuals should help to reduce the overall burden. Copyright (C) 2021 The Author(s). Published by Elsevier Ltd.

Background Pain is undertreated in older populations. At the same time, increased use of opioids is of concern in the Western world. Aims We sought to analyze temporal trends in musculoskeletal pain and prescribed analgesic treatment among community-dwelling people aged 75-95 years using cross-sectional cohort data spanning 20 years. Methods The Helsinki Aging Study recruited random samples of people aged 75, 80, 85, 90, and 95 years in 1999, 2009, and 2019. In total, 5707 community-dwelling persons participated in the study. The participants reported their medical diagnoses, regular prescription medications, and the presence of back pain or joint pain within the last 2 weeks (never, sometimes, or daily). We compared analgesic use among participants reporting and not reporting musculoskeletal pain in 1999, 2009, and 2019. Results Of the participants, 57-61% reported intermittent or daily musculoskeletal pain. The percentage receiving a prescribed daily analgesic increased from 9% in 1999 to 16% in 2019. The use of non-steroidal anti-inflammatory drugs (NSAIDs) decreased from 1999 to 2019, while the use of paracetamol increased from 2 to 11%. Opioids were taken by 2% in 1999 and 3% in 2019. Of those reporting daily musculoskeletal pain, 20%, 35%, and 32% received regular pain medication in 1999, 2009, and 2019, respectively. Conclusions Pain remains undertreated in the community-dwelling older population, although the use of regular prescribed analgesics increased between 1999 and 2019. The use of NSAIDs has decreased, while the use of paracetamol has increased. Daily opioid use has remained modest.

Background It is known that drug shortages represent a major challenge for all stakeholders involved in the process, but there is little evidence regarding insights into patients′ awareness and perspectives. This study aimed to investigate the patients-perceived drug shortages experience and their view on outcomes in different European hospital settings. Furthermore, we wanted to explore information preferences on drug shortages. Methods A retrospective, cross sectional, a mixed method study was conducted in six European hospital settings. One hospital (H) from each of this country agreed to participate: Bosnia and Herzegovina (H-BiH), Croatia (H-CR), Germany (H-GE), Greece (H-GR), Serbia (H-SE) and Poland (H-PO). Recruitment and data collection was conducted over 27 months from November 2017 until January 2020. Overall, we surveyed 607 patients which completed paper-based questionnaire. Questions related to: general information (demographic data), basic knowledge on drug shortages, drug shortages experienced during hospitalization and information preferences on drug shortage. Differences between hospital settings were analyzed using Chi-squared test or Fisher’s exact test. For more complex contingency tables, Monte Carlo simulations (N = 2000) were applied for Fisher’s test. Post-hoc hospital-wise analyses were performed using Fisher’s exact tests. False discovery rate was controlled using the Bonferroni method. Analyses were performed using R: a language and environment for statistical computing (v 3.6.3). Results 6 % of patients reported experiences with drug shortages while hospitalized which led to a deterioration of their health. The majority of affected patients were hospitalized at hematology and/or oncology wards in H-BiH, H-PO and H-GE. H-BiH had the highest number of affected patients (18.1 %, N = 19/105, p N = 1/100, p = 0.001). In addition, 82.5 %, (N = 501/607) of respondents wanted to be informed of alternative treatment options if there was a drug shortage without a generic substitute available. Majority of these patients (66.4 %, N = 386/501) prefer to be informed by a healthcare professional. Conclusions Although drug shortages led to serious medical consequences, our findings show that most of the patients did not perceive shortages as a problem. One possible interpretation is that good hospital management practices by healthcare professionals helped to mitigate the perceived impact of shortages. Our study highlights the importance of a good communication especially between patients and healthcare professionals in whom our patients have the greatest trust.

Introduction: Life expectancy is rising and consequently also the number of older patients with head and neck cancer. Different treatment regimens are often applied for older patients. The aim of this study is to investigate how treatment patterns and survival rates have changed over the past 20 years in older patients with head and neck squamous cell carcinoma (HNSCC). Materials: Patient and tumour characteristics, treatment and 5-year survival data from the Netherlands Cancer Registry of patients aged >60 years diagnosed with HNSCC in 1990-1995 and 2010-2015 were compared using chi-square test and relative survival analysis.Results: Data of 14,114 patients were analyzed. Oral cavity cancer treatment did not change over time, while survival improved from 54% to 58% (p 1/4 0.03). Oropharyngeal and hypopharyngeal cancer treatment shifted towards non-surgical, with survival improving from 31% to 51% (p < 0.01) and 26% to 34% (p < 0.01), respectively. Laryngeal cancer treatment changed towards surgery in stage I and non-surgical treatment in stage III and IV disease. Survival in laryngeal cancer stage I remained stable and favorable at a relative survival rate of around 90%. Survival non-significantly changed from 54% to 49% for stage III disease and from 37% to 33% for disease.Conclusion: Relative survival increased for all head and neck cancer sites in older patients, except for laryngeal cancer. For oropharyngeal, hypopharyngeal and advanced laryngeal cancer, a shift towards non-surgical treatment modalities was observed.(c) 2021 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY license

Background: Cryptococcosis is one of the major causes of mortality among HIV patients worldwide. Though most often associated with late stage HIV infection/AIDS, a significant number of cases occur in other immunocompromised patients such as solid organ transplant recipients and patients with hematological malignancies. Immunocompromised patients are a heterogeneous group and their number increases constantly. Since little is known about the incidence and the clinical features of cryptococcosis in Northern Europe, our aim was to investigate the clinical characteristics of cryptococcosis patients in Finland. Methods: We retrospectively reviewed the laboratory confirmed cryptococcosis cases in Finland during 2004–2018. Only those who were treated for cryptococcosis were included in the study. Initial laboratory findings and medical records were also collected. Results: A total of 22 patients with cryptococcosis were included in our study. The annual incidence of cryptococcosis was 0.03 cases per 100,000 population. Ten patients were HIV-positive and 12 out of 22 were HIV-negative. Hematological malignancy was the most common underlying condition among HIV-negative patients. Conclusions: To our knowledge, this is the first study of the clinical presentation and incidence of cryptococcosis in Finland. We demonstrate that invasive cryptococcal infection occurs not only in HIV/AIDS patients or otherwise immunocompromised patients but also in immunocompetent individuals. Even though cryptococcosis is extremely rare in Finland, its recognition is important since the prognosis depends on rapid diagnostics and early antifungal therapy. publishedVersion

Devices designed to enhance and diversify sexual pleasure are useful in clinical practice; however, many taboos still seem to exist and the scientific literature on the prevalence, application and effectiveness of sexual devices for therapeutic use is sparse. In this Review, Dewitte and Reisman discuss the clinical use of sex toys and sexual devices, as well as sexually explicit media, across a variety of indications to expand individual and partnered sexuality and to treat sexual difficulties. Given that sexual pleasure is a core component of sexual health, devices that are designed to enhance and diversify sexual pleasure are particularly useful in clinical practice. Despite their growing popularity and widespread use in various biopsychosocial circumstances, many taboos still seem to exist, as indicated by the paucity of scientific literature on the prevalence, application and effectiveness of sexual devices for therapeutic use. However, sex toys and sexual devices are commonly used and have a variety of indications to expand individual and partnered sexuality and to treat sexual difficulties. Different devices are associated with specific advantages and potential risks, opportunities, barriers and ethical challenges when used in a clinical context. Increased knowledge about the aim and functional possibilities of sexual devices might help health-care professionals overcome potential embarrassment, preconceptions and other barriers, learn which patients might benefit from which products, consider their use in treatment programmes, educate about correct use and safety issues, and facilitate open communication about sexual pleasure with their patients.

The kidney is one of the most sensitive organs to cadmium-induced toxicity, particularly in conditions of long-term oxidative stress. We hypothesized that, in kidney transplant recipients, nephrotoxic exposure to cadmium represents an overlooked hazard for optimal graft function. To test this, we performed a prospective cohort study and included 672 outpatient kidney transplant recipients with a functioning graft of beyond one year. The median plasma cadmium was 58 ng/L. During a median 4.9 years of follow-up, 78 kidney transplant recipients developed graft failure with a significantly different distribution across tertiles of plasma cadmium (13, 26, and 39 events, respectively). Plasma cadmium was associated with an increased risk of graft failure (hazard ratio 1.96, 95% confidence interval 1.56-2.47 per log(2) ng/L). Similarly, a dose-response relationship was observed over increasing tertiles of plasma cadmium, after adjustments for potential confounders (donor, recipient, transplant and lifestyle characteristics), robust in both competing risk and sensitivity analyses. These findings were also consistent for kidney function decline (graft failure or doubling of serum creatinine). Thus, plasma cadmium is independently associated with an increased risk of long-term kidney graft failure and decline in kidney function. Further studies are needed to investigate whether exposure to cadmium represents an otherwise overlooked modifiable risk factor for adverse long-term graft outcomes in different populations.

Depression is a leading cause of disability worldwide, but is often underdiagnosed and undertreated. Cognitive behavioural therapy holds that individuals with depression exhibit distorted modes of thinking, that is, cognitive distortions, that can negatively affect their emotions and motivation. Here, we show that the language of individuals with a self-reported diagnosis of depression on social media is characterized by higher levels of distorted thinking compared with a random sample. This effect is specific to the distorted nature of the expression and cannot be explained by the presence of specific topics, sentiment or first-person pronouns. This study identifies online language patterns that are indicative of depression-related distorted thinking. We caution that any future applications of this research should carefully consider ethical and data privacy issues.Cognitive distortions have a central role in the development of depression. Here, the authors examine the tweets of thousands of individuals who report a diagnosis of depression, revealing significantly higher levels of distortions compared with a control group of Twitter users.

This article charts the popularization of and eventual disengagement with an approach to wound infection control centered on the medical efficacy of living beings (maggots) in 1920s and 1930s America. Baltimore surgeon William Stevenson Baer successfully drew on his wartime experience to promote the use of sterile or “surgical” maggots in the treatment for deep-seated bone infection at this time. This article situates the practices he promoted in the context of President Herbert Hoover's contemporary establishment of the “associative state,” thereby drawing out the relevance of the latter to medical governance. In so doing, it conveys an image of the development of early twentieth-century infection control that contrasts with narratives centered on medically productive aspects of biomedical industrialization and specialization. The incorporation of surgical maggot research and evaluation within the United States Department of Agriculture played a critical role in the subsequent abandonment of the use of maggots as medical aides. Hoover's orientation of this institution towards the support of large-scale private enterprise helped motivate efforts to synthetically replicate (and thereby displace) maggots' medical efficacy. Ultimately, maggot-based therapeutics proved incompatible with conditions created by the orientation of American governmental institutions towards corporate subsidy rather than the support of individuals.

Background Long-acting reversible contraceptives (LARCs) have superior contraceptive efficacy compared to short-acting reversible contraceptives (SARCs) and choosing LARCs over SARC methods reduces the need for abortion care. However, little is known how initiating these methods associates with the subsequent overall need of reproductive health services including family planning services, and visits for gynecological reasons in primary and specialized care. Methods We followed altogether 5839 non-sterilized women aged 15–44 years initiating free-of-charge LARC methods (n = 1689), initiating or switching SARC methods (n = 1524), or continuing with the same SARC method (n = 2626) at primary care family planning clinics in the City of Vantaa, Finland, 2013–2014 for 2 years using Finnish national health registers. We assessed the use of reproductive health services, namely attending public primary or specialized health care for gynecological reasons or attending the family planning clinics by applying unadjusted and adjusted negative binomial regression models on visit counts. Results A total of 11,290 visits accumulated during the two-year follow-up: 7260 (64.3%) at family planning clinics, 3385 (30.0%) for gynecological reasons in primary, and 645 (5.7%) in specialized health care. Altogether 3804 (52.4%) visits at the family planning clinics were for routine checkup, and 3456 (47.6%) for other reasons. Women initiating LARC methods used reproductive health services for reasons other than routine checkups similarly as women initiating or switching SARC methods (adjusted incidence rate ratio 0.93, 95% CI 0.82–1.05), while women continuing with SARC methods used the services less frequently (0.65, 0.59–0.72). Women initiating free-of-charge LARC and those continuing with the same SARC method used services less for abortion care than women initiating or switching SARC (adjusted incidence rate ratios 0.05, 95% CI 0.03–0.08 and 0.16, 95% CI 0.11–0.24, respectively). Conclusions While women initiating LARC methods have lower need for abortion care compared to women initiating SARC methods, women initiating both LARC and SARC methods have similar overall need for reproductive health services. In contrast, women continuing with their SARC method need reproductive health services less than women initiating LARC or a new SARC method. These service needs should be acknowledged when planning and organizing family planning services, and when promoting long-acting reversible contraception.

© 2022 International League Against Epilepsy.Objective: The link between headache and epilepsy is more prominent in patients with idiopathic/genetic epilepsy (I/GE). We aimed to investigate the prevalence of headache and to cluster patients with regard to their headache and epilepsy features. Methods: Patients aged 6–40 years, with a definite diagnosis of I/GE, were consecutively enrolled. The patients were interviewed using standardized epilepsy and headache questionnaires, and their headache characteristics were investigated by experts in headache. Demographic and clinical variables were analyzed, and patients were clustered according to their epilepsy and headache characteristics using an unsupervised K-means algorithm. Results: Among 809 patients, 508 (62.8%) reported having any type of headache; 87.4% had interictal headache, and 41.2% had migraine. Cluster analysis revealed two distinct groups for both adults and children/adolescents. In adults, subjects having a family history of headache, ≥5 headache attacks, duration of headache ≥ 24 months, headaches lasting ≥1 h, and visual analog scale scores > 5 were grouped in one cluster, and subjects with juvenile myoclonic epilepsy (JME), myoclonic seizures, and generalized tonic–clonic seizures (GTCS) were clustered in this group (Cluster 1). Self-limited epilepsy with centrotemporal spikes and epilepsy with GTCS alone were clustered in Cluster 2 with the opposite characteristics. For children/adolescents, the same features as in adult Cluster 1 were clustered in a separate group, except for the presence of JME syndrome and GTCS alone as a seizure type. Focal seizures were clustered in another group with the opposite characteristics. In the entire group, the model revealed an additional cluster, including patients with the syndrome of GTCS alone (50.51%), with ≥5 attacks, headache lasting >4 h, and throbbing headache; 65.66% of patients had a family history of headache in this third cluster (n = 99). Significance: Patients with I/GE can be clustered into distinct groups according to headache features along with seizures. Our findings may help in management and planning for future studies.

BackgroundLow-value pharmaceutical care exists in general practice. However, the extent among Dutch GPs remains unknown.AimTo assess the prevalence of low-value pharmaceutical care among Dutch GPs.Design and settingRetrospective cohort study using data from patient records.MethodThe prevalence of three types of pharmaceutical care prescribed by GPs between 2016 and 2019 were examined: topical antibiotics for conjunctivitis, benzodiazepines for non-specific lower back pain, and chronic acid-reducing medication (ARM) prescriptions. Multilevel logistic regression analysis was performed to assess prescribing variation and the influence of patient characteristics on receiving a low-value prescription.ResultsLarge variation in prevalence as well as practice variation was observed among the types of low-value pharmaceutical GP care examined. Between 53% and 61% of patients received an inappropriate antibiotics prescription for conjunctivitis, around 3% of patients with lower back pain received an inappropriate benzodiazepine prescription, and 88% received an inappropriate chronic ARM prescription during the years examined. The odds of receiving an inappropriate antibiotic or benzodiazepine prescription increased with age (PPPPPConclusionThe results show that the prevalence of low-value pharmaceutical GP care varies among these three clinical problems. Significant variation in inappropriate prescribing exists between different types of pharmaceutical care — and GP practices.

Age and gender differences are prominent in the temperament literature, with the former particularly salient in infancy and the latter noted as early as the first year of life. This study represents a meta-analysis utilizing Infant Behavior Questionnaire-Revised (IBQ-R) data collected across multiple laboratories (N = 4438) to overcome limitations of smaller samples in elucidating links among temperament, age, and gender in early childhood. Algorithmic modeling techniques were leveraged to discern the extent to which the 14 IBQ-R subscale scores accurately classified participating children as boys (n = 2,298) and girls (n = 2,093), and into three age groups: youngest (< 24 weeks; n = 1,102), mid-range (24 to 48 weeks; n = 2,557), and oldest (> 48 weeks; n = 779). Additionally, simultaneous classification into age and gender categories was performed, providing an opportunity to consider the extent to which gender differences in temperament are informed by infant age. Results indicated that overall age group classification was more accurate than child gender models, suggesting that age-related changes are more salient than gender differences in early childhood with respect to temperament attributes. However, gender-based classification was superior in the oldest age group, suggesting temperament differences between boys and girls are accentuated with development. Fear emerged as the subscale contributing to accurate classifications most notably overall. This study leads infancy research and meta-analytic investigations more broadly in a new direction as a methodological demonstration, and also provides most optimal comparative data for the IBQ-R based on the largest and most representative dataset to date. National Institutes of Health [R01HL095606, R01HD082078, NIH R01 MH109692, R21 MH103627, R01 HD049878, R03 HD043057, 1P50 MH58922-01A1, 1P50 MH077928-01A1, 5R01HD080851-05, R01MH78033, 8P0GM103436, P20GM103436, 8P20GM103436, DK72996, M01RR10732]; Western Washington University [MFS 901, MFS 907] Published version MBE: R01HL095606, R01HD082078; National Institutes of Health https://www.nih.gov KPE, KB, & VL: NIH R01 MH109692; R21 MH103627 National Institutes of Health https://www.nih.gov MAB: R01 HD049878; R03 HD043057 National Institutes of Health https://www.nih.gov SG: 1P50 MH58922-01A1; 1P50 MH077928-01A1 National Institutes of Health https://www.nih.gov SS: 5R01HD080851-05 National Institutes of Health https://www.nih.gov AS: R01MH78033 National Institutes of Health https://www.nih.gov DL: 8P0GM103436; P20GM103436; 8P20GM103436 National Institutes of Health https://www.nih.gov TDRS: MFS 901; MFS 907 Western Washington University https://www.wwu.edu SAF: DK72996; M01RR10732 National Institutes of Health https://www.nih.gov None of the funders had any role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Background Drug shortages are a growing global problem, posing clinical and economic challenges. To understand them better, we conducted an inventory of national public drug shortage registers and their comparability in Europe and the USA. Methods The study was based on openly accessible drug shortage notifications published by national drug authorities. These data were obtained from all national data sources mentioned on the European Medicines Agency’s (EMA’s) web page and FDA in the USA. After selection of the countries with comparable data, descriptive statistics were used to present characteristics of the shortages both across countries and within countries for 9 months (January–September) in 2020. We studied whether the shortages that occurred in these countries were the same, and how shortages were distributed by therapeutic uses and formulations. We also investigated price variation between the United States and Finland among drugs in shortage in one formulation category (creams and gels). Results Finland, Sweden, Norway, Spain, and the United States had suitable registers and were included. Altogether 5132 shortage reports from Finland (n = 1522), Sweden (n = 890), Norway (n = 800), Spain (n = 814), and the United States (n = 1106) were published during the study period. Of active ingredient level shortages 54% occurred in only one country, and 1% occurred in all five. However, at the country level, where there was one or more shortage notifications in an ATC active ingredient category, 19–41% were in a single country. The distributions by ATC therapeutic class and drug formulation differed substantially between countries, particularly between the USA and European countries. Injectables had a high shortage risk in the USA (57% of all shortages versus 17–31% of all shortages in the European countries). By contrast, shortages in gels and creams occurred only in European data (4–6% of all shortages). In the price comparison, creams and gels in shortage in Finland were 160% more expensive in the USA where these shortages were not detected. Conclusions Public drug shortage registers are vital data sources for proactively maintaining and managing a reliable drug supply. However, our study demonstrates that much work remains to standardize the contents and quality of public register data. Shortages may not be solely a consequence of manufacturing disruptions but may reflect other contributing factors in the international drug distribution and supply mechanisms, including price differences and profit margins between national pharmaceutical markets. Data to perform practical and useful international comparisons to understand these shortages are required.

Introduction: To calculate the maternal mortality ratio (MMR) for 2006-2018 in the Netherlands and compare this with 1993-2005, and to describe women's characteristics, causes of death and improvable factors. Material and Methods: We performed a nationwide, cohort study of all maternal deaths between January 1, 2006 and December 31, 2018 reported to the Audit Committee Maternal Mortality and Morbidity. Main outcome measures were the national MMR and causes of death. Results: Overall MMR was 6.2 per 100 000 live births, a decrease from 12.1 in 1993-2005 (risk ratio [RR] 0.5). Women with a non-western ethnic background had an increased MMR compared with Dutch women (MMR 6.5 vs. 5.0, RR 1.3). The MMR was increased among women with a background from Surinam/Dutch Antilles (MMR 14.7, RR 2.9). Half of all women had an uncomplicated medical history (79/161, 49.1%). Of 171 pregnancy-related deaths within 1 year postpartum, 102 (60%) had a direct and 69 (40%) an indirect cause of death. Leading causes within 42 days postpartum were cardiac disease (n = 21, 14.9%), hypertensive disorders (n = 20, 14.2%) and thrombosis (n = 19, 13.5%). Up to 1 year postpartum, the most common cause of death was cardiac disease (n = 32, 18.7%). Improvable care factors were identified in 76 (47.5%) of all deaths. Conclusions: Maternal mortality halved in 2006-2018 compared with 1993-2005. Cardiac disease became the main cause. In almost half of all deaths, improvable factors were identified and women with a background from Surinam/Dutch Antilles had a threefold increased risk of death compared with Dutch women without a background of migration.

BackgroundRecent years have seen a rapid increase in the popularity of electronic cigarettes (e-cigarettes) among adolescents in the USA. Evidence on their role in the continuation of or abstinence from cigarette smoking among young smokers remains scarce.ObjectiveTo examine the relationship between e-cigarette use initiated after cigarette smoking and abstinence from cigarette smoking among US adolescent established smokers.MethodsThe data were drawn from the 2015–2018 National Youth Tobacco Survey—a nationally representative survey of US middle and high school students. Multivariable logistic regression was used to assess the association between ever e-cigarette use and past 30-day abstinence from cigarette smoking. The analytical sample comprised ever established cigarette smokers with or without a history of e-cigarette use after smoking initiation.ResultsNeither experimental (adjusted OR 0.67, 95% CI 0.39–1.14) nor prior established (adjusted OR 1.56, 95% CI 0.96–2.56) nor current established (adjusted OR 0.65, 95% CI 0.41–1.03) e-cigarette use was statistically significantly associated with subsequent abstinence from cigarette smoking among adolescent ever established smokers. These findings were largely consistent across sensitivity analyses using alternative key definitions, although experimental and current established e-cigarette use was significantly negatively associated with past 6-month abstinence.ConclusionsWe found no evidence that e-cigarette use among US adolescents already smoking cigarettes is associated with subsequent abstinence from cigarette smoking; there was some evidence of an inverse association among experimental and current established e-cigarette users. These findings could inform future regulatory and public health efforts regarding youth e-cigarette use and the reduction of youth cigarette smoking in the USA.

Context Distant metastases (DM) from childhood differentiated thyroid carcinoma (DTC) are uncommon and published studies are limited. Objective This work aimed to describe the outcomes of patients with DM from childhood DTC and to evaluate the molecular landscape of these tumors. Methods A retrospective study was conducted at a tertiary cancer center including patients with pediatric DTC (diagnosed at age ≤ 18 years from 1946 to 2019) and DM. Results We identified 148 patients; 144 (97%) had papillary thyroid carcinoma (PTC) and 104 (70%) were female. Median age at DTC diagnosis was 13.4 years (interquartile range [IQR], 9.9-15.9 years). Evaluable individuals received a median of 2 (IQR, 1-3) radioactive iodine (RAI) treatments at a median cumulative administered activity of 238.0 mCi (IQR, 147.5-351.0 mCi). The oncogenic driver was determined in 64 of 69 PTC samples: RET fusion (38/64; 59%), NTRK1/3 fusions (18/64; 28%), and the BRAF V600E mutation (8/64; 13%). At last evaluation, 93% had persistent disease. The median overall and disease-specific survival after DTC diagnosis were 50.7 and 52.8 years, respectively. Eight (5%) PTC patients died of disease after a median of 30.7 years (IQR, 20.6-37.6 years). Conclusion Childhood DTC with DM persists in most patients despite multiple courses of RAI, but disease-specific death is uncommon, typically occurring decades after diagnosis. Fusion genes are highly prevalent in PTC, and all identified molecular alterations have appropriate targeted therapies. Future studies should focus on expanding genotype-phenotype correlations, determining how to integrate molecularly targeted therapy into treatment paradigms, and relying less on repeated courses of RAI to achieve cure in patients with DM from childhood DTC.

BACKGROUND: Epidemiologic studies suggest cadmium exposure is associated with cardiovascular disease risk, including heart failure. However, prior findings may be influenced by tobacco smoking, a dominant source of cadmium exposure and risk factor for heart failure. The present study leverages up to 20 years of follow-up in the Danish Diet, Cancer and Health cohort to examine the relationship between urinary cadmium and incident heart failure among people who never smoked.METHODS: Between 1993 and 1997, 19,394 never-smoking participants (ages 50-64 years) enrolled and provided a urine sample. From this sample, we randomly selected a subcohort of 600 men and 600 women and identified 958 incident heart failure cases occurring between baseline and 2015. Using a case-cohort approach, we estimated adjusted hazard ratios (aHR) for heart failure in Cox proportional hazards models with age as the time scale.RESULTS: Participants had relatively low concentrations of urinary cadmium, as expected for never smokers (median= 0.20; 25th, 75th= 0.13, 0.32 µg cadmium/g creatinine). In adjusted models, we found that higher urinary cadmium was associated with a higher rate of incident heart failure overall (aHR=1.1 per interquartile range difference; 95% CI= 1.0 - 1.2). In sex-stratified analyses the association seemed restricted to men (aHR= 1.5; 95% CI= 1.2 - 1.9).CONCLUSION: In this cohort of people who never smoked tobacco, environmental cadmium was positively associated with incident heart failure, especially among men.

Little is known about socioeconomic diferences in epilepsy mortality. This study examined educational inequalities in epilepsy mortality in the general population in the Baltic countries and Finland in 2000–2015. Education-specifc mortality estimates for individuals aged 30–74 in Estonia, Latvia and Lithuania were obtained from census-linked mortality datasets while data for Finland came from the register-based population and death data fle of Statistics Finland. Trends and educational inequalities in epilepsy mortality were assessed using age-standardised mortality rates (ASMRs) per 100,000 person years and age-adjusted mortality rate ratios (RRs) calculated using Poisson regression. ASMRs were higher in men than women in all countries. ASMRs reduced in 2000–2015 among all men and women except for Finnish women. Among men, an inverse educational gradient in epilepsy mortality in 2000–2007 widened in 2008–2015 with ASMRs falling among high and mid educated men in all countries but increasing among low educated men in three countries. An inverse educational gradient in female mortality remained in all countries throughout 2000–2015. Although epilepsy mortality fell in the Baltic countries and Finland (men only) in 2000–2015, this masked a clear inverse educational gradient in mortality that became steeper across the period. Little is known about socioeconomic differences in epilepsy mortality. This study examined educational inequalities in epilepsy mortality in the general population in the Baltic countries and Finland in 2000-2015. Education-specific mortality estimates for individuals aged 30-74 in Estonia, Latvia and Lithuania were obtained from census-linked mortality datasets while data for Finland came from the register-based population and death data file of Statistics Finland. Trends and educational inequalities in epilepsy mortality were assessed using age-standardised mortality rates (ASMRs) per 100,000 person years and age-adjusted mortality rate ratios (RRs) calculated using Poisson regression. ASMRs were higher in men than women in all countries. ASMRs reduced in 2000-2015 among all men and women except for Finnish women. Among men, an inverse educational gradient in epilepsy mortality in 2000-2007 widened in 2008-2015 with ASMRs falling among high and mid educated men in all countries but increasing among low educated men in three countries. An inverse educational gradient in female mortality remained in all countries throughout 2000-2015. Although epilepsy mortality fell in the Baltic countries and Finland (men only) in 2000-2015, this masked a clear inverse educational gradient in mortality that became steeper across the period.

Background: In many Western countries, the state pension age is being raised to stimulate the extension of working lives. It is not yet well understood whether the health of older adults supports this increase. In this study, future health of Dutch adults aged 60 to 68 (i.e., the expected state pension age) is explored up to 2040. Methods: Data are from the Dutch Health Interview Survey 1990–2017 (N ≈ 10,000 yearly) and the Dutch Public Health Monitor 2016 (N = 205,151). Health is operationalized using combined scores of self-reported health and limitations in mobility, hearing or seeing. Categories are: good, moderate and poor health. Based on historical health trends, two scenarios are explored: a stable health trend (neither improving nor declining) and an improving health trend. Results: In 2040, the health distribution among men aged 60–68 is estimated to be 63–71% in good, 17–28% in moderate and 9–12% in poor health. Among women, this is estimated to be 64–69%, 17–24% and 12–14%, respectively. Conclusions: This study’s explorations suggest that a substantial share of people will be in moderate or poor health and, thus, may have difficulty continuing working. Policy aiming at sustainable employability will, therefore, remain important, even in the case of the most favorable scenario.

Background Incidence rates in Denmark of central nervous system (CNS) tumors remain among the highest in the world. Survival rates, however, have improved in the past decades in high‐income countries. Methods We analyzed incidence and survival of childhood CNS tumors in Denmark diagnosed from 1997 to 2019 based on data from the Danish Childhood Cancer Registry and information on histological types, tumor localization, and treatment from medical records. Results From 1997 to 2019, 949 children, Incidence of childhood central nervous system (CNS) tumors in Denmark from 1997 to 2019 was 42.1 per million person‐years and did not increase from 1997 to 2019. Survival has improved especially among younger children with CNS tumors. Still, some subgroups in particular have a poor prognosis.

Background Antimicrobial resistance (AMR) poses a major threat to human health around the world. Previous publications have estimated the effect of AMR on incidence, deaths, hospital length of stay, and health-care costs for specific pathogen–drug combinations in select locations. To our knowledge, this study presents the most comprehensive estimates of AMR burden to date. Methods We estimated deaths and disability-adjusted life-years (DALYs) attributable to and associated with bacterial AMR for 23 pathogens and 88 pathogen–drug combinations in 204 countries and territories in 2019. We obtained data from systematic literature reviews, hospital systems, surveillance systems, and other sources, covering 471 million individual records or isolates and 7585 study-location-years. We used predictive statistical modelling to produce estimates of AMR burden for all locations, including for locations with no data. Our approach can be divided into five broad components: number of deaths where infection played a role, proportion of infectious deaths attributable to a given infectious syndrome, proportion of infectious syndrome deaths attributable to a given pathogen, the percentage of a given pathogen resistant to an antibiotic of interest, and the excess risk of death or duration of an infection associated with this resistance. Using these components, we estimated disease burden based on two counterfactuals: deaths attributable to AMR (based on an alternative scenario in which all drug-resistant infections were replaced by drug-susceptible infections), and deaths associated with AMR (based on an alternative scenario in which all drug-resistant infections were replaced by no infection). We generated 95% uncertainty intervals (UIs) for final estimates as the 25th and 975th ordered values across 1000 posterior draws, and models were cross-validated for out-of-sample predictive validity. We present final estimates aggregated to the global and regional level. Findings On the basis of our predictive statistical models, there were an estimated 4·95 million (3·62–6·57) deaths associated with bacterial AMR in 2019, including 1·27 million (95% UI 0·911–1·71) deaths attributable to bacterial AMR. At the regional level, we estimated the all-age death rate attributable to resistance to be highest in western sub-Saharan Africa, at 27·3 deaths per 100 000 (20·9–35·3), and lowest in Australasia, at 6·5 deaths (4·3–9·4) per 100 000. Lower respiratory infections accounted for more than 1·5 million deaths associated with resistance in 2019, making it the most burdensome infectious syndrome. The six leading pathogens for deaths associated with resistance (Escherichia coli, followed by Staphylococcus aureus, Klebsiella pneumoniae, Streptococcus pneumoniae, Acinetobacter baumannii, and Pseudomonas aeruginosa) were responsible for 929 000 (660 000–1 270 000) deaths attributable to AMR and 3·57 million (2·62–4·78) deaths associated with AMR in 2019. One pathogen–drug combination, meticillin-resistant S aureus, caused more than 100 000 deaths attributable to AMR in 2019, while six more each caused 50 000–100 000 deaths: multidrug-resistant excluding extensively drug-resistant tuberculosis, third-generation cephalosporin-resistant E coli, carbapenem-resistant A baumannii, fluoroquinolone-resistant E coli, carbapenem-resistant K pneumoniae, and third-generation cephalosporin-resistant K pneumoniae. Interpretation To our knowledge, this study provides the first comprehensive assessment of the global burden of AMR, as well as an evaluation of the availability of data. AMR is a leading cause of death around the world, with the highest burdens in low-resource settings. Understanding the burden of AMR and the leading pathogen–drug combinations contributing to it is crucial to making informed and location-specific policy decisions, particularly about infection prevention and control programmes, access to essential antibiotics, and research and development of new vaccines and antibiotics. There are serious data gaps in many low-income settings, emphasising the need to expand microbiology laboratory capacity and data collection systems to improve our understanding of this important human health threat. Funding Bill & Melinda Gates Foundation, Wellcome Trust, and Department of Health and Social Care using UK aid funding managed by the Fleming Fund.

Funding: J A Loureiro acknowledges support from Base Funding UIDB/00511/2020 of the LEPABE funded by national funds through the FCT/MCTES (PIDDAC) and Scientific Employment Stimulus (FCT) [CEECINST/00049/2018]. Background: In estimating the global burden of cancer, adolescents and young adults with cancer are often overlooked, despite being a distinct subgroup with unique epidemiology, clinical care needs, and societal impact. Comprehensive estimates of the global cancer burden in adolescents and young adults (aged 15–39 years) are lacking. To address this gap, we analysed results from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019, with a focus on the outcome of disability-adjusted life-years (DALYs), to inform global cancer control measures in adolescents and young adults. Methods: Using the GBD 2019 methodology, international mortality data were collected from vital registration systems, verbal autopsies, and population-based cancer registry inputs modelled with mortality-to-incidence ratios (MIRs). Incidence was computed with mortality estimates and corresponding MIRs. Prevalence estimates were calculated using modelled survival and multiplied by disability weights to obtain years lived with disability (YLDs). Years of life lost (YLLs) were calculated as age-specific cancer deaths multiplied by the standard life expectancy at the age of death. The main outcome was DALYs (the sum of YLLs and YLDs). Estimates were presented globally and by Socio-demographic Index (SDI) quintiles (countries ranked and divided into five equal SDI groups), and all estimates were presented with corresponding 95% uncertainty intervals (UIs). For this analysis, we used the age range of 15–39 years to define adolescents and young adults. Findings: There were 1·19 million (95% UI 1·11–1·28) incident cancer cases and 396 000 (370 000–425 000) deaths due to cancer among people aged 15–39 years worldwide in 2019. The highest age-standardised incidence rates occurred in high SDI (59·6 [54·5–65·7] per 100 000 person-years) and high-middle SDI countries (53·2 [48·8–57·9] per 100 000 person-years), while the highest age-standardised mortality rates were in low-middle SDI (14·2 [12·9–15·6] per 100 000 person-years) and middle SDI (13·6 [12·6–14·8] per 100 000 person-years) countries. In 2019, adolescent and young adult cancers contributed 23·5 million (21·9–25·2) DALYs to the global burden of disease, of which 2·7% (1·9–3·6) came from YLDs and 97·3% (96·4–98·1) from YLLs. Cancer was the fourth leading cause of death and tenth leading cause of DALYs in adolescents and young adults globally. Interpretation: Adolescent and young adult cancers contributed substantially to the overall adolescent and young adult disease burden globally in 2019. These results provide new insights into the distribution and magnitude of the adolescent and young adult cancer burden around the world. With notable differences observed across SDI settings, these estimates can inform global and country-level cancer control efforts. Funding: Bill & Melinda Gates Foundation, American Lebanese Syrian Associated Charities, St Baldrick's Foundation, and the National Cancer Institute. publishersversion published

Importance: During the past decades, improvements in the prevention and management of myocardial infarction, stroke, and pulmonary embolism have led to a decline in cardiovascular mortality in the general population. However, it is unknown whether patients receiving dialysis have also benefited from these improvements. Objective: To assess the mortality rates for myocardial infarction, stroke, and pulmonary embolism in a large cohort of European patients receiving dialysis compared with the general population. Design, Setting, and Participants: In this cohort study, adult patients who started dialysis between 1998 and 2015 from 11 European countries providing data to the European Renal Association Registry were and followed up for 3 years. Data were analyzed from September 2020 to February 2022. Exposures: Start of dialysis. Main Outcomes and Measures: The age- and sex-standardized mortality rate ratios (SMRs) with 95% CIs were calculated by dividing the mortality rates in patients receiving dialysis by the mortality rates in the general population for 3 equal periods (1998-2003, 2004-2009, and 2010-2015). Results: In total, 220 467 patients receiving dialysis were included in the study. Their median (IQR) age was 68.2 (56.5-76.4) years, and 82 068 patients (37.2%) were female. During follow-up, 83 912 patients died, of whom 7662 (9.1%) died because of myocardial infarction, 5030 (6.0%) died because of stroke, and 435 (0.5%) died because of pulmonary embolism. Between the periods 1998 to 2003 and 2010 to 2015, the SMR of myocardial infarction decreased from 8.1 (95% CI, 7.8-8.3) to 6.8 (95% CI, 6.5-7.1), the SMR of stroke decreased from 7.3 (95% CI, 7.0-7.6) to 5.8 (95% CI, 5.5-6.2), and the SMR of pulmonary embolism decreased from 8.7 (95% CI, 7.6-10.1) to 5.5 (95% CI, 4.5-6.6). Conclusions and Relevance: In this cohort study of patients receiving dialysis, mortality rates for myocardial infarction, stroke, and pulmonary embolism decreased more over time than in the general population. publishedVersion

Background Postoperative opioid use plays an important role in the global opioid crisis, but little is known about in-hospital opioid use trends of large surgical units. We investigated whether postoperative in-hospital opioid consumption changed in a large academic neurosurgical unit between 2007 and 2018. Methods We extracted the data of consumed opioids in the neurosurgical intensive care unit and two bed wards between 2007 and 2018. Besides overall consumption, we analyzed the trends for weak (tramadol and codeine), strong, and the most commonly used opioids. The use of various opioids was standardized using the defined daily doses (DDDs) of each opioid agent. A linear regression analysis was performed to estimate annual treatment day-adjusted changes with 95% confidence intervals. Results Overall, 121 361 opioid DDDs were consumed during the 196 199 treatment days. Oxycodone was the most commonly used postoperative opioid (49% of all used opioids) in neurosurgery. In the bed wards, the use of oral oxycodone increased 375% (on average 13% (9–17%) per year), and the use of transdermal buprenorphine 930% (on average 26% (9–45%) per year) over the 12-year period. Despite the increased use of strong opioids in the bed wards (on average 3% (1–4%) per year), overall opioid use decreased 39% (on average 6% (4–7%) per year) between 2007 and 2018. Conclusions Due to the increase of strong opioid use in the surgical bed wards, we encourage other large teaching hospitals and surgical units to investigate whether their opioid use trends are similarly worrisome and whether the opioid consumption changes in the hospital setting are transferred to opioid use patterns or opioid-related harms after discharge.

Background The literature on the prognostic relevance of signet-ring cell (SRC) histology in gastric cancer (GC) is controversial which is most likely related to inconsistent SRC classification based on haematoxylin–eosin staining. We hypothesised that mucin stains can consistently identify SRC-GC and predict GC patient outcome. Methods We performed a comprehensive literature review on mucin stains in SRC-GC and characterised the mucin expression in 851 Caucasian GC and 410 Asian GC using Alcian Blue (AB)-Periodic Acid-Schiff (PAS), MUC2 (intestinal-type mucin), and MUC5AC (gastric-type mucin). The relationship between mucin expression and histological phenotype [poorly cohesive (PC) including proportion of SRCs, non-poorly cohesive (non-PC), or mucinous (MC)], clinicopathological variables, and patient outcome was analysed. Results Depending on mucin expression and cut-offs, the positivity rates of SRC-GC reported in the literature varied from 6 to 100%. Patients with MUC2 positive SRC-GC or SRC-GC with (gastro)intestinal phenotype had poorest outcome. In our cohort study, PC with ≥ 10% SRCs expressed more frequently MUC2, MUC5AC, and ABPAS (p p = 0.004 and p p = 0.002). This association was not seen in Asian patients. Conclusions This is the first study to suggest that mucin stains do not help to differentiate between SRC-GC and non-SRC-GC. However, mucin stains appear to be able to identify GC patients with different outcome. To our surprise, the relationship between outcome and mucin expression seems to differ between Caucasian and Asian GC patients which warrants further investigations.

The opportunistic pathogen Staphylococcus aureus has become a major threat for human health and well-being by developing resistance to antibiotics and by fast evolution into new lineages that rapidly spread within the healthy human population. This calls for development of active or passive immunization strategies to prevent or treat acute phase infections. Since no such anti-staphylococcal immunization approaches are available for clinical implementation, the present studies were aimed at identifying new leads for their development. For this purpose, we profiled the cell-surface-exposed staphylococcal proteome under infection-mimicking conditions by combining two approaches for "bacterial shaving" with immobilized or soluble trypsin and subsequent mass spectrometry analysis of liberated peptides. In parallel, non-covalently cell-wall-bound proteins extracted with potassium thiocyanate and the exoproteome fraction were analyzed by gel-free proteomics. All data are available through ProteomeXchange accession PXD000156. To pinpoint immunodominant bacterial-surface-exposed epitopes, we screened selected cell-wall-attached proteins of S. aureus for binding of immunoglobulin G from patients who have been challenged by different types of S. aureus due to chronic wound colonization. The combined results of these analyses highlight particular cell-surface-exposed S. aureus proteins with highly immunogenic exposed epitopes as potential targets for development of protective anti-staphylococcal immunization strategies.

The COVID-19 pandemic is not only a challenge for public health and hospitals, but affects many aspects of our societies. This Lilliput minireview deals with problems that the pandemic causes for the food industry, addressing the presence and persistence of SARS-CoV-2 in the food environment, methods of virus inactivation and the protection of the food worker and the consumer. So far food has not been implicated in the transmission of the infection, but social disruptions caused by the pandemic could cause problems with food security. ispartof: MICROBIAL BIOTECHNOLOGY vol:13 issue:6 pages:1689-1701 ispartof: location:United States status: published

Purpose To systematically investigate the frequency and types of allegations related to radiology practice handled by the Dutch Medical Disciplinary Court in the past 10 years. Methods The Dutch Medical Disciplinary Court database was searched for verdicts concerning radiology practice between 2010 and 2019. The association between the number of verdicts and time (years) was assessed by Spearman’s rho. Other data were summarized using descriptive statistics. Results There were 48 verdicts (mean 4.8 per year). There was no significant association between the number of verdicts and time (Spearman’s rho p = 0.99). Most allegations were in breast imaging and musculoskeletal radiology (each 18.8%), followed by interventional radiology, head and neck imaging, and abdominal imaging (each 12.5%), neuroradiology and vascular imaging (each 10.4%), and chest imaging (4.2%). There were 46 allegations against radiologists (95.8%) and 2 against residents (4.2%). The most common allegation (37.5%) was error in diagnosis. In 20.8% of verdicts, the allegation was judged (partially) founded; disciplinary measures were warnings (n = 8) and reprimands (n = 2). An appeal was submitted by the patient in 11 cases and by the radiologist in 3 cases. All appeals by patients were rejected, whereas 2 of the 3 appeals by radiologists were granted and previously imposed disciplinary measures were reversed. Conclusion Allegations against radiologists at the Dutch Medical Disciplinary Court are relatively few, their number has remained stable over the past 10 years, and a minority were judged to be (partially) founded. We can learn from the cases presented in this article, which may improve patient care. Key Points • The frequency of allegations against radiologists at the Dutch Medical Disciplinary Court is relatively low and has not exhibited any temporal change over the past 10 years. • These allegations reflect patient dissatisfaction, but this infrequently equals malpractice. • Knowledge of the circumstances under which these allegations have arisen may improve patient care.

ObjectiveTo provide an in-depth systematic assessment of the global epidemiology of gonorrhoea infection in infertile populations.MethodsA systematic literature review was conducted up to 29 April 2019 on international databases and WHO regional databases, and reported following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. All prevalence measures of gonorrhoea infection among infertile populations, based on primary data, qualified for inclusion. Infertile populations were broadly defined to encompass women/men undergoing infertility evaluation or treatment (infertility clinic attendees and partners). Pooled mean prevalence by relevant strata was estimated using random-effects meta-analysis. Associations with prevalence and sources of heterogeneity were explored using metaregression. Risk of bias was assessed using four quality domains.FindingsA total of 147 gonorrhoea prevalence studies were identified from 56 countries. The pooled mean prevalence of current gonorrhoea infection was estimated globally at 2.2% (95% CI 1.3% to 3.2%), with the highest prevalence in Africa at 5.0% (95% CI 1.9% to 9.3%). The mean prevalence was higher for populations with tubal factor infertility (3.6%, 95% CI 0.9%–7.7%) and mixed cause and unexplained infertility (3.6%, 95% CI 0.0% to 11.6%) compared with other diagnoses, such as ovarian and non-tubal infertility (0.1%, 95% CI 0.0% to 0.8%), and for secondary (2.5%, 95% CI 0.2% to 6.5%) compared with primary (0.5%, 95% CI 0.0% to 1.7%) infertility. Metaregression identified evidence of variations in prevalence by region and by infertility diagnosis, higher prevalence in women than men and a small-study effect. There was a trend of declining prevalence by about 3% per year over the last four decades (OR=0.97, 95% CI 0.95 to 0.99).ConclusionsGonorrhoea prevalence in infertile populations is several folds higher than that in the general population, with even higher prevalence in women with tubal factor infertility and in individuals with secondary infertility. These findings support the potential role of gonorrhoea in infertility and suggest that some infertility is possibly preventable by controlling gonorrhoea transmission.PROSPERO registration numberCRD42018102934.

Background This study investigated (i) whether compassion is associated with blood pressure or hypertension in adulthood and (ii) whether familial risk for hypertension modifies these associations. Method The participants (N = 1112–1293) came from the prospective Young Finns Study. Parental hypertension was assessed in 1983–2007; participants’ blood pressure in 2001, 2007, and 2011; hypertension in 2007 and 2011 (participants were aged 30–49 years in 2007–2011); and compassion in 2001. Results High compassion predicted lower levels of diastolic and systolic blood pressure in adulthood. Additionally, high compassion was related to lower risk for hypertension in adulthood among individuals with no familial risk for hypertension (independently of age, sex, participants’ and their parents’ socioeconomic factors, and participants’ health behaviors). Compassion was not related to hypertension in adulthood among individuals with familial risk for hypertension. Conclusion High compassion predicts lower diastolic and systolic blood pressure in adulthood. Moreover, high compassion may protect against hypertension among individuals without familial risk for hypertension. As our sample consisted of comparatively young participants, our findings provide novel implications for especially early-onset hypertension.

Background and Aims Hepatitis B virus (HBV) vaccination is recommended to all employees who have an occupational risk in the Netherlands. This study assessed the determinants of the immune response to primary standard three-dose HBV vaccination (0, 1, 6 months), with the main focus on ethnicity. Methods Out of 76 239 individuals who received HBV vaccination between April 1983 and December 2017, 11 567 persons with a known country of birth and complete vaccination schedule were included in this study. Weighted multiple logistic regression with Firth's bias adjustment was used to assess the determinants of nonresponse (anti-HBs < 10 mIU/mL) and low response (anti-HBs 10-99 mIU/mL). Results Baseline characteristics of the study population (n = 11 567) were as follows: mean age 27.5 years (95% confidence interval [CI], 27.23-27.72), 99.4% born in the Netherlands and 93.5% of Western European origin. Of all identified subjects, 180 (1.6%) were HBV vaccine nonresponders and 549 (4.8%) were low responders. When compared with individuals aged 40 years in comparison with those younger than 40 years, P < .001. All nonresponders were born in the Netherlands. Although no significant association was found between nonresponse and individuals of Western European origin (adjusted odds ratio [aOR] = 1.20; 95% CI, 0.66-2.44; P = .163), low response to HBV vaccination was significantly associated with Western European origin (aOR = 2.21; 95% CI, 1.41-3.86; P = .001). Significant determinants for nonresponse were older age at vaccination (aOR = 1.06; 95% CI, 1.06-1.07; P < .001) and male gender (aOR = 2.51; 95% CI, 1.97-3.22; P < .001). Conclusions The nonresponse rate was low in our study population. Our findings suggest that the vaccines being used for the primary vaccination are probably less immunogenic for older individuals, males, and persons of Western European origin. foundation Limburg Sterk Merk; province of Limburg; Flemish government; Hasselt University; Ziekenhuis OostLimburg; Jessa Hospital

Objectives The aim of the study was to examine the prevalence of third molars in panoramic radiographs in a population-based study of adults aged >= 30 years. Methods Out of a sample of 8028 inhabitants of Finland, selected with two-staged stratified cluster-sampling method for the Health 2000 Survey, 5989 participated in clinical oral examination and panoramic radiography. Mean age was 52.5 years (SD 14.6; range 30-97 years). The following variables were included in the analysis: participant characteristics, clinical number of all teeth, and radiographic prevalence and characteristics of third molars. Statistics included chi-squared, Fisher's exact, and Kruskal-Wallis tests and SAS-SUDAAN calculations. Results A total of 5912 third molars in 47.8% of the study population were recorded from panoramic radiographs. At least one impacted third molar was found in 21.9% of the study population. More than half (57.3%) of the remaining third molars were located in the mandible. A preponderance of participants with all third molars missing were observed in the oldest age group, women, those with lower education and those living in the countryside. Third molars or remnants thereof were observed radiographically in 3.9% of clinically edentulous study population. Conclusions The panoramic radiographs disclosed many remaining third molars in adult Finns aged >= 30 years. One-third of the third molars located impacted which may cause unexpected need for care.

Background Adults 65 years and older (seniors) experience more complications following influenza infection than younger adults. We estimated the relative vaccine effectiveness (rVE) of a trivalent high dose (HD-IIV3) versus an adjuvanted trivalent influenza vaccine (aIIV3) in seniors for respiratory-related hospitalizations. Methods We conducted a retrospective cohort study using claims data from Optum’s Clinformatics® Data Mart to compare outcome rates between seniors who received HD-IIV3 versus aIIV3 during the 2016/17 and 2017/18, predominantly A/H3N2 respiratory seasons. Rates were adjusted for demographic characteristics, comorbid conditions, previous influenza vaccination, and geography. We used the previous event rate ratio (PERR) approach to address bias by time-fixed unmeasured confounders. Results We identified 842,282 HD-IIV3 and 34,157 aIIV3 recipients for the 2016/17 season and 1,058,638 HD-IIV3 and 189,636 aIIV3 recipients for the 2017/18 season. The pooled rVE of HD-IIV3 versus aIIV3 for respiratory-related hospitalizations over both seasons was 12% (95% confidence interval: 3.3%–20%); 13% (−6.4% to 32%) for the 2016/17 season and 12% (2.1%–21%) for the 2017/18 season. Conclusions Pooled over two predominantly A/H3N2 respiratory seasons, HD-IIV3 was associated with fewer respiratory hospital admissions than aIIV3 in senior members of large national managed health care company in the U.S.

INTRODUCTION: Asthma, allergic rhinitis, atopic dermatitis, and food allergy affect approximately 20% of the global population. Few studies describe the burden of the totality of these diseases and only a handful studies provide a comprehensive overview of the socioeconomic impact of these diseases. AREAS COVERED: For this narrative review, we searched Pubmed using selected keywords and inspected relevant references using a snowballing process. We provide an overview of the socioeconomic burden of allergic diseases (in particular, asthma, allergic rhinitis, atopic dermatitis, and food allergy). The focus of this review is on their epidemiology (incidence, prevalence), burden (disability-adjusted life years, quality of life), and direct and indirect costs (absenteeism and presenteeism). We have put special emphasis on differences between countries. EXPERT COMMENTARY: Both the prevalence and the burden of allergic diseases are considerable with prevalence varying between 1% and 20%. We identified a plethora of studies on asthma, but studies were generally difficult to compare due to the heterogeneity in measures used. There were only few studies on the burden of food allergy; therefore, more studies on this allergy are required. For future studies, we recommend standardizing epidemiologic, socioeconomic impact, and quality of life measures of allergic diseases.

Background:Diabetes is positively associated with various cancers, but its relationship with tumors of the esophagus/esophagogastric junction remains unclear.Methods:Data were harmonized across 13 studies in the International Barrett's and Esophageal Adenocarcinoma Consortium, comprising 2309 esophageal adenocarcinoma (EA) cases, 1938 esophagogastric junction adenocarcinoma (EGJA) cases, 1728 Barrett's esophagus (BE) cases, and 16,354 controls. Logistic regression was used to estimate study‐specific odds ratios (ORs) and 95% CIs for self‐reported diabetes in association with EA, EGJA, and BE. Adjusted ORs were then combined using random‐effects meta‐analysis.Results:Diabetes was associated with a 34% increased risk of EA (OR, 1.34; 95% CI, 1.00‐1.80; I2 = 48.8% [where 0% indicates no heterogeneity, and larger values indicate increasing heterogeneity between studies]), 27% for EGJA (OR, 1.27; 95% CI, 1.05‐1.55; I2 = 0.0%), and 30% for EA/EGJA combined (OR, 1.30; 95% CI, 1.06‐1.58; I2 = 34.9%). Regurgitation symptoms modified the diabetes‐EA/EGJA association (P for interaction = .04) with a 63% increased risk among participants with regurgitation (OR, 1.63; 95% CI, 1.19‐2.22), but not among those without regurgitation (OR, 1.03; 95% CI, 0.74‐1.43). No consistent association was found between diabetes and BE.Conclusions:Diabetes was associated with increased EA and EGJA risk, which was confined to individuals with regurgitation symptoms. Lack of an association between diabetes and BE suggests that diabetes may influence progression of BE to cancer.

Background Many individuals aspire to attain various goals in life, such as committing to a healthful diet to slim down or saving for retirement to enhance future welfare. While these behaviors (weight loss and saving) share the common denominator of self-regulation, it is unclear whether success in one domain is related to the other. Therefore, we examined the relationship between long term weight loss (LTWL) success and monetary savings among U.S. adults who at one point in life diverged from normal weight status. Methods Data on 1994 adults with a maximum BMI ≥ 25 kg/m2 and with an annual household income equal or less than 200% poverty level. Data were derived from a U.S. population-based study (NHANES). The independent variable was LTWL success (loss maintained for at least 1 year), which was operationalized as Results Multivariable analysis revealed that adjusting for income, education and other covariates, being in the highest LTWL category (≥20.00%) significantly reduced the likelihood of monetary savings in comparison to the reference group (OR = 0.55, 95%CI = 0.34–0.91). This relationship was not observed in the lower LTWL category (10.00–19.99%). Conclusions Adults who in the past were overweight or obese and who presently exhibit high levels of LTWL, were markedly less successful when it came to their finances. This might stem from significant cognitive-affective resources exerted during the weight loss process coupled with a paucity of financial resources which impede financial decision making. This supposition, however, warrants future research.

Summary Different vaccine strains included in the live attenuated influenza vaccine (LAIV) have variable efficacy. The reasons for this are not clear and may include differences in immunogenicity. We report a Phase IV open‐label study on the immunogenicity of a single dose of quadrivalent LAIV (Fluenz™ Tetra) in children during the 2015/16 season, to investigate the antibody responses to different strains. Eligible children were enrolled to receive LAIV; nasal samples were collected before and approximately 4 weeks after immunization. There was a significant increase in nasal immunoglobulin (Ig)A to the H3N2, B/Victoria lineage (B/Brisbane) and B/Yamagata lineage (B/Phuket) components, but not to the H1N1 component. The fold change in nasal IgA response was inversely proportional to the baseline nasal IgA titre for H1N1, H3N2 and B/Brisbane. We investigated possible associations that may explain baseline nasal IgA, including age and prior vaccination status, but found different patterns for different antigens, suggesting that the response is multi‐factorial. Overall, we observed differences in immune responses to different viral strains included in the vaccine; the reasons for this require further investigation., Different vaccine strains included in the Live Attenuated Influenza Vaccine (LAIV) have variable efficacy. We performed an immunogenicity study of quadrivalent LAIV in children during the 2015/16 season. There was a significant increase in nasal IgA to the H3N2, B/Victoria lineage (B/Brisbane), and B/Yamagata lineage (B/Phuket) components, but not to the H1N1 component.

Although personality is associated with the onset of substance use (i.e., conventional smoking, alcohol use, and cannabis use) during adolescence, it is unclear whether personality traits are also associated with the onset of use of alternative tobacco products (ATPs), i.e., electronic cigarettes, shisha-pens, and water pipes. This study examines whether personality traits are associated with the onset of use of both conventional cigarettes and ATPs. Longitudinal data (baseline and 18-month follow-up) were used. The sample consisted of 1114 non-user adolescents (mean age = 13.36, SD = 0.93, 56% female) at baseline. To measure personality traits, the Substance Use Risk Profile Scale was used with four subscales: anxiety sensitivity, hopelessness, sensation seeking, and impulsivity. Structural equation models were conducted using Mplus 7.3. Results showed that both hopelessness and sensation seeking were associated with the onset of use of e-cigarettes and conventional cigarettes. Further, sensation seeking and impulsivity were associated with the onset of use of shisha-pens and water pipes. In conclusion, to prevent adolescents from using ATPs and/or conventional cigarettes, it is important to take their personality traits into account. More research on other (shared) risk factors and on more advanced stages of ATP use is needed before effective prevention strategies can be developed.

New tobacco and nicotine products have emerged on the market in recent years. Most research has concerned only one product at a time, usually e-cigarettes, while little is known about the multiple use of tobacco and nicotine products among adolescents. We examined single, dual, and triple use of cigarettes, e-cigarettes, and snus among Nordic adolescents, using data of 15–16-year-olds (n = 16,125) from the European School Survey Project on Alcohol and other Drugs (ESPAD) collected in 2015 and 2019 from Denmark, Finland, Iceland, Norway, Sweden, and the Faroe Islands. Country-specific lifetime use of any of these products ranged between 40% and 50%, and current use between 17% and 31%. Cigarettes were the most common product in all countries except for Iceland, where e-cigarettes were remarkably more common. The proportion of dual and triple users was unexpectedly high among both experimental (24%–49%) and current users (31–42%). Triple use was less common than dual use. The users’ patterns varied somewhat between the countries, and Iceland differed substantially from the other countries, with a high proportion of single e-cigarette users. More knowledge on the patterns of multiple use of tobacco and nicotine products and on the potential risk and protective factors is needed for targeted intervention and prevention efforts. This research was financially supported by the Nordic Cancer Union (R250-A14491), Juho Vainio Foundation (202010401), and Tampere University Hospital (State Research Funding numbers 9X048 and 9AA066).