Schools under mandatory testing can mitigate the spread of SARS-CoV-2.

We use event study models based on staggered summer vacations in Germany to estimate the effect of school reopenings after the summer of 2021 on the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Estimations are based on daily counts of confirmed coronavirus infections across all 401 German counties. A central antipandemic measure in German schools included mandatory rapid testing multiple times per week. Our results are consistent with mandatory testing contributing to the containment of the viral spread. We find a short-term increase in infection rates right after summer breaks, indicating the uncovering of otherwise undetected (asymptomatic) cases through the testing. After a period of about 2 wk after school reopenings, the growth of case numbers is smaller in states that reopened schools compared with the control group of states still in summer break. The results show a similar pattern for older age groups as well, arguably as a result of detected clusters through the school testing. This means that under certain conditions, open schools can play a role in containing the spread of the virus. Our results suggest that closing schools as a means to reduce infections may have unintended consequences by giving up surveillance and should be considered only as a last resort.

Costs of a structured early detection program for advanced liver fibrosis and cirrhosis: insights on the "plus" of Check-up 35.

BACKGROUND: The implementation of an early detection program for liver cirrhosis in a general population has been discussed for some time. Recently, the effectiveness of a structured screening procedure, called SEAL (Structured Early detection of Asymptomatic Liver cirrhosis), using liver function tests (AST and ALT) and APRI to early detect advanced fibrosis and cirrhosis in participants of the German "Check-up 35" was investigated. METHODS: This study identifies the expected diagnostic costs of SEAL in routine care and their drivers and reports on prevailing CLD etiologies in this check-up population. The analysis is based on theoretical unit costs, as well as on the empirical billing and diagnostic data of SEAL participants. RESULTS: Screening costs are mainly driven by liver biopsies, which are performed in a final step in some patients. Depending on the assumed biopsy rates and the diagnostic procedure, the average diagnostic costs are between EUR 5.99 and 13.74 per Check-up 35 participant and between EUR 1,577.06 and 3,620.52 per patient diagnosed with fibrosis/cirrhosis (F3/F4). The prevailing underlying etiology in 60% of cases is non-alcoholic fatty liver disease. DISCUSSION: A liver screening following the SEAL algorithm could be performed at moderate costs. Screening costs in routine care depend on actual biopsy rates and procedures, attendance rates at liver specialists, and the prevalence of fibrosis in the Check-up 35 population. The test for viral hepatitis newly introduced to Check-up 35 as once-in-a-lifetime part of Check-up 35 is no alternative to SEAL.

Structured Early detection of Asymptomatic Liver Cirrhosis: Results of the population-based liver screening program SEAL.

BACKGROUND & AIMS: Detection of patients with early cirrhosis is of importance to prevent the occurrence of complications and improve prognosis. The SEAL program aimed at evaluating the usefulness of a structured screening procedure to detect cirrhosis as early as possible. METHODS: SEAL was a prospective cohort study with a control cohort from routine care data. Individuals participating in the general German health check-up after the age of 35 ("Check-up 35") at their primary care physicians were offered a questionnaire, liver function tests (aspartate and alanine aminotransferase [AST and ALT]), and follow-up. If AST/ALT levels were elevated, the AST-to-platelet ratio index (APRI) score was calculated, and patients with a score >0.5 were referred to a liver expert in secondary and/or tertiary care. RESULTS: A total of 11,859 participants were enrolled and available for final analysis. The control group comprised 349,570 participants of the regular Check-up 35. SEAL detected 488 individuals with elevated APRI scores (4.12%) and 45 incident cases of advanced fibrosis/cirrhosis. The standardized incidence of advanced fibrosis/cirrhosis in the screening program was slightly higher than in controls (3.83‰ vs. 3.36‰). The comparison of the chance of fibrosis/cirrhosis diagnosis in SEAL vs. in standard care was inconclusive (marginal odds ratio 1.141, one-sided 95% CI 0.801, +Inf). Of note, when patients with decompensated cirrhosis at initial diagnosis were excluded from both cohorts in a post hoc analysis, SEAL was associated with a 59% higher chance of early cirrhosis detection on average than routine care (marginal odds ratio 1.590, one-sided 95% CI 1.080, +Inf; SEAL 3.51‰, controls: 2.21‰). CONCLUSIONS: The implementation of a structured screening program may increase the early detection rate of cirrhosis in the general population. In this context, the SEAL pathway represents a feasible and potentially cost-effective screening program. REGISTRATION: DRKS00013460 LAY SUMMARY: Detection of patients with early liver cirrhosis is of importance to prevent the occurrence of complications and improve prognosis. This study demonstrates that the implementation of a structured screening program using easily obtainable measures of liver function may increase the early detection rate of cirrhosis in the general population. In this context, the 'SEAL' pathway represents a feasible and potentially cost-effective screening program.

As Long as the Breath Lasts: In Utero Exposure to Ramadan and the Occurrence of Wheezing in Adulthood.

While prenatal exposure to Ramadan has been shown to be negatively associated with general physical and mental health, studies on specific organs remain scarce. In this study, we explored whether Ramadan exposure during pregnancy affects the occurrence of wheezing, a main symptom of obstructive airway disease. Using data from the Indonesian Family Life Survey collected between 1997 and 2008 (waves 2-4), we compared wheezing occurrence among adult Muslims who had been in utero during Ramadan with that in adult Muslims who had not been in utero during Ramadan. Wheezing prevalence was higher among adult Muslims who had been in utero during Ramadan, independent of the pregnancy phase in which the exposure to Ramadan occurred. Moreover, this association tended to increase with age, being strongest among those aged about 45 years or older. This is in line with fetal programming theory, suggesting that impacts of in utero exposures often manifest only after reproductive age. Particularly strong associations were detected for smokers. The respiratory system of prenatally exposed Muslims thus seems to perform worse in mitigating later ex utero harmful influences such as smoking. This study suggests that exposure to Ramadan during pregnancy may have lasting consequences for adult lung functionality.

Ramadan Exposure In Utero and Child Mortality in Burkina Faso: Analysis of a Population-Based Cohort Including 41,025 Children.

Ramadan exposure in utero can be regarded as a natural experiment with which to study how nutritional conditions in utero influence susceptibility to disease later in life. We analyzed data from rural Burkina Faso on 41,025 children born between 1993 and 2012, of whom 25,093 were born to Muslim mothers. Ramadan exposure was assigned on the basis of overlap between Ramadan dates and gestation, creating 7 exclusive categories. We used proportional hazards regression with difference-in-differences analysis to estimate the association between Ramadan exposure at different gestational ages and mortality among children under 5 years of age. Under-5 mortality was 32 deaths per 1,000 child-years. Under-5 mortality among Muslims was 15% higher than that among non-Muslims (P < 0.001). In the difference-in-differences analysis, the occurrence of Ramadan during conception or the first or second trimester was associated with higher under-5 mortality rates among Muslims only. The mortality rates of children born to Muslim mothers were 33%, 29%, and 22% higher when Ramadan occurred during conception, the first trimester, and the second trimester, respectively, compared with children of non-Muslim mothers born at the same time (P = 0.01, P < 0.001, and P = 0.007). Having a Muslim mother was not associated with mortality when the child was not exposed to Ramadan, born during Ramadan, or exposed during the third trimester. Observance of Ramadan during early pregnancy can have detrimental consequences for the future health of the unborn child.

The course of psychiatric co-morbidity in patients with breast cancer--results from the prospective multi-centre BRENDA II study.

PURPOSE: This study examined the frequency of psychiatric co-morbidity in patients with breast cancer, its changes over time and predictors for these changes. METHODS: In a prospective study with measurements before surgery (t1, baseline), 1 month (t2) and 8 months thereafter (t3) using the Patient Health Questionnaire, we examined the course of psychiatric co-morbidity in breast cancer patients. The co-morbidity courses were grouped into healthy (no co-morbidity during the study), acute (co-morbidity at t1 and/or t2, but not at t3), emerging (no co-morbidity at t1, but at t3) and chronic (co-morbidity at t1 and t3). RESULTS: Of the 598 participants, 19% had acute, 10% emerging and 9% chronic psychiatric co-morbidity. Acute co-morbidity was more common in patients with poor quality of life (odds ratio (OR) 9.6, 95% confidence interval (CI) 4.4-20.8) and somatic co-morbidity (OR 3.8, CI 1.1-12.4). Patients who perceived support from their doctors had acute co-morbidity less frequently (OR 0.7, CI 0.5-1.0). Emerging co-morbidity occurred more often in younger patients (OR 2.4, CI 1.2-4.7) and in patients with another cancer in their own (OR 2.0, CI 1.1-3.9) or family (OR 2.1, CI 1.1-4.3) histories, less often in patients with support from doctors (OR 0.6, CI 0.4-1.0). Chronic co-morbidity was related to poor quality of life (OR 12.1, CI 3.6-39.9). CONCLUSION: We found acute and emerging psychiatric co-morbidities less often in patients who reported having a supportive doctor-patient relationship. Patients that require psycho-oncological support often have poor quality of life and have experienced cancer before. Copyright © 2015 John Wiley & Sons, Ltd.

Exploring patient- and physician-related factors preventing breast cancer patients from guideline-adherent adjuvant chemotherapy-results from the prospective multi-center study BRENDA II.

BACKGROUND: This study examined which patient- and physician-related factors influence guideline violations in adjuvant chemotherapy. PATIENTS AND METHODS: In a prospective multi-center cohort study, patients with primary breast cancer were sampled consecutively over a period of four years (2009-2012). Patients completed a questionnaire prior to surgery and prior to adjuvant therapy. This questionnaire assessed health-related quality of life (QoL) using the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30, psychiatric co-morbidity with the Patient Health Questionnaire (PHQ), demographic characteristics (age, education), and the intensity of fear for chemotherapy. After surgery, a multi-professional team discussed recommendation for adjuvant chemotherapy, and this decision was documented in a database together with the indication for chemotherapy according to the German S3 guideline. This multi-professional team was blinded to that algorithm-based decision. Six months later, it was documented whether the patient had received adjuvant chemotherapy or not. RESULTS: Altogether, 857 patients were included in the study. In 391 of these patients, the tumor board (TB) decided to recommend chemotherapy. The most important reasons for not recommending chemotherapy were somatic co-morbidity not allowing adjuvant chemotherapy and age >75 years. Of these 391 patients, 73 (19 %) patients eventually did not receive chemotherapy. Deviations from the initial therapy decision were more frequent in older patients (≥75 years) with poor QoL. If the QoL was good, higher age was not related to deviation. There was some evidence that patients with higher education less frequently received chemotherapy (CT). Furthermore, if patients were very afraid of chemotherapy, deviations from the initial therapy decision were more likely. Co-morbidity and fear of CT were not related to the likelihood of deviating from the initial therapy decision. CONCLUSION: Nineteen percent of patients eventually did not receive chemotherapy, despite guideline and TB recommendations. In these patients, this mainly occurred in association with poor QoL in elderly patients >75 years old. In the group with a chemotherapy recommendation, patients' fear of chemotherapy is another factor preventing patients from undergoing adjuvant chemotherapy.

Colorectal cancer stage at diagnosis in migrants versus non-migrants (KoMigra): study protocol of a cross-sectional study in Germany.

BACKGROUND: In Germany, about 20% of the total population have a migration background. Differences exist between migrants and non-migrants in terms of health care access and utilisation. Colorectal cancer is the second most common malignant tumour in Germany, and incidence, staging and survival chances depend, amongst other things, on ethnicity and lifestyle. The current study investigates whether stage at diagnosis differs between migrants and non-migrants with colorectal cancer in an area of high migration and attempts to identify factors that can explain any differences. METHODS/DESIGN: Data on tumour and migration status will be collected for 1,200 consecutive patients that have received a new, histologically verified diagnosis of colorectal cancer in a high migration area in Germany in the previous three months. The recruitment process is expected to take 16 months and will include gastroenterological private practices and certified centres for intestinal diseases. Descriptive and analytical analysis will be performed: the distribution of variables for migrants versus non-migrants and participants versus non-participants will be analysed using appropriate χ2-, t-, F- or Wilcoxon tests. Multivariable, logistic regression models will be performed, with the dependent variable being the dichotomized stage of the tumour (UICC stage I versus more advanced than UICC stage I). Odds ratios and associated 95%-confidence intervals will be calculated. Furthermore, ordered logistic regression models will be estimated, with the exact stage of the tumour at diagnosis as the dependent variable. Predictors used in the ordered logistic regression will be patient characteristics that are specific to migrants as well as patient characteristics that are not. Interaction models will be estimated in order to investigate whether the effects of patient characteristics on stage of tumour at the time of the initial diagnosis is different in migrants, compared to non-migrants. DISCUSSION: An association of migration status or other socioeconomic variables with stage at diagnosis of colorectal cancer would be an important finding with respect to equal health care access among migrants. It would point to access barriers or different symptom appraisal and, in the long term, could contribute to the development of new health care concepts for migrants. TRIAL REGISTRATION: German Clinical Trials Register DRKS00005056.

Ramadan fasting and newborn's birth weight in pregnant Muslim women in The Netherlands.

Many Muslim women worldwide are pregnant during Ramadan and adhere to Ramadan fasting during pregnancy. In the present study, we determined whether maternal adherence to Ramadan fasting during pregnancy has an impact on the birth weight of the newborn, and whether the effects differed according to trimester in which Ramadan fasting took place. A prospective cohort study was conducted in 130 pregnant Muslim women who attended antenatal care in Amsterdam and Zaanstad, The Netherlands. Data on adherence to Ramadan fasting during pregnancy and demographics were self-reported by pregnant women, and the outcome of the newborn was retrieved from medical records after delivery. The results showed that half of all the women adhered to Ramadan fasting. With strict adherence to Ramadan fasting in pregnancy, the birth weight of newborns tended to be lower than that of newborns of non-fasting mothers, although this was not statistically significant ( - 198 g, 95 % CI - 447, 51, P= 0·12). Children of mothers who fasted in the first trimester of pregnancy were lighter at birth than those whose mothers had not fasted ( - 272 g, 95 % CI - 547, 3, P= 0·05). There were no differences in birth weight between children whose mothers had or had not fasted if Ramadan fasting had taken place later in pregnancy. Ramadan fasting during early pregnancy may lead to lower birth weight of newborns. These findings call for further confirmation in larger studies that should also investigate potential implications for perinatal and long-term morbidity and mortality.

Associations of prenatal exposure to Ramadan with small stature and thinness in adulthood: results from a large Indonesian population-based study.

A growing body of evidence suggests that maternal diet during pregnancy can lead to permanent alterations to the physiology of the fetus. It is unknown whether intermittent maternal fasting during Ramadan has long-term associations with the offspring's body composition. By using data from the third wave of the Indonesian Family Life Survey (2000), we compared the body mass indices (weight (kg)/height (m)(2)) of Muslims who had been in utero during Ramadan with those of Muslims who had not been in utero during Ramadan. Adult Muslims who had been in utero during Ramadan were slightly thinner than Muslims who had not been in utero during Ramadan (adjusted adult body mass index: -0.32, 95% confidence interval: -0.57, -0.06). Those who were conceived during Ramadan also had smaller stature, being on average 0.80 cm shorter than those who were not exposed to Ramadan prenatally. Among non-Muslims, no such associations were found. This study suggests that exposure to Ramadan during pregnancy may have lasting consequences for adult body size of the offspring.

Adherence to treatment guidelines and survival in triple-negative breast cancer: a retrospective multi-center cohort study with 9,156 patients.

BACKGROUND: Triple-negative breast cancer (TNBC) remains a challenging topic for clinical oncologists. This study sought to evaluate TNBC versus other breast cancer subtypes with respect to survival parameters. We evaluated possible differences in survival in TNBC by age and by the extent to which evidence-based treatment guidelines were adhered. METHODS: This German retrospective multi-center cohort study included 9156 patients with primary breast cancer recruited from 1992 to 2008. RESULTS: The rates of guideline adherence are significantly lower in TNBC compared to non-TNBC subtypes. These lower rates of guideline adherence can be observed in all age groups and are most pronounced in the >65 subgroup [<50 (20.9% vs. 42.0%), 50-64 (25.1% vs. 51.1%), and >65 (38.4% vs. 74.6%)]. In TNBC patients of all age groups, disease-free survival and overall survival were associated with an improvement by 100% guideline-adherent adjuvant treatment compared to non-adherence. Furthermore, TNBC patients of all ages had similar outcome parameters if 100% guideline-adherent adjuvant treatment was applied. CONCLUSION: The rates of guideline-adherent treatment were significantly lower in TNBC, even though guideline adherence was strongly associated with improved survival. In the case of 100% guideline-adherent treatment, no difference in survival was observed over all the age groups examined, even in the group of >65-year-old TNBC patients.

Treatment of coronary bifurcation lesions: stent-covering of the side branch with and without PCI of the side branch: a retrospective analysis of all consecutive patients.

BACKGROUND: Treatment of coronary bifurcation lesions is a complex problem. METHODS: This retrospective single-center study included all consecutive patients with PCI of coronary bifurcations with stent covering of the side branch (SB) between January 2008 - August 2011. RESULTS: Our study group (n = 98) was group A (n = 64, 65.3%) and group B (n = 34, 34.7%). Mean follow-up was 14.1 (group A) vs 12.3 (group B, p = ns) months. CONCLUSION: In patients with coronary bifurcations a simpler strategy has a significantly lower MACE. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01538186.

Ramadan during pregnancy and neonatal health-Fasting, dietary composition and sleep patterns.

BACKGROUND AND OBJECTIVES: Large shares of pregnant Muslims worldwide observe the Ramadan fast. Previous research showed that Ramadan during pregnancy is associated with adverse offspring health outcomes lasting throughout the life-course. Evidence on effects on birth outcomes is inconclusive, however, and previous research did not consider the role of dietary composition and sleep patterns during Ramadan. This study systematically documents maternal lifestyle during Ramadan and assesses if diet and sleep adaptations to Ramadan, independent of and in addition to maternal fasting, are associated with neonatal health outcomes. METHODS: This study reports a survey of 326 Muslims who delivered their baby in Mainz, Germany, linked to maternal & infant hospital records. Participants reported on fasting, dietary composition and sleep schedules while pregnant during Ramadan. RESULTS: Fasting during pregnancy was associated with reduced birthweight, in particular for fasting during the first trimester (-352ˑ92g, 95% CI: -537ˑ38; -168ˑ46). Neither dietary composition nor altered sleep were directly associated with birthweight. However, dietary composition during Ramadan outside of fasting hours seems to moderate the fasting-birthweight association, which disappeared for women switching to high-fat diets. CONCLUSIONS: The finding that dietary intake during Ramadan potentially moderates the fasting-birthweight association is of high relevance to pregnant Muslims who wish to fast and their healthcare professionals, since dietary choices outside of fasting hours are often relatively easily modifiable. This is the first study to include information on maternal diet and sleep during Ramadan, and additional research is needed to assess the roles of specific (macro)nutrients and food groups.

Selective mortality and fertility and long run health effects of prenatal wartime exposure.

Many previous studies have shown that prenatal exposure to adverse historical circumstances negatively affects long-run health. Most women who are pregnant during wars experience clearly adverse circumstances that are however not as harsh as the typically studied extreme episodes such as famines, combat and wide-scale destruction. We show that prenatal exposure to World War II (WWII) in five Western European countries did not lead to a population-wide poorer health among the elderly. We even find indications of a better than expected health. This is likely due to selective fertility and mortality. We attempt to quantify these selection effects and show that when taking them into account, the initially positively estimated health effects on almost all outcomes are substantially attenuated. Selective mortality and fertility likely occur in similar directions for many historical episodes of adversity. Our results therefore suggest that a part of the previous research on such exposures likely under estimated the true sizes of the long-run effects.

Are grandchildren good for you? Well-being and health effects of becoming a grandparent.

Older individuals commonly go through a few major life transitions which can impact their health and well-being. While transitions like that into retirement have been extensively investigated, little research focused on the transition into grandparenthood. Understanding effects of this highly common event is not only important from a descriptive viewpoint, but is also informative for the active aging policies that are increasingly pursued to deal with aging populations. Using data from ten Western European countries, we show that grandparenthood on average leads to a reduction in well-being while hardly impacting physical, cognitive and mental health. The effect is heterogeneous by family closeness, though. Grandparenthood reduces well-being for those having relatively little family contact and not providing child care. But it leaves well-being unaffected while improving health along some dimensions among those with the opposite profile. The only exception to the latter are grandmothers providing daily child care, for whom grandparenthood appears to be burdensome. This pattern of results suggests that involving grandparents non-intensively in child care may lead to beneficial side-effects. Becoming a grandparent induces people to retire, but retirement seems no relevant channel for well-being and health effects.

No "honeymoon phase": whose health benefits from retirement and when.

Does retirement lead to a short, transitory health boost, followed by a stable longer-run effect? The short-run effect has been hypothesized to be a kind of honeymoon effect, that is followed by a longer-run effect that may be either positive or negative. We examine the time path of the health effect of retirement and study effect heterogeneities between individuals along several dimensions. Moreover, we study a broad range of health outcomes, all in order to come to an understanding of the effect patterns that lie behind the diverse findings reported in previous research. For identification we use a fixed effects instrumental variable approach in which the normal and early retirement age thresholds serve as instruments. Using data for 10 countries from the Survey of Health, Retirement and Ageing in Europe (SHARE), we find that retiring both at the normal and early retirement eligibility ages significantly improves all the health aspects we consider. Other than hypothesized, results do not show a honeymoon phase-like transitory health boost. Instead, especially blue-collar workers go through an adjustment period after retiring, in which their health worsens. Afterwards, health stabilizes and improves, so that retirement has a health preserving effect in the longer run. This beneficial health effect of retirement occurs across all occupational groups, across a range of health outcomes, and for both sexes, though there are a number of heterogeneities between groups regarding which health outcomes are particularly affected.

Ramadan exposure and birth outcomes: a population-based study from the Netherlands.

BACKGROUND: Ramadan, the Islamic month of daytime fasting, is observed by many pregnant Muslims. Although pregnant women are exempt, many prefer to fast. Previous research has shown long-term adverse effects on various health outcomes among the offspring, but evidence on effects on perinatal outcomes is mixed. This study investigates effects of Ramadan during pregnancy among Muslims in the Netherlands. METHODS: Data from the Perinatal Registry of the Netherlands (Perined) on all births between 2000 and 2010 to mothers recorded as Mediterranean (i.e. of Turkish/Moroccan descent, a proxy for Muslim) (n = 139,322) or as ethnically Dutch (n = 1,481,435) were used. Ramadan exposure was defined using an intention-to-treat approach as the occurrence of a Ramadan during gestation. Muslims with versus without a Ramadan occurring during gestation were compared using difference-in-differences analyses. In these multiple linear/logistic regressions, non-Muslims were additionally included in order to take out potentially remaining confounding through seasonal effects. RESULTS: The occurrence of a Ramadan during pregnancy among Muslims was not associated with altered birth weight, gestational length, newborn's sex, perinatal mortality, low Apgar, or mild congenital anomalies. Odds for severe congenital anomalies were higher among the exposed (odds ratio: 1.17; 95% confidence interval: 1.00, 1.37), but this association became non-significant when adjusting for multiple testing. CONCLUSIONS: Despite earlier research showing long-term adverse health effects of prenatal exposure to Ramadan, there seems to be little or no relation between exposure to Ramadan during pregnancy and birth outcomes.

Low-risk isn't no-risk: Perinatal treatments and the health of low-income newborns.

We investigate the effects of perinatal medical treatments on low-income newborns who are classified as low-risk. A policy rule in The Netherlands states that low-risk deliveries before week 37 should be supervised by physicians and later deliveries only by midwives with no physician present. This creates large discontinuities in the probability of receiving medical interventions only physicians are allowed to perform. Using a regression discontinuity design, we find that babies born slightly before the week-37 cutoff are significantly less likely to die than babies born slightly later. Our data suggest that physician supervision of birth reduces the likelihood of adverse events such as fetal distress or emergency C-section. Our results indicate that low-income women benefit from receiving a higher level of medical care even if no explicit risk factors have been recognized, pointing to challenges in identifying all high-risk pregnancies. "Back-of-the-envelope" calculations suggest this additional care is highly cost-effective.