Protocol for a randomised controlled trial evaluating the effect of a CBT-I smartphone application (Sleep Ninja®) on insomnia symptoms in children.

BACKGROUND: Sleep is necessary for healthy development and mental wellbeing. Despite this, many children do not get the recommended duration of sleep each night, and many experience sleep problems. Although treatable, existing interventions for sleep disturbance are time-consuming, burdensome for families, and focus on providing behavioural strategies to parents rather than upskilling children directly. To address this gap, we modified Sleep Ninja®, an evidence-based cognitive behavioural therapy for insomnia (CBT-I) smartphone app for adolescent sleep disturbance, to be appropriate for 10 to 12 year olds. Here, we describe the protocol for a randomised controlled trial to evaluate the effect of Sleep Ninja on insomnia and other outcomes, including depression, anxiety, sleep quality, and daytime sleepiness, and explore effects on the emergence of Major Depressive Disorder (MDD), compared to an active control group. METHODS: We aim to recruit 214 children aged 10 to 12 years old experiencing disturbed sleep. Participants will be screened for inclusion, complete the baseline assessment, and then be randomly allocated to receive Sleep Ninja, or digital psychoeducation flyers (active control) for 6-weeks. The primary outcome, insomnia symptoms, along with depression, anxiety, sleep quality, and daytime sleepiness will be assessed at 6-weeks (primary endpoint), 3-months, and 9-months post-baseline (secondary and tertiary endpoints, respectively). A mixed model repeated measures analytic approach will be used to conduct intention-to-treat analyses to determine whether reductions in insomnia and secondary outcomes are greater for those receiving Sleep Ninja relative to the control condition at the primary and secondary endpoints. The difference in relative risk for MDD onset will be explored at 9-months and compared between conditions. DISCUSSION: This is the first clinical trial examining the effects of a CBT-I smartphone app in children experiencing sleep disturbance. Results will provide empirical evidence about the effects of Sleep Ninja on insomnia and other mental health outcomes. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry (ACTRN12623000587606). UNIVERSAL TRIAL NUMBER: U1111-1294-4167.

Are patients benefiting from participation in the German skin cancer screening programme? A large cohort study based on administrative data.

BACKGROUND: The German programme for skin cancer screening was established in 2008 with the aim of reducing skin cancer mortality. However, the effectiveness and risk-benefit ratio of the programme remain unclear. OBJECTIVES: To compare the mortality rates of patients with melanoma who participate in a screening programme to those who do not. METHODS: A retrospective cohort study, based on pseudonymized health insurance data of 1 431 327 individuals from Saxony, Germany, was conducted for the period 2010-2016. Patients with prevalent and incident melanoma were defined based on diagnosis, medical procedures and prescriptions. Patients who underwent screening and had a first diagnosis of melanoma within 2 years of screening were assigned to the intervention group. Relative survival and Cox regression were used to assess potential differences in mortality. RESULTS: We identified 4552 individuals with prevalent and 2475 individuals with incident melanoma. The percentage of screening participants (n = 1801) who had locoregional (4·2% vs. 13·5%) and/or distant metastases (4·3% vs. 8·0%), or who were treated with systemic anticancer therapies (11·6% vs. 21·8%) was lower vs. nonparticipants (n = 674). Screening participants had significantly better survival rates. The unadjusted Cox model gave a hazard ratio (HR) of 0·37 [95% confidence interval (CI) 0·30-0·46]. After adjusting for named confounders, the effect remained (HR 0·62, 95% CI 0·48-0·80). CONCLUSIONS: Patients who participated in the screening programme had lower mortality than those who had not undergone screening. However, these findings may result from a healthy screen bias and/or overdiagnosis associated with screening, and not from the screening itself.

Protocol for a randomised controlled trial evaluating the effectiveness of a CBT-based smartphone application for improving mental health outcomes in adolescents: the MobiliseMe study.

BACKGROUND: Depression is a leading cause of disability in adolescents, however few receive evidence-based treatment. Despite having the potential to overcome barriers to treatment uptake and adherence, there are very few CBT-based smartphone apps for adolescents. To address this gap, we developed ClearlyMe®, a self-guided CBT smartphone app for adolescent depression and anxiety. ClearlyMe® consists of 37 brief lessons containing core CBT elements, accessed either individually or as part of a 'collection'. Here, we describe the protocol for a randomised controlled trial aiming to evaluate the effect of ClearlyMe® on depressive symptoms and secondary outcomes, including engagement, anxiety and wellbeing, when delivered with and without guided support compared to an attention matched control. METHODS: We aim to recruit 489 adolescents aged 12-17 years with mild to moderately-severe depressive symptoms. Participants will be screened for inclusion, complete the baseline assessment and are then randomly allocated to receive ClearlyMe® (self-directed use), ClearlyMe® with guided SMS support (guided use) or digital psychoeducation (attention-matched control). Depressive symptoms and secondary outcomes will be assessed at 6-weeks (primary endpoint) and 4-months post-baseline (secondary endpoint). Engagement, conceptualised as uptake, adherence and completion, will also be assessed 6-weeks post-baseline. Mixed-effects linear modelling will be used to conduct intention-to-treat analyses to determine whether reductions in depressive symptoms and secondary outcomes are greater for conditions receiving ClearlyMe® relative to control at 6-weeks and 4-months post-baseline and greater for intervention adherers relative to non-adherers. To minimise risk, participants will be encouraged to use the Get Help section of the app and can also opt to receive a call from the team clinical psychologist at baseline, and at the 6-week and 4-month post-baseline assessments when reporting suicidal ideation. DISCUSSION: This is the first clinical trial examining a CBT smartphone app specifically designed for adolescent depression. It will provide empirical evidence on the effects of ClearlyMe® on depressive symptoms when used with and without guided support. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry (ACTRN12622000131752). UNIVERSAL TRIAL NUMBER: U1111-1271-8519.

[Update on occupational skin cancer-basal cell carcinoma and solar UV exposure]. / Neues zum berufsbedingten Hautkrebs ­ Basalzellkarzinom und solare UV-Exposition.

BACKGROUND: Outdoor workers are occupationally exposed to significantly higher ultraviolet (UV) doses than the rest of the population. Recent data show a doubling of basal cell carcinoma (BCC) risk in outdoor workers with high occupational UV exposure. OBJECTIVES: To examine the stability and robustness of BCC risk estimators. METHODS: Sensitivity analyses to test model assumptions considering socioeconomic status, influence of matching procedure, gender and latency, regional differences (east/west), urban/rural cases/controls, and dual diagnoses (squamous cell carcinoma [SCC]/actinic keratoses grade III [AKIII]/Bowen disease [BD] and BCC) were performed. RESULTS: BCC risk was consistently higher for high occupationally UV-exposed individuals than for intermediate UV-exposed individuals, regardless of matching procedure, latency, regional differences (east/west), urban/rural recruitment of cases/controls, and dual diagnoses (SCC/AKIII/BD and BCC), sex, and socioeconomic status. CONCLUSION: The risk estimator for the association between exposure to solar UV radiation at work and the risk of developing BCC showed a high degree of stability and robustness for all variables investigated. The analyses support the recently published findings on the doubling of BCC risk in outdoor workers with high occupational UV exposure.

Is ultraviolet exposure acquired at work the most important risk factor for cutaneous squamous cell carcinoma? Results of the population-based case-control study FB-181.

BACKGROUND: Squamous cell carcinoma (SCC) is one of the most frequent types of cancer constituting a significant public health burden. Prevention strategies focus on limiting ultraviolet (UV) exposure during leisure time. However, the relative impact of occupational and nonoccupational UV exposure for SCC occurrence is unclear. OBJECTIVES: To investigate the association between occupational and nonoccupational UV exposure for SCC in a multicentre population-based case-control study hypothesizing that high occupational UV exposure increases the risk of SCC. METHODS: Consecutive patients with incident SCC (n = 632) were recruited from a German national dermatology network. Population-based controls (n = 996) without history of skin cancer were recruited from corresponding residents' registration offices and propensity score matched to cases. Lifetime UV exposure, sociodemographic and clinical characteristics were assessed by trained physicians. Occupational and nonoccupational UV exposure doses were estimated by masked investigators using established reference values. Odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were assessed using conditional logistic regression adjusting for relevant confounders. RESULTS: Total solar UV exposure was significantly associated with increased SCC. The OR for high (> 90th percentile) vs. low (< 40th percentile) and high vs, moderate (40-59th percentile) occupational UV exposure was 1·95 (95% CI 1·19-3·18) and 2·44 (95% CI 1·47-4·06) for SCC. Adjusting for occupational UV exposure, nonoccupational UV exposure was not significantly related to SCC incidence. Dose-response relationships were observed for occupational but not for nonoccupational solar UV exposure. CONCLUSIONS: Solar occupational UV exposure is a major determinant of incident SCC. Our findings indicate that prevention strategies should be further expanded to the occupational setting.

Associations of fatigue to work-related stress, mental and physical health in an employed community sample.

BACKGROUND: While work-related fatigue has become an issue of concern among European employees, the relationship between fatigue, depression and work-related stressors is far from clear. The purposes of this study were (1) to determine the associations of fatigue with work-related stressors, severe medical disease, health behavior and depression in the working population and (2) to determine the unique impact of work-related stressors on fatigue. METHODS: We used cross-sectional data of N = 7,930 working participants enrolled in the Gutenberg Health Study (GHS) from 2007 to 2012 filled out the Personal Burnout Scale (PBS) of the Copenhagen Psychosocial Questionnaire (COPSOQ), the PHQ-9, and a list of work-related stressors. RESULTS: A total of 27.5% reported increased fatigue, esp. women, younger persons with a lower social status and income, smokers, severely medically ill, previously and currently depressed participants. Fatigue was consistently associated with severe medical disease, health behavior and depression, which need to be taken into account as potential confounders when analyzing its relationship to work-related strains. Depression was consistently associated with work-related stressors. However, after statistically partialling out depression, fatigue was still significantly associated with work-related stress. CONCLUSIONS: Fatigue as an indicator of allostatic load is consistently associated with work-related stressors such as work overload after controlling for depression. The brief Personal Burn-out Scale is suitable for assessing work-related fatigue in the general population.

Effects of the German skin cancer screening programme on melanoma incidence and indicators of disease severity.

BACKGROUND: In Germany a nationwide melanoma screening programme for adults aged ≥ 35 years was introduced in July 2008. Evidence on utilization and effects is limited. OBJECTIVES: To examine the uptake and effects of the German nationwide screening programme. METHODS: This analysis is based on pseudonymized outpatient routine data of a German health insurance company covering data of > 2 million individuals from Saxony for the years 2005-2012. Cases of melanoma and nonmelanoma skin cancer (NMSC) were identified using an algorithm based on the International Classification of Diseases, 10th Revision. Cross-sectional and longitudinal analyses were applied to determine the utilization of the screening programme and effects on skin cancer incidence and disease severity as a proxy for prognosis. RESULTS: Overall, 38·0% of eligible persons (≥ 35 years) were screened at least once between July 2008 and December 2012. The annual participation rate was 12·4%. Out of 533 393 persons screened, melanoma and NMSC were diagnosed in 0·3% and 2·5%, respectively. The 6-month melanoma incidence per 100 000 insured persons decreased from 12·8 before screening introduction (January to June 2008) to 10·2 after introduction (July to December 2008). NMSC incidence increased from 173·8 to 175·5 per 100 000. The numbers of screening participants receiving interferon alpha and/or being diagnosed with lymph node and/or distant metastasis (8·6%, 5·9%, 1·5%, respectively) were lower than in nonparticipants (11·2%, 8·5%, 3·5%). These differences were not significant. CONCLUSIONS: The results suggest that the introduction of a generic skin cancer screening programme in Germany was not associated with significant changes in incidence. No firm conclusions regarding the effects of skin cancer screening on prognosis can be drawn. Longer follow-up and linkage with clinical registry data are necessary to clarify the effect of screening participation on incidence and prognosis.

Does the use of small aids during patient handling activities lead to a decreased occurrence of musculoskeletal complaints and diseases? A systematic review.

PURPOSE: Patient handling increases the risk of musculoskeletal complaints and diseases among healthcare workers. Thus, the use of small aids for patient handling is recommended. Small aids are non-electrical and handy assistive devices that support caregivers during patient handling. To date, there is no evidence about the clinical efficacy of small aids. Hence, the objective of this systematic review was to systematically analyze whether the use of small aids during patient handling leads to a decreased occurrence of musculoskeletal disorders. METHODS: A systematic literature search was carried out. The review process was done independently by two reviewers. Methodology was assessed with the "Downs and Black checklist" and the "Risk of Bias tool." Quality of evidence was determined with the GRADE method. RESULTS: One randomized and two non-randomized trials were included. Three comparisons of intervention assessing the lumbar spine and shoulder joint were investigated. A statistically significant improvement of the 7-day prevalence of low back pain and shoulder pain was achieved within the intervention group over time of questionable clinical importance in a study with comparisons made between small aids and usual practice or mechanical aids. No comparison between the intervention group and control group at follow-up was made. Each trial showed an insufficient methodology and a high risk of bias. Quality of evidence was low for disability scores and very low for pain outcomes. CONCLUSIONS: To date, there is no convincing evidence (from low-quality studies) for the preventability of musculoskeletal complaints and diseases by the use of small aids. The literature also lacks evidence for the opposite. Generalizability of the study results is further debatable due to the different populations and settings that were investigated. Robust, high-quality intervention studies are necessary to clarify the clinical efficacy of small aids in healthcare work. PROSPERO REGISTRY NUMBER: CRD42014009767.

Current and cumulative night shift work and subclinical atherosclerosis: results of the Gutenberg Health Study.

PURPOSE: The study examines the association between exposure to current and cumulative night shift work and subclinical parameters of atherosclerosis. METHODS: Participants of a population-based cohort study (the Gutenberg Health Study, N = 15,010) aged 35-64 years were examined at baseline (2007-2012). Investigations included measurements of arterial stiffness, vascular function [reactive hyperaemia (RH) index], and intima media thickness (IMT). Also, a complete job history (including up to 15 periods), occupational exposures, a variety of lifestyle, and dispositional variables were enquired. RESULTS: Night shift work was performed by 1071 out of 8065 currently employed individuals. The strongest association after adjustment for age, sex, job complexity level, being a manager, overtime work, and noise appeared for more than 660 night shifts within the last 10 years and a significantly increased arterial stiffness of 0.33 m/s. This reflects a 4 % flow velocity increase for individuals with more than 660 night shifts compared to non-night workers. Regarding the entire professional life, night shift workers showed a significantly decreased vascular function by -0.054 RH index points by using the same adjustment. IMT values did not differ statistically from non-night workers. Lifestyle and dispositional factors showed an influence on all used subclinical atherosclerosis parameters. CONCLUSIONS: The cross-sectional results demonstrate an association between night work and detrimental changes in the atherosclerotic process. The association is more pronounced with more years in night shift and is partly explained by lifestyle and dispositional factors. Longitudinal analyses are necessary to confirm the results.

Identification of a molecular defect in a stillborn fetus with perinatal lethal hypophosphatasia using a disease-associated genome sequencing approach.

Lethal skeletal disorders represent a heterogeneous and clinically variable group of genetic conditions, usually difficult to diagnose without post-mortem radiological assessment. Here we report on a stillborn patient delivered at 22 weeks of gestation who presented with severe skeletal symptoms comprising limb shortening and intrauterine fractures detected upon prenatal ultrasound and autopsy examination. Since post-mortem X-ray was refused and no phenotypic diagnosis could be attempted, we performed next-generation sequencing (NGS) of 2741 genes associated with all known Mendelian disorders. With this strategy, we were able to demonstrate the diagnosis at a molecular level, which turned out to be perinatal lethal hypophosphatasia (HPP). This severe form of HPP represents an inborn defect of ossification often resulting in stillbirth or postnatal death. The NGS panel revealed compound heterozygous ALPL missense mutations: c.1283G>C(p.Arg428Pro) and c.1363G>A(p.Gly455Ser). Mutations detected in our case, although previously described in other patients, have not been reported to co-occur in a single individual. The diagnosis established in our index using the NGS-based approach could have been successfully reached by standard radiography. Thus, our report points to the importance of X-ray examination in stillborn cases and highlights the emerging role of NGS strategies in the diagnostic process of prenatally manifesting skeletal disorders.

[Mental health and work: concepts, evidence and implications for research and practice]. / Psychische Gesundheit und Arbeit : Konzepte, Evidenz und Implikationen für Forschung und Praxis.

This paper reviews the concepts, evidence and implications regarding mental health at the workplace. The theoretical background with the most common theories (e.g. effort-reward imbalance model and job-demand control model) are briefly reviewed and findings from systematic reviews and from a meta-analysis regarding psychosocial factors at the workplace and common mental disorders, which indicate that psychosocial factors increase the risk of mental disorder are outlined. Implications for primary prevention as well as early intervention and treatment following a stepped care model including a variety of agents from different backgrounds are discussed. Implications to enhance research in the field are outlined.

Systematic review: Progression of beryllium sensitization to chronic beryllium disease.

BACKGROUND: The relevance of beryllium sensitization testing for occupational health practice and prevention is unclear. AIMS: To analyse the natural course of beryllium sensitization and clarify the prognosis following cessation of exposure among sensitized workers. METHODS: An electronic literature search was conducted in PubMed, Embase, Toxline and Cochrane databases supplemented by a manual search. Data abstraction and study quality assessment with adapted guideline checklists were performed independently by three reviewers. Seven studies met the eligibility criteria and were included in the systematic review; however, six of the seven studies were of low methodological quality. RESULTS: A substantial (although not specifically quantifiable) proportion of beryllium-sensitized employees will develop chronic beryllium disease (CBD). To date, it is unknown if cessation of exposure in sensitized workers reduces the progression rate to CBD. CONCLUSIONS: To determine the utility of regular assessments for beryllium sensitization among exposed workers, there is a need for prospective studies. This should include detailed and continuous exposure monitoring, regular tests for beryllium sensitization and a thorough diagnostic evaluation of sensitized workers to confirm or exclude CBD.

Occupational ultraviolet light exposure increases the risk for the development of cutaneous squamous cell carcinoma: a systematic review and meta-analysis.

BACKGROUND: Despite the fact that ultraviolet (UV) light exposure is the most important risk factor for cutaneous squamous cell carcinoma (SCC) there is an ongoing debate concerning the relationship between cumulative work-related UV exposure and SCC occurrence. OBJECTIVES: To analyse comprehensively the relationship between work-related UV exposure and SCC risk. METHODS: We conducted a systematic electronic literature search in PubMed (up to 5 May 2010) supplemented by a hand search, which identified 18 relevant studies that were included in the review. Data abstraction and study quality assessment was done independently by two reviewers. Maximally adjusted odds ratios (ORs) and corresponding 95% confidence intervals (CIs) of all included studies were pooled in a random-effects meta-analysis. Sensitivity analysis included meta-regression on study-specific covariates to explore the robustness of the results and to identify sources of heterogeneity between studies. Eighteen studies (six cohort studies, 12 case-control studies) met the eligibility criteria and were included in the systematic review. RESULTS: Sixteen studies (89%) found an increased risk of SCC in individuals with occupational UV light exposure compared with individuals without occupational UV light exposure, reaching statistical significance in 12 studies. Two studies found no association between occupational UV light exposure and SCC occurrence. The pooled OR (95% CI) was 1·77 (1·40-2·22) and did not differ significantly between cohort studies [OR (95% CI): 1·68 (1·08-2·63)] and case-control studies [OR (95% CI): 1·77 (1·37-2·30)]. Meta-regression analyses suggested an increasing strength of the association between occupational UV light exposure and SCC risk with decreasing latitude. CONCLUSIONS: In summary, there is consistent epidemiological evidence for a positive association between occupational UV light exposure and SCC risk.

Quantifying the advantages of conducting a prospective meta-analysis (PMA): a case study of early childhood obesity prevention.

BACKGROUND: For prospective meta-analyses (PMAs), eligible studies are identified, and the PMA hypotheses, selection criteria, and analysis methods are pre-specified before the results of any of the studies are known. This reduces publication bias and selective outcome reporting and provides a unique opportunity for outcome standardisation/harmonisation. We conducted a world-first PMA of four trials investigating interventions to prevent early childhood obesity. The aims of this study were to quantitatively analyse the effects of prospective planning on variations across trials, outcome harmonisation, and the power to detect intervention effects, and to derive recommendations for future PMA. METHODS: We examined intervention design, participant characteristics, and outcomes collected across the four trials included in the EPOCH PMA using their registration records, protocol publications, and variable lists. The outcomes that trials planned to collect prior to inclusion in the PMA were compared to the outcomes that trials collected after PMA inclusion. We analysed the proportion of matching outcome definitions across trials, the number of outcomes per trial, and how collaboration increased the statistical power to detect intervention effects. RESULTS: The included trials varied in intervention design and participants, this improved external validity and the ability to perform subgroup analyses for the meta-analysis. While individual trials had limited power to detect the main intervention effect (BMI z-score), synthesising data substantially increased statistical power. Prospective planning led to an increase in the number of collected outcome categories (e.g. weight, child's diet, sleep), and greater outcome harmonisation. Prior to PMA inclusion, only 18% of outcome categories were included in all trials. After PMA inclusion, this increased to 91% of outcome categories. However, while trials mostly collected the same outcome categories after PMA inclusion, some inconsistencies in how the outcomes were measured remained (such as measuring physical activity by hours of outside play versus using an activity monitor). CONCLUSION: Prospective planning led to greater outcome harmonisation and greater power to detect intervention effects, while maintaining acceptable variation in trial designs and populations, which improved external validity. Recommendations for future PMA include more detailed harmonisation of outcome measures and careful pre-specification of analyses to avoid research waste by unnecessary over-collection of data.

Basal cell carcinoma risk and solar UV exposure in occupationally relevant anatomic sites: do histological subtype, tumor localization and Fitzpatrick phototype play a role? A population-based case-control study.

BACKGROUND: A two-fold risk increase to develop basal cell carcinoma was seen in outdoor workers exposed to high solar UV radiation compared to controls. However, there is an ongoing discussion whether histopathological subtype, tumor localization and Fitzpatrick phototype may influence the risk estimates. OBJECTIVES: To evaluate the influence of histological subtype, tumor localization and Fitzpatrick phototype on the risk to develop basal cell carcinoma in highly UV-exposed cases and controls compared to those with moderate or low solar UV exposure. METHODS: Six hundred forty-three participants suffering from incident basal cell carcinoma in commonly sun-exposed anatomic sites (capillitium, face, lip, neck, dorsum of the hands, forearms outside, décolleté) of a population-based, case-control, multicenter study performed from 2013 to 2015 in Germany were matched to controls without skin cancer. Multivariate logistic regression analysis was conducted stratified for histological subtype, phototype 1/2 and 3/4. Dose-response curves adjusted for age, age2, sex, phototype and non-occupational UV exposure were calculated. RESULTS: Participants with high versus no (OR 2.08; 95% CI 1.24-3.50; p = 0.006) or versus moderate (OR 2.05; 95% CI 1.15-3.65; p = 0.015) occupational UV exposure showed a more than two-fold significantly increased risk to develop BCC in commonly UV-exposed body sites. Multivariate regression analysis did not show an influence of phototype or histological subtype on risk estimates. The restriction of the analysis to BCC cases in commonly sun-exposed body sites did not influence the risk estimates. The occupational UV dosage leading to a 2-fold increased basal cell carcinoma risk was 6126 standard erythema doses. CONCLUSION: The risk to develop basal cell carcinoma in highly occupationally UV-exposed skin was doubled consistently, independent of histological subtype, tumor localization and Fitzpatrick phototype.

Genetic ablation of carbonic anhydrase IX disrupts gastric barrier function via claudin-18 downregulation and acid backflux.

AIM: This study aimed to explore the molecular mechanisms for the parietal cell loss and fundic hyperplasia observed in gastric mucosa of mice lacking the carbonic anhydrase 9 (CAIX). METHODS: We assessed the ability of CAIX-knockout and WT gastric surface epithelial cells to withstand a luminal acid load by measuring the pHi of exteriorized gastric mucosa in vivo using two-photon confocal laser scanning microscopy. Cytokines and claudin-18A2 expression was analysed by RT-PCR. RESULTS: CAIX-knockout gastric surface epithelial cells showed significantly faster pHi decline after luminal acid load compared to WT. Increased gastric mucosal IL-1ß and iNOS, but decreased claudin-18A2 expression (which confer acid resistance) was observed shortly after weaning, prior to the loss of parietal and chief cells. At birth, neither inflammatory cytokines nor claudin-18 expression were altered between CAIX and WT gastric mucosa. The gradual loss of acid secretory capacity was paralleled by an increase in serum gastrin, IL-11 and foveolar hyperplasia. Mild chronic proton pump inhibition from the time of weaning did not prevent the claudin-18 decrease nor the increase in inflammatory markers at 1 month of age, except for IL-1ß. However, the treatment reduced the parietal cell loss in CAIX-KO mice in the subsequent months. CONCLUSIONS: We propose that CAIX converts protons that either backflux or are extruded from the cells rapidly to CO2 and H2 O, contributing to tight junction protection and gastric epithelial pHi regulation. Lack of CAIX results in persistent acid backflux via claudin-18 downregulation, causing loss of parietal cells, hypergastrinaemia and foveolar hyperplasia.

Occupation and malignant lymphoma: a population based case control study in Germany.

AIMS: To identify occupations suspected to be associated with malignant lymphoma and to generate new hypotheses about occupational risks in a multicentre, population based case control study. METHODS: Male and female patients with malignant lymphoma (n = 710) aged 18-80 years of age were prospectively recruited in six study regions in Germany. For each newly recruited lymphoma case, a sex, region, and age matched control was drawn from the population registers. Odds ratios and 95% confidence intervals for major occupations and industries were calculated using conditional logistic regression analysis, adjusted for smoking (in pack-years) and alcohol consumption. Patients with specific lymphoma subentities were additionally compared with the entire control group using unconditional logistic regression analysis. RESULTS: The following economic/industrial sectors were positively associated with lymphoma: food products, beverages, tobacco; paper products, publishing and printing; and metals. Chemicals; real estate, renting, and business activities were negatively associated with lymphoma diagnosis. The authors observed an increased overall lymphoma risk among architects; maids; farmers; glass formers; and construction workers. Shoemaking and leather goods making was negatively associated with the lymphoma diagnosis (although based on small numbers). In the occupational group analysis of lymphoma subentities, Hodgkin's lymphoma was significantly associated only with rubber and plastic products making; diffuse large B cell lymphoma risk was considerably increased among metal processors; follicular lymphoma showed highly significant risk increases for several occupational groups (medical, dental, and veterinary workers; sales workers; machinery fitters; and electrical fitters); and multiple myeloma showed a particularly pronounced risk increase for farmers as well as for agriculture and animal husbandry workers. CONCLUSIONS: The results partly confirm previously defined occupational risks. Occupational risk factors for follicular lymphomas might differ from the overall risk factors for malignant lymphoma.