Long-term medication for ADHD (LMA) trial: 2-year prospective observational study in children and adolescents. Core symptoms, daily functioning, and comorbidity outcomes.

More knowledge is needed about long-term ADHD medication and symptom, daily functioning, comorbidity, and tolerability outcomes. This "Long-term Medication for ADHD (LMA) trial" was a prospective observational 2-year trial in children and adolescents aged 6-18 years (extension of 1-year trial). Participants met criteria for DSM-5 ADHD (inattentive or combined), with complex comorbidities; autism spectrum disorder (31%), autistic traits (24%), oppositional symptoms (59%), anxiety (32%), dyslexia/language disorder (16%), borderline intellectual functioning (17%). Medication was individually tailored and followed-up at clinical visits (1, 2, 3, 6, 12, 18, 24 months). Primary outcome: Clinical Global Impression-Severity and Improvement scales (CGI-S, CGI-I). Secondary outcomes: Investigator-rated ADHD-Rating Scale, Weiss Functional Impairment Rating Scale-Parent report (WFIRS-P; Family, School Learning and Behavior, Life Skills, Self-Concept, Social Activities, and Risky Activities domains), comorbidity symptoms and adverse events (AEs). One hundred twenty-eight participants were enrolled (1-year trial only n = 27, LMA trial n = 101). Of these 29 (23%) discontinued, mainly due to AEs (n = 7), moving (n = 7), or no longer needing medication (n = 6). Main AEs were poor appetite, low mood, anxiety, irritability, fatigue. Improvements from baseline to 2 years were large in CGI-S (effect size (ES) 2.28), ADHD-RS (ES 2.06), and moderate to large in WFIRS-P (ES total 0.73, learning 0.4, family 0.67). Overall, the trial showed robust and sustained improvements in ADHD symptom severity and daily functioning over a period of 2 years of ADHD medication in children and adolescents with ADHD and complex comorbidities. Most AEs were mild. Comorbidity symptoms were improved after 1 year, particularly oppositional symptoms, depression, and anxiety.

Occupational risk of COVID-19 in foreign-born employees in Denmark.

BACKGROUND: Foreign-born workers in high-income countries experience higher rates of COVID-19 but the causes are only partially known. AIMS: To examine if the occupational risk of COVID-19 in foreign-born workers deviates from the risk in native-born employees in Denmark. METHODS: Within a registry-based cohort of all residents employed in Denmark (n = 2 451 542), we identified four-digit DISCO-08 occupations associated with an increased incidence of COVID-19-related hospital admission during 2020-21 (at-risk occupations). The sex-specific prevalence of at-risk employment in foreign born was compared with the prevalence in native born. Moreover, we examined if the country of birth modified the risk of a positive SARS-CoV-2 polymerase chain reaction (PCR) test and COVID-19-related hospital admission in at-risk occupations. RESULTS: Workers born in low-income countries and male workers from Eastern Europe more often worked in at-risk occupations (relative risks between 1.16 [95% confidence interval {CI} 1.14-1.17] and 1.87 [95% CI 1.82-1.90]). Being foreign-born modified the adjusted risk of PCR test positivity (test for interaction P < 0.0001), primarily because of higher risk in at-risk occupations among men born in Eastern European countries (incidence rate ratio [IRR] 2.39 [95% CI 2.09-2.72] versus IRR 1.19 [95% CI 1.14-1.23] in native-born men). For COVID-19-related hospital admission, no overall interaction was seen, and in women, country of birth did not consistently modify the occupational risk. CONCLUSIONS: Workplace viral transmission may contribute to an excess risk of COVID-19 in male workers born in Eastern Europe, but most foreign-born employees in at-risk occupations seem not to be at higher occupational risk than native born.

Diabetes and pre-diabetes among police officers in Guinea-Bissau

This study has investigated the prevalence of type 2 diabetes among 1119 police officers in Guinea-Bissau.Those with a random blood glucose (RBG) >8.0 mol/l had HbA1c (glycated haemoglobin) testing. Diabetes (HbA1c >6.5%) was present in 4.1%, and pre-diabetes (HbA1c 5.7­6.5%) was present in a further 4.2%. Factors associated with diabetes were age, weight and ethnicity

Cancer incidence in cohorts of workers in the rubber manufacturing industry first employed since 1975 in the UK and Sweden.

OBJECTIVES: Increased cancer risks have been reported among workers in the rubber manufacturing industry employed before the 1960s, but it is unclear for workers hired subsequently. The present study focused on cancer incidence among rubber workers first employed after 1975 in Sweden and the UK. METHODS: Two cohorts of rubber workers employed for at least 1 year were analysed. Standardised incidence ratios (SIRs), based on country-specific and period-specific incidence rates, were analysed for all cancers combined (except non-melanoma skin), bladder, lung, stomach cancer, leukaemia, non-Hodgkin's lymphoma and multiple myeloma. Exploratory analyses were conducted for other cancers with a minimum of 10 cases in both genders combined. RESULTS: 16 026 individuals (12 441 men; 3585 women) contributed to 397 975 person-years of observation, with 846 cancers observed overall (437 in the UK, 409 in Sweden). No statistically significant increased risk was observed for any site of cancer. A reduced risk was evident for all cancers combined (SIR=0.83, 95% CI (0.74 to 0.92)), lung cancer (SIR=0.74, 95% CI (0.59 to 0.93)), non-Hodgkin's lymphoma (SIR=0.67, 95% CI (0.45 to 1.00)) and prostate cancer (SIR=0.77, 95% CI (0.64 to 0.92)). For stomach cancer and multiple myeloma, SIRs were 0.93 (95% CI (0.61 to 1.43)) and 0.92 (95% CI 0.44 to 1.91), respectively. No increased risk of bladder cancer was observed (SIR=0.88, 95% CI (0.61 to 1.28)). CONCLUSIONS: No significantly increased risk of cancer incidence was observed in the combined cohort of rubber workers first employed since 1975. Continued surveillance of the present cohorts is required to confirm absence of long-term risk and confirmatory findings from other cohorts would be important.

Intervention to reduce heat stress and improve efficiency among sugarcane workers in El Salvador: Phase 1.

BACKGROUND: Chronic heat stress and dehydration from strenuous work in hot environments is considered an essential component of the epidemic of chronic kidney disease in Central America. OBJECTIVE: (1) To assess feasibility of providing an intervention modelled on OSHA's Water.Rest.Shade programme (WRS) during sugarcane cutting and (2) to prevent heat stress and dehydration without decreasing productivity. METHODS: Midway through the 6-month harvest, the intervention introduced WRS practices. A 60-person cutting group was provided water supplied in individual backpacks, mobile shaded rest areas and scheduled rest periods. Ergonomically improved machetes and efficiency strategies were also implemented. Health data (anthropometric, blood, urine, questionnaires) were collected preharvest, preintervention, mid-intervention and at the end of harvest. A subsample participated in focus group discussions. Daily wet bulb globe temperatures (WBGT) were recorded. The employer provided individual production records. RESULTS: Over the harvest WBGT was >26°C from 9:00 onwards reaching average maximum of 29.3±1.7°C, around 13:00. Postintervention self-reported water consumption increased 25%. Symptoms associated with heat stress and with dehydration decreased. Individual daily production increased from 5.1 to a high of 7.3 tons/person/day postintervention. This increase was greater than in other cutting groups at the company. Focus groups reported a positive perception of components of the WRS, and the new machete and cutting programmes. CONCLUSIONS: A WRS intervention is feasible in sugarcane fields, and appears to markedly reduce the impact of the heat stress conditions for the workforce. With proper attention to work practices, production can be maintained with less impact on worker health.

Cancer mortality in cohorts of workers in the European rubber manufacturing industry first employed since 1975.

BACKGROUND: Increased cancer risk has been reported among workers in the rubber manufacturing industry employed before the 1960s. It is unclear whether risk remains increased among workers hired subsequently. The present study focused on risk of cancer mortality for rubber workers first employed since 1975 in 64 factories. PATIENTS AND METHODS: Anonymized data from cohorts of rubber workers employed for at least 1 year from Germany, Italy, Poland, Sweden, and the UK were pooled. Standardized mortality ratios (SMRs), based on country-specific death rates, were reported for bladder and lung cancer (primary outcomes of interest), for other selected cancer sites, and for cancer sites with a minimum of 10 deaths in men or women. Analyses stratified by type of industry, period, and duration of employment were carried out. RESULTS: A total of 38 457 individuals (29 768 men; 8689 women) contributed to 949 370 person-years. No increased risk of bladder cancer was observed [SMR = 0.80, 95% confidence interval (CI) 0.46; 1.38]. The risk of lung cancer death was reduced (SMR = 0.81, 95% CI 0.70; 0.94). No statistically significant increased risk was observed for any other cause of death. A reduced risk was evident for total cancer mortality (SMR = 0.81, 95% CI 0.76; 0.87). Risks were lower for workers in the tyre industry compared with workers in the general rubber goods sector. Analysis by employment duration showed a negative trend with SMRs decreasing with increasing duration of employment. In an analysis of secondary end points, when stratified by type of industry and period of first employment, excess risks of myeloma and gastric cancer were observed each due, essentially, to results from one centre. CONCLUSION: No consistent increased risk of cancer death was observed among rubber workers first employed since 1975, no overall analysis of the pooled cohort produced significantly increased risk. Continued surveillance of the present cohorts is required to confirm the absence of long-term risk.

Polybrominated diphenyl ethers in maternal serum, umbilical cord serum, colostrum and mature breast milk. Insights from a pilot study and the literature.

Human serum and mother's milk are frequently used to assess exposure to polybrominated diphenyl ethers (PBDEs), including transplacental transfer to the foetus. However, little is known about the kinetics of PBDEs, especially the highly brominated BDE congeners. In this pilot study, maternal serum samples were collected from 10 women at delivery and five to six weeks post partum. Umbilical serum was also obtained. Milk was donated two to five days, and five to six weeks after delivery. The amount of PBDEs in these samples was determined using liquid-liquid extraction and GC/MS. Low, moderately and highly brominated diphenyl ethers were present in umbilical cord serum, indicating placental transfer. The lipid-adjusted levels of BDE-47, BDE-207 and BDE-209 were similar in maternal and umbilical cord serum, whereas the cord serum levels for the penta- to octa-BDEs quantified were lower than in maternal serum. Marked changes were seen in the congener pattern in breast milk during the first month of lactation, whereas maternal serum levels did not change significantly. The general pattern was an enrichment of low to moderately brominated congeners (i.e. from BDE-17 to BDE-154, with the exception of BDE-28) in colostrum compared with maternal serum. In contrast, more highly brominated congeners were found at similar, or lower levels in colostrum than in maternal serum. After the transition from colostrum to mature milk, the levels of BDE-153 and BDE-209 were substantially reduced, and BDE-209 was below the limit of detection in 6 out of 9 samples. A literature review on the design and reporting of studies on the transfer of PBDEs from mother to infant revealed a lack of transparency in many cases. The use of the recently published STROBE-ME guidelines is therefore recommended.

Tumour recurrence and enlargement in patients with craniopharyngioma with and without GH replacement therapy during more than 10 years of follow-up.

OBJECTIVE: Most patients who have been treated for craniopharyngioma (CP) are GH deficient (GHD). GH replacement therapy (GHRT) may stimulate tumour regrowth; and one of the concerns with long-term GHRT is the risk of tumour progression. Therefore, the objective was to study tumour progression in CP patients on long-term GHRT. DESIGN: Case-control study. PATIENTS AND METHODS: The criteria for inclusion of cases were: i) GHD caused by CP; ii) GHRT >3 years; and iii) regular imaging. This resulted in 56 patients (mean age at diagnosis 25±16 years) with a mean duration of GHRT of 13.6±5.0 years. As controls, 70 CP patients who had not received GHRT were sampled with regard to follow-up, gender, age at diagnosis and initial radiation therapy (RT). RESULTS: The 10-year tumour progression-free survival rate (PFSR) for the entire population was 72%. There was an association (hazard ratio, P value) between PFSR and initial RT (0.13, 0.001) and residual tumour (3.2, 0.001). The 10-year PFSR was 88% for the GHRT group and 57% for the control group. Substitution with GHRT resulted in the following associations to PFSR: GHRT (0.57, 0.17), initial RT (0.16, <0.001), residual tumour (2.6, <0.01) and gender (0.57, 0.10). Adjusted for these factors, the 10-year PFSR was 85% for the GHRT group and 65% for the control group. CONCLUSIONS: In patients with CP, the most important prognostic factors for the PFSR were initial RT and residual tumour after initial treatment. Long-term GHRT did not affect the PFSR in patients with CP.

Comparing progression of non-functioning pituitary adenomas in hypopituitarism patients with and without long-term GH replacement therapy.

OBJECTIVE: An important safety issue with GH replacement therapy (GHRT) in hypopituitary patients with a history of a pituitary adenoma is the risk for tumour recurrence or enlargement. Design Case-control study. SUBJECTS AND METHODS: We studied tumour progression rate in 121 patients with hypopituitarism on the basis of non-functioning pituitary adenomas (NFPA) receiving long-term GHRT. A group of 114 NFPA patients not receiving GHRT who were matched in terms of duration of follow-up, gender, age, age at diagnosis and radiotherapy status were used as a control population. The average duration of GHRT was 10+/-4 years (range 2-17). RESULTS: In patients with a known residual adenoma, 63% had no detectable enlargement of tumour during the study. In patients who had no visible residual tumour prior to GHRT, 90% did not suffer from recurrence. In total, the 10-year tumour progression-free survival rate in patients with NFPA receiving GHRT was 74%. In the control population not receiving GHRT, the 10-year progression-free survival rate was 70%. Radiotherapy as part of the initial tumour treatment reduced the rate of tumour progression in both GHRT and non-GHRT patients to a similar extent. CONCLUSIONS: The rate of tumour progression was similar in this large group of GHRT patients and the control population not receiving GHRT. Our results provide further support that long-term use of GH replacement in hypopituitarism may be considered safe in patients with residual pituitary adenomas.

Occupational exposure to NDMA and NMor in the European rubber industry.

Many nitrosamines are suspected of being human carcinogens, with the highest concentrations in the environment being measured in the rubber industry. Time trends of personal exposure to N-nitrosodimethylamine (NDMA) and to N-nitrosomorpholine (NMor) during the past two decades in the German rubber industry were analysed and compared with cross-sectional studies in the same period in the Netherlands, Poland, the UK and Sweden. In the majority of the surveyed departments exposures reduced over time, but considerable heterogeneity was present between departments and sectors. Significant reductions were primarily found in curing and post-treating departments and ranged from -3% year(-1) to -19% year(-1). In contrast, NDMA levels increased (+13% year(-1)) in maintenance and engineering in the tyres industry. Average NDMA-levels in general rubber goods (GRG) and NMor-levels in tyre production in Germany did not decrease significantly in the past two decades, whereas NDMA-levels in tyre production (-10% year(-1)) and NMor-levels in GRG (-7% year(-1)) declined significantly after the introduction of an exposure limit for total nitrosamines in Germany in 1988. Confidence intervals of average exposures in other studied countries largely overlap trends observed in Germany. Exposure to N-nitrosamines decreased on average two-to-five fold in the German rubber industry with comparable concentration levels in other European countries. Although average levels are well below the current limits exposure has not been eliminated, and incidental high exposures do still occur.

Classification of left main coronary obstruction--feasibility of surgical angioplasty and survival after coronary artery bypass surgery.

Angiographies of 384 patients who had coronary artery bypass surgery because of left main coronary artery (LMCA) obstruction during 1970-1989 were reviewed by analysing the pathology, feasibility of surgical angioplasty and survival. Complete LMCA occlusion was found in 2%, proximal ostial stenosis in 9%, mid-shaft stenosis in 24%, circular stenosis in 25% and distal bifurcation stenosis in 40% of the patients. Patients with an ostial stenosis were younger, more often women with less coronary artery disease and less calcified obstructions. Surgical angioplasty could have been an option in 22% of the patients. Early mortality was higher in patients with (4.7%) than in those without (1.9%) LMCA obstruction. The relative risk (RR) of early death was 1.9 (95% CL 1.1-3.5) after adjustment for patient characteristics. Similarly, the RR at 10 years was 1.3 (95% CL 1.0-1.6). LMCA obstruction was associated with an early and long-term increased mortality after surgery compared to patients without LMCA obstruction.

[Don't miss prolactinoma! On the importance of measuring prolactin and how it is done]. / Missa inte prolaktinomen! Om vikten av mätning av prolaktin och hur den utförs.

Prolactinoma is the most common functional pituitary tumor. Since appropriate treatment is often pharmacological rather than surgical, all patients with a tumor within or close to the sella turcica should be evaluated for prolactinoma before being sent for neurosurgery. Preanalytical factors affecting serum prolactin concentration should be taken into account when planning blood sampling. Diagnostic laboratories should aim for the use of common international calibrators and a common unitage for expressing concentrations. Assays should be carried out in such a way that the risk of falsely high or low values is minimized. Any patient with high values due to an immunometric method should be evaluated for the possible presence of endogenous antibodies against prolactin ("macroprolactinemia").

Transsphenoidal adenomectomy in Cushing's disease via a lateral rhinotomy approach.

BACKGROUND: Cushing's disease may be treated by surgical pituitary adenomectomy. We present a surgical approach to the pituitary gland that increases the possibilities of a selective adenomectomy, and compare our results with those of other studies. METHODS: A retrospective study of patients with Cushing's disease undergoing transsphenoidal selective adenomectomy via a lateral rhinotomy at Sahlgrenska University Hospital from 1984-93 is presented. Thirty-one patients (26 women, five men; mean age: 44 years, range: 13-75 years) with Cushing's disease were followed for a median time of 4.5 years after operation (range: 1-10 years). Preoperative and postoperative urinary and serum cortisol, and circadian rhythm of serum cortisol were measured. We also measured serum TSH, T4, PRL, FSH, LH, and testosterone as well as urine and plasma osmolality. RESULTS: Our remission rate was 77% and the recurrence rate 3%. Hormonal insufficiency was rare. Hypothyroidism and hypogonadism were present in 3% of the patients, and diabetes insipidus occurred in 6% of the patients. CONCLUSION: Selective adenomectomy with its good opportunities for cure and improvement should be regarded as the treatment of choice for Cushing's disease. Using the lateral rhinotomy approach to the sphenoidal cavity results in good accessibility to the sella turcica and its pituitary adenomas, a low frequency of postoperative pituitary insufficiency, and a high remission rate.

Airway symptoms and lung function in pipelayers exposed to thermal degradation products from MDI-based polyurethane.

OBJECTIVES: To study the prevalence of symptoms from the eyes and the upper and lower respiratory tract, lung function, and immunological sensitisation towards isocyanates in pipelayers exposed to thermal degradation products from methylene diphenyl diisocyanate (MDI)-based polyurethane (PUR). MATERIAL AND METHODS: 50 presently active and 113 formerly active pipelayers were examined. Also, 65 unexposed workers were investigated for comparison. The one year prevalence of symptoms and smoking history (questionnaire data), lung function (vital capacity (VC) and forced expiratory volume in one second (FEV1), and atopy (positive skin prick tests towards standard allergens) were assessed among pipelayers and controls. For the pipelayers, the presence of work related symptoms and estimates of isocyanate and welding exposure were obtained from an interview. Skin prick tests towards specific isocyanate antigens and determinations of IgE-MDI and IgG-MDI in serum were also performed. RESULTS: The prevalence of episodes (more than once a month) of irritative eye symptoms, congestion of the nose, and soreness or dryness in the throat was much higher among the PUR pipelayers than among the controls. Most of the pipelayers with symptoms reported that these had started and occurred in relation to the PUR welding tasks. Presently active pipelayers with recent high PUR exposure showed a significant reduction of FEV1 compared with the controls. The estimated reduction, adjusted for smoking, was -0.3 l (P = 0.04). There was no confounding effect of ordinary welding. None of the pipelayers showed positive skin prick reactions against the specific isocyanate antigens used, or positive IgE-MDI, and only two had increased IgG-MDI. CONCLUSIONS: The findings indicate that exposure to thermal degradation products from MDI-based polyurethane has adverse effects on the mucous membranes and airways.

Deaths and tumours among workers grinding stainless steel: a follow up.

OBJECTIVE: To study cause specific mortality and cancer morbidity in workers exposed to the dust of grinding materials, grinding agents, and stainless steel, especially with regard to a possibly increased risk of respiratory, stomach, and colorectal cancer. METHODS: Retrospective cohort study, using reference cohorts of blue collar workers and population rates for comparison. The exposed cohort comprises workers with at least 12 months employment time at two plants, producing stainless steel sinks and saucepans (n = 727). Also, reference cohorts of other industrial workers (n = 3965) and fishermen (n = 8092) were analysed. The observation period began 15 years after the start of employment. Standardised mortality or incidence ratios (SMRs, SIRs; county reference rates) were calculated for cause-specific mortality between 1952 and 1993, and for cancer morbidity between 1958 and 1992. RESULTS: In the exposed cohort, overall mortality, cardiovascular mortality, and all malignant mortality and morbidity were slightly lower than expected. Also, the risk estimates for cancer in the upper and lower respiratory tracts and for stomach cancer were lower than expected. There was an increase in morbidity from colon cancer, which was explained by an excess of tumours in the sigmoid part only. Here, the risk estimates were higher in workers with long employment time (1-14 years: four observed cases, SIR 1.7, 95% confidence interval (95% CI) 0.4 to 4.5; > or = 15 years: three observed cases, SIR 4.3, 95% CI 0.9 to 13) and the increased risk was especially pronounced among those first employed before 1942. A slight nominal excess of rectal cancers (nine observed cases, SIR 1.4, 95% CI 0.6 to 2.6), and a significant excess of prostate cancer morbidity (36 observed cases, SIR 1.7, 95% CI 1.2 to 2.4) were found. These risk estimates did not, however, increase with employment time. CONCLUSIONS: The finding of an increased risk of cancer in the sigmoid part of the colon, which was not found in the reference cohorts, and with indication of a relation between duration of employment and response, is consistent with a causal relation. The limited size of the exposed cohort makes a detailed exposure-response analysis unstable, and the confidence limits are wide. Albeit slightly raised, the risk estimate for rectal cancer in the exposed cohort was not different from the estimate among the other industrial workers.

Warning leak and management outcome in aneurysmal subarachnoid hemorrhage.

The impact of warning leaks on management results in patients with aneurysmal subarachnoid hemorrhage (SAH) was evaluated in this prospective study. In a consecutive series of 422 patients with aneurysmal SAH, 84 patients (19.9%) had an episode suggesting a warning leak; 34 (40.5%) of these patients were seen by a physician without the condition being recognized. The warning leak occurred less than 2 weeks before a major SAH in 75% of the patients. A good outcome was experienced by 53.6% of patients who had a warning leak versus 63.3% of those who had no warning leak. In a subgroup of patients who had an interval of 3 days or less from warning leak to SAH, only 36.4% had a good outcome. The proportion of patients in good neurological condition (Hunt and Hess Grades I and II) who had a good outcome was 88.1% in the group with no warning leak versus 53.6% in the group whose SAH was preceded by a warning leak. A difference of 35% between these two groups reflects the impact of an undiagnosed warning leak on patient outcome, based on the assumption that patients with a warning leak had clinical conditions no worse than Hunt and Hess Grade II at the time of the episode. In the subgroup of patients with the short interval between warning leak and SAH, the difference was almost 52%. The difference in outcome also reflects the potential improvement in outcome that can be achieved by a correct diagnosis of the warning leak. If the correct diagnosis is made in patients seeking medical attention due to a warning leak, favorable outcomes in the overall management of aneurysmal SAH are estimated to increase by 2.8%. An active diagnostic attitude toward patients experiencing a sudden and severe headache is warranted as it offers a means of improving overall outcome in patients with SAH.

Overall management outcome of ruptured posterior fossa aneurysms.

A study of the overall management of ruptured posterior fossa aneurysms was conducted over a 1-year period (1993) in five neurosurgical centers in Sweden, serving a population of 6.93 million people. Forty-nine cases were identified and treated. One-third of the patients were in the seventh or eighth decade of life. Good overall management outcomes at 6 months were achieved in 30 cases (61%). The overall mortality rate was 27%. Patients with Hunt and Hess Grades I and II had a good overall recovery rate of 87%. On admission, 69% of the patients were assigned Hunt and Hess Grades III to V. The impact on patient outcomes of the intraoperative difficulties encountered, especially in the basilar tip area, is stressed. The authors found that delayed operation is not warranted in most cases. Frequent devastating rebleeding was observed among patients not offered early aneurysm clipping and the operative results were not at significant variance between the early and late surgical groups. Only 50% of the patients scheduled for delayed surgery ultimately made a good recovery, whereas 72% of patients scheduled for early operation did so. The data demonstrate that overall management results with posterior fossa aneurysms, comparable to achievements with supratentorial lesions, are within the reach of modern strategies, even in centers not specializing in these problems.