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.

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.

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.

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.

Measurement of lung density by x-ray computed tomography. Relation to lung mechanics in workers exposed to asbestos cement.

We measured lung density by means of x-ray computed tomography and lung mechanics in 33 workers exposed to asbestos cement and in 39 normal subjects. The exposed group showed evidence of lung fibrosis with reduced static lung volumes and lung compliance, although only three subjects had signs of interstitial fibrosis at standard chest radiography. Lung density was significantly increased in the exposed workers compared to control subjects, with greater differences between nonsmokers than between smokers. Lung density correlated inversely with static lung volumes. There was no appreciable difference in the regional distribution of lung density between exposed workers and control subjects. We conclude that lung density is often increased in workers with mild asbestosis, even in the presence of a normal chest radiograph. Measurement of lung density may be of value in the evaluation of asbestos-exposed workers for assessment of the extent of parenchymal disease.

Stability and validity of a single serum cholesterol measurement in a prospective cohort study.

The variation of serum cholesterol level was studied in a cohort of 16,281 individuals, with repeated measurements of cholesterol. The mean correlation coefficient between the two cholesterol values taken with a six-week interval on two occasions was 0.74. This correlation coefficient indicates a short-term variation of serum cholesterol, and reflects measurement errors and intra-individual fluctuations in cholesterol level, eg due to variations in dietary habits. The correlation coefficient for serum cholesterol values taken with a two-year interval was 0.66 and reflects a long-term variation. The ratio between these coefficients may be interpreted as a rough estimate of a correlation between the true cholesterol levels at a two-year interval, free from measurement errors and short-term intra-individual variations in dietary habits. The validity was assessed with the correlation between a single serum cholesterol value and mortality from myocardial infarction, in a cohort of 92,839 individuals followed-up for 14-16 years. The relative risks (RR) for death in myocardial infarction increased with increasing cholesterol levels. The RRs were in accordance with the well-established correlation between serum cholesterol and death from myocardial infarction. The results indicated a fairly high stability of the cholesterol level in blood and that the cholesterol values in the studied cohort were not less reliable than in comparable studies.

Overall outcome in aneurysmal subarachnoid hemorrhage. A prospective study from neurosurgical units in Sweden during a 1-year period.

The present prospective study, with participation of five of the six neurosurgical centers in Sweden, was conducted to evaluate the overall management results in patients with aneurysmal subarachnoid hemorrhage (SAH). The participating centers covered 6.93 million (81%) of Sweden's 8.59 million inhabitants. All patients with verified aneurysmal SAH admitted between June 1, 1989, and May 31, 1990, were included in this prospective study. A uniform management protocol was adopted involving ultra-early referral, earliest possible surgery, and aggressive anti-ischemic treatment. A total of 325 patients were admitted during the study period, 69% within 24 hours after hemorrhage. On admission, the patients were graded according to the scale of Hunt and Hess: 43 patients (13%) were classified in Grade I, 119 (37%) in Grade II, 53 (16%) in Grade III, 76 (23%) in Grade IV, and 34 (11%) in Grade V. Nimodipine was administered to 269 of the 325 patients: intravenously in 218, orally in 15, and intravenously followed by orally in 36. At follow-up examination 3 to 6 months after SAH, 183 patients (56%) were classified as having made a good neurological recovery, 73 patients (23%) suffered some morbidity, and 69 (21%) were dead. Surgery was performed in 276 (85%) of the patients; emergency surgery with evacuation of an associated intracerebral hematoma was carried out in 30 patients. Early surgery (within 72 hours after SAH) was performed in 170 individuals, intermediate surgery (between Days 4 and 6 post-SAH) in 29 patients, and late surgery (Day 7 or later after SAH) in 47 individuals. Of 145 patients with supratentorial aneurysms who were preoperatively in Hunt and Hess Grades I to III and who were treated within 72 hours, 81% made a good recovery; in 5.5% of patients, the unfavorable outcome was ascribed to delayed ischemia. It is concluded that, among patients with all clinical grades and aneurysmal locations, almost six of 10 SAH victims referred to a neurosurgical unit can be saved and can recover to a normal life.

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.

Cerebral blood flow in experimental intracranial mass lesions. Part I: The compression phase.

We have shown that a rebound of intracranial pressure (ICP) occurring after decompression of an intracranial mass lesion is a threshold phenomenon dependent upon the cerebral perfusion pressure (CPP) during compression and the duration of the compression. In the present study regional cerebral blood flow (rCBF) was measured during balloon compression of a degree critical for the development of a postdecompression rebound. The effects were compared with those of hydrostatically raised pressure which under similar conditions rarely produces a rebound of ICP. Disproportionately marked reductions in flow occurred in the hemisphere ipsilateral to the balloon, especially in white matter and in cortex adjacent to the balloon with flow values of, respectively, 1.1 +/- 0.9 and 6.4 +/- 3.4 ml 100 g-1 min-1. The differences in flow between balloon and hydrostatic compression were found to be due to an increased cerebrovascular resistance (CVR) caused by a direct compressive effect by the balloon overriding the generalized vasodilation which occurs in response to the raised ICP. Thus the increase in CVR attributable to compression by the balloon added to the reduction in CPP caused by the diffuse increase in ICP. As a consequence flow in large regions of the brain was reduced below the thresholds for structural infarction and for ischaemic damage to the blood-brain barrier.

Cerebral blood flow in experimental intracranial mass lesions. Part II: The postdecompression phase.

Cerebral haemodynamics were evaluated after a period of cerebral compression produced by subarachnoid fluid infusion or inflation of an epidural balloon. Release of the compression resulted in a marked cerebral hyperperfusion which was generalized in the case of hydrostatically raised pressure but restricted to supratentorial structures after balloon compression. A rebound of intracranial pressure (ICP) occurred only after balloon compression, indicating that loss of vasomotor tone per se was not the primary reason for the rebound of ICP. In the balloon compression experiments the hyperaemia passed into a stage of hypoperfusion attributable in part to a reduction in cerebral perfusion pressure due to the rebound of ICP and in part to an increase in flow resistance probably related to external compression of the vascular bed by the accumulation of brain oedema. The observed flow changes, i.e. delayed hypoperfusion preceded by hyperaemia, were similar to those after temporary ischaemia, indicating that the rebound response is a non-specific postischaemic phenomenon.

Mechanical conditions of rebound of the intracranial pressure after a period of cerebral compression.

Brain compression of precisely defined degree and duration was produced by means of expansion of a supratentorial epidural balloon in anaesthetized and mechanically ventilated dogs. After deflation of the balloon there was a rebound of the intracranial pressure (ICP) to values in the range 30-89 mm Hg when critical thresholds of time and compression had been exceeded during the period of compression. A time versus cerebral perfusion pressure (CPP) graph indicated a CPP threshold of about 50 mm Hg and time threshold of about 6 min. Within these limits the critical CPP varied as a function of time. The ICP rebound had an approximately exponential time course with an initial rapid rise levelling off towards a final plateau in about 30 min. The final value was dependent on the time of compression but independent of the CPP. A transtentorial pressure gradient was induced during the compression phase and reestablished after the decompression when a rebound of ICP developed. Hydrostatic compression by means of infusion of fluid into the subarachnoid space was followed by a rebound of ICP in only 2/21 of the experiments in spite of time and CPP parameters which crossed the critical thresholds defined in the balloon compression experiments. These results support the hypothesis that the rebound phenomenon is related to an ischaemic mechanism. The difference in incidence of rebound in balloon compression and hydrostatic compression can probably be accounted for by a greater depth of ischaemia in the former case because of a direct compressive effect on the vascular bed by the balloon.

Radiographic changes and lung function in relation to activity of the glutathione transferases theta and mu among asbestos cement workers.

Experimental data indicate that active oxygen species may be casually involved in the development of asbestos-related disease. Thus, it was hypothesized that individual differences in glutathione transferase activity, which may affect the ability to inactivate molecules formed in relation to oxidative stress, could influence the biological response to asbestos exposure. We could, however, not demonstrate an increased risk for radiographic changes or reduced lung function among asbestos cement workers deficient for glutathione transferase theta (GSTT1), glutathione transferase mu (GSTM1), or having a combined deficiency of enzyme activity.

Five-year follow-up of nonsecreting pituitary adenomas.

Nowadays, nonsecreting pituitary adenomas are usually operated on by means of a transsphenoidal approach, and the transseptal way is the most widely used. Since 1982 we have been using lateral rhinotomy instead, resecting bone in the piriform aperture up to the orbit to obtain a good intrasellar view during surgery. In all, 48 patients were operated on between 1982 and 1987, and all of them have since been evaluated in a 5-year follow-up. The only recurrence occurred in the only patient previously operated on transcranially. Computed tomography was performed in 44 patients (92%) after an average of 4 years and revealed no signs of tumor in any of them. New pituitary insufficiencies developed in six (12%). An improvement in vision was observed in 38 patients (79%), none of whom suffered an impaired visual field or acuity. The frequency of new hormonal insufficiencies and improvement of vision that we observed in our patients is comparable with that reported by other investigators, but the recurrence rate is lower and the optic nerves and chiasma were never damaged thereby causing an impairment of vision. These benefits can most probably be explained by the surgical approach we used, in which the tumor and surrounding structures are very well visualized because the operative field is broader and closer than it is with the transseptal approach, which is normally used for this kind of tumor.

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.

[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").

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

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.