Updated assessment of occupational safety and health hazards of climate change.

Workers, particularly outdoor workers, are among the populations most disproportionately affected by climate-related hazards. However, scientific research and control actions to comprehensively address these hazards are notably absent. To assess this absence, a seven-category framework was developed in 2009 to characterize the scientific literature published from 1988-2008. Using this framework, a second assessment examined the literature published through 2014, and the current one examines literature from 2014-2021. The objectives were to present literature that updates the framework and related topics and increases awareness of the role of climate change in occupational safety and health. In general, there is substantial literature on worker hazards related to ambient temperatures, biological hazards, and extreme weather but less on air pollution, ultraviolet radiation, industrial transitions, and the built environment. There is growing literature on mental health and health equity issues related to climate change, but much more research is needed. The socioeconomic impacts of climate change also require more research. This study illustrates that workers are experiencing increased morbidity and mortality related to climate change. In all areas of climate-related worker risk, including geoengineering, research is needed on the causality and prevalence of hazards, along with surveillance to identify, and interventions for hazard prevention and control.

[Dealing with opioid dependence and withdrawal in hospitals]. / Omgaan met opioïdafhankelijkheid en -onthouding in het ziekenhuis.

BACKGROUND: In opioid addiction tolerance occurs requiring substitution with unusually high doses. A balance must be struck between the risk of overdose with respiratory depression and QTc interval prolongation on one hand and underdosing with withdrawal syndrome on the other hand. An unreliable anamnesis can complicate adequate dosing. CASE DESCRIPTION: A 30-year-old polydrug user with a severe dependence on methadone and heroin was admitted to the Intensive Care Unit after surgery for thoracic surgery. Upon cautious initiation with methadone, severe withdrawal and pain symptoms occurred. Doubling the dose made the withdrawal symptoms disappear without signs of overdose. CONCLUSION: During hospital admission of patients with high opioid tolerance the anamnestic equivalent high opioid dose can be started immediately, provided there is a possibility of monitoring the respiration and heart rhythm. The risk of withdrawal and insufficient pain relief in a hospital is generally greater than the risk of an overdose.

[COVID-19 and severe mental illness, especially in clozapine use]. / COVID-19 en ernstige psychiatrische aandoeningen, in het bijzonder bij clozapinegebruik.

BACKGROUND: The Clozapine Plus Working Group is frequently consulted for advice on measures in case of infection with SARSCoV-2 and on vaccination against COVID-19 in patients receiving clozapine.

AIM: Inform about risks of infection with SARS-CoV-2 in patients with severe mental illness (SMI), patients with schizophrenia spectrum disorders (SSD), and patients treated with clozapine. Advise on monitoring of clozapine plasma levels and white blood cell count and differential in COVID-19 and after vaccination, as well as measures to be taken.

METHOD: Literature research and case studies.

RESULTS: SMI patients and in particular SSD patients have an increased risk of infection with SARS-CoV-2 with more hospitalizations and higher mortality than non-psychiatric patients. Patients using clozapine may be at greater risk of infection. SARS-CoV-2 infection may cause a dangerous increase of clozapine plasma levels and generally mild and short-term granulocytopenia and lymphocytopenia, which are usually not a result of clozapine treatment.

CONCLUSION: In case of COVID-19 extra alertness is required in patients with SMI and especially SSD. In clozapine users, in case of COVID-19, reduction in dose by half to three quarters of the original dose is recommended. When patients develop granulocytopenia, SARS-CoV-2 should be considered as the cause and not immediately clozapine. SMI patients and clozapine users in particular belong to a high risk group with a medical indication for early vaccination.

Creating a model to predict time intervals from induction of labor to induction of anesthesia and delivery to coordinate workload.

BACKGROUND: Induction of labor continues to become more common. We analyzed induction of labor and timing of obstetric and anesthesia work to create a model to predict the induction-anesthesia interval and the induction-delivery interval in order to co-ordinate workload to occur when staff are most available. METHODS: Patients who underwent induction of labor at a single medical center were identified and multivariable linear regression was used to model anesthesia and delivery times. Data were collected on date of birth, race/ethnicity, body mass index, gestational age, gravidity, parity, indication for labor induction, number of prior deliveries, time of induction, induction agent, cervical dilation, effacement, and fetal station on admission, date and time of anesthesia administration, date and time of delivery, and delivery type. RESULTS: A total of 1746 women met inclusion criteria. Associations which significantly influenced time from induction of labor to anesthesia and delivery included maternal age (anesthesia P <0.001, delivery P =0.002), body mass index (both P <0.001), prior vaginal delivery (both P <0.001), gestational age (anesthesia P <0.001, delivery P <0.018), simplified Bishop score (both P <0.001), and first induction agent (both P <0.001). Induction of labor of nulliparous women at 02:00 h and parous women at 04:00 or 05:00 h had the highest estimated probability of the mother having her first anesthesia encounter and delivering during optimally staffed hours when our institution's specialty personnel are most available. CONCLUSIONS: Time to obstetric and anesthesia tasks can be estimated to optimize induction of labor start times, and shift anesthesia and delivery workload to hours when staff are most available.

[Clozapine for behavioural and psychological symptoms of dementia]. / Clozapine voor probleemgedrag bij dementie.

BACKGROUND: Behavioural and psychological symptoms of dementia (BPSD) are common and contribute significantly to caregiver burden and institutionalization of the patient. Unfortunately, current guideline-based interventions are sometimes ineffective and BPSD can become extreme. CASE DESCRIPTION: A 75-year-old man with dementia was admitted to a psychogeriatric unit because of very severe BPSD in a nursing home. Different kinds of pharmaceutical and psychological interventions had been tried but turned out to be ineffective. Therefore, we started with low dose clozapine which improved his behavior. We reduced the dose twice, whereupon the behavior deteriorated. By reintroducing the proper dose, his behavior became better again. CONCLUSION: Our case is in accordance with the available literature on Clozapine for BPSD: Six uncontrolled studies have shown a positive effect of clozapine for BPSD, even if other interventions failed. We conclude that clozapine may be tried in cases of serious refractory BPSD when guideline-based interventions are ineffective.

[Reactions on 'The effectiveness of monoamine oxidase inhibitors in treatment-resistant depressive disorders in clinical practice; a retrospective open-label study']. / Reacties op: 'De effectiviteit van monoamineoxidaseremmers bij therapieresistente depressie in de klinische praktijk; een retrospectieve openlabelstudie'.

Reactions on 'The effectiveness of monoamine oxidase inhibitors in treatment-resistant depressive disorders in clinical practice; a retrospective open-label study'.

[A protocol for light therapy in bipolar disorder]. / Protocol voor lichttherapie bij bipolaire stoornis.

BACKGROUND: There is no national protocol for the use of light therapy in bipolar depression.
AIM: The chronotherapy collaboration group of the Foundation for Bipolar Disorders intended to write a protocol for light therapy in bipolar depressive episodes.
METHOD: Narrative review of several systematic reviews, two clinician's guides and deliberation with the sub-commission Guidelines of the Dutch Ophthalmologic Society.
RESULTS: The following indication was established: depressive episode, with or without seasonal features, in bipolar I or II disorder, including subsyndromal (depressive) seasonal complaints. The list of relative contra-indications (pre-existent retinal illnesses, systemic illnesses with effect on the retina and use of photosensitive medication) was shortened. In this case the medical professional discusses the possibility of an ophthalmologic consultation with the patient. Use of a mood stabilizer/antimanic medication in order to prevent mania or a mixed episode is only necessary in a depressive episode in bipolar I, but not in bipolar II disorder. Standard treatment is 10.000 lux white light during 30 minutes in the morning.
CONCLUSION: There is sufficient evidence to propose light therapy in a bipolar depressive episode with or without seasonal features.

Delegating Clozapine Monitoring to Advanced Nurse Practitioners: An Exploratory, Randomized Study to Assess the Effect on Prescription and Its Safety.

To test whether: (1) psychiatrists will prescribe clozapine more often if they can delegate the monitoring tasks to an advanced nurse practitioner (ANP), (2) clozapine monitoring by an ANP is at least as safe as monitoring by a psychiatrist. Patients from 23 Dutch outpatient teams were assessed for an indication for clozapine. ANPs affiliated to these teams were randomized to Condition A: clozapine monitoring by an ANP, or Condition B: monitoring by the psychiatrist. The safety of monitoring was evaluated by determining whether the weekly neutrophil measurements were performed. Staff and patients were blinded regarding the first hypothesis. Of the 173 patients with an indication for clozapine at baseline, only seven in Condition A and four in Condition B were prescribed clozapine (Odds Ratio = 2.24, 95% CI 0.61-8.21; p = 0.225). These low figures affected the power of this study. When we considered all patients who started with clozapine over the 15-month period (N = 49), the Odds Ratio was 1.90 (95% CI 0.93-3.87; p = 0.078). With regard to the safety of the monitoring of the latter group of patients, 71.2% of the required neutrophil measurements were performed in condition A and 67.3% in condition B (OR = 0.98; CI = 0.16-3.04; p = 0.98). Identifying patients with an indication for clozapine does not automatically lead to improved prescription rates, even when an ANP is available for the monitoring. Clozapine-monitoring performed by an ANP seemed as safe as that by a psychiatrist.

Association between exposure to anaesthesia and surgery and long-term cognitive trajectories in older adults: report from the Mayo Clinic Study of Aging.

BACKGROUND: The link between exposure to general anaesthesia and surgery (exposure) and cognitive decline in older adults is debated. We hypothesised that it is associated with cognitive decline. METHODS: We analysed the longitudinal cognitive function trajectory in a cohort of older adults. Models assessed the rate of change in cognition over time, and its association with exposure to anaesthesia and surgery. Analyses assessed whether exposure in the 20 yr before enrolment is associated with cognitive decline when compared with those unexposed, and whether post-enrolment exposure is associated with a change in cognition in those unexposed before enrolment. RESULTS: We included 1819 subjects with median (25th and 75th percentiles) follow-up of 5.1 (2.7-7.6) yr and 4 (3-6) cognitive assessments. Exposure in the previous 20 yr was associated with a greater negative slope compared with not exposed (slope: -0.077 vs -0.059; difference: -0.018; 95% confidence interval: -0.032, -0.003; P=0.015). Post-enrolment exposure in those previously unexposed was associated with a change in slope after exposure (slope: -0.100 vs -0.059 for post-exposure vs pre-exposure, respectively; difference: -0.041; 95% confidence interval: -0.074, -0.008; P=0.016). Cognitive impairment could be attributed to declines in memory and attention/executive cognitive domains. CONCLUSIONS: In older adults, exposure to general anaesthesia and surgery was associated with a subtle decline in cognitive z-scores. For an individual with no prior exposure and with exposure after enrolment, the decline in cognitive function over a 5 yr period after the exposure would be 0.2 standard deviations more than the expected decline as a result of ageing. This small cognitive decline could be meaningful for individuals with already low baseline cognition.

Biological monitoring of workers exposed to engineered nanomaterials.

As the number of nanomaterial workers increase there is need to consider whether biomonitoring of exposure should be used as a routine risk management tool. Currently, no biomonitoring of nanomaterials is mandated by authoritative or regulatory agencies. However, there is a growing knowledge base to support such biomonitoring, but further research is needed as are investigations of priorities for biomonitoring. That research should be focused on validation of biomarkers of exposure and effect. Some biomarkers of effect are generally nonspecific. These biomarkers need further interpretation before they should be used. Overall biomonitoring of nanomaterial workers may be important to supplement risk assessment and risk management efforts.

Characterizing risk assessments for the development of occupational exposure limits for engineered nanomaterials.

The commercialization of engineered nanomaterials (ENMs) began in the early 2000's. Since then the number of commercial products and the number of workers potentially exposed to ENMs is growing, as is the need to evaluate and manage the potential health risks. Occupational exposure limits (OELs) have been developed for some of the first generation of ENMs. These OELs have been based on risk assessments that progressed from qualitative to quantitative as nanotoxicology data became available. In this paper, that progression is characterized. It traces OEL development through the qualitative approach of general groups of ENMs based primarily on read-across with other materials to quantitative risk assessments for nanoscale particles including titanium dioxide, carbon nanotubes and nanofibers, silver nanoparticles, and cellulose nanocrystals. These represent prototypic approaches to risk assessment and OEL development for ENMs. Such substance-by-substance efforts are not practical given the insufficient data for many ENMs that are currently being used or potentially entering commerce. Consequently, categorical approaches are emerging to group and rank ENMs by hazard and potential health risk. The strengths and limitations of these approaches are described, and future derivations and research needs are discussed. Critical needs in moving forward with understanding the health effects of the numerous EMNs include more standardized and accessible quantitative data on the toxicity and physicochemical properties of ENMs.

50 years of comparative biochemistry: The legacy of Peter Hochachka.

Peter Hochachka was an early pioneer in the field of comparative biochemistry. He passed away in 2002 after 4 decades of research in the discipline. To celebrate his contributions and to coincide with what would have been his 80th birthday, a group of his former students organized a symposium that ran as a satellite to the 2017 Canadian Society of Zoologists annual meeting in Winnipeg, Manitoba (Canada). This Special Issue of CBP brings together manuscripts from symposium attendees and other authors who recognize the role Peter played in the evolution of the discipline. In this article, the symposium organizers and guest editors look back on his career, celebrating his many contributions to research, acknowledging his role in training of generations of graduate students and post-doctoral fellows in comparative biochemistry and physiology.

A rainbow trout Oncorhynchus mykiss strain with higher aerobic scope in normoxia also has superior tolerance of hypoxia.

This study compared parr from three strains of rainbow trout Oncorhynchus mykiss to examine intraspecific variation in metabolic traits, hypoxia tolerance and upper thermal tolerance in this species. At the strain level, variation in absolute aerobic scope (AAS), critical oxygen level (O2crit ), incipient lethal oxygen saturation (ILOS) and critical thermal maximum (CTmax ) generally exhibited consistent differences among the strains, suggesting the possibility of functional associations among these traits. This possibility was further supported at the individual level by a positive correlation between ILOS and O2crit and a negative correlation between O2crit and AAS. These results indicate that intraspecific differences in hypoxia tolerance among strains of O. mykiss may be primarily determined by differences in the ability to maintain oxygen uptake in hypoxia and that variation in aerobic scope in normoxia probably plays a role in determining the ability of these fish to sustain metabolism aerobically as water oxygen saturation is reduced.

[The use of anticonvulsants and the levels of folate, vitamin B12 and homocysteine]. / Invloed van anti-epileptica op foliumzuur-, vitamine B12- en homocysteïnewaarden.

BACKGROUND Patients with epilepsy who use anticonvulsants frequently show low levels of folate and vitamin B12 and high levels of homocysteine. Patients with bipolar disorder use some anticonvulsants as mood stabilisers.
AIM: To determine whether some anticonvulsants lower folate and vitamin B12 and raise homocysteine levels.
METHOD: Systematic literature search to determine the relation between the anticonvulsants valproic acid, carbamazepine, lamotrigine and topiramate on the one hand and blood levels of folate, vitamin B12 and homocysteine on the other hand.
RESULTS: The vast majority of studies in adults and children showed a correlation between use of anticonvulsant carbamazepine and decrease of the folate level. Hardly any of the studies that examined the effect of valproic acid on folate levels found a correlation. There was next to no evidence of a correlation between the use of carbamazepine and a low vitamin B12 level in adults or children. In adults and children the use of valproic acid was found to correlate with a higher vitamin B12 level. Nearly all studies found an increase in homocysteine in adults and children using carbamazepine. Among the users of valproic acid, it was only children who showed a clear association with a rise in homocysteine level. The results for adults were contradictory. We were unable to make any clear statement about topiramate or lamotrigine because there have been very few publications about these anticonvulsants.
CONCLUSION: In adults and children with epilepsy use of carbamazepine is associated with a decrease of folate, valproic acid with a rise in the vitamin B12 level, and carbamazepine with an increase in homocysteine. Valproic acid showed only in children an association with the rise of the homocysteine level. Psychiatrists may find it advisable to control the levels of folate and homocysteine in adults and children who are taking carbamazepine and to measure homocysteine level in children taking valproic acid.

Intraspecific variation and plasticity in mitochondrial oxygen binding affinity as a response to environmental temperature.

Mitochondrial function has been suggested to underlie constraints on whole-organism aerobic performance and associated hypoxia and thermal tolerance limits, but most studies have focused on measures of maximum mitochondrial capacity. Here we investigated whether variation in mitochondrial oxygen kinetics could contribute to local adaptation and plasticity in response to temperature using two subspecies of the Atlantic killifish (Fundulus heteroclitus) acclimated to a range of temperatures (5, 15, and 33 °C). The southern subspecies of F. heteroclitus, which has superior thermal and hypoxia tolerances compared to the northern subspecies, exhibited lower mitochondrial O2 P50 (higher O2 affinity). Acclimation to thermal extremes (5 or 33 °C) altered mitochondrial O2 P50 in both subspecies consistent with the effects of thermal acclimation on whole-organism thermal tolerance limits. We also examined differences between subspecies and thermal acclimation effects on whole-blood Hb O2-P50 to assess whether variation in oxygen delivery is involved in these responses. In contrast to the clear differences between subspecies in mitochondrial O2-P50 there were no differences in whole-blood Hb-O2 P50 between subspecies. Taken together these findings support a general role for mitochondrial oxygen kinetics in differentiating whole-organism aerobic performance and thus in influencing species responses to environmental change.

[Pimavanserin: a new treatment for the Parkinson's disease psychosis]. / Pimavanserine: een nieuwe behandeling voor psychose bij de ziekte van Parkinson.

BACKGROUND: Clozapine is an effective drug for treating psychosis in Parkinson's disease (PDP) and is registered as such in the Netherlands. However, clozapine can have adverse effects, including agranulocytosis. The new drug pimavanserin was recently registered in the United States for the treatment of PDP.
AIM: To review the literature on pimavanserin and discuss the position it currently occupies in the Netherlands as a potential treatment for PDP.
METHOD: Systematic search of the literature.
RESULTS: We found reports on four randomised controlled trials (RCTs), one review and six articles about the pharmacokinetics and pharmacodynamics of pimavanserin. Pimavanserin is an effective treatment for PDP, and, like clozapine, it has very few negative effects on motor skills. However, all of the RCTs were funded by the manufacturer of pimavanserin and the trials were conducted in a very selective patient population. This means that results cannot be generalised. Long-term results are not yet available. In earlier trials clozapine was shown to have a greater and faster antipsychotic effect. Many clinicians and psychiatrists have a great deal of experience with this drug. Another important point is that no-one has yet conducted a trial comparing clozapine and pimavanserin.
CONCLUSION: Given that the current second drug of choice, namely quetiapine, has not been found to be effective for PDP, we are of the opinion that - if pimavanserin is registered in the Netherlands - pimavanserin could be used when the current drug of choice, clozapine, is not completely effective or is poorly tolerated. For patients who have cognitive impairments in addition to psychosis, we advise testing the patient's reaction to a cholinesterase inhibitor before starting the patient on a course of antipsychotics.

[Lithium and its protective effect in Alzheimer's disease]. / Het beschermende effect van lithium bij de ziekte van Alzheimer.

BACKGROUND: Lithium is associated with adverse effects on cognitive functioning. However, there are published trials that have investigated the protective effects of lithium in cognitive decline.
AIM: To review studies that investigate the potentially protective effects of lithium on cognitive disorders.
METHOD: We studied English-language and Dutch reports on controlled, clinical trials published up to October 2016.
RESULTS: We found four relevant articles. Two studies indicated that cognitive functioning remained more stable when patients were given lithium than when they were given a placebo. One study, however, could not detect any difference between the effects of lithium and the effects of placebos. The fourth study, which examined patients' ability to tolerate lithium, could not find any difference in the cognitive functioning of patients.
CONCLUSION: The reported results indicate that the cognitive functioning of patients with pre-stage Alzheimer's disease remains more stable after patients have taken lithium than after they have taken a placebo.