Novel Oral Poliovirus Vaccine 2 Safety Evaluation during Nationwide Supplemental Immunization Activity, Uganda, 2022.

Given its enhanced genetic stability, novel oral poliovirus vaccine type 2 was deployed for type 2 poliovirus outbreak responses under World Health Organization Emergency Use Listing. We evaluated the safety profile of this vaccine. No safety signals were identified using a multipronged approach of passive and active surveillance.

Is COVID-19 finally just a bad flu? Follow-up study comparing disease severity among COVID-19 and seasonal influenza hospital in-patients across pandemic waves in Ireland.

OBJECTIVES: Coronavirus disease 2019 (COVID-19) was a more severe illness than seasonal influenza in hospitalised cohorts during the early phase of the pandemic. This study's aim was to determine if COVID-19 severity, relative to seasonal influenza, evolved across subsequent disease waves. STUDY DESIGN: Retrospective population-based cohort study. METHODS: COVID-19 hospital episodes and seasonal influenza hospital episodes were identified using relevant International Classification of Disease (ICD-10) codes from the Irish national hospitalisation dataset. Descriptive comparative analysis of each group was carried out using Pearson's Chi-squared tests. Length of stay (LOS), intensive care unit (ICU) admission and in-hospital mortality were measured and compared using logistic regression analysis. RESULTS: Compared to influenza episodes, COVID-19 episodes for all ages and all waves combined, had a longer mean LOS (15.8 days, vs 11.4 days, P < 0.001); were more likely to receive ICU care (OR 1.24 95% CI 1.15-1.33, P < 0.001) and were more likely to die in hospital (OR 2.61, 95% CI 2.36-2-88). Despite the reduction in the proportion of patients with an intensive care unit (ICU) stay and dying in hospital in Wave 5 compared to the previous waves, the risk of having an ICU admission or dying in hospital remained higher in patients with COVID-19 in Wave 5 compared to those with influenza diagnosis. CONCLUSION: While the severity of COVID-19 has reduced with successive pandemic waves, it remains a more severe disease than influenza. Despite changes in strain, population immunity, vaccination and treatment, policymakers and the public must continue to approach COVID-19 as more than 'just a bad flu'.

Identification, validation and biological characterisation of novel glioblastoma tumour microenvironment subtypes: implications for precision immunotherapy.

BACKGROUND: New precision medicine therapies are urgently required for glioblastoma (GBM). However, to date, efforts to subtype patients based on molecular profiles have failed to direct treatment strategies. We hypothesised that interrogation of the GBM tumour microenvironment (TME) and identification of novel TME-specific subtypes could inform new precision immunotherapy treatment strategies. MATERIALS AND METHODS: A refined and validated microenvironment cell population (MCP) counter method was applied to >800 GBM patient tumours (GBM-MCP-counter). Specifically, partition around medoids (PAM) clustering of GBM-MCP-counter scores in the GLIOTRAIN discovery cohort identified three novel patient clusters, uniquely characterised by TME composition, functional orientation markers and immune checkpoint proteins. Validation was carried out in three independent GBM-RNA-seq datasets. Neoantigen, mutational and gene ontology analysis identified mutations and uniquely altered pathways across subtypes. The longitudinal Glioma Longitudinal AnalySiS (GLASS) cohort and three immunotherapy clinical trial cohorts [treatment with neoadjuvant/adjuvant anti-programmed cell death protein 1 (PD-1) or PSVRIPO] were further interrogated to assess subtype alterations between primary and recurrent tumours and to assess the utility of TME classifiers as immunotherapy biomarkers. RESULTS: TMEHigh tumours (30%) displayed elevated lymphocyte, myeloid cell immune checkpoint, programmed cell death protein 1 (PD-1) and cytotoxic T-lymphocyte-associated protein 4 transcripts. TMEHigh/mesenchymal+ patients featured tertiary lymphoid structures. TMEMed (46%) tumours were enriched for endothelial cell gene expression profiles and displayed heterogeneous immune populations. TMELow (24%) tumours were manifest as an 'immune-desert' group. TME subtype transitions upon recurrence were identified in the longitudinal GLASS cohort. Assessment of GBM immunotherapy trial datasets revealed that TMEHigh patients receiving neoadjuvant anti-PD-1 had significantly increased overall survival (P = 0.04). Moreover, TMEHigh patients treated with adjuvant anti-PD-1 or oncolytic virus (PVSRIPO) showed a trend towards improved survival. CONCLUSIONS: We have established a novel TME-based classification system for application in intracranial malignancies. TME subtypes represent canonical 'termini a quo' (starting points) to support an improved precision immunotherapy treatment approach.

Update on Wild Poliovirus Type 1 Outbreak - Southeastern Africa, 2021-2022.

Since the Global Polio Eradication Initiative (GPEI) began in 1988, the number of wild poliovirus (WPV) cases has declined by >99.99%. Five of the six World Health Organization (WHO) regions have been certified free of indigenous WPV, and WPV serotypes 2 and 3 have been declared eradicated globally (1). WPV type 1 (WPV1) remains endemic only in Afghanistan and Pakistan (2,3). Before the outbreak described in this report, WPV1 had not been detected in southeastern Africa since the 1990s, and on August 25, 2020, the WHO African Region was certified free of indigenous WPV (4). On February 16, 2022, WPV1 infection was confirmed in one child living in Malawi, with onset of paralysis on November 19, 2021. Genomic sequence analysis of the isolated poliovirus indicated that it originated in Pakistan (5). Cases were subsequently identified in Mozambique. This report summarizes progress in the outbreak response since the initial report (5). During November 2021-December 2022, nine children and adolescents with paralytic polio caused by WPV1 were identified in southeastern Africa: one in Malawi and eight in Mozambique. Malawi, Mozambique, and three neighboring countries at high risk for WPV1 importation (Tanzania, Zambia, and Zimbabwe) responded by increasing surveillance and organizing up to six rounds of national and subnational polio supplementary immunization activities (SIAs).* Although no cases of paralytic WPV1 infection have been reported in Malawi since November 2021 or in Mozambique since August 2022, undetected transmission might be ongoing because of poliovirus surveillance gaps and testing delays. Efforts to further enhance poliovirus surveillance sensitivity, improve SIA quality, and strengthen routine immunization are needed to ensure that WPV1 transmission has been interrupted within 12 months of the first case, thereby preserving the WHO African Region's WPV-free status.

Evaluating the Presence of Replication-Competent Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) From Nursing Home Residents With Persistently Positive Reverse Transcription Polymerase Chain Reaction (RT-PCR) Results.

Replication-competent virus has not been detected in individuals with mild to moderate coronavirus disease 2019 (COVID-19) more than 10 days after symptom onset. It is unknown whether these findings apply to nursing home residents. Of 273 specimens collected from nursing home residents >10 days from the initial positive test, none were culture positive.

Salmonella Serotypes Associated with Illnesses after Thanksgiving Holiday, United States, 1998-2018.

We sought to determine which Salmonella serotypes cause illness related to the Thanksgiving holiday in the United States and to foods disproportionately eaten then (e.g., turkey). Using routine surveillance for 1998-2018 and a case-crossover design, we found serotype Reading to be most strongly associated with Thanksgiving.

Clinical Use of Tecovirimat (Tpoxx) for Treatment of Monkeypox Under an Investigational New Drug Protocol - United States, May-August 2022.

Currently, no Food and Drug Administration (FDA)-approved treatments for human monkeypox are available. Tecovirimat (Tpoxx), however, is an antiviral drug that has demonstrated efficacy in animal studies and is FDA-approved for treating smallpox. Use of tecovirimat for treatment of monkeypox in the United States is permitted only through an FDA-regulated Expanded Access Investigational New Drug (EA-IND) mechanism. CDC holds a nonresearch EA-IND protocol that facilitates access to and use of tecovirimat for treatment of monkeypox.§ The protocol includes patient treatment and adverse event reporting forms to monitor safety and ensure intended clinical use in accordance with FDA EA-IND requirements. The current multinational monkeypox outbreak, first detected in a country where Monkeypox virus infection is not endemic in May 2022, has predominantly affected gay, bisexual, and other men who have sex with men (MSM) (1,2). To describe characteristics of persons treated with tecovirimat for Monkeypox virus infection, demographic and clinical data abstracted from available tecovirimat EA-IND treatment forms were analyzed. As of August 20, 2022, intake and outcome forms were available for 549 and 369 patients, respectively; 97.7% of patients were men, with a median age of 36.5 years. Among patients with available data, 38.8% were reported to be non-Hispanic White (White) persons, 99.8% were prescribed oral tecovirimat, and 93.1% were not hospitalized. Approximately one half of patients with Monkeypox virus infection who received tecovirimat were living with HIV infection. The median interval from initiation of tecovirimat to subjective improvement was 3 days and did not differ by HIV infection status. Adverse events were reported in 3.5% of patients; all but one adverse event were nonserious. These data support the continued access to and treatment with tecovirimat for patients with or at risk for severe disease in the ongoing monkeypox outbreak.

Performance Evaluation of Serial SARS-CoV-2 Rapid Antigen Testing During a Nursing Home Outbreak.

BACKGROUND: To address high COVID-19 burden in U.S. nursing homes, rapid SARS-CoV-2 antigen tests have been widely distributed in those facilities. However, performance data are lacking, especially in asymptomatic people. OBJECTIVE: To evaluate the performance of SARS-CoV-2 antigen testing when used for facility-wide testing during a nursing home outbreak. DESIGN: A prospective evaluation involving 3 facility-wide rounds of testing where paired respiratory specimens were collected to evaluate the performance of the BinaxNOW antigen test compared with virus culture and real-time reverse transcription polymerase chain reaction (RT-PCR). Early and late infection were defined using changes in RT-PCR cycle threshold values and prior test results. SETTING: A nursing home with an ongoing SARS-CoV-2 outbreak. PARTICIPANTS: 532 paired specimens collected from 234 available residents and staff. MEASUREMENTS: Percentage of positive agreement (PPA) and percentage of negative agreement (PNA) for BinaxNOW compared with RT-PCR and virus culture. RESULTS: BinaxNOW PPA with virus culture, used for detection of replication-competent virus, was 95%. However, the overall PPA of antigen testing with RT-PCR was 69%, and PNA was 98%. When only the first positive test result was analyzed for each participant, PPA of antigen testing with RT-PCR was 82% among 45 symptomatic people and 52% among 343 asymptomatic people. Compared with RT-PCR and virus culture, the BinaxNOW test performed well in early infection (86% and 95%, respectively) and poorly in late infection (51% and no recovered virus, respectively). LIMITATION: Accurate symptom ascertainment was challenging in nursing home residents; test performance may not be representative of testing done by nonlaboratory staff. CONCLUSION: Despite lower positive agreement compared with RT-PCR, antigen test positivity had higher agreement with shedding of replication-competent virus. These results suggest that antigen testing could be a useful tool to rapidly identify contagious people at risk for transmitting SARS-CoV-2 during nascent outbreaks and help reduce COVID-19 burden in nursing homes. PRIMARY FUNDING SOURCE: None.

Coronavirus Disease 2019 (COVID-19) in Americans Aboard the Diamond Princess Cruise Ship.

BACKGROUND: The Diamond Princess cruise ship was the site of a large outbreak of coronavirus disease 2019 (COVID-19). Of 437 Americans and their travel companions on the ship, 114 (26%) tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). METHODS: We interviewed 229 American passengers and crew after disembarkation following a ship-based quarantine to identify risk factors for infection and characterize transmission onboard the ship. RESULTS: The attack rate for passengers in single-person cabins or without infected cabinmates was 18% (58/329), compared with 63% (27/43) for those sharing a cabin with an asymptomatic infected cabinmate, and 81% (25/31) for those with a symptomatic infected cabinmate. Whole genome sequences from specimens from passengers who shared cabins clustered together. Of 66 SARS-CoV-2-positive American travelers with complete symptom information, 14 (21%) were asymptomatic while on the ship. Among SARS-CoV-2-positive Americans, 10 (9%) required intensive care, of whom 7 were ≥70 years. CONCLUSIONS: Our findings highlight the high risk of SARS-CoV-2 transmission on cruise ships. High rates of SARS-CoV-2 positivity in cabinmates of individuals with asymptomatic infections suggest that triage by symptom status in shared quarters is insufficient to halt transmission. A high rate of intensive care unit admission among older individuals complicates the prospect of future cruise travel during the pandemic, given typical cruise passenger demographics. The magnitude and severe outcomes of this outbreak were major factors contributing to the Centers for Disease Control and Prevention's decision to halt cruise ship travel in US waters in March 2020.

Rapid Transmission of Severe Acute Respiratory Syndrome Coronavirus 2 in Detention Facility, Louisiana, USA, May-June, 2020.

To assess transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in a detention facility experiencing a coronavirus disease outbreak and evaluate testing strategies, we conducted a prospective cohort investigation in a facility in Louisiana, USA. We conducted SARS-CoV-2 testing for detained persons in 6 quarantined dormitories at various time points. Of 143 persons, 53 were positive at the initial test, and an additional 58 persons were positive at later time points (cumulative incidence 78%). In 1 dormitory, all 45 detained persons initially were negative; 18 days later, 40 (89%) were positive. Among persons who were SARS-CoV-2 positive, 47% (52/111) were asymptomatic at the time of specimen collection; 14 had replication-competent virus isolated. Serial SARS-CoV-2 testing might help interrupt transmission through medical isolation and quarantine. Testing in correctional and detention facilities will be most effective when initiated early in an outbreak, inclusive of all exposed persons, and paired with infection prevention and control.

Whispering Tuberculosis.

Presentation We describe a case of reactivation of latent pulmonary tuberculosis (TB) invading the larynx and causing dysphonia. Diagnosis A previously healthy 30-year old woman was found to have bilateral pulmonary TB 5-months after being thoroughly investigated for hoarseness. Initial chest x-ray (CXR) and CT-neck were normal. Vocal cord biopsies were negative for granulomata. Treatment The patient was commenced on standard four drug Anti-TB treatment (ATT) and completed a one-year course. Unfortunately, the development of a laryngeal web caused persistent dysphonia. Discussion Patients with laryngeal TB are more likely to present to ENT surgeons, because of the initial symptom of hoarseness. Multiple tests must be completed before out-ruling TB. HRCT or sputum culture is recommended, as TB may not be evident on initial CXR. A collaborative approach between Respiratory and ENT teams is required. Prompt diagnosis is essential. Speech therapy input will be important in our patient's recovery.

New hints towards a precision medicine strategy for IDH wild-type glioblastoma.

Glioblastoma represents the most common primary malignancy of the central nervous system in adults and remains a largely incurable disease. The elucidation of disease subtypes based on mutational profiling, gene expression and DNA methylation has so far failed to translate into improved clinical outcomes. However, new knowledge emerging from the subtyping effort in the IDH-wild-type setting may provide directions for future precision therapies. Here, we review recent learnings in the field, and further consider how tumour microenvironment differences across subtypes may reveal novel contexts of vulnerability. We discuss recent treatment approaches and ongoing trials in the IDH-wild-type glioblastoma setting, and propose an integrated discovery stratagem incorporating multi-omics, single-cell technologies and computational approaches.

Reduced lactate dehydrogenase activity in the heart and suppressed sex hormone levels are associated with female-biased mortality during thermal stress in Pacific salmon.

Female-biased mortality has been repeatedly reported in Pacific salmon during their upriver migration in both field studies and laboratory holding experiments, especially in the presence of multiple environmental stressors, including thermal stress. Here, we used coho salmon (Oncorhynchus kisutch) to test whether females exposed to elevated water temperatures (18°C) (i) suppress circulating sex hormones (testosterone, 11-ketotestosterone and estradiol), owing to elevated cortisol levels, (ii) have higher activities of enzymes supporting anaerobic metabolism (e.g. lactate dehydrogenase, LDH), (iii) have lower activities of enzymes driving oxidative metabolism (e.g. citrate synthase, CS) in skeletal and cardiac muscle, and (iv) have more oxidative stress damage and reduced capacity for antioxidant defense [lower catalase (CAT) activity]. We found no evidence that a higher susceptibility to oxidative stress contributes to female-biased mortality at warm temperatures. We did, however, find that females had significantly lower cardiac LDH and that 18°C significantly reduced plasma levels of testosterone and estradiol, especially in females. We also found that relative gonad size was significantly lower in the 18°C treatment regardless of sex, whereas relative liver size was significantly lower in females held at 18°C. Further, relative spleen size was significantly elevated in the 18°C treatments across both sexes, with larger warm-induced increases in females. Our results suggest that males may better tolerate bouts of cardiac hypoxia at high temperature, and that thermal stress may also disrupt testosterone- and estradiol-mediated protein catabolism, and the immune response (larger spleens), in migratory female salmon.

Serial Laboratory Testing for SARS-CoV-2 Infection Among Incarcerated and Detained Persons in a Correctional and Detention Facility - Louisiana, April-May 2020.

Transmission of SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19), by asymptomatic and presymptomatic persons poses important challenges to controlling spread of the disease, particularly in congregate settings such as correctional and detention facilities (1). On March 29, 2020, a staff member in a correctional and detention facility in Louisiana developed symptoms† and later had a positive test result for SARS-CoV-2. During April 2-May 7, two additional cases were detected among staff members, and 36 cases were detected among incarcerated and detained persons at the facility; these persons were removed from dormitories and isolated, and the five dormitories that they had resided in before diagnosis were quarantined. On May 7, CDC and the Louisiana Department of Health initiated an investigation to assess the prevalence of SARS-CoV-2 infection among incarcerated and detained persons residing in quarantined dormitories. Goals of this investigation included evaluating COVID-19 symptoms in this setting and assessing the effectiveness of serial testing to identify additional persons with SARS-CoV-2 infection as part of efforts to mitigate transmission. During May 7-21, testing of 98 incarcerated and detained persons residing in the five quarantined dormitories (A-E) identified an additional 71 cases of SARS-CoV-2 infection; 32 (45%) were among persons who reported no symptoms at the time of testing, including three who were presymptomatic. Eighteen cases (25%) were identified in persons who had received negative test results during previous testing rounds. Serial testing of contacts from shared living quarters identified persons with SARS-CoV-2 infection who would not have been detected by symptom screening alone or by testing at a single time point. Prompt identification and isolation of infected persons is important to reduce further transmission in congregate settings such as correctional and detention facilities and the communities to which persons return when released.

COVID-19 Outbreak Among Three Affiliated Homeless Service Sites - King County, Washington, 2020.

On March 30, 2020, Public Health - Seattle and King County (PHSKC) was notified of a confirmed case of coronavirus disease 2019 (COVID-19) in a resident of a homeless shelter and day center (shelter A). Residents from two other homeless shelters (B and C) used shelter A's day center services. Testing for SARS-CoV-2, the virus that causes COVID-19, was offered to available residents and staff members at the three shelters during March 30-April 1, 2020. Among the 181 persons tested, 19 (10.5%) had positive test results (15 residents and four staff members). On April 1, PHSKC and CDC collaborated to conduct site assessments and symptom screening, isolate ill residents and staff members, reinforce infection prevention and control practices, provide face masks, and advise on sheltering-in-place. Repeat testing was offered April 7-8 to all residents and staff members who were not tested initially or who had negative test results. Among the 118 persons tested in the second round of testing, 18 (15.3%) had positive test results (16 residents and two staff members). In addition to the 31 residents and six staff members identified through testing at the shelters, two additional cases in residents were identified during separate symptom screening events, and four were identified after two residents and two staff members independently sought health care. In total, COVID-19 was diagnosed in 35 of 195 (18%) residents and eight of 38 (21%) staff members who received testing at the shelter or were evaluated elsewhere. COVID-19 can spread quickly in homeless shelters; rapid interventions including testing and isolation to identify cases and minimize transmission are necessary. CDC recommends that homeless service providers implement appropriate infection control practices, apply physical distancing measures including ensuring resident's heads are at least 6 feet (2 meters) apart while sleeping, and promote use of cloth face coverings among all residents (1).

Sodium-glucose cotransporter 2 (SGLT-2) inhibitors and microvascular outcomes in patients with type 2 diabetes: systematic review and meta-analysis.

PURPOSE: The effect of the sodium-glucose 2 (SGLT-2) inhibitors on microvascular complications remains uncertain. We performed a systematic review to determine the efficacy of the SGLT-2 inhibitors on microvascular outcomes in patients with type 2 diabetes. METHODS: A comprehensive search was performed using Ovid, MEDLINE, EMBASE, Web of Science, and Scopus from inception to May 2019. Randomized trials comparing SGLT-2 inhibitors with placebo or other medication for type 2 diabetes for ≥ 4 weeks were included. Diabetes-related microvascular complications such as nephropathy, retinopathy, neuropathy, and peripheral vascular disease were evaluated. A random-effect model using mean differences for continuous outcomes and risk ratio for dichotomous outcomes was used to synthesize data. PROSPERO (CRD 42017076460). RESULTS: A total of 40 RCTs with overall moderate quality of evidence were included. SGLT-2 inhibitors reduced the risk of renal-replacement therapy (0.65; 95% CI 0.54-0.79), renal death (0.57; 95% CI 0.49-0.65), and progression of albuminuria (0.69; 95% CI 0.66-0.73). Conversely, they appeared ineffective in maintaining eGFR (0.33; 95% CI - 0.74 to 1.41) or reducing serum creatinine (- 0.07; 95% CI - 0.26 to 0.11), whereas urine albumin-creatinine ratio (- 23.4; 95% CI - 44.6 to - 2.2) was reduced. Risk of amputation was non-significant (1.30; 95% CI 0.93-1.83). No available data were found regarding neuropathy and retinopathy to perform a quantitative analysis. CONCLUSION: SGLT-2 inhibitors may reduce the risk of renal patient-important outcomes but fail to improve surrogate outcomes. Apparently, no increased risk of amputations was observed with these medications. No data were available regarding other microvascular complications.

Next Stop a Longer Life.

Aim A request was made to the Department of Public Health in early 2019 for some interesting statistics (funtistics) for a planned health promotion campaign encouraging public transport users to increase their physical activity levels by alighting one stop earlier and walking to their destination. For a novel presentation of the benefits of increasing physical activity it was decided to calculate the potential increase in life-expectancy that a given amount of physical activity would correspond to (at a population level). Method Estimated increase in weekly walking time was calculated for the Dublin Bus commuter walking the last stop of their journey. The reduced risk of mortality was estimated for this increase in physical activity and applied to Irish life tables to calculate change in life expectancy. Results Alighting from a bus one stop earlier in Dublin would lead to an average of 4.42 minutes additional walking (44.21 minutes additional walking per week for a commuter). In the Dublin Bus commuter population, this leads to an estimated 50 day increase in life expectancy (male population). Conclusion At the lower end of the dose response curve for physical activity, health benefits include: reduced risk of cardiovascular disease, reduced risk of diabetes, psychosocial benefit, reduced risk of musculoskeletal problems. For the prevention of weight gain and some cancers, activity at the upper end of the range (1000 MET.min/week, approximately 300 minutes of walking/week) is thought to be required.

Comorbidity of bipolar I disorder and conduct disorder: a familial risk analysis.

OBJECTIVE: To investigate the association between pediatric bipolar I (BP-I) disorder and conduct disorder (CD) using familial risk analysis. METHOD: We compared diagnoses in relatives of youth in four proband groups defined by the presence or absence of BP-I and CD: (1) probands with neither CD nor BP-I (probands: N = 550; relatives: N = 1656), (2) probands with CD and without BP-I (probands: N = 40; relatives: N = 127), (3) probands with BP-I and without CD (probands: N = 197; relatives: N = 579), and (4) probands with both CD and BP-I (probands: N = 176; relatives: N = 488). All subjects were evaluated with structured diagnostic interviews, and diagnoses of relatives were made blind to the diagnoses of probands. RESULTS: Relatives of probands with BP-I disorder had high rates of BP-I, and relatives of probands with CD had high rates of CD irrespective of the comorbidity with the other disorder. Relatives of probands with the combined condition of CD and BP-I had high rates of the combined condition. CONCLUSION: The finding of cosegregation between BP-I disorder and CD is consistent with the hypothesis that the combined condition represents a distinct subtype of either disorder.

Cannabis use and Associated Health Problems ­ What's the Harm?

Aim Cannabis is the most widely used illegal drug in Ireland. We sought to describe the changing pattern of cannabis use and cannabis related health harms. Methods Data was collated from two national population surveys and three national treatment databases, focusing on people under 34 years. Results Past month cannabis use among adolescents and young adults increased after 2011, coinciding with a decline in perceived risk of regular use. The prevalence estimate for cannabis dependence increased from 1.1% to 3.6% from 2011 to 2015. From 2008 to 2016, there were increases in the rates of cannabis related addiction treatment episodes among adolescents and among young adults of 40% and 168% respectively. Cannabis related admissions to general and psychiatric hospitals increased by 90% and 185% respectively. Conclusion A concerted public health response is required to address escalating cannabis related health harms which have coincided with the arrival of more potent cannabis.

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.