ABSTRACT
Non-tuberculosis mycobacteria (NTM) can cause severe respiratory infection in patients with underlying pulmonary conditions, and these infections are extremely difficult to treat. In this report, we evaluate a nitric oxide (NO)-releasing prodrug [methyl tris diazeniumdiolate (MD3)] against a panel of NTM clinical isolates and as a treatment for acute and chronic NTM infections in vivo. Its efficacy in inhibiting growth or killing mycobacteria was explored in vitro alongside evaluation of the impact to primary human airway epithelial tissue. Airway epithelial tissues remained viable after exposure at concentrations of MD3 needed to kill mycobacteria, with no inherent toxic effect from drug scaffold after NO liberation. Resistance studies conducted via serial passage with representative Mycobacterium abscessus isolates demonstrated no resistance to MD3. When administered directly into the lung via intra-tracheal administration in mice, MD3 demonstrated significant reduction in M. abscessus bacterial load in both acute and chronic models of M. abscessus lung infection. In summary, MD3 is a promising treatment for complex NTM pulmonary infection, specifically those caused by M. abscessus, and warrants further exploration as a therapeutic.
Subject(s)
Mycobacterium Infections, Nontuberculous , Mycobacterium , Prodrugs , Humans , Animals , Mice , Nitric Oxide , Anti-Bacterial Agents/pharmacology , Prodrugs/pharmacology , Mycobacterium Infections, Nontuberculous/drug therapy , Nontuberculous Mycobacteria , Microbial Sensitivity TestsABSTRACT
BACKGROUND: For patients receiving daily opioid agonist treatment (OAT) for opioid dependence, several countries relaxed treatment guidelines at the beginning of the COVID-19 pandemic. This involved longer take-home intervals for methadone and buprenorphine doses as well as a reduction in supervised dosing and drug screening. To date, little is known about the medium or long-term experience of OAT deregulation. Therefore, we conducted a survey to explore how OAT providers perceived greater flexibility in OAT service delivery at the end of the second year of the pandemic. METHODS: Nationwide cross-sectional study of twenty-three OAT units in 19 publicly funded hospital trusts in Norway. OAT units were sent a 29-item online questionnaire comprising closed-format and open-ended questions on treatment provider experiences and changes in OAT service delivery during the past 12 months (January to December 2021). RESULTS: Twenty-three (of whom female: 14; 60.8%) managers or lead physicians of OAT units completed the questionnaire reporting that, in 2021, most OAT units (91.3%, n = 21) still practiced some adjusted approaches as established in the beginning of the pandemic. The most common adaptions were special protocols for COVID-19 cases (95.7%, n = 22), increased use of telephone- (91.3%, n = 21) and video consultations (87.0%, n = 20), and longer take-home intervals for OAT medications (52.2%, n = 12). The use of depot buprenorphine also increased substantially during the pandemic. According to the OAT providers, most patients handled flexible treatment provision well. In individual cases, patients' substance use was identified as key factor necessitating a reintroduction of supervised dosing and drug screening. Collaboration with general practitioners and municipal health and social services was generally perceived as crucial for successful treatment delivery. CONCLUSIONS: Overall, the Norwegian OAT system proved resilient in the second year of the COVID-19 pandemic, as its healthcare workforce embraced innovation in technology (telemedicine) and drug development (depot buprenorphine). According to our nationally representative sample of OAT providers, most patients were compliant with longer take-home doses of methadone and buprenorphine. Our findings suggest that telemedicine can be useful as adjunct to face-to-face treatment and provide greater flexibility for patients.
Subject(s)
Buprenorphine , COVID-19 , General Practitioners , Humans , Female , Analgesics, Opioid/therapeutic use , Cross-Sectional Studies , Pandemics , COVID-19/epidemiology , Norway/epidemiology , Buprenorphine/therapeutic use , Methadone/therapeutic use , Surveys and QuestionnairesABSTRACT
BACKGROUND: Among individuals receiving buprenorphine or methadone as opioid maintenance treatment (OMT), concomitant use of other central nervous system depressants, including prescription drugs, can increase risk of overdose. We aimed to 1) determine the prevalence of use of high-risk prescription drugs (opioid analgesics, benzodiazepines, benzodiazepine-related drugs, and gabapentinoids) among OMT patients, 2) calculate its associations with different mental health and pain-related diagnoses, and 3) compare prevalence of concomitant use with the general population. METHODS: A national sample comprising all individuals filling at least one prescription of OMT drugs in Norway in 2019 was formed. Healthcare registry data were linked to investigate high-risk prescription drug use and different diagnoses. We calculated one-year prevalence of use, amount dispensed in defined daily doses (DDDs), and the number of prescribers for the different high-risk prescription drugs. Logistic regression was used to determine associations (adjusted odds ratios; aOR, 95% confidence intervals (CIs)) between diagnoses and use. Prevalence of use was calculated both in the OMT patient sample and the general population. RESULTS: Among the OMT patient sample (n=7,299), 47.6% (n=3,476) filled prescriptions for benzodiazepines. For each high-risk prescription drug group, there was a median of 1-2 prescribers. Musculoskeletal diagnoses were the strongest factor for concomitant high-risk prescription drug use for both males (aOR 3.23, CI: 2.72-3.85) and females (aOR 3.07, CI: 2.42- 3.90). The 1-year prevalence of benzodiazepine use was 11.4 times higher for males and 7.1 times higher for females in OMT than the general population. The amount in DDDs was higher for every drug for OMT patients than the general population, particularly for benzodiazepines. CONCLUSIONS: OMT patients frequently filled prescriptions for high-risk drugs, and in higher dosages than the general population. However, we found little evidence of 'doctor shopping.' Given that these prescription drugs carry overdose risk, particularly when combined with OMT drugs, our findings emphasize the continued need for education and caution to both prescribers and patients on their concomitant use with OMT.
ABSTRACT
BACKGROUND: Worldwide, opioid use causes more than 100,000 overdose deaths annually. Naloxone has proven efficacy in reversing opioid overdoses and is approved as an emergency antidote to opioid overdose. Take home naloxone (THN) programmes have been introduced to provide 'community members', who are likely to observe opioid overdoses, with naloxone kits and train them to recognise an overdose and administer naloxone. The acceptability and feasibility of THN programmes has been demonstrated, but the real-life effectiveness of naloxone administration by community members is not known. In recent years, the approval of several concentrated naloxone nasal-spray formulations (in addition to injectable formulations, eg.prenoxad) potentially increases acceptability and scope for wider provision. This study aims to determine the effectiveness of THN (all formulations) in real-world conditions. METHODS: A European, multi-country, prospective cohort study, to assess the use of THN by community members to reverse opioid overdoses in a six-month, follow-up period. Participants provided with THN from participating harm reduction and drug treatment sites will be recruited to the study and followed-up for six months. We are particularly interested in the experiences of community members who have been provided with THN and have witnessed an opioid overdose. All participants who witness an opioid overdose during the six-month period (target approx. 600) will be asked to take part in a structured interview about this event. Of these, 60 will be invited to participate in a qualitative interview. A Post Authorisation Efficacy Study (PAES) for the concentrated nasal naloxone, Nyxoid, has been integrated into the study design. DISCUSSION: There are many challenges involved in evaluating the real-life effectiveness of THN. It is not possible to use a randomised trial design, recruitment of community members provided with THN will depend upon recruitment sites distributing THN kits, and the type of THN received by participants will depend on regulations and on local clinical and policy decision-makers. Following up this population, some of whom may be itinerant, over the 6-month study period will be challenging, but we plan to maintain contact with participants through regular text message reminders and staff contact. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05072249. Date of Registration: 8.10.2021.
Subject(s)
Drug Overdose , Opiate Overdose , Humans , Naloxone/therapeutic use , Cohort Studies , Prospective Studies , Drug Overdose/drug therapy , Randomized Controlled Trials as TopicABSTRACT
Since March 2020, the COVID-19 pandemic has had a disproportionately high toll on vulnerable populations, coinciding with increased prevalence of alcohol-and drug-related deaths and pre-existing societal issues such as rising income inequality and homelessness. This poly-crisis has posed unique challenges to service delivery for people with substance use disorders, and innovative approaches have emerged. In this Perspectives paper we reflect on the poly-crisis and the changes to research and practice for those experiencing substance use disorders, following work undertaken as part of the InterGLAM project (part of the 2022. Lisbon Addictions conference). The authors, who were part of an InterGLAM working group, identified a range of creative and novel responses by gathering information from conference attendees about COVID-19-related changes to substance use disorder treatment in their countries. In this paper we describe these responses across a range of countries, focusing on changes to telehealth, provision of medications for opioid use disorder and alcohol harm reduction, as well as changes to how research was conducted. Implications include better equity in access to technology and secure data systems; increased prescribed safer supply in countries where this currently does not exist; flexible provision of medication for opioid use disorder; scale up of alcohol harm reduction for people with alcohol use disorders; greater involvement of people with lived/living experience in research; and additional support for research in low- and middle-income countries. The COVID-19 pandemic has changed the addictions field and there are lessons for ongoing and emerging crises.
Subject(s)
Alcoholism , Behavior, Addictive , COVID-19 , Opioid-Related Disorders , Humans , Alcoholism/epidemiology , Pandemics , COVID-19/epidemiology , EthanolABSTRACT
BACKGROUND: Internationally, approximately 15 million babies are born prematurely every year. In New Zealand, 1 neonatal ward may care for 1000 infants annually. Family-centered care (FCC) is a philosophy used in neonates to enhance positive outcomes for infants, parents, and staff by recognizing the strengths and needs of infants and their families. OBJECTIVE: This research assessed how a neonatal environment could be improved to ensure parents feel welcomed and empowered to participate in their infant's care. PARTICIPANTS: Survey data from 67 health professionals and 51 parents of infants who received neonatal care for more than 7 days. Four in-depth interviews with parents and 5 with health professionals. METHODS: A mixed-methods research design was used. Phase 1 collected quantitative data using the Family-Centered Care Questionnaire. Phase 2 composed of face-to-face interviews with health professionals and parents. RESULTS: Implementing FCC practices to improve health outcomes for infants, parents, and staff is important. Recommendations for improvement were formulated from the themes. CONCLUSION: The perspectives of parents and health professionals have enabled the development of recommendations to improve the implementation of FCC practice in the neonatal environment. These may lead to better parental experience and improved infant health outcomes.
Subject(s)
Intensive Care Units, Neonatal , Parents , Infant, Newborn , Infant , Child , Humans , Infant Care , Patient-Centered Care , Power, PsychologicalABSTRACT
Information about individual behaviour is collected regularly by organisations. This information has value to businesses, the government and third parties. It is not clear what value this personal data has to consumers themselves. Much of the modern economy is predicated on people sharing personal data, however if individuals value their privacy, they may choose to withhold this data unless the perceived benefits of sharing outweigh the perceived value of keeping the data private. One technique to assess how much individuals value their privacy is to ask them whether they might be willing to pay for an otherwise free service if paying allowed them to avoid sharing personal data. Our research extends previous work on factors affecting individuals' decisions about whether to share personal data. We take an experimental approach and focus on whether consumers place a positive value on protecting their data by examining their willingness to share personal data in a variety of data sharing environments. Using five evaluation techniques, we systematically investigate whether members of the public value keeping their personal data private. We show that the extent to which participants value protecting their information differs by data type, suggesting there is no simple function to assign a value for individual privacy. The majority of participants displayed remarkable consistency in their rankings of the importance of different types of data through a variety of elicitation procedures, a finding consistent with the existence of stable individual privacy preferences in protecting personal data. We discuss our findings in the context of research on the value of privacy and privacy preferences.
Subject(s)
Information Dissemination , Privacy , Humans , Information Dissemination/methods , Trust , Computer SecurityABSTRACT
Policy makers aim to respect public preferences when making trade-offs between policies, yet most estimates of the value of safety neglect individuals' preferences over how safety is distributed. Incorporating these preferences into policy first requires measuring them. Arroyos-Calvera et al. (2019) documented that people cared most about efficiency, but that equity followed closely, and self-interest mattered too, but not enough to override preferences for efficiency and equity. Early 2020 saw the outbreak of the COVID-19 pandemic. This event would impose major changes in how people perceived and experienced risk to life, creating an opportunity to test whether safety-related preferences are stable and robust to important contextual changes. Further developing Arroyos-Calvera et al.'s methodology and re-inviting an international general population sample of participants that had taken part in pre-pandemic online surveys in 2017 and 2018, we collected an April 2020 wave of the survey and showed that overall preferences for efficiency, equity and self-interest were remarkably stable before and after the pandemic outbreak. We hope this offers policy makers reassurance that once these preferences have been elicited from a representative sample of the population, they need not be re-estimated after important contextual changes.
Subject(s)
COVID-19 , Humans , COVID-19/epidemiology , Pandemics , Health Policy , Administrative Personnel , Surveys and QuestionnairesABSTRACT
Long-range interactions between regulatory elements and promoters are key in gene transcriptional control; however, their study requires large amounts of starting material, which is not compatible with clinical scenarios nor the study of rare cell populations. Here we introduce low input capture Hi-C (liCHi-C) as a cost-effective, flexible method to map and robustly compare promoter interactomes at high resolution. As proof of its broad applicability, we implement liCHi-C to study normal and malignant human hematopoietic hierarchy in clinical samples. We demonstrate that the dynamic promoter architecture identifies developmental trajectories and orchestrates transcriptional transitions during cell-state commitment. Moreover, liCHi-C enables the identification of disease-relevant cell types, genes and pathways potentially deregulated by non-coding alterations at distal regulatory elements. Finally, we show that liCHi-C can be harnessed to uncover genome-wide structural variants, resolve their breakpoints and infer their pathogenic effects. Collectively, our optimized liCHi-C method expands the study of 3D chromatin organization to unique, low-abundance cell populations, and offers an opportunity to uncover factors and regulatory networks involved in disease pathogenesis.
Subject(s)
Gene Expression Regulation , Regulatory Sequences, Nucleic Acid , Humans , Promoter Regions, Genetic/genetics , Chromatin/genetics , Enhancer Elements, Genetic/geneticsABSTRACT
A 33-year-old female presented with lethargy due to multidrug toxicity. At physical examination, both gluteal regions showed brown patchy scars. The atrophic scars surrounding necrotic lesions were round and brown in appearance, and gluteal mass had gradually been lost. The patient disclosed using intramuscular ketamine injections for 3.5 years along with smoking hashish, alcohol use, intranasal use of methamphetamine (sniffing), and oral use of methadone. Since recreational drug use can affect multiple organs, dermatologists should be familiar with the dermatologic features of intravenous or intramuscular injecting drug use.
Subject(s)
Ketamine , Methamphetamine , Female , Humans , Adult , Ketamine/adverse effects , Cicatrix , Injections, Intramuscular , Methadone , Methamphetamine/adverse effectsABSTRACT
The prescription opioid epidemic has slowly evolved over the past quarter century with increasingly detrimental consequences for public health. Man-made crises are often unforeseen and characterized by a situation without natural causes where - because of human intent, error, negligence, or the failure of manmade systems - the level of needs in the population exceeds available resources to counter the problem. This paper presents the prescription opioid epidemic as a man-made crisis and explores the public health impact of opioid manufacturers and other industries producing commodities with addictive potential as a shared vulnerability among countries. We examine this concept within the framework of the commercial determinants of health. We address three key aspects of the commercial determinants of health: (1) Cross-industry mechanisms, (2) policy inertia, and (3) the role of industry in science. Within cross-industry mechanisms, we explore parallels between prescription opioid epidemic and unhealthy commodity industries in terms of marketing, corporate use of misinformation, and diversionary tactics. Next, we examine how policy inertia has dominated the slow response to this man-made crisis. Lastly, we discuss how results from clinical trials are used as a key marketing strategy for drugs. The origins of the prescription opioid epidemic may be traced to innovations in drug development with the promise of improved pain management. However, through multiple factors, including fraudulent marketing from pharmaceutical industry and policy inertia, the resulting crisis represents a multi-system failure of regulation exploited by corporate greed.
Subject(s)
Epidemics , Opioid-Related Disorders , Humans , Analgesics, Opioid/therapeutic use , Opioid-Related Disorders/epidemiology , Opioid-Related Disorders/drug therapy , Opioid Epidemic , Pain ManagementABSTRACT
Background: Ingestion of methanol can result in severe irreversible morbidity, and death. Simple and easy methods to detect methanol and other hazardous additives prior to consumption can prevent fatalities. This form of harm reduction is analogous to the widely practiced "pill testing" of recreational drugs in various countries. We aimed to evaluate the performance of two qualitative and quantitative kits to simultaneously identify the presence of methanol and formaldehyde in alcoholic beverages, and compare this to the standard gas chromatographic (GC) method. Methods: Two-hundred samples of Indian and Iranian alcoholic drinks were examined by two new qualitative and quantitative chemical kits designed based on a modified chromotropic acid (CA) method, as well as a gold standard GC method. Results: Methanol levels were similar when evaluated by GC and quantitative method (Z = - 0.328, p = 0.743). The 75th percentile of methanol level detection was 4,290 mg L-1 (range; 0-83,132) using GC compared to that of 4,671 mg L-1 (range; 0-84,960) using the qualitative kit (predefined color intensity reflecting the methanol/ethanol ratio). The quantitative kit was able to detect all methanol-contaminated and non-contaminated samples (110 and 60 cases, respectively: 100% sensitivity). In 25 samples, GC analysis showed no methanol; but the qualitative kit detected possible toxic substances. Formaldehyde measurement by UV/Vis analysis showed the presence of formaldehyde in 23 samples (92%) with a median 912 [IQR 249, 2,109; range 112-2,742] mg L-1. Conclusion: Methanol and formaldehyde can be easily detected using these simple CA chemical kits. Qualitative positive results may indicate the risk of poisoning if the beverage is consumed. CA kits can be used in community setting by public health units and community organizations to monitor for methanol contamination and inform a public health response to reduce methanol-related harms to the public.
Subject(s)
Alcoholic Beverages , Harm Reduction , Iran , Alcoholic Beverages/analysis , Methanol/analysis , Formaldehyde/analysisABSTRACT
OBJECTIVES: The impact of a coronavirus disease (COVID-19)-specific professional development programme on the well-being of obstetrics and gynaecology (O&G) doctors in training (DiT) working during the pandemic. DESIGN: A mixed-method evaluation of a single group pre-post test design study. SETTING: Melbourne, Australia between September 2020 and April 2021. PARTICIPANTS: 55 O&G DiT working across four healthcare sites of a major tertiary hospital in Victoria, Australia, were included in the programme. INTERVENTIONS: The delivery of a codesigned peer-to-peer programme, which identified and addressed the well-being goals of O&G DiT. Seven interactive workshops were run alongside the implementation of a number of participant-led wellness initiatives. MAIN OUTCOME MEASURES: Repeated-measures analysis of WHO Well-being Index (WHO-5) and Copenhagen Burnout Innovatory (CBI) scores across three time points during the programme. Multilevel generalised linear mixed-effects models with random intercept were fit to the data, both in the entire population (intention-to-treat) and restricted to those who attended the workshop ('per-protocol' analysis). Participatory experiences and programme learning were captured using the Most Significant Change (MSC) technique, which included inductive thematic analysis. RESULTS: We demonstrated an overall 31.9% improvement in well-being scores (p=0.006). The MSC evaluation captured a shift in workplace culture as a result of the programme, with improvement across the domains of connection, caring, communication, confidence and cooperation. CONCLUSIONS: We have successfully used a mixed-method approach to contextualise a productive programme to improve the well-being of COVID-19 front-line healthcare workers.
Subject(s)
COVID-19 , Medicine , Physicians , Female , Pregnancy , Humans , COVID-19/epidemiology , Pandemics , VictoriaABSTRACT
PURPOSE: Hysterectomy is a common but expensive and morbid procedure. Alternative treatments for heavy menstrual bleeding (HMB) are effective in up to 80% of cases, but there is substantial variation in surgical approach and pre-operative management of HMB. This study aims to assess the approach to hysterectomies for benign indications including alternative treatments and route of operation. METHODS: We retrospectively collected patient and surgical data on all hysterectomies for benign indications from 1/4/2018 to 31/6/2020 at our tertiary-led hospital network. RESULTS: Hysterectomies were performed in 582 women at a median age of 49(44-56) with a median BMI of 27.9(24.5-33.3)kg/m2 and 251(43%) were referred from private rooms. Hysterectomies for HMB were performed laparoscopically (TLH)(156, 51.7%) more often than abdominally (TAH)(133, 44%) or vaginally (4.3, 13%), with wide variation between sites. Approach was predicted by a history of previous abdomino-pelvic surgery and uterine size but not by other patient factors (BMI, parity or comorbidities). Referral source, on the other hand, was a significant predictor of route of hysterectomy. In women with HMB without uterine abnormalities, 45% tried a levonorgestrel intrauterine device and 25% tried endometrial ablation before proceeding to surgery. The use of alternative therapies pre-operatively did not vary between sites or referral sources. CONCLUSIONS: The variations in route of hysterectomy that are unexplained by patient factors suggest room for improvement and raises the question whether some of the patients undergoing a TAH may have been candidates for less invasive surgery. Uptake of alternative management strategies for HMB could also be improved.
Subject(s)
Laparoscopy , Menorrhagia , Humans , Female , Retrospective Studies , Tertiary Care Centers , Australia , Hysterectomy/methods , Menorrhagia/surgeryABSTRACT
BACKGROUND: In March 2020, the World Health Organization declared COVID-19 a global pandemic. In the following weeks, most European countries implemented national lockdowns to mitigate viral spread. Services for people who use drugs had to quickly revise their operating procedures to rearrange service provision while adhering to lockdown requirements. Given the scarcity of literature published on overdose prevention during COVID-19 in Europe, we aimed to examine how these changes to service provision affected take-home naloxone (THN) programmes and naloxone availability across Europe. METHODS: Between November 2020 and January 2021, we conducted a rapid assessment with country experts from European countries that provide THN. We sent country experts a template to report monthly THN distribution data (January 1, 2019-October 31, 2020) and a structured 6-item survey for completion. RESULTS: Responses were received from 14 of the 15 European countries with THN provision of which 11 participated in the rapid assessment: Austria, Denmark, England, Estonia, Lithuania, Northern Ireland, Norway, Scotland, Spain (Catalonia only), Sweden, and Wales. All reported reduced organisational capacity during COVID-19, and some put into place a range of novel approaches to manage the restrictions on face-to-face service provision. In six countries, the introduction of programme innovation occurred alongside the publication of government guidelines recommending increased THN provision during COVID-19. Eight of the eleven participating countries managed to maintain 2019-level monthly THN distribution rates or even increase provision during the pandemic. CONCLUSION: Through programme innovation supported by public guidelines, many European THN programmes managed to ensure stable or even increased THN provision during the pandemic, despite social distancing and stay-at-home orders affecting client mobility.
Subject(s)
COVID-19 , Drug Overdose , Opioid-Related Disorders , Communicable Disease Control , Drug Overdose/drug therapy , Drug Overdose/epidemiology , Drug Overdose/prevention & control , Humans , Naloxone/therapeutic use , Narcotic Antagonists/therapeutic use , Opioid-Related Disorders/drug therapyABSTRACT
A methanol poisoning outbreak occurred in Iran during the initial months of coronavirus disease 2019 (COVID-19) pandemic. We aimed to evaluate the epidemiology of the outbreak in terms of hospitalizations and deaths. A cross-sectional linkage study was conducted based on the hospitalization data collected from thirteen referral toxicology centers throughout Iran as well as mortality data obtained from the Iranian Legal Medicine Organization (LMO). Patient data were extracted for all cases aged > 19 years with toxic alcohol poisoning during the study period from February until June 2020. A total of 795 patients were hospitalized due to methanol poisoning, of whom 84 died. Median [interquartile ratio; IQR] age was 32 [26, 40] years (range 19-91 years). Patients had generally ingested alcohol for recreational motives (653, 82.1%) while 3.1% (n = 25) had consumed alcohol-based hand sanitizers to prevent or cure COVID-19 infection. Age was significantly lower in survivors than in non-survivors (P < 0.001) and in patients without sequelae vs. with sequelae (P = 0.026). Twenty non-survivors presented with a Glasgow Coma Scale (GCS) score > 8, six of whom were completely alert on presentation to the emergency departments. The time from alcohol ingestion to hospital admission was not significantly different between provinces. In East Azerbaijan province, where hemodialysis was started within on average 60 min of admission, the rate of sequelae was 11.4% (compared to 19.6% average of other provinces)-equivalent to a reduction of the odds of sequelae by 2.1 times [95% CI 1.2, 3.7; p = 0.009]. Older patients were more prone to fatal outcome and sequelae, including visual disturbances. Early arrival at the hospital can facilitate timely diagnosis and treatment and may reduce long-term morbidity from methanol poisoning. Our data thus suggest the importance of raising public awareness of the risks and early symptoms of methanol intoxication.
Subject(s)
Alcoholism , COVID-19 , Poisoning , Adult , Alcoholism/epidemiology , COVID-19/epidemiology , Cross-Sectional Studies , Hospitalization , Hospitals , Humans , Iran/epidemiology , Methanol , PandemicsABSTRACT
OBJECTIVE: Using a battery of preclinical tests to support development of a light-based treatment for COVID-19, establish a range of 425 nm light doses that are non-hazardous to the tissues of the oral cavity and assess whether a 425 nm light dose in this non-hazardous range can inactivate SARS-CoV-2 in artificial saliva. METHODS: The potential hazards to oral tissues associated with a range of acute 425 nm light doses were assessed using a battery of four preclinical tests: (1) cytotoxicity, using well-differentiated human large airway and buccal epithelial models; (2) toxicity to commensal oral bacteria, using a panel of model organisms; (3) light-induced histopathological changes, using ex vivo porcine esophageal tissue, and (4) thermal damage, by dosing the oropharynx of intact porcine head specimens. Then, 425 nm light doses established as non-hazardous using these tests were evaluated for their potential to inactivate SARS-CoV-2 in artificial saliva. RESULTS: A dose range was established at which 425 nm light is not cytotoxic in well-differentiated human large airway or buccal epithelial models, is not cytotoxic to a panel of commensal oral bacteria, does not induce histopathological damage in ex vivo porcine esophageal tissue, and does not induce thermal damage to the oropharynx of intact porcine head specimens. Using these tests, no hazards were observed for 425 nm light doses less than 63 J/cm2 delivered at irradiance less than 200 mW/cm2. A non-hazardous 425 nm light dose in this range (30 J/cm2 at 50 mW/cm2) was shown to inactivate SARS-CoV-2 in vitro in artificial saliva. CONCLUSION: Preclinical hazard assessments and SARS-CoV-2 inactivation efficacy testing were combined to guide the development of a 425 nm light-based treatment for COVID-19. CLINICAL SIGNIFICANCE: The process used here to evaluate the potential hazards associated with 425 nm acute light dosing of the oral cavity to treat COVID-19 can be extended to other wavelengths, anatomical targets, and therapeutic applications to accelerate the development of novel photomedicine treatments.
Subject(s)
COVID-19 , SARS-CoV-2 , Animals , Humans , Mouth , Oropharynx , Saliva , Saliva, Artificial , SwineABSTRACT
The COVID-19 outbreak affected mental health globally. One of the major concerns following the COVID-19 pandemic was increased incidence of risky behaviors including alcohol consumption. This study evaluates the trend of alcohol poisoning in Loghman-Hakim Hospital (LHH), the main referral center of poisoning in Tehran, during the 2-year period from 1 year prior to 1 year after the onset (February 23rd, 2020) of the COVID-19 epidemic in Iran. All patients admitted with alcohol intoxication from February 23rd, 2019 to February 22nd, 2021 were evaluated and patient data extracted from LHH electronic hospital records. Alcohols were categorized as toxic (methyl alcohol) and non-toxic (ethyl alcohol). Of 2483 patients admitted, 796/14,493 (5.49%) and 1687/13,883 (12.15%) had been hospitalized before and after the onset of the COVID-19 epidemic in Iran, respectively. In total, 140 patients did not survive, of whom 131 (93.6%) were confirmed to have methanol intoxication. Mortality was significantly higher during the outbreak (127 vs 13; P < 0.001; OR: 4.90; CI 95%: 2.75 to 8.73). Among the patients, 503 were younger than age 20. Trend of alcohol intoxication showed increases in children (57 vs 17) and adolescents (246 vs 183) when compared before and after the COVID-19 epidemic outbreak. A total of 955 patients were diagnosed with methanol toxicity which occurred more frequently during the COVID-19 era (877 vs 78; P < 0.001; OR: 10.00; CI 95%: 7.75 to12.82). Interrupted time series analysis (April 2016-February 2021) showed that in the first month of the COVID-19 epidemic (March 2020), there was a significant increase in the alcohol intoxication rate by 13.76% (P < 0.02, CI = [2.42-24.91]). The trend of alcohol intoxication as well as resulting mortality increased in all age groups during the COVID-19 epidemic in Iran, indicating urgent need for the prevention of high-risk alcohol use as well as improved treatment.
Subject(s)
Alcoholic Intoxication , COVID-19 , Adolescent , Adult , Alcoholic Intoxication/epidemiology , COVID-19/epidemiology , Child , Hospitals , Humans , Interrupted Time Series Analysis , Iran/epidemiology , Methanol , Pandemics , SARS-CoV-2 , Young AdultABSTRACT
Hospital-treated intentional self-poisoning is common. The possibility of changed (increased) suicidal behaviors during the COVID-19 pandemic has been raised. To compare frequencies in self-poisoning events (SPEs) and the proportions with in-hospital mortality, in the year prior to and following the official onset of the COVID-19 pandemic, in a population of hospital-treated self-poisoning patients in Iran. All self-poisoned patients admitted to Loghman-Hakim Hospital, a clinical toxicology specialty hospital in Tehran, were included. The frequency of SPEs was compared between the one-year periods immediately before and after the onset of COVID-19 pandemic using Poisson regression. Differences in proportions of in-hospital mortality were also compared using logistic regression. A total of 14,478 patients with 15,391 SPEs (8,863 [61.2%] females) were evaluated in the study. There was no difference in the overall frequency of SPEs (relative risk [RR] of 0.99 [CI95% 0.96-1.03]), but a small increase in males (RR 1.07; 1.02-1.13) and a minor decrease in females (RR 0.95; 0.91-0.99). In total, 330 patients died (2.3% of all SPEs). There was no difference in overall in-hospital mortality odds ratio (OR: 0.98 [0.79-1.22]), in females (OR = 1.14 [0.80-1.60]) or males (OR = 0.92 [0.69-1.23]). There was no change in the frequency of SPEs and no difference in the in-hospital mortality proportions, suggesting that the COVID-19 pandemic had little or no effect on these aspects of suicidal behavior in Iran. Supplementary Information: The online version contains supplementary material available at 10.1007/s12144-022-03248-y.