Perceived stigma related to TB preventive therapy.

BACKGROUND: TB preventative therapy (TPT) is crucial for reducing the burden of TB in endemic settings. We assessed stigma associated with TPT and the social groups from whom stigma was anticipated.METHODS: We conducted an anonymous cross-sectional survey of community-dwelling adults in rural South Africa. Descriptive statistics, exploratory factor analysis, χ² tests, Kruskal-Wallis tests, and Poisson regression were used to identify factors associated with TPT stigma.RESULTS: The mean age of the 104 participants was 35 years, 65% were female, and 26% had completed secondary school. The vast majority perceived stigma associated with TPT (71%; mean score 1.7, SD ± 1.4). Factor analysis identified a two-factor solution that explained 61.9% of the variance. Being single (P < 0.001), previously screened for TB (P = 0.04), worried about being infected by TB (P = 0.006), and interested in taking TPT (P = 0.01) were associated with higher perceived stigma scores. TPT stigma was perceived among 8%, 16%, and 66% of their family, friends, and other community members, respectively.CONCLUSION: The prevalence of TPT-related stigma in a rural South African community was high. Community members anticipated less stigma from family members compared to other social groups. Global expansion and implementation of TPT will require novel interventions, such as engaging patients´ families to support uptake and promote adherence.

Range-wide sources of variation in reproductive rates of northern spotted owls.

We conducted a range-wide investigation of the dynamics of site-level reproductive rate of northern spotted owls using survey data from 11 study areas across the subspecies geographic range collected during 1993-2018. Our analytical approach accounted for imperfect detection of owl pairs and misclassification of successful reproduction (i.e., at least one young fledged) and contributed further insights into northern spotted owl population ecology and dynamics. Both nondetection and state misclassification were important, especially because factors affecting these sources of error also affected focal ecological parameters. Annual probabilities of site occupancy were greatest at sites with successful reproduction in the previous year and lowest for sites not occupied by a pair in the previous year. Site-specific occupancy transition probabilities declined over time and were negatively affected by barred owl presence. Overall, the site-specific probability of successful reproduction showed substantial year-to-year fluctuations and was similar for occupied sites that did or did not experience successful reproduction the previous year. Site-specific probabilities for successful reproduction were very small for sites that were unoccupied the previous year. Barred owl presence negatively affected the probability of successful reproduction by northern spotted owls in Washington and California, as predicted, but the effect in Oregon was mixed. The proportions of sites occupied by northern spotted owl pairs showed steep, near-monotonic declines over the study period, with all study areas showing the lowest observed levels of occupancy to date. If trends continue it is likely that northern spotted owls will become extirpated throughout large portions of their range in the coming decades.

Establishment of local wastewater-based surveillance programmes in response to the spread and infection of COVID-19 - case studies from South Africa, the Netherlands, Turkey and England.

The COVID-19 pandemic has resulted in over 340 million infection cases (as of 21 January 2022) and more than 5.57 million deaths globally. In reaction, science, technology and innovation communities across the globe have organised themselves to contribute to national responses to COVID-19 disease. A significant contribution has been from the establishment of wastewater-based epidemiological (WBE) surveillance interventions and programmes for monitoring the spread of COVID-19 in at least 55 countries. Here, we examine and share experiences and lessons learnt in establishing such surveillance programmes. We use case studies to highlight testing methods and logistics considerations associated in scaling the implementing of such programmes in South Africa, the Netherlands, Turkey and England. The four countries were selected to represent different regions of the world and the perspective based on the considerable progress made in establishing and implementing their national WBE programmes. The selected countries also represent different climatic zones, economies, and development stages, which influence the implementation of national programmes of this nature and magnitude. In addition, the four countries' programmes offer good experiences and lessons learnt since they are systematic, and cover extensive areas, disseminate knowledge locally and internationally and partnered with authorities (government). The programmes also strengthened working relations and partnerships between and among local and global organisations. This paper shares these experiences and lessons to encourage others in the water and public health sectors on the benefits and value of WBE in tackling SARS-CoV-2 and related future circumstances.

Phenotypic and genotypic analysis of benzimidazole resistance in reciprocal genetic crosses of Haemonchus contortus.

Haemonchus contortus is arguably one of the most economically important and ubiquitous parasites of livestock globally and commonly involved in cases of anthelmintic resistance. Here, we performed reciprocal genetic crosses using susceptible (MHco3(ISE)) and multiple anthelmintic resistant (MHco18(UGA2004)) H. contortus isolates. Resultant admixed populations were designated MHco3/18 or MHco18/3, where the lead isolate reflects the origin of the females. Three independent filial generations were generated for each cross, which were subjected to bioassays, molecular approaches and population genetic analyses to investigate the phenotypic and genotypic inheritance of benzimidazole (BZ) resistance at each stage. A panel of microsatellite markers confirmed the success of the genetic cross as markers from both parents were seen in the F1 crosses. Egg hatch tests revealed a stark difference between the two F1 crosses with ED50 estimates for MHco18/3 being 9 times greater than those for MHco3/18. Resistance factors based on ED50 estimates ranged from 6 to 57 fold in the filial progeny compared to MHco3(ISE) parents. Molecular analysis of the F167Y and F200Y SNP markers associated with BZ resistance were analysed by pyrosequencing and MiSeq deep amplicon sequencing, which showed that MHco3/18.F1 and MHco18/3.F1 both had similar frequencies of the F200Y resistant allele (45.3% and 44.3%, respectively), whereas for F167Y, MHco18/3.F1 had a two-fold greater frequency of the resistant-allele compared to MHco3/18.F1 (18.2% and 8.8%, respectively). Comparison between pyrosequencing and MiSeq amplicon sequencing revealed that the allele frequencies derived from both methods were concordant at codon 200 (rc = 0.97), but were less comparable for codon 167 (rc = 0.55). The use of controlled reciprocal genetic crosses have revealed a potential difference in BZ resistance phenotype dependent on whether the resistant allele is paternally or maternally inherited. These findings provide new insight and prompt further investigation into the inheritance of BZ resistance in H. contortus.

Conspecific and congeneric interactions shape increasing rates of breeding dispersal of northern spotted owls.

Breeding dispersal, the movement from one breeding territory to another, is rare for philopatric species that evolved within relatively stable environments, such as the old-growth coniferous forests of the Pacific Northwest. Although dispersal is not inherently maladaptive, the consequences of increased dispersal on population dynamics in populations whose historical dispersal rates are low could be significant, particularly for a declining species. We examined rates and possible causes of breeding dispersal based on a sample of 4,118 northern spotted owls (Strix occidentalis caurina) monitored in seven study areas over 28 yr, 1990-2017, in Oregon and Washington, USA. Using a multistate mark-resight analysis, we investigated the potential impacts of an emergent congeneric competitor (barred owl Strix varia) and forest alteration (extrinsic factors), and social and individual conditions (intrinsic factors) on 408 successive and 1,372 nonsuccessive dispersal events between years. The annual probability of breeding dispersal increased for individual owls that had also dispersed in the previous year and decreased for owls on territories with historically high levels of reproduction. Intrinsic factors including pair status, prior reproductive success, and experience at a site, were also associated with breeding dispersal movements. The percent of monitored owls dispersing each year increased from ˜7% early in the study to ˜25% at the end of the study, which coincided with a rapid increase in numbers of invasive and competitively dominant barred owls. We suggest that the results presented here can inform spotted owl conservation efforts as we identify factors contributing to changing rates of demographic parameters including site fidelity and breeding dispersal. Our study further shows that increasing rates of breeding dispersal associated with population declines contribute to population instability and vulnerability of northern spotted owls to extinction, and the prognosis is unlikely to change unless active management interventions are undertaken.

Precision worm control in grazing lambs by targeting group treatment based on performance of sentinels.

Given the economic impact of gastrointestinal nematode infection on livestock farming worldwide, and increasing anthelmintic resistance, it is imperative to develop practical, efficient and sustainable control strategies. Targeted selective treatment (TST), whereby anthelmintic treatments are administered to animals individually, based on selection criteria such as weight gain, has been shown to successfully maintain animal productivity whilst reducing the selection pressure for anthelmintic resistance and the economic cost of treatment in experimental and commercial settings. Despite the benefits of the TST approach, the equipment and time required to monitor animals individually make this strategy unsuitable for some farming enterprises. The sentinel group approach aims to maintain the benefits observed using TST whilst reducing these requirements. The study involved two experiments, each following a group of 80 lambs through their first grazing season. Anthelmintic treatment of the whole group was determined by monitoring the weight gain of identified sentinel lambs within it every 2 weeks: when 40% of the sentinel lambs failed to reach their weight gain targets, the whole group was treated. The sentinel lambs consisted of 45% of the group (n = 36) in experiment one and 20% (n = 16) in experiment two. A control group of 20 lambs was co-grazed with the main group during both experiments; in experiment one, the sentinel approach was compared with a TST approach, in which control lambs were treated on an individual basis in response to weight gain. In experiment two, the sentinel approach was compared with conventional prophylaxis, where all lambs in the control group were treated at strategic time points throughout the season (= strategic prophylactic treatment). The sentinel lambs were found to be representative of overall group performance regardless of the proportion of sentinels within the group: they recorded similar growth rates and reached weight gain targets simultaneously at each time point and overall. Live-weight gain was also similar between sentinel and control animals in both experiments. The findings of the current study suggest that monitoring sentinel lambs comprising 20% of a group of grazing lambs is sufficient to determine the need for anthelmintic treatment within the whole group, and that this approach maintains production in line with conventional or TST treatment regimes.

Necrotizing enterocolitis and its association with the neonatal abstinence syndrome.

OBJECTIVE: The purpose of this study was to describe an identified association between necrotizing enterocolitis (NEC) and prenatal opioid exposure with neonatal abstinence syndrome (NAS) in late preterm and full-term neonates. STUDY DESIGN: In this single-center retrospective cohort study, we analyzed inborn neonates with the diagnosis of NEC discharged from 2012 through 2017. We compared infants with NEC > 35 weeks' gestation to those with NEC<35 weeks' gestation. We compared gestational age, birth weight, age of onset of symptoms, and incidence of prenatal drug exposure between groups. Significance was determined using Mann-Whitney and Fisher's exact tests. RESULTS: Over the study period, 23 infants were identified with NEC, 9 (39%) were babies > 35 weeks at birth and 14 (61%) < 35 weeks. Those > 35 weeks had a higher birth weight, earlier onset of symptoms, and a higher percentage of prenatal exposure to opioids compared to those < 35 weeks' gestation. We further described seven infants with late gestational age onset NEC associated with prenatal opioid exposure. CONCLUSIONS: In this cohort of infants with NEC discharged over a 6 year period we found a higher than expected percentage of infants born at a later gestational age. We speculate that prenatal opioid exposure might be a risk factor for NEC in neonates born at > 35 weeks.

Design errors in vital sign charts used in consultant-led maternity units in the United Kingdom.

BACKGROUND: Paper-based charts remain the principal means of documenting the vital signs of hospitalised pregnant and postnatal women. However, poor chart design may contribute to both incorrect charting of data and clinical responses. We decided to identify design faults that might have an adverse clinical impact. METHODS: One hundred and twenty obstetric early warning charts and escalation protocols from consultant-led maternity units in the United Kingdom and the Channel Islands were analysed using an objective and systematic approach. We identified design errors that might impede their successful use (e.g. generate confusion regarding vital sign documentation, hamper the recognition of maternal deterioration, cause a failure of the early warning system or of any clinical response). RESULTS: We found 30% (n=36/120) of charts contained at least one design error with the potential to confuse staff, render the charts difficult to use or compromise patient safety. Amongst the most common areas were inadequate patient identification, poor use of colour, illogical weighting, poor alignment and labelling of axes, and the opportunity for staff to 'game' the escalation. CONCLUSIONS: We recommend the urgent development of an evidence-based, standardised obstetric observation chart, which integrates 'human factors' and user experience. It should have a clear layout and style, appropriate colour scheme, correct language and labelling, and the ability for vital signs to be documented accurately and quickly. It should incorporate a suitable early warning score to guide clinical management.

Massive hemorrhage protocol activation in obstetrics: a 5-year quality performance review.

BACKGROUND: A structured approach to hemorrhagic emergencies in obstetrics has gained popularity with the implementation of massive hemorrhage protocols. The trauma literature suggests that routine quality reviews should be in place to improve patient outcomes. The aim of this study was to develop quality indicators and assess compliance by the clinical team. METHODS: A multidisciplinary team set the institutional quality indicators for the massive hemorrhage protocol review. A retrospective review of all obstetrical massive hemorrhage protocol activation events from September 2010 to January 2015 was performed. All protocol events occurred before the creation of the quality indicators. Data were retrieved from patient records. RESULTS: There were 17 (0.09%) protocol activations for 19 790 deliveries during the study period. All 17 (100%) patients received at least one unit of red blood cells. Overactivation, defined as the transfusion of <2 units of red blood cells, occurred in two cases (12%). Common causes of non-compliance were: 24% (4/17) temperature monitoring, 18% (3/17) lactate measurement, 41% (7/17) arterial blood gas sampling, and 18% (3/17) hemoglobin maintenance within the target range of 55-95 g/L. Admission to intensive care and peripartum hysterectomy occurred in 12 and 5 cases (71% and 29%), respectively. CONCLUSIONS: Suboptimal compliance was found in multiple areas, which may be attributable to the low frequency of activation of our massive haemorrhage protocol in obstetrics. The quality targets identified in this report can act as a basis for other institutions developing quality indicators to evaluate performance.

A population pharmacokinetic model to predict the individual starting dose of tacrolimus in adult renal transplant recipients.

AIMS: The aims of this study were to describe the pharmacokinetics of tacrolimus immediately after kidney transplantation, and to develop a clinical tool for selecting the best starting dose for each patient. METHODS: Data on tacrolimus exposure were collected for the first 3 months following renal transplantation. A population pharmacokinetic analysis was conducted using nonlinear mixed-effects modelling. Demographic, clinical and genetic parameters were evaluated as covariates. RESULTS: A total of 4527 tacrolimus blood samples collected from 337 kidney transplant recipients were available. Data were best described using a two-compartment model. The mean absorption rate was 3.6 h-1 , clearance was 23.0 l h-1 (39% interindividual variability, IIV), central volume of distribution was 692 l (49% IIV) and the peripheral volume of distribution 5340 l (53% IIV). Interoccasion variability was added to clearance (14%). Higher body surface area (BSA), lower serum creatinine, younger age, higher albumin and lower haematocrit levels were identified as covariates enhancing tacrolimus clearance. Cytochrome P450 (CYP) 3A5 expressers had a significantly higher tacrolimus clearance (160%), whereas CYP3A4*22 carriers had a significantly lower clearance (80%). From these significant covariates, age, BSA, CYP3A4 and CYP3A5 genotype were incorporated in a second model to individualize the tacrolimus starting dose: [Formula: see text] Both models were successfully internally and externally validated. A clinical trial was simulated to demonstrate the added value of the starting dose model. CONCLUSIONS: For a good prediction of tacrolimus pharmacokinetics, age, BSA, CYP3A4 and CYP3A5 genotype are important covariates. These covariates explained 30% of the variability in CL/F. The model proved effective in calculating the optimal tacrolimus dose based on these parameters and can be used to individualize the tacrolimus dose in the early period after transplantation.

Personalized immunosuppression in elderly renal transplant recipients.

The number of elderly people has increased considerably over the last decades, due to a rising life expectancy and ageing populations. As a result, an increased number of elderly with end-stage-renal-disease are diagnosed, for which the preferred treatment is renal transplantation. Over the past years the awareness of the elderly as a specific patient population has grown, which increases the importance of research in this group. Elderly patients often receive kidneys from elderly donors while younger donor kidneys are preferentially reserved for younger recipients. Although the rate of acute rejection after transplantation is lower in the elderly, these rejections may lead to graft loss more frequently, as kidneys from elderly donors have marginal reserve capacity. To prevent acute rejection, immunosuppressive therapy is needed. On the other hand, elderly patients have a higher risk to die from infectious complications, and thus less immunosuppression would be preferable. Immunosuppressive treatment in the elderly is complicated further by changes in the pharmacokinetics and pharmacodynamics, with increasing age. Adjustments in standard immunosuppressive regimes are therefore suggested for this population. An unmet need in transplantation medicine is a tool to guide a personalized approach to immunosuppression. Recently several promising biomarkers that identify injury to the graft at an early stage or predict acute rejection have been identified. Unfortunately, none of these biomarkers were tested specifically in the elderly. We believe there is an urgent need to perform clinical trials investigating novel immunosuppressive regimens in conjunction with biomarker studies in this specific population.

Vital signs and other observations used to detect deterioration in pregnant women: an analysis of vital sign charts in consultant-led UK maternity units.

BACKGROUND: Obstetric early warning systems are recommended for monitoring hospitalised pregnant and postnatal women. We decided to compare: (i) vital sign values used to define physiological normality; (ii) symptoms and signs used to escalate care; (iii) type of chart used; and (iv) presence of explicit instructions for escalating care. METHODS: One-hundred-and-twenty obstetric early warning charts and escalation protocols were obtained from consultant-led maternity units in the UK and Channel Islands. These data were extracted: values used to determine normality for each maternal vital sign; chart colour-coding; instructions following early warning system triggering; other criteria used as triggers. RESULTS: There was considerable variation in the charts, warning systems and escalation protocols. Of 120 charts, 89.2% used colour; 69.2% used colour-coded escalation systems. Forty-one (34.2%) systems required the calculation of weighted scores. Seventy-five discrete combinations of 'normal' vital sign ranges were found, the most common being: heart rate=50-99beats/min; respiratory rate=11-20breaths/min; blood pressure, systolic=100-149mmHg, diastolic ≤89mmHg; SpO2=95-100%; temperature=36.0-37.9°C; and Alert-Voice-Pain-Unresponsive assessment=Alert. Most charts (90.8%) provided instructions about who to contact following triggering, but only 41.7% gave instructions about subsequent observation frequency. CONCLUSION: The wide range of 'normal' vital sign values in different systems suggests a lack of equity in the processes for detecting deterioration and escalating care in hospitalised pregnant and postnatal women. Agreement regarding 'normal' vital sign ranges is urgently required and would assist the development of a standardised obstetric early warning system and chart.

Pharmacogenetic aspects of the use of tacrolimus in renal transplantation: recent developments and ethnic considerations.

INTRODUCTION: Tacrolimus (Tac) is effective in preventing acute rejection but has considerable toxicity and inter-individual variability in pharmacokinetics and pharmacodynamics. Part of this is explained by polymorphisms in genes encoding Tac-metabolizing enzymes and transporters. A better understanding of Tac pharmacokinetics and pharmacodynamics may help to minimize different outcomes amongst transplant recipients by personalizing immunosuppression. AREAS COVERED: The pharmacogenetic contribution of Tac metabolism will be examined, with a focus on recent discoveries, new developments and ethnic considerations. EXPERT OPINION: The strongest and most consistent association in pharmacogenetics is between the CYP3A5 genotype and Tac dose requirement, with CYP3A5 expressers having a ~ 40-50% higher dose requirement compared to non-expressers. Two recent randomized-controlled clinical trials using CYP3A5 genotype, however, did not show a decrease in acute rejections nor reduced toxicity. CYP3A4*22, CYP3A4*26, and POR*28 are also associated with Tac dose requirements and may be included to provide the expected improvement of Tac therapy. Studies focusing on the intracellular drug concentrations and on calcineurin inhibitor-induced nephrotoxicity also seem promising. For all studies, however, the ethnic prevalence of genotypes should be taken into account, as this may significantly impact the effect of pre-emptive genotyping.

A snapshot of biologic drug development: Challenges and opportunities.

Since the approval of insulin as the first recombinant therapeutic protein, the prominence of biologic therapies in drug development has grown significantly. Many modalities beyond traditional biologics are now being developed or explored for various indications with significant unmet medical needs. From early traditional replacement proteins to more recent, highly engineered antibodies, oligonucleotides, fusion proteins, and gene constructs, biologic agents have delivered life-changing therapies, despite often having scientifically and technically challenging development programs. This brief review outlines some of the major biotherapeutic classes and identifies the advantages and challenges with the development of these products.

Multiple, synchronous, unilateral parotid adenomas: a case series.

Most tumours of the major salivary glands are single and unilateral, and involve the parotid. It is uncommon for synchronous, multifocal tumours of the same histological type to affect one gland, and cases with multiple types are rare. Extracapsular dissection, an established technique for the safe removal of benign tumours of the parotid gland, has low rates of morbidity and recurrence, but relies on careful preoperative assessment and selection of cases. In a consecutive series of 70 cases of extracapsular dissection over 5 years by one surgeon, we found a 4% incidence (n=3) of synchronous, unilateral, multiple adenomas in the parotid gland.

Prevalence rates and risk factors for mental health difficulties in adolescents aged 16 and 17 years living in rural Ireland.

OBJECTIVE: This study sought to ascertain the prevalence rates and risk factors for a range of mental health difficulties, including suicidal ideation/self-harm among 16 and 17-year-old rural Irish adolescents, a vulnerable group in transition from childhood to adulthood. METHOD: Adolescents (n=237) took part in this cross-sectional study. Participants completed a questionnaire compendium consisting of generic questions on demographic information, use of mental health services and four normed questionnaires: The Youth Self-Report, the Children's Depression Inventory, the Coping Inventory for Stressful Situations-Adolescent and The Family Assessment Device. RESULTS: We found that 16.9% of adolescents reported clinically significant mental health difficulties. Significant gender differences were found on internalising and externalising difficulties. There were no gender differences in suicidal ideation or self-harm. Only 3.4% of adolescents were receiving professional help for mental health difficulties. Multiple regression analyses revealed that family dysfunction, emotion-focussed coping and poor academic competence were significant predictors of poorer mental health difficulties in both genders. Family dysfunction was the strongest predictor of mental health difficulties in males. Among females, emotion-focussed coping was the strongest predictor of internalising difficulties and depression. Social diversion (social support) was predictive of less internalising difficulties and depression for females. CONCLUSION: The study shows that a significant number of Irish 16 and 17 year olds have mental health difficulties, yet very few are receiving treatment. Emotion-focussed coping, family dysfunction, poor academic competence and less social support were important predictors of mental health difficulties. A new finding is the stronger association that family dysfunction has with poorer mental health in males than females, when controlling for academic competence and coping skills. The findings may have implications for psychological interventions.

Implementation of a pharmacist-driven pain management consultation service for hospitalised adults with a history of substance abuse.

BACKGROUND: Pain management in adult patients with concomitant substance use disorders (SUDs) presents a clinical challenge in the absence of objective assessment criteria. Effective pain management is dependent on the clinician's ability to differentiate true pain symptoms from manipulative behaviours. Successful strategies for achieving effective pain control in these patients include implementing a multidisciplinary team approach, use of non-opioid and non-pharmacologic alternatives, and judicious use of opioid analgesics. OBJECTIVE: To describe the implementation of a pharmacist-driven pain management service for patients with concomitant SUDs. METHODS: In an urban teaching hospital located in Trenton, New Jersey, United States, a clinical pharmacist-led pain management service evolved to provide formal consultation. Standardised assessment and treatment approaches were developed to assure consistency. Multidisciplinary education was provided to the medical staff. MAIN OUTCOME MEASURE: The study describes a variety of patterns associated with the program from its pilot period through the first 6 years of service, including opioid utilisation, volume and source of consultations, and multidisciplinary perceptions regarding the program's impact. RESULTS: The establishment of a pharmacist-led pain management consult service successfully addressed patient's needs while modifying drug-seeking behaviours. A significant decrease in opioid usage was noted during the program's pilot period and sustained over time. The program's success has extended the pharmacist's role beyond the program's initial scope to address general pain management needs and to address educational needs of the medical staff. Today, clinical pharmacists are utilised most often for refractory cases for which the most appropriate method of pain management may not be clear.

Economic burden of gouty arthritis attacks for employees with frequent and infrequent attacks.

The objective of this study was to compare episode-related and annual costs and work absence days for employees with <3 versus ≥ 3 annual gout attacks. Human Capital Management Services data (2009-2010) from adult employees with gout (International Classification of Diseases, Ninth Revision code 274.x) and ≥ 12 months of medical and pharmacy benefits were studied. Outcomes of interest included medical and drug costs, number of emergency department and urgent care visits, number of inpatient days, short- and long-term disability, sick leave, workers' compensation costs, and work absence days. An algorithm based on diagnosis code and antigout medication use identified acute gout treatment episodes. Multivariate analysis compared annual and pre-episode vs. during-episode outcomes for employees with ≥ 3 vs. <3 gout annual attacks. Of 3361 employees with gout, 76 had ≥ 3 attacks; these employees had higher short-term disability costs ($1663 vs. $643, P=0.06) and days (11.68 versus 4.61, P<0.05), more emergency room visits (0.55 vs. 0.23, P<0.0001), and urgent care visits (0.07 vs. 0.04, P<0.01), and lower pharmacy costs ($1677 vs. $1108, P<0.0001) than those with <3 attacks. Medical costs both before ($203 higher) and during attacks ($136 higher) were significantly higher for those with ≥ 3 attacks than for those with <3 attacks. Additionally, a quadratic increasing relationship was found between number of attacks and cost. Frequency of acute gout attacks (≥ 3 episodes per year) among employees with gout was associated with greater short-term disability cost, absence days, and emergency department and urgent care visits, and trends toward higher overall costs.

Life-threatening complications of ibogaine: three case reports.

Ibogaine is a naturally occurring psychoactive alkaloid extracted from the roots of the Tabernanthe iboga plant, which in alternative medicine is used to treat drug dependency. However, this upcoming, online advocated therapy can be dangerous due to its potentially lethal adverse effects. We present three cases in which toxic side effects were noted. We used the Naranjo scale to estimate the probability of a causal relationship between these effects and ibogaine. Findings in these three cases are suggestive of a causal relationship between the use of ibogaine and serious respiratory and cardiac problems (including lengthening of the QT interval). In our opinion it is of great importance that clinicians are aware of these potentially serious side effects and realise that widespread online marketing practices will give many more people access to ibogaine.