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Methadone, a long-acting opioid agonist commonly used in the treatment of opiate dependence, has been reported to cause QTc interval prolongation, increasing the risk of a fatal cardiac arrhythmia – Torsades-de-Pointes (TdP). This effect seems to be attributable to methadone's inhibitory effect on the cardiac “hERG”-K+ ion channel and is dose-dependent. There is a lack of consensus regarding when to perform an ECG for patients on methadone.
Identifying other TdPPRFs in a cohort of patients receiving ≥ 85 mg (high dose) methadone daily to inform local clinical safety guidelines.
Our outpatient caseload was filtered to select opiate-dependent patients receiving more than 85 mg methadone daily. Primary care summaries and laboratory results databases were analysed for the presence of other TdPPRFs: female sex a documented history of ECG abnormalities, electrolyte imbalance, liver or renal failure, and concomitant use of other QT prolonging medication or stimulants.
Fourteen opiate-dependent patients (10.29% of patients on methadone) were maintained on ≥ 85 mg methadone daily. Gender distribution was F:M = 1:1.8; 64% misused illicit stimulants; 57% were prescribed other QTc prolonging medication and 29% had a documented history of liver/renal failure or electrolyte imbalance. Only 14% had previous ECGs documented in primary care summaries. Of patients on high dose methadone, 85.7% had at least one TdPPRFs present and 64.3% had at least two.
These results demonstrate an increased rate of TdPPRFs in this patient group and highlight the importance of ECG monitoring which ideally should be offered to patients receiving even lower doses of methadone.
Disclosure of interest
The authors have not supplied their declaration of competing interest.
Global inequity in access to and availability of essential mental health services is well recognized. The mental health treatment gap is approximately 50% in all countries, with up to 90% of people in the lowest-income countries lacking access to required mental health services. Increased investment in global mental health (GMH) has increased innovation in mental health service delivery in LMICs. Situational analyses in areas where mental health services and systems are poorly developed and resourced are essential when planning for research and implementation, however, little guidance is available to inform methodological approaches to conducting these types of studies. This scoping review provides an analysis of methodological approaches to situational analysis in GMH, including an assessment of the extent to which situational analyses include equity in study designs. It is intended as a resource that identifies current gaps and areas for future development in GMH. Formative research, including situational analysis, is an essential first step in conducting robust implementation research, an essential area of study in GMH that will help to promote improved availability of, access to and reach of mental health services for people living with mental illness in low- and middle-income countries (LMICs). While strong leadership in this field exists, there remain significant opportunities for enhanced research representing different LMICs and regions.
The appeal of ketamine – in promptly ameliorating depressive symptoms even in those with non-response – has led to a dramatic increase in its off-label use. Initial promising results await robust corroboration and key questions remain, particularly concerning its long-term administration. It is, therefore, timely to review the opinions of mood disorder experts worldwide pertaining to ketamine's potential as an option for treating depression and provide a synthesis of perspectives – derived from evidence and clinical experience – and to consider strategies for future investigations.
Heightened reactivity to unpredictable threat (U-threat) is a core individual difference factor underlying fear-based psychopathology. Little is known, however, about whether reactivity to U-threat is a stable marker of fear-based psychopathology or if it is malleable to treatment. The aim of the current study was to address this question by examining differences in reactivity to U-threat within patients before and after 12-weeks of selective serotonin reuptake inhibitors (SSRIs) or cognitive-behavioral therapy (CBT).
Participants included patients with principal fear (n = 22) and distress/misery disorders (n = 29), and a group of healthy controls (n = 21) assessed 12-weeks apart. A well-validated threat-of-shock task was used to probe reactivity to predictable (P-) and U-threat and startle eyeblink magnitude was recorded as an index of defensive responding.
Across both assessments, individuals with fear-based disorders displayed greater startle magnitude to U-threat relative to healthy controls and distress/misery patients (who did not differ). From pre- to post-treatment, startle magnitude during U-threat decreased only within the fear patients who received CBT. Moreover, within fear patients, the magnitude of decline in startle to U-threat correlated with the magnitude of decline in fear symptoms. For the healthy controls, startle to U-threat across the two time points was highly reliable and stable.
Together, these results indicate that startle to U-threat characterizes fear disorder patients and is malleable to treatment with CBT but not SSRIs within fear patients. Startle to U-threat may therefore reflect an objective, psychophysiological indicator of fear disorder status and CBT treatment response.
The literature suggests that grain number largely determines and as such limits yield in barley. Many of the reported studies were conducted in relatively low-yielding environments and it is unclear if grain number is also a limiting factor in high-yield potential climates. Nor is it known with certainty what physiological or morphological traits must be targeted in order to increase grain number. A detailed programme of assessments was carried out on replicated field plots of a two-row spring barley variety (Hordeum vulgare L. cvar Quench) at three sites (Carlow, Wexford and Cork) in Ireland from 2011 to 2013. Plots were managed for high yield potential as per current best farm practice. Destructive sampling and in-field assessments were carried out at approximately weekly intervals from emergence onwards to gather growth, development and yield component data. Across nine site/seasons, grand means of 8·52 t/ha for yield, 18 419 for grain number/m2 and 46·41 mg for mean grain weight were achieved. Grain number/m2 accounted for most of the variation in yield and ear number/m2 accounted for most of the variation in grain number/m2. Early-season maximum shoot number/m2 had little influence on harvest ear number/m2. The period over which final ear number was determined was more flexible than the literature suggests, where the phases of tiller production and senescence varied considerably. Significant post-anthesis re-tillering occurred following the initial phase of shoot mortality at two out of nine site/seasons, but this appeared to contribute little to yield. Yield was positively associated with the proportion of shoots surviving from an early season maximum to a mid-season minimum (R2 = 0·62). Shoot size and weight at the beginning of stem extension had the largest influence on shoot survival, indicating that crop condition and hence growth and development pre-stem extension may be more important for shoot survival than growth and development during the stem extension period. Achieving high shoot numbers of adequate size and weight at the beginning of stem extension may be an appropriate target for establishing a high-yield potential crop.
Cognitive dysfunction is common in major depressive disorder (MDD) and a critical determinant of health outcome. Anhedonia is a criterion item toward the diagnosis of a major depressive episode (MDE) and a well-characterized domain in MDD. We sought to determine the extent to which variability in self-reported cognitive function correlates with anhedonia.
A post hoc analysis was conducted using data from (N=369) participants with a Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision (DSM-IV-TR)-defined diagnosis of MDD who were enrolled in the International Mood Disorders Collaborative Project (IMDCP) between January 2008 and July 2013. The IMDCP is a collaborative research platform at the Mood Disorders Psychopharmacology Unit, University of Toronto, Toronto, Canada, and the Cleveland Clinic, Cleveland, Ohio. Measures of cognitive function, anhedonia, and depression severity were analyzed using linear regression equations.
A total of 369 adults with DSM-IV-TR–defined MDD were included in this analysis. Self-rated cognitive impairment [ie, as measured by the Adult ADHD Self-Report Scale (ASRS)] was significantly correlated with a proxy measure of anhedonia (r=0.131, p=0.012). Moreover, total depression symptom severity, as measured by the total Montgomery–Åsberg Depression Rating Scale (MADRS) score, was also significantly correlated with self-rated measures of cognitive dysfunction (r=0.147, p=0.005). The association between anhedonia and self-rated cognitive dysfunction remained significant after adjusting for illness severity (r=0.162, p=0.007).
These preliminary results provide empirical data for the testable hypothesis that anhedonia and self-reported cognitive function in MDD are correlated yet dissociable domains. The foregoing observation supports the hypothesis of overlapping yet discrete neurobiological substrates for these domains.
This work considers debris disks whose spectra can be modelled by dust emission at two different temperatures. These disks are typically assumed to be a sign of multiple belts, but only a few cases have been confirmed via high resolution observations. We derive the properties of a sample of two-temperature disks, and explore whether this emission can arise from dust in a single narrow belt. While some two-temperature disks arise from single belts, it is probable that most have multiple spatial components. These disks are plausibly similar to the outer Solar System's configuration of Asteroid and Edgeworth-Kuiper belts separated by giant planets. Alternatively, the inner component could arise from inward scattering of material from the outer belt, again due to intervening planets. For either scenario, the ratio of warm/cool component temperatures is indicative of the scale of outer planetary systems, which typically span a factor of about ten in radius.
The gut microbiota has been implicated in obesity and its progression towards metabolic disease. Dietary interventions that target the gut microbiota have been suggested to improve metabolic health. The aim of the present study was to investigate the effect of interventions with Lactobacillus paracasei F19 or flaxseed mucilage on the gut microbiota and metabolic risk markers in obesity. A total of fifty-eight obese postmenopausal women were randomised to a single-blinded, parallel-group intervention of 6-week duration, with a daily intake of either L. paracasei F19 (9·4 × 1010 colony-forming units), flaxseed mucilage (10 g) or placebo. Quantitative metagenomic analysis of faecal DNA was performed to identify the changes in the gut microbiota. Diet-induced changes in metabolic markers were explored using adjusted linear regression models. The intake of flaxseed mucilage over 6 weeks led to a reduction in serum C-peptide and insulin release during an oral glucose tolerance test (P< 0·05) and improved insulin sensitivity measured by Matsuda index (P< 0·05). Comparison of gut microbiota composition at baseline and after 6 weeks of intervention with flaxseed mucilage showed alterations in abundance of thirty-three metagenomic species (P< 0·01), including decreased relative abundance of eight Faecalibacterium species. These changes in the microbiota could not explain the effect of flaxseed mucilage on insulin sensitivity. The intake of L. paracasei F19 did not modulate metabolic markers compared with placebo. In conclusion, flaxseed mucilage improves insulin sensitivity and alters the gut microbiota; however, the improvement in insulin sensitivity was not mediated by the observed changes in relative abundance of bacterial species.
Using photometry at just two wavelengths it is possible to fit a blackbody to the spectrum of infrared excess that is the signature of a debris disc. From this the location of the dust can be inferred. However, it is well known that dust in debris discs is not a perfect blackbody. By resolving debris discs we can find the actual location of the dust and compare this to that inferred from the blackbody fit. Using the Herschel Space Observatory we resolved many systems as part of the DEBRIS survey. Here we discuss a sample of 9 discs surrounding A stars and find that the discs are actually located between 1 and 2.5 times further from their star than predicted by blackbody fits to the spectral energy distribution (SED). The variation in this ratio is due to differences in stellar luminosities, location of the dust, size distribution and composition of the dust.
Hepatitis C virus is the most common chronic blood-borne infection in the USA. Based on results of a serosurvey, national prevalence is estimated to be 1·3% or 3·2 million people. Sub-national estimates are not available for most jurisdictions. Hepatitis C surveillance data was adjusted for death, out-migration, under-diagnosis, and undetectable blood RNA, to estimate prevalence in New York City (NYC). The prevalence of hepatitis C infection in adults aged ⩾20 years in NYC is 2·37% (range 1·53–4·90%) or 146 500 cases of hepatitis C. This analysis presents a mechanism for generating prevalence estimates using local surveillance data accounting for biases and difficulty in accessing hard to reach populations. As the cohort of patients with hepatitis C age and require additional medical care, local public health officials will need a method to generate prevalence estimates to allocate resources. This approach can serve as a guideline for generating local estimates using surveillance data that is less resource prohibitive.
To monitor risk factors for illness, we conducted a case-control study of sporadic Shiga toxin-producing Escherichia coli O157 (STEC O157) infections in 1999–2000. Laboratory-confirmed cases of STEC O157 infection were identified through active laboratory surveillance in all or part of seven states. Patients and age-matched controls were interviewed by telephone using a standard questionnaire. Information was collected on demographics, clinical illness, and exposures to food, water, and animals in the 7 days before the patient's illness onset. During the 12-month study, 283 patients and 534 controls were enrolled. STEC O157 infection was associated with eating pink hamburgers, drinking untreated surface water, and contact with cattle. Eating produce was inversely associated with infection. Direct or indirect contact with cattle waste continues to be a leading identified source of sporadic STEC O157 infections.