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Introduction: Increasing opioid prescribing has been linked to an epidemic of opioid misuse. Our objective was to synthesize available evidence about patient-, prescriber-, medication-, and system-level risk factors for developing opioid misuse from prescribed opioids among patients presenting with pain unrelated to cancer. Our hypothesis was that we would identify risk factors predisposing patients to developing opioid misuse. Methods: We developed a systematic search strategy and applied it to nine electronic reference databases and six clinical trial registries. We hand searched related journals and conference proceedings, the reference lists of included studies, and the top 100 hits on Google. We included studies where a medical professional exposed adults or children to an opioid through a prescription. We excluded studies with over 50% cancer patients, palliative patients, and those with illicit opioid initiation. Two reviewers independently reviewed titles, abstracts, and full texts, and extracted data using standardized forms. We assessed study quality using risk of bias. We synthesized effect sizes of dichotomous risk factors on opioid misuse using inverse variance random-effects meta-analysis, and the inverse variance-weighted mean difference between opioid misusers and non-misusers for continuously measured factors. We conducted an a priori defined subgroup analysis among opioid-naïve patients. Results: Among 9,629 studies, 67 met our inclusion criteria. Among those who had been prescribed outpatient opioids, the following factors were associated with the development of misuse: a prior history of illicit drug use (OR: 4.21, 95% CI: 2.31-7.65), recent benzodiazepine use (OR: 2.57, 95% CI: 1.23-5.38), any mental health diagnosis (OR: 2.45, 95% CI: 1.91-3.15), any short acting (IR) opioid prescription (OR: 2.40, 95% CI: 1.15-5.02), younger age (OR: 2.19, 95%CI: 1.81-2.64), and male sex (OR: 1.23, 95% CI: 1.10-1.36). Among studies limiting their population to opioid-naïve patients, younger age was the most significant risk factor for opioid misuse (OR: 5.42, 95% CI:1.51-19.43). Conclusion: Of the risk factors examined, non-cancer pain patients with a prior history of substance use or mental health diagnoses were at highest risk for prescription opioid misuse. Younger opioid-naïve patients were at highest risk of misuse. Clinicians should consider these risk factors when managing acute pain in the emergency department.
Introduction: Adverse drug events (ADEs), unintended and harmful events associated with medications, cause or contribute to 2 million emergency department (ED) visits in Canada each year. Our objective was to determine the proportion of preventable ADEs by event type, severity, drug and drug class, and describe associated factors. Methods: We reviewed the charts of ADE patients enrolled in 1 of 3 prospective studies conducted in 3 tertiary care and 1 urban community ED. In the parent studies, researchers enrolled patients by applying a systematic selection algorithm to minimize selection bias, and physicians and pharmacists evaluated patients prospectively to evaluate causal associations between the drug regimens and patient presentations. After completion of the prospective study, a research pharmacist and physician independently reviewed the charts of all ADE patients, abstracted data using an electronic form and applied 3 preventability algorithms. The main outcome was a probably or definitely preventable ADE defined as avoidable by adhering to best medical practice, appropriate monitoring, taking a history of prior ADEs, compliance with recommended therapy, and avoidance of errors. Reviewers discussed discordant ratings until reaching consensus. We used kappa scores to evaluate between rater agreement, and investigated risk factors for preventability using logistic regression. Sample size was based on enrolment into the parent studies. Results: We reviewed the charts of 670 patients diagnosed with 725 ADEs. We excluded 44 patients with incomplete assessments. The inter-rater agreement in categorizing ADEs as preventable was 0.51 (95%CI 0.42-0.59). We deemed 61% (95%CI 57-65%) of ADEs preventable. Of preventable events, 30% were due to non-adherence, 24% to adverse reactions, and 15% to an excessive dose, and 29% required hospital admission. Among preventable events, 8% were due to warfarin, 5% hydrochlorothiazide, 3% acetylsalicylic acid, and 3% insulin. On multivariate analysis, mental health diagnoses were associated with preventable ADEs (OR 2.1, 95%CI 1.3-3.3, p=0.002). Conclusion: In this large multi-centre cohort, preventable events made up the majority of ADEs, and utilized substantial hospital resources. Strategies to reduce ED visits due to ADEs should target improving adherence behavior, and developing interventions for patients with mental health diagnoses and on high-risk medications.
Introduction: Adverse drug events (ADEs), unintended and harmful events associated with medications, cause or contribute to 2 million annual emergency department (ED) visits in Canada. Australian data indicate that 27% of ADEs requiring admission are events caused by re-exposure to drugs that previously caused harm. Our objective was to estimate the frequency of repeat ADEs. Methods: We reviewed the charts of ADE patients who had been enrolled in 1 of 3 prospective studies conducted in 2 tertiary care and 1 urban community ED. In the parent studies, researchers enrolled patients by applying a systematic selection algorithm to minimize selection bias, and physicians and pharmacists evaluated patients prospectively to evaluate the causal association between the drug regimens and patient presentations. After completion of the parent studies, a research pharmacist and a physician independently reviewed the charts of ADE patients, abstracted data using electronic forms, and searched that hospital’s records for previously recorded ADEs. The main outcome was a repeat ADE, defined as a same or same-class drug re-exposure, or repeat inappropriate drug withdrawal, causing a same or similar presentation as a prior ADE. Sample size was based on enrolment into the parent studies. Results: We reviewed the charts of 614 ED patients diagnosed with 655 ADEs. Of these, 20% (133/665, 95%CI 17.0-23.0%) were repeat events. Most repeat ADEs were moderate (61%) or severe (32%) in nature, and 33% (95%CI 25.1-41.1%) required hospital admission. The most commonly implicated drugs were warfarin (10%), hydrochlorothiazide (4%) and insulin (4%), and the most commonly implicated drug classes were antithrombotics (17%), psychotropics (12%) and analgesics (9%). Repeat ADEs commonly required clinical monitoring (59%), additional medications to treat the ADE (50%) and follow-up lab testing (35%). Overall, 61% (95%CI 51.3-70.7%) of culprit drug re-exposures were deemed potentially or definitely inappropriate. Conclusion: Inappropriate re-exposures to previously harmful medications cause a substantial number of recurrent ADEs, and may represent an ideal target for prevention. We were unable to search for repeat ADEs in the records of other hospitals that our patients may have visited, and could not detect ADEs that were not documented in the medical record. As a result, we likely underestimated the frequency of repeat ADEs.
Introduction: Adverse drug events (ADEs), unintended and harmful events associated with medications, commonly cause or contribute to emergency department (ED) presentations. Understanding provider, patient and system factors that contribute to their development may assist in developing effective preventative strategies. Our objective was to identify factors that contributed to the development of ADEs that caused ED presentations. Methods: We reviewed the charts of ADE patients enrolled in 1 of 3 prospective studies conducted in 3 tertiary care and 1 urban community ED. In the parent studies, researchers enrolled patients by applying a systematic selection algorithm to minimize selection bias, and physicians and pharmacists evaluated patients prospectively to evaluate the causal associations between the drug regimens and patient presentations. Subsequently, a research pharmacist and physician independently reviewed the charts of ADE patients from these cohorts, abstracting data using electronic forms. Reviewers recorded patient, provider and system factors that contributed to the development of ADEs. The main outcome was the presence of at least one contributing factor in the development of an ADE. We used descriptive statistics with appropriate measures of variance. The sample size was determined by enrolment into the primary studies. Results: We reviewed the charts of 670 patients diagnosed with 725 ADEs. We identified ≥1 contributing factors in 62% (95%CI 58-65%) of ADEs. Multiple contributing factors were present in 17% of ADEs (95%CI 13-20%). The most common contributing factors were inadequate patient counseling or instructions about medication use (15%), insufficient laboratory monitoring or follow-up of monitoring tests (12%), lack of staff education (7%), lack of provider adherence with recommended treatment guidelines (7%), and delayed or inadequate clinical reassessment after a medication change (6%). Provider errors in drug administration contributed to 0.3% of ADEs (95%CI 0.0-0.7). Conclusion: Contributing factors were identified for most ADEs. They were often related to inadequate counseling and follow-up, and were rarely the result of errors. Further research is required to understand how communication of medication instructions can be improved. Investments in technologies to reduce provider errors may not significantly reduce the numbers of ADE patients presenting to EDs.
We have used the Australia Telescope Compact Array to search for a number of centimetre wavelength methanol transitions which are predicted to show weak maser emission towards star formation regions. Sensitive, high spatial, and spectral resolution observations towards four high-mass star formation regions which show emission in a large number of class II methanol maser transitions did not result in any detections. From these observations, we are able to place an upper limit of ≲ 1300 K on the brightness temperature of any emission from the 31A+–31A−, 17−2–18−3 E (vt = 1), 124–133 A−, 124–133 A+, and 41A+–41A− transitions of methanol in these sources on angular scales of 2 arcsec. This upper limit is consistent with current models for class II methanol masers in high-mass star formation regions and better constraints than those provided here will likely require observations with next-generation radio telescopes.
Background: Amyotrophic lateral sclerosis (ALS) is a fatal degenerative neurological disease with significant effects on quality of life. International studies continue to provide consistent incidence values, though complete case ascertainment remains a challenge. The Canadian population has been understudied, and there are currently no quantitative data on the incidence of ALS in British Columbia (BC). The objectives of this study were to determine the five-year incidence rates of ALS in BC and to characterize the demographic patterns of the disease. Methods: The capture–recapture method was employed to estimate ALS incidence over a five-year period (2010-2015). Two sources were used to identify ALS cases: one database from an ALS medical centre and another from a not-for-profit ALS organization. Results: During this time period, there were 690 incident cases within the two sources. The capture–recapture method estimated 57 unobserved cases, corresponding to a crude five-year incidence rate of 3.29 cases per 100,000 (CI95%=3.05-3.53). The mean age of diagnosis was 64.6 (CI95%=59.7-69.4), with 63.5 (CI95%=56.9-70.1) for men and 65.7 (CI95%=58.6-72.7) for women. There was a slight male preponderance in incidence, with a 1.05:1 ratio to females. Peak numbers in incidence occurred between the ages of 70 and 79. Conclusions: The incidence of ALS in BC was found to be consistent with international findings though nominally higher than that in other Canadian provinces to date.
The introduction of the Manila clam into British coastal waters in the 1980s was contested by conservation agencies. While recognizing the value of the clam for aquaculture, the government decided that it posed no invasive risk, as British sea temperatures would prevent naturalization. This proved incorrect. Here we establish the pattern of introduction and spread of the species over the first 30 years of its presence in Britain. We report archival research on the sequence of licensed introductions and examine their relationship in time and space to the appearance of wild populations as revealed in the literature and by field surveys. By 2010 the species had naturalized in at least 11 estuaries in southern England. These included estuaries with no history of licensed introduction. In these cases activities such as storage of catch before market or deliberate unlicensed introduction represent the probable mechanisms of dispersal. In any event naturalization is not an inevitable consequence of introduction and the chances of establishment over the period in question were finely balanced. Consequently in Britain the species is not currently aggressively invasive and appears not to present significant risk to indigenous diversity or ecosystem function. However it is likely to gradually continue its spread should sea surface temperatures rise as predicted.
The effect of increased levels of suspended sediment on fertilization success in the scleractinian coral Pectinia lactuca was investigated in a laboratory experiment following a mass coral spawning event on reefs off Singapore. Egg–sperm bundles were collected from tank-spawned coral colonies collected from the field several days prior to the anticipated mass spawning. Eggs and sperm from each colony were separated and distributed systematically across replicated treatments (N = 9) with three concentrations of fine suspended sediment. Spawning and embryo development in Pectinia lactuca followed a pattern similar to other scleractinian coral species. There was a significant effect of increased suspended sediment concentration on fertilization success (P < 0.05). Both high- (169 mg l−1) and medium- (43 mg l−1) suspended sediment treatments decreased fertilization success compared to controls. These results imply that increased turbidity levels (whether chronic, such as in the waters around Singapore, or short-term, caused by a dredging operation)—when coinciding with the coral spawning season—may affect the reproductive success of corals and compromise coral recruitment and recovery of degraded reefs.
Central to the United Nations Framework setting out the human rights responsibilities of corporations proposed by John Ruggie is the principle that corporations have a responsibility to respect human rights in their operations whether or not doing so is required by law and whether or not human rights laws are actively enforced. Ruggie proposes that corporations should respect this principle in their strategic management and day-to-day operations for reasons of corporate (enlightened) self-interest. This paper identifies this as a serious weakness and argues that identifying the responsibility to respect human rights as an explicitly ethical obligation to be respected for that reason would provide a much stronger justificatory foundation for respecting the principle seen from a corporate perspective, given that corporations are accountable to their shareholders for their deployment of the firm’s financial resources.
Transport is an essential part of any society. Transport systems support economic growth and meet expectations for travel and communication in an increasingly mobile society. Despite its importance, investment in transport infrastructure was limited during the twentieth century – a situation aggravated by unprecedented growth in private car use throughout the UK and elsewhere. The last UK Conservative government introduced a range of measures that altered the balance between subsidised public services and market-driven private services. Competition became a key driver in government policy and the deregulation of bus services transformed the lynchpin of the public transport system.
There has also been an increasing awareness of the environmental costs of travel and the need to address environmental impacts of travel and transport systems. The damaging effects of road congestion on economic activity and growth and of vehicle emissions on climate change were being increasingly recognised at the same time as vehicle use became increasingly essential to people's everyday lives.
These were the transport issues and challenges facing the new Scottish Parliament – challenges which had to be addressed in the context of national and local government structures, the legal framework for transport and the environment, and the availability of funding to support investment. In dealing with these challenges, the Scottish Parliament has taken into account the key drivers of infrastructure investment, environmental mitigation and social inclusion.
A significant proportion of a consignment of branded Parma Ham was found to have ‘blown’ tins; the associated bacterial flora was therefore investigated. No Salmonella or Shigella were found. Clostridium welchii type A and Clostridium bifermentans were isolated in moderate numbers only from enrichment cultures of the ham. Staphylococcus spp. and coryneform bacteria were obtained from all tins and Group D streptococci were present in a few. No food-poisoning cases were associated with this ham.
Toughness is a determinant of meat quality, a common cause of unacceptability in meat products and consumers are willing to pay higher prices for meat which is guaranteed to be tender. The calpain proteolytic enzymes are involved in the process of meat tenderisation through their degradation of muscle proteins postmortem (Sensky et al., 2001) and their activity is influenced by fluctuating levels of Ca2+, pH and temperature, all of which change rapidly in the immediate postmortem period. As vitamin D (vit D3) is responsible for Ca2+ homeostasis, we hypothesised that supplementing feed with vitamin D or vitamin D plus calcium propionate (CaPr) before slaughter would result in more tender meat through enhanced postmortem calpain system activity.
General characteristics of methanol (CH3OH) maser emission are summarized. It is shown that methanol maser sources are concentrated in the spiral arms. Most of the methanol maser sources from the Perseus arm are associated with embedded stellar clusters and a considerable portion is situated close to compact HII regions. Almost 1/3 of the Perseus Arm sources lie at the edges of optically identified HII regions which means that massive star formation in the Perseus Arm is to a great extent triggered by local phenomena. A multiline analysis of the methanol masers allows us to determine the physical parameters in the regions of maser formation. Maser modelling shows that class II methanol masers can be pumped by the radiation of the warm dust as well as by free-free emission of a hypercompact region (hcHII) with a turnover frequency exceeding 100 GHz. Methanol masers of both classes can reside in the vicinity of hcHIIs. Modelling shows that periodic changes of maser fluxes can be reproduced by variations of the dust temperature by a few percent which may be caused by variations in the brightness of the central young stellar object reflecting the character of the accretion process. Sensitive observations have shown that the masers with low flux densities can still have considerable amplification factors. The analysis of class I maser surveys allows us to identify four distinct regimes that differ by the series of their brightest lines.
Interstellar masers are unique probes of the environments in which they arise. In studies of high-mass star formation their primary function has been as signposts of these regions and they have been used as probes of the kinematics and physical conditions in only a few sources. With a few notable exceptions, we know relatively little about the evolutionary phase the different maser species trace, nor their location with respect to other star formation tracers. While detailed studies of a small number of maser regions can reveal much about them, other information can only be obtained through large, systematic searches. In particular, such surveys are vital in efforts to determine an evolutionary sequence for the common maser species, and there is growing evidence that methanol masers may trace an earlier phase than the other common maser species of OH and water.
The use of imaging for the evaluation of developmental anomalies of the female pelvis has rapidly expanded since the 1980s mainly because of the development and availability of imaging technology, particularly high-resolution ultrasound with Doppler, spiral computed tomography (CT) and magnetic resonance imaging (MRI). Imaging is now used in virtually every case to confirm diagnosis or to show the anatomy of the structural abnormalities of the genital tract and other related disorders. Imaging is used extensively for planning the surgical management of the primary condition and any associated complications.
The most commonly used imaging modalities are fluoroscopy (usually with contrast agents), ultrasound and MRI. Each technique has particular advantages and disadvantages, and knowledge of these is important for the appropriate choice of imaging technique. A major consideration when imaging children is the use and dose of ionizing radiation, particularly as many patients are likely to need multiple investigations during the course of their lifetime.
Genitograms and micturating cystourethrography are the traditional fluoroscopic methods for evaluating children with disorders of sexual differentiation. All perineal orifices are examined with the catheter inserted only a short distance into the orifice. Contrast is injected gently under direct fluoroscopic screening to allow visualization of the morphology of the urogenital sinus. The important features that are noted include the presence or absence of a vagina, its relationship to the urethra and the level of the external sphincter (which has important surgical implications), and the recognition of a male or female type urethral configuration (Aaronson, 1992).