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We assessed patterns of enteric infections caused by 14 pathogens, in a longitudinal cohort study of sequelae in British Columbia (BC) Canada, 2005–2014. Our population cohort of 5.8 million individuals was followed for an average of 7.5 years/person; during this time, 40 523 individuals experienced 42 308 incident laboratory-confirmed, provincially reported enteric infections (96.4 incident infections per 100 000 person-years). Most individuals (38 882/40 523; 96%) had only one, but 4% had multiple concurrent infections or more than one infection across the study. Among individuals with more than one infection, the pathogens and combinations occurring most frequently per individual matched the pathogens occurring most frequently in the BC population. An additional 298 557 new fee-for-service physician visits and hospitalisations for enteric infections, that did not coincide with a reported enteric infection, also occurred, and some may be potentially unreported enteric infections. Our findings demonstrate that sequelae risk analyses should explore the possible impacts of multiple infections, and that estimating risk for individuals who may have had a potentially unreported enteric infection is warranted.
Clozapine is licensed for treatment-resistant psychosis and remains underutilised. This may berelated to the stringent haematological monitoring requirements that are mandatory in most countries. We aimed to compare guidelines internationally and develop a novel Stringency Index. We hypothesised that the most stringent countries would have increased healthcare costs and reduced prescription rates.
Method
We conducted a literature review and survey of guidelines internationally. Guideline identification involved a literature review and consultation with clinical academics. We focused on the haematological monitoring parameters, frequency and thresholds for discontinuation and rechallenge after suspected clozapine-induced neutropenia. In addition, indicators reflecting monitoring guideline stringency were scored and visualised using a choropleth map. We developed a Stringency Index with an international panel of clozapine experts, through a modified-Delphi-survey. The Stringency Index was compared to health expenditure per-capita and clozapine prescription per 100 000 persons.
Results
One hundred twocountries were included, from Europe (n = 35), Asia (n = 24), Africa (n = 20), South America (n = 11), North America (n = 7) and Oceania and Australia (n = 5). Guidelines differed in frequency of haematological monitoring and discontinuation thresholds. Overall, 5% of included countries had explicit guidelines for clozapine-rechallenge and 40% explicitly prohibited clozapine-rechallenge. Furthermore, 7% of included countries had modified discontinuation thresholds for benign ethnic neutropenia. None of the guidelines specified how long haematological monitoring should continue. The most stringent guidelines were in Europe, and the least stringent were in Africa and South America. There was a positive association (r = 0.43, p < 0.001) between a country's Stringency Index and healthcare expenditure per capita.
Conclusions
Recommendations on how haematological function should be monitored in patients treated with clozapine vary considerably between countries. It would be useful to standardise guidelines on haematological monitoring worldwide.
The coronavirus disease 2019 (COVID-19) pandemic challenged not only the health-care industry, but also the public health infrastructure in new and wide-ranging ways. Environmental health (EH) professionals have proven to be an essential component of the interdisciplinary public health solution required to prevent, respond, and recover from the COVID-19 pandemic. The Indian Health Service’s Division of Environmental Health Services is a community-based program offering a broad scope of environmental health services and technical assistance. Significant COVID-19 workload activities were recorded from March 2020 through March 2021. A total of 62.7% of the Division’s federal staff completed a 24-question survey in February/March 2021. Primary roles relating to community-based EH, institutional EH, and incident command system support/teams became apparent. Results indicated Division of Environmental Health Services staff provided critical leadership and used their established, trusted, interdisciplinary partnerships to help ensure critical resources and services were available in Indian Country.
Intracerebral abscess is a life-threatening condition for which there are no current, widely accepted neurosurgical management guidelines. The purpose of this study was to investigate Canadian practice patterns for the medical and surgical management of primary, recurrent, and multiple intracerebral abscesses.
Methods:
A self-administered, cross-sectional, electronic survey was distributed to active staff and resident members of the Canadian Neurosurgical Society and Canadian Neurosurgery Research Collaborative. Responses between subgroups were analyzed using the Chi-square test.
Results:
In total, 101 respondents (57.7%) completed the survey. The majority (60.0%) were staff neurosurgeons working in an academic, adult care setting (80%). We identified a consensus that abscesses >2.5 cm in diameter should be considered for surgical intervention. The majority of respondents were in favor of excising an intracerebral abscess over performing aspiration if located superficially in non-eloquent cortex (60.4%), located in the posterior fossa (65.4%), or causing mass effect leading to herniation (75.3%). The majority of respondents were in favor of reoperation for recurrent abscesses if measuring greater than 2.5 cm, associated with progressive neurological deterioration, the index operation was an aspiration and did not include resection of the abscess capsule, and if the recurrence occurred despite prior surgery combined with maximal antibiotic therapy. There was no consensus on the use of topical intraoperative antibiotics.
Conclusion:
This survey demonstrated heterogeneity in the medical and surgical management of primary, recurrent, and multiple brain abscesses among Canadian neurosurgery attending staff and residents.1
Coronavirus Disease 2019 (COVID-19) instigated a flurry of clinical research activity. The unprecedented pace with which trials were launched left an early void in data standardization, limiting the potential for subsequent data pooling. To facilitate data standardization across emerging studies, the National Heart, Lung, and Blood Institute (NHLBI) charged two groups with harmonizing data collection, and these groups collaborated to create a concise set of COVID-19 Common Data Elements (CDEs) for clinical research.
Methods:
Our iterative approach followed three guiding principles: 1) draw from existing multi-center COVID-19 clinical trials as precedents, 2) incorporate existing data elements and data standards whenever possible, and 3) alignment to data standards that facilitate data sharing and regulatory submission. We also supported rapid implementation of the CDEs in NHLBI-funded studies and iteratively refined the CDEs based on feedback from those study teams
Results:
The NHLBI COVID-19 CDEs are publicly available and being used for current COVID-19 clinical trials. CDEs are organized into domains, and each data element is classified within a three-tiered prioritization system. The CDE manual is hosted publicly at https://nhlbi-connects.org/common_data_elements with an accompanying data dictionary and implementation guidance.
Conclusions:
The NHLBI COVID-19 CDEs are designed to aid data harmonization across studies to achieve the benefits of pooled analyses. We found that organizing CDE development around our three guiding principles focused our efforts and allowed us to adapt as COVID-19 knowledge advanced. As these CDEs continue to evolve, they could be generalized for use in other acute respiratory illnesses.
Non-penetrating head and neck trauma is associated with extracranial traumatic vertebral artery injury (eTVAI) in approximately 1–2% of cases. Most patients are initially asymptomatic but have an increased risk for delayed stroke and mortality. Limited evidence is available to guide the management of asymptomatic eTVAI. As such, we sought to investigate national practice patterns regarding screening, treatment, and follow-up domains.
Methods:
A cross-sectional, electronic survey was distributed to members of the Canadian Neurosurgical Society and Canadian Spine Society. We presented two cases of asymptomatic eTVAI, stratified by injury mechanism, fracture type, and angiographic findings. Screening questions were answered prior to presentation of angiographic findings. Survey responses were analyzed using descriptive statistics.
Results:
One hundred-eight of 232 (46%) participants, representing 20 academic institutions, completed the survey. Case 1: 78% of respondents would screen for eTVAI with computed topography angiography (CTA) (97%), immediately (88%). The majority of respondents (97%) would treat with aspirin (89%) for 3–6 months (46%). Respondents would follow up clinically (89%) or radiographically (75%), every 1–3 months. Case 2: 73% of respondents would screen with CTA (96%), immediately (88%). Most respondents (94%) would treat with aspirin (50%) for 3–6 months (35%). Thirty-six percent of respondents would utilize endovascular therapy. Respondents would follow up clinically (97%) or radiographically (89%), every 1–3 months.
Conclusion:
This survey of Canadian practice patterns highlights consistency in the approach to screening, treatment, and follow-up of asymptomatic eTVAI. These findings are relevant to neurosurgeons, spinal surgeons, stroke neurologists, and neuro-interventionalists.
Child protection systems monitoring is key to ensuring children’s wellbeing. In England, monitoring is rooted in onsite inspection, culminating in judgements ranging from ‘outstanding’ to ‘inadequate’. But inspection may carry unintended consequences where child protection systems are weak. One potential consequence is increased child welfare intervention rates. In this longitudinal ecological study of local authorities in England, we used Poisson mixed-effects regression models to assess whether child welfare intervention rates are higher in an inspection year, whether this is driven by inspection judgement, and whether more deprived areas experience different rates for a given inspection judgement. We investigated the impact of inspection on care entry, Child Protection Plan-initiation, and child-in-need status. We found that inspection was associated with a rise in rates across the spectrum of interventions. Worse judgements yielded higher rates. Inspection may also exacerbate existing inequalities. Unlike less deprived areas, more deprived areas judged inadequate did not experience an increase in the less intrusive ‘child-in-need’ interventions. Our findings suggest that a narrow focus on social work practice is unlikely to address weaknesses in the child protection system. Child protection systems monitoring should be guided by a holistic model of systems improvement, encompassing the socioeconomic determinants of quality.
We now recognise that withdrawal symptoms from antidepressants are common, and can be severe and long-lasting in some people. Many withdrawal symptoms overlap with symptoms of anxiety or depression, making it difficult to distinguish withdrawal from relapse. We describe how their onset soon after dose reduction, the association of psychological with physical symptoms, their prompt response to reinstatement, and their typical ‘wave’ pattern of onset, peak and resolution can help distinguish withdrawal symptoms from relapse. We also examine evidence that suggests that antidepressant withdrawal symptoms are misdiagnosed as relapse in discontinuation studies aimed at demonstrating the ability of antidepressants to prevent future relapse (relapse prevention properties). In these discontinuation studies people have their antidepressants stopped abruptly, or rapidly, making withdrawal symptoms very likely, and little effort is made to measure withdrawal symptoms or distinguish them from relapse. We conclude that there is currently no robust evidence for the relapse prevention properties of antidepressants, and current guidance might need to be re-evaluated.
Clozapine is the only drug licensed for treatment-resistant schizophrenia (TRS) but the real-world clinical and cost-effectiveness of community initiation of clozapine is unclear.
Aims
The aim was to assess the feasibility and cost-effectiveness of community initiation of clozapine.
Method
This was a naturalistic study of community patients recommended for clozapine treatment.
Results
Of 158 patients recommended for clozapine treatment, 88 (56%) patients agreed to clozapine initiation and, of these, 58 (66%) were successfully established on clozapine. The success rate for community initiation was 65.4%; which was not significantly different from that for in-patient initiation (58.82%, χ2(1,88) = 0.47, P = 0.49). Following clozapine initiation, there was a significant reduction in median out-patient visits over 1 year (from 24.00 (interquartile range (IQR) = 14.00–41.00) to 13.00 visits (IQR = 5.00–24.00), P < 0.001), and 2 years (from 47.50 visits (IQR = 24.75–71.00) to 22.00 (IQR = 11.00–42.00), P < 0.001), and a 74.71% decrease in psychiatric hospital bed days (z = −2.50, P = 0.01). Service-use costs decreased (1 year: –£963/patient (P < 0.001); 2 years: –£1598.10/patient (P < 0.001). Subanalyses for community-only initiation also showed significant cost reductions (1 year: –£827.40/patient (P < 0.001); 2 year: –£1668.50/patient (P < 0.001) relative to costs prior to starting clozapine. Relative to before initiation, symptom severity was improved in patients taking clozapine at discharge (median Positive and Negative Syndrome Scale total score: initial visit: 80 (IQR = 71.00–104.00); discharge visit 50.5 (IQR = 44.75–75.00), P < 0.001) and at 2 year follow-up (Health of Nation Outcome Scales total score median initial visit: 13.00 (IQR = 9.00–15.00); 2 year follow-up: 8.00 (IQR = 3.00–13.00), P = 0.023).
Conclusions
These findings indicate that community initiation of clozapine is feasible and is associated with significant reductions in costs, service use and symptom severity.
Despite the integral role of the judiciary to democracy, and the importance of judicial trust for judicial system performance, we know relatively little about the bases of public trust in this institution. How does institutional quality affect judicial trust? We explore this question in the context of Latin America, using a multilevel data set comprising survey data spanning 2001 to 2016 and country-level institutional and economic factors. We find that the effects of institutional quality on judicial trust are highly circumscribed. Factors like rule of law and corruption impact the judicial trust of only the best-educated survey respondents. Among the broader public, however, judicial trust is shaped more strongly by individuals' subjective economic and regime evaluations, as well as one's personal experiences with the judiciary.
An increasing number of innovative therapies (e.g., gene- and cell-based treatments) have been developed in the past 20 years. Despite the significant clinical potential of these therapies, access delays may arise because of differing perspectives of manufacturers and payers regarding issues such as the value of the product, clinical and financial uncertainties, and sustainability.
Managed entry agreements (MEAs) can enable access to treatments that would not be reimbursed by conventional methods because of such concerns. However, although MEA typologies exist, there is currently no structured process to come to agreements on MEAs, which can be difficult to decide upon and implement.
To facilitate more structured MEA negotiations, we propose a conceptual “value-based negotiation framework” with corresponding application tools.
Methods
The framework was developed based on an iterative process of scientific literature review and expert input.
Results
The framework aims to (i) systematically identify and prioritize manufacturer and payer concerns about a new treatment, and (ii) select a mutually acceptable combination of MEA terms that can best address priority concerns, with the lowest possible implementation burden.
Conclusions
The proposed framework will be tested in practice, and is a step toward supporting payers and manufacturers to engage in more structured, transparent negotiations to balance the needs of both sides, and enabling quicker, more transparent MEA negotiations and patient access to innovative products.
This chapter considers the legacy of respect for individual autonomy and ‘informed consent’ in health research. The primacy of informed consent as a safeguard has led to a systemic regulatory tendency to conceive of and protect privacy as an individual rather than a collective concern. This has limited any regulatory ability to grasp broader social concerns with the use and disclosure of data gathered and generated by health research. Any systemic failure to recognise collective interests in data, and the public interest in (non-personal) data protection, has profound implications for an information age. The chapter reflects on the value of re-negotiating the interests and expectations protected by health research regulation. It recognises the significance of Graeme Laurie’s preferred conception of privacy to enabling such negotiation, and the value of stewardship in establishing normative expectations free of historical encumbrance. Laurie’s conceptualisation of ‘privacy as separateness’, when placed alongside the idea of stewardship, may allow us to rebalance respect to encompass collective interests as fundamental to self-determination and mutual respect.
Psychology's tendency to focus on confirmatory analyses before ensuring constructs are clearly defined and accurately measured is exacerbating the generalizability crisis. Our growing use of digital behaviors as predictors has revealed the fragility of subjective measures and the latent constructs they scaffold. However, new technologies can provide opportunities to improve conceptualizations, theories, and measurement practices.
Lithium is viewed as the first-line long-term treatment for prevention of relapse in people with bipolar disorder.
Aims
This study examined factors associated with the likelihood of maintaining serum lithium levels within the recommended range and explored whether the monitoring interval could be extended in some cases.
Method
We included 46 555 lithium rest requests in 3371 individuals over 7 years from three UK centres. Using lithium results in four categories (<0.4 mmol/L; 0.40–0.79 mmol/L; 0.80–0.99 mmol/L; ≥1.0 mmol/L), we determined the proportion of instances where lithium results remained stable or switched category on subsequent testing, considering the effects of age, duration of lithium therapy and testing history.
Results
For tests within the recommended range (0.40–0.99 mmol/L categories), 84.5% of subsequent tests remained within this range. Overall, 3 monthly testing was associated with 90% of lithium results remaining within range, compared with 85% at 6 monthly intervals. In cases where the lithium level in the previous 12 months was on target (0.40–0.79 mmol/L; British National Formulary/National Institute for Health and Care Excellence criteria), 90% remained within the target range at 6 months. Neither age nor duration of lithium therapy had any significant effect on lithium level stability. Levels within the 0.80–0.99 mmol/L category were linked to a higher probability of moving to the ≥1.0 mmol/L category (10%) compared with those in the 0.4–0.79 mmol/L group (2%), irrespective of testing frequency.
Conclusion
We propose that for those who achieve 12 months of lithium tests within the 0.40–0.79 mmol/L range, the interval between tests could increase to 6 months, irrespective of age. Where lithium levels are 0.80–0.99 mmol/L, the test interval should remain at 3 months. This could reduce lithium test numbers by 15% and costs by ~$0.4 m p.a.
To understand the transmission dynamics of severe acute respiratory coronavirus virus 2 (SARS-CoV-2) in a hospital outbreak to inform infection control actions.
Design:
Retrospective cohort study.
Setting:
General medical and elderly inpatient wards in a hospital in England.
Methods:
Coronavirus disease 2019 (COVID-19) patients were classified as community or healthcare associated by time from admission to onset or positivity using European Centre for Disease Prevention and Control definitions. COVID-19 symptoms were classified as asymptomatic, nonrespiratory, or respiratory. Infectiousness was calculated from 2 days prior to 14 days after symptom onset or positive test. Cases were defined as healthcare-associated COVID-19 when infection was acquired from the wards under investigation. COVID-19 exposures were calculated based on symptoms and bed proximity to an infectious patient. Risk ratios and adjusted odds ratios (aORs) were calculated from univariable and multivariable logistic regression.
Results:
Of 153 patients, 65 were COVID-19 patients and 45 of these were healthcare-associated cases. Exposure to a COVID-19 patient with respiratory symptoms was associated with healthcare-associated infection irrespective of proximity (aOR, 3.81; 95% CI, 1.6.3–8.87). Nonrespiratory exposure was only significant within 2.5 m (aOR, 5.21; 95% CI, 1.15–23.48). A small increase in risk ratio was observed for exposure to a respiratory patient for >1 day compared to 1 day from 2.04 (95% CI, 0.99–4.22) to 2.36 (95% CI, 1.44–3.88).
Conclusions:
Respiratory exposure anywhere within a 4-bed bay was a risk, whereas nonrespiratory exposure required bed distance ≤2.5 m. Standard infection control measures required beds to be >2 m apart. Our findings suggest that this may be insufficient to stop SARS-CoV-2 transmission. We recommend improving cohorting and further studies into bed distance and transmission factors.
Using a new measure of urbanity for every federal electoral district in Canada from 1896 to the present, this article describes the long-term development of the urban-rural divide in Canadian federal elections. We focus on three questions: (1) when the urban-rural divide has existed in Canada, identifying three main periods—the 1920s, the 1960s and 1993–present—in which the urban-rural cleavage has been especially important in federal elections; (2) where the urban-rural divide has existed, finding that in the postwar period the urban-rural cleavage is a pan-Canadian phenomenon; and (3) how well urbanity predicts district-level election outcomes. We argue that the urban-rural divide is important for understanding election outcomes during several periods of Canadian political development, and never more so than in recent decades. We conclude by discussing the implications of our findings for research on urban-rural cleavages, Canadian electoral politics and Canadian political development.
Paliperidone 3-monthly (PP3M) long-acting injection has proven efficacy and effectiveness in schizophrenia. Little is known of its effectiveness in other diagnoses.
Methods
All patients starting PP3M were followed up for 2 years. Main outcome measures were relapse and discontinuation from PP3M. Post hoc we examined outcomes in those switched back to one monthly paliperidone (PP1M) long-acting injection.
Results
Overall, 186 patients were followed-up. At the 2-year end point, 110 patients (59%) were still receiving PP3M, and 129 (70%) were receiving some form of paliperidone long-acting injection. Discontinuation from paliperidone long-acting injections (PPLAIs) was more likely with a nonschizophrenia diagnosis (hazard ratio [HR] for continuation 0.429 [95% confidence intervals (CI) – 0.21, 0.87 p = 0.018)), and prior clozapine use [in PP3M patients; HR for discontinuation 1.87 [95% CI – 1.05, 3.30 p = 0.032]). Relapse occurred in 20 (11%) of those receiving PP3M. Relapse on PP3M and PPLAIs was more likely in nonschizophrenia diagnosis (HR 0.17 for remaining relapse-free [95% CI – 0.06, 0.50; p = 0.001]; HR 0.21 [95% CI – 0.08, 0.58 p = 0.002], respectively), polypharmacy in PP3M patients (HR for relapse 7.91 [95% CI – 3.73, 22.9; p < 0.001]) and PPLAI patients (HR for relapse 6.45 [95% CI – 2.49, 16.5; p < 0.001]), and prior clozapine use in PP3M patients (HR for relapse 6.11 [95% CI – 1.82, 20.5; p = 0.003]) and PPLAI patients (HR for relapse 4.52 (95% CI – 1.51, 13.5; p = 0.007).
Conclusions
Outcomes with PP3M are excellent in practice, even when used outside its formal license. PP3M was relatively more effective in those with an F20 schizophrenia diagnosis and in those never before considered for or prescribed clozapine.
Approximately 60 000 people in England have coexisting type 2 diabetes mellitus (T2DM) and severe mental illness (SMI). They are more likely to have poorer health outcomes and require more complex care pathways compared with those with T2DM alone. Despite increasing prevalence, little is known about the healthcare resource use and costs for people with both conditions.
Aims
To assess the impact of SMI on healthcare resource use and service costs for adults with T2DM, and explore the predictors of healthcare costs and lifetime costs for people with both conditions.
Method
This was a matched-cohort study using data from the Clinical Practice Research Datalink linked to Hospital Episode Statistics for 1620 people with comorbid SMI and T2DM and 4763 people with T2DM alone. Generalised linear models and the Bang and Tsiatis method were used to explore cost predictors and mean lifetime costs respectively.
Results
There were higher average annual costs for people with T2DM and SMI (£1930 higher) than people with T2DM alone, driven primarily by mental health and non-mental health-related hospital admissions. Key predictors of higher total costs were older age, comorbid hypertension, use of antidepressants, use of first-generation antipsychotics, and increased duration of living with both conditions. Expected lifetime costs were approximately £35 000 per person with both SMI and T2DM. Extrapolating nationally, this would generate total annual costs to the National Health Service of around £250 m per year.
Conclusions
Our estimates of resource use and costs for people with both T2DM and SMI will aid policymakers and commissioners in service planning and resource allocation.