Abstract
Introduction
Comprehensive, population-based investigations of the extent and temporality of associations between common neurological and psychiatric disorders are scarce.
Methods
This ...retrospective cohort study used linked health administrative data for Ontarians aged 40–85 years on 1 April 2002, to estimate the adjusted rate of incident dementia, Parkinson’s disease (PD), stroke or mood/anxiety disorder (over 14 years) according to the presence and time since diagnosis of a prior disorder. Sex differences in the cumulative incidence of a later disorder were also examined.
Results
The cohort included 5,283,546 Ontarians (mean age 56.2 ± 12.1 years, 52% female). The rate of dementia was significantly higher for those with prior PD (adjusted hazard ratio adjHR 4.05, 95% confidence interval CI 3.99–4.11); stroke (adjHR 2.49, CI 2.47–2.52) and psychiatric disorder (adjHR 1.79, CI 1.78–1.80). The rate of PD was significantly higher for those with prior dementia (adjHR 2.23, CI 2.17–2.30) and psychiatric disorder (adjHR 1.77, CI 1.74–1.81). The rate of stroke was significantly higher among those with prior dementia (adjHR 1.56, CI 1.53–1.58). Prior dementia (adjHR 2.36, CI 2.33–2.39), PD (adjHR 1.80, CI 1.75–1.85) and stroke (adjHR 1.47, CI 1.45–1.49) were associated with a higher rate of an incident psychiatric disorder. Generally, associations were strongest in the 6 months following a prior diagnosis and demonstrated a J-shape relationship over time. Significant sex differences were evident in the absolute risks for several disorders.
Conclusions
The observed nature of bidirectional associations between these neurological and psychiatric disorders indicates opportunities for earlier diagnosis and interventions to improve patient care.
The goal of this study was to determine the outcomes of stage IC endometrial carcinoma patients who are managed with and without adjuvant radiation therapy after comprehensive surgical staging.
...Patients with FIGO stage IC adenocarcinoma of the endometrium diagnosed from 1988 to 1999 were identified from tumor registry databases at four institutions. A retrospective chart review identified 220 women who underwent comprehensive surgical staging including a total hysterectomy, bilateral salpingo-oophorectomy, pelvic/paraaortic lymphadenectomy, and peritoneal cytology.
Of the 220 stage IC patients, 56 (25%) patients received adjuvant brachytherapy (BT), 19 (9%) received whole-pelvis radiation (WPRT), and 24 (11%) received both WPRT and BT. One hundred twenty-one patients (55%) did not receive adjuvant radiation. There were 6 recurrences (6%) in the radiated group and 14 (12%) in the observation group (
P = 0.20). Seven of fourteen recurrences in the observation group were local, and all local recurrences were salvaged with radiation therapy. Two of seven distant recurrences in this group were also salvaged with surgery and chemotherapy. The overall salvage rate for the observation group was 64%. There was a statistical difference in 5-year disease-free survival between the radiated and observation groups (93% vs 75%,
P = 0.013). However, the 5-year overall survival was similar in the two groups (92% vs 90%,
P = 0.717).
Adjuvant radiation therapy improves disease-free survival in surgical stage IC patients; however, overall survival is not improved with adjuvant radiation therapy since the majority of local recurrences in conservatively managed patients can be salvaged with radiation therapy.
Recreational boating activity has the potential to generate noise pollution that may influence wild fish. Such noise may be particularly relevant to fish engaged in parental care (PC), where ...alterations in behaviour could influence individual fitness and productivity of fish populations.
Here, the PC behaviour of the freshwater largemouth bass (Micropterus salmoides) was examined to determine whether disturbance from boat noise altered paternal behaviour. Changes in nest‐tending and brood‐guarding behaviour were measured following exposure to noise treatments of 1‐min duration using underwater playbacks of recorded boat noises.
One experiment compared the behaviour of bass tending eggs before, during, and after exposure to high‐speed or idling combustion motors, or an electronic bow‐mounted trolling motor. No significant differences in the time on nest, number of pectoral fin beats, and number of turns between the pre‐treatment, treatment, and post‐treatment periods for all three motor types were observed.
A second experiment assessed the impacts of noise (high‐speed combustion motor only) on the behaviour of nesting bass across the development stages of offspring (i.e. egg, egg‐sac fry, and swim‐up fry). During the egg‐sac fry stage, nest‐guarding males turned significantly less on the nest during the noise treatment compared with the long‐term post‐treatment period, indicating a stage‐specific impact of boat noise on parental behaviour. The effect was transient, however, and limited to the period that the noise was present.
Given that PC and recreational boating activity tend to co‐occur in nearshore areas, prolonged or frequent repeated exposure of nesting fish to boat noise during the egg‐sac fry stage could have adverse consequences for fitness and reproductive output. Efforts to restrict recreational boating activity in the vicinity of fish engaged in PC (e.g. through the use of set‐backs) would be a risk‐averse approach to mitigating the effects of noise pollution on fish.
Antipsychotic reduction in nursing homes has been a focus of research and policy attention for several decades; however, there is evidence that these initiatives may have had unintended consequences, ...such as medication substitution and changes in diagnosis coding. Our objectives were to describe temporal changes in the use of antipsychotics, potential substitution medications, and diagnoses and symptoms used to establish the appropriateness of antipsychotic prescribing.
Repeated cross-sectional study design.
Individuals, 66 to 105 years of age, living in nursing homes in Ontario, Canada between April 1, 2010 and December 31, 2019.
Linked health administrative and clinical data were used to estimate the quarterly prevalence of dispensed antipsychotics, antidepressants, anticonvulsants, and benzodiazepines, as well as diagnoses and symptoms (eg, schizophrenia and delusions) applied to establish the appropriateness of antipsychotic use. Generalized linear models with generalized estimating equations, binomial distribution, and identity link function estimated the absolute changes over time among the population overall, by dementia diagnosis, and by severity of aggressive behaviors and cognitive impairment.
Among over 70,000 nursing home residents each quarter, we observed general declines in antipsychotic (-0.70% per year 95% confidence limit (CL) -0.74%, -0.66%) and benzodiazepine use (-1.17% per year 95% CL -1.20%, -1.14%), and increases in antidepressant (0.89% per year 95% CL 0.84%, 0.94%) and anticonvulsant use (1.06% per year 95% CL 1.03%, 1.09%). Although initially stable, the coding of delusions increased from 3.5% to 10.2% (1.18% per year 95% CL 1.12%, 1.24%) between 2014 and 2019, whereas schizophrenia remained stable. Increases in antidepressant use and recorded delusions were more pronounced among residents with dementia and aggressive behaviors.
Medication substitution and changes in diagnosis/symptom coding may be potential unintended consequences of initiatives to reduce inappropriate antipsychotic use. How this corresponds to resident-level prescribing and clinical outcomes warrants further investigation.
Abstract Objective. To determine the response rate, progression-free survival and toxicity associated with weekly topotecan administered to patients with platinum-sensitive recurrent epithelial ...ovarian (EOC) in the third-line setting. Methods. Patients with measurable platinum-sensitive EOC following failure of second-line chemotherapy were eligible for this phase II study. All patients were initially treated with cytoreductive surgery and platinum/paclitaxel-based chemotherapy. Continuous, weekly topotecan was administered at a starting dose of 4 mg/m2 . Toxicity and efficacy were assessed at various time points after initiation of therapy. Results. Twenty nine patients were enrolled in this prospective study. Toxicity was acceptable with grade 1/2 nausea being the most commonly experienced side effect (52%). Nine patients (31%) had grade 3/4 leukopenia; however, only 3 patients had febrile neutropenia. Thirteen patients had a treatment delay and six required dose reductions. Twenty two patients were evaluable for efficacy. The overall response rate for weekly topotecan was 13.6% 95% CI; − 0.7–27.9% with 1 complete response, and 2 partial responses. Twelve patients (54.5%), including 2 with minor responses, had stable disease for a median duration of 18 weeks. Conclusions. Weekly topotecan at the current schedule in the third-line setting in patients with platinum-sensitive recurrent EOC has modest clinical activity. Toxicity associated with this regimen is acceptable but growth factor support, dose reductions, or schedule alterations may need to be considered in many of these patients.
Purpose
To examine the association between new antipsychotic use and mortality over 6 months among community‐based older adults with cognitive impairment, and variation in risk by frailty and sex.
...Methods
We conducted a retrospective cohort study of older (aged 66+) home care clients in Ontario, Canada, using linked administrative health and clinical databases. Included were clients with dementia and/or significant cognitive impairment assessed during April 2008 to March 2013. Frailty was defined using a validated 72‐item index. Exposed were those newly dispensed an antipsychotic in the 6 months post cohort entry, with no such claims in the year prior to drug index date. Two‐stage matching defined unexposed clients and their index date (matching on age, sex, frailty, assessment year, and propensity score). Outcome was time to death following index date. Cause‐specific hazards models were used, and number needed to harm at 6 months was estimated from cumulative incidence function curves.
Results
Among 4955 matched exposed‐unexposed pairs, new antipsychotic users showed a significantly increased hazard of mortality at 1, 3, and 6 months relative to unexposed, with the highest risk observed in the first month (hazard ratio HR = 2.08 95% CI, 1.79‐2.43). At 1 month, risk was significantly higher for robust (HR = 3.72 95% CI, 2.45‐5.66) vs frail (HR = 1.74 95% CI, 1.40‐2.17, P = .002) clients. The number needed to harm was 22.7 and did not vary by frailty but was lower for men (14.9) than for women (35.0).
Conclusions
Risk of antipsychotic‐associated mortality was highest in the first month following exposure, varied significantly by client frailty, and was greater among men than among women.
Importance Persons with dementia and Parkinson disease (PD) are vulnerable to disruptions in health care and services. Objective To examine changes in health service use among community-dwelling ...persons with dementia, persons with PD, and older adults without neurodegenerative disease during the first wave of the COVID-19 pandemic. Design, Setting, and Participants Repeated cross-sectional analysis using population-based administrative data among community-dwelling persons with dementia, persons with PD, and adults 65 years and older at the start of each week from March 1 through the week of September 20, 2020 (pandemic period), and March 3 through the week of September 22, 2019 (historical period), in Ontario, Canada. Exposures COVID-19 pandemic as of March 1, 2020. Main Outcomes and Measures Main outcomes were weekly rates of emergency department visits, hospitalizations, nursing home admissions, home care, virtual and in-person physician visits, and all-cause mortality. Poisson regression models were used to calculate weekly rate ratios (RRs) with 95% CIs comparing pandemic weeks with historical levels. Results Among those living in the community as of March 1, 2020, persons with dementia (n = 131 466; mean SD age, 80.1 10.1 years) were older than persons with PD (n = 30 606; 73.7 10.2 years) and older adults (n = 2 363 742; 74.0 7.1 years). While all services experienced declines, the largest drops occurred in nursing home admissions (RR for dementia: 0.10; 95% CI, 0.07-0.15; RR for PD: 0.03; 95% CI, 0.00-0.21; RR for older adults: 0.11; 95% CI, 0.06-0.18) and emergency department visits (RR for dementia: 0.45; 95% CI, 0.41-0.48; RR for PD: 0.40; 95% CI, 0.34-0.48; RR for older adults: 0.45; 95% CI, 0.44-0.47). After the first wave, most services returned to historical levels except physician visits, which remained elevated (RR for dementia: 1.07; 95% CI, 1.05-1.09; RR for PD: 1.10, 95% CI, 1.06-1.13) and shifted toward virtual visits. Older adults continued to experience lower hospitalizations. All-cause mortality was elevated across cohorts. Conclusions and Relevance In this population-based repeated cross-sectional study in Ontario, Canada, those with dementia, those with PD, and older adults sought hospital care far less than usual, were not admitted to nursing homes, and experienced excess mortality during the first wave of the pandemic. Most services returned to historical levels, but virtual physician visits remained a feature of care. While issues of equity and quality of care are still emerging among persons with neurodegenerative diseases, policies to support virtual care are necessary.
Background
Little has been quantified, at a population‐level, about the magnitude of heath service disruption to persons living with dementia in community settings during the COVID‐19 pandemic. ...Sustained access to health care services is particularly important for persons with dementia and other neurodegenerative diseases as they are vulnerable to decline.
Method
Health administrative data from Ontario, Canada were used to examine patterns of health service use among all persons with Alzheimer disease and related dementias (dementia) who were alive and living in the community. This cohort was compared to persons with Parkinson’s disease (PD) as well as all older adults (age 65+ years) without neurodegenerative diseases. Rates of all‐cause hospital admissions, emergency department visits, primary care and specialist physician visits and home care visits were analyzed for all individuals alive and eligible for provincial health insurance at the start of each weekly period from March 1, 2020 to September 20, 2020 (pandemic period) and from March 3, 2019 to September 22, 2019 (pre‐pandemic period). Rates of health service use during specific weeks in the pandemic period (i.e., lowest week, last available week) were compared to corresponding weeks in the pre‐pandemic period within each cohort using percent changes.
Results
On March 1, 2020, 128,696 persons with dementia, 30,099 with PD and 2,460,358 older adults were eligible for provincial health services. Across cohorts and services, dramatic declines in use of health services were observed at the lowest week: hospitalization (‐38.7% dementia, ‐72.3% PD, ‐44.2% older adults); emergency department (‐54.9% dementia, ‐57.7% PD, ‐53.6% older adults); home care (‐14.8% dementia, ‐19.4% PD, ‐7.4% older adults). Health services varied in how quickly they rebounded to pre‐pandemic levels within cohorts; notably, by the end of the study period, emergency department visits had increased to a level higher than corresponding 2019 weekly rates (24.2% dementia, 15.2% PD, 7.4% older adults).
Conclusions
The first wave of the COVID‐19 pandemic meaningfully and immediately disrupted use of health care services for persons living with dementia and PD and may have resulted in long‐term consequences that should be monitored.
Background
Neurological disorders and mental health conditions, including mood/anxiety disorders, are a leading cause of disability and healthcare use. These disorders have shared risk factors and ...commonly co‐occur in older adults. Mood/anxiety disorders are often under‐diagnosed and under‐treated among those with neurological disorders, potentially leading to more rapid symptom progression, worse health outcomes and increased health care use. We estimated the relative and absolute rates of neurological and mood/anxiety disorder comorbidity among adults in Ontario, Canada.
Method
We identified adults aged 40‐85 years on April 1st, 2002 in Ontario, Canada using health administrative databases. These individuals were followed for up to 14 years until March 31st, 2016. We estimated the association between between having a prior neurological disorder (dementia, Parkinson’s disease (PD), and stroke) or mood/anxiety disorder and developing a different, incident neurological or mood/anxiety disorder using cause‐specific hazard models. Exposure to prior disorders was modeled as a time‐varying covariate and death was considered a competing risk. Individuals who were not at risk for the specific incident outcome disorder were excluded from that model.
Result
All prior disorders were associated with increased rates of dementia: PD (adjHR= 4.05, 95%CI, 3.99‐4.11), stroke (adjHR=2.49, 95%CI, 2.47‐2.52), and mood/anxiety disorder (adjHR=1.79, 95%CI, 1.78‐1.80). Increased rates of PD were associated with prior dementia (adjHR=2.23, 95%CI, 2.17‐2.30) and mood/anxiety disorder (adjHR=1.77, 95% CI 1.74‐1.81), but not stroke (adjHR=1.04, 95% CI, 0.99 to 1.10). Rates of stroke were highest in persons with prior dementia (adjHR=1.56, 95% CI, 1.53 to 1.58) and showed more modest associations with PD (adjHR=1.21, 95% CI, 1.16 to 1.25) and mood/anxiety disorder (adjHR=1.09, 95% CI, 1.08 to 1.11). The associations were generally strongest in the six months following the prior disorder diagnosis, lowest in the interim periods (>six months to 10 years) and elevated in the later periods (10+ years) following diagnosis.
Conclusion
We observed associations between pairs of prior and incident neurological disorders and mood/anxiety disorder among middle‐ and older‐aged adults. Neurological and mental health comorbidity is common. This should be considered in clinical practice guidelines for these conditions and may necessitate care across multiple providers.
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