Secondary prevention after stroke and transient ischemic attack (TIA) has focused on high early risk of recurrence, but survivors of stroke can have substantial long-term morbidity and mortality. We ...quantified long-term morbidity and mortality for patients who had no early complications after stroke or TIA and community-based controls.
This longitudinal case-control study included all ambulatory or hospitalized patients with stroke or TIA (discharged from regional stroke centres in Ontario from 2003 to 2013) who survived for 90 days without recurrent stroke, myocardial infarction, all-cause admission to hospital, admission to an institution or death. Cases and controls were matched on age, sex and geographic location. The primary composite outcome was death, stroke, myocardial infarction, or admission to long-term or continuing care. We calculated 1-, 3- and 5-year rates of composite and individual outcomes and used cause-specific Cox regression to estimate long-term hazards for cases versus controls and for patients with stroke versus those with TIA.
Among patients who were initially stable after stroke or TIA (
= 26 366), the hazard of the primary outcome was more than double at 1 year (hazard ratio HR 2.4, 95% confidence interval CI 2.3-2.5), 3 years (HR 2.2, 95% CI 2.1-2.3) and 5 years (HR 2.1, 95% CI 2.1-2.2). Hazard was highest for recurrent stroke at 1 year (HR 6.8, 95% CI 6.1-7.5), continuing to 5 years (HR 5.1, 95% CI 4.8-5.5), and for admission to an institution (HR 2.1, 95% CI 1.9-2.2). Survivors of stroke had higher mortality and morbidity, but 31.5% (1789/5677) of patients with TIA experienced an adverse event within 5 years.
Patients who survive stroke or TIA without early complications are typically discharged from secondary stroke prevention services. However, these patients remain at substantial long-term risk, particularly for recurrent stroke and admission to an institution. Novel approaches to prevention, potentially embedded in community or primary care, are required for long-term management of these initially stable but high-risk patients.
Although endogenous fistulae and grafts are preferred for permanent hemodialysis access, central venous catheters are often required for varying intervals when creating permanent access is not ...feasible. The prospective experience with 118 catheters in over a 3.5-yr period is reported; 93 (79%) were placed by percutaneous techniques, and 25 (21%) were placed by operative techniques. Seventy seven catheters (65%) were placed in the subclavian vein, 36 (31%) were placed in the internal jugular vein (usually right side), and 5 (4%) were placed in the femoral vein. Early postplacement complications were infrequent. Catheter function at last local follow-up ranged from several days to nearly 2 yr, averaging approximately 3 mo, even though many patients returned to their referring centers with a functioning catheter after only a short follow-up. Actuarial survival for percutaneously placed catheters was approximately 60% at 6 mo and 30% at 12 mo. Catheter failure occurred in 36% of cases, equally divided between malfunction (thrombosis refractory to fibrinolysis, extrusion, kinking, or related event) and infection with septicemia requiring removal. Such failure was not more frequent after percutaneous placement than after operative placement. Failure due to mechanical malfunction, but not that due to infection, tended to be less frequent among catheters placed in the internal jugular vein than among catheters placed in the subclavian vein. Finally, infection with septicemia involved 22% of all catheters and occurred at an average cumulated rate of approximately one infection per patient-year. Coagulase-positive staphylococcus was the most common organism isolated.
When a schizophrenia patient has an inadequate response to treatment with an antipsychotic drug, it is unclear what other antipsychotic to switch to and when to use clozapine. In this study, the ...authors compared switching to clozapine with switching to another atypical antipsychotic in patients who had discontinued treatment with a newer atypical antipsychotic in the context of the Clinical Antipsychotic Trials for Interventions Effectiveness (CATIE) investigation.
Ninety-nine patients who discontinued treatment with olanzapine, quetiapine, risperidone, or ziprasidone in phase 1 or 1B of the trials, primarily because of inadequate efficacy, were randomly assigned to open-label treatment with clozapine (N=49) or blinded treatment with another newer atypical antipsychotic not previously received in the trial (olanzapine N=19, quetiapine N=15, or risperidone N=16).
Time until treatment discontinuation for any reason was significantly longer for clozapine (median=10.5 months) than for quetiapine (median=3.3), or risperidone (median=2.8), but not for olanzapine (median=2.7). Time to discontinuation because of inadequate therapeutic effect was significantly longer for clozapine than for olanzapine, quetiapine, or risperidone. At 3-month assessments, Positive and Negative Syndrome Scale total scores had decreased more in patients treated with clozapine than in patients treated with quetiapine or risperidone but not olanzapine. One patient treated with clozapine developed agranulocytosis, and another developed eosinophilia; both required treatment discontinuation.
For these patients with schizophrenia who prospectively failed to improve with an atypical antipsychotic, clozapine was more effective than switching to another newer atypical antipsychotic. Safety monitoring is necessary to detect and manage clozapine's serious side effects.
Flight is a demanding form of locomotion, requiring fast activation and relaxation in wing muscles to produce the necessary wingbeat frequencies. Bats maintain high body temperatures during flight, ...but their wing muscles cool under typical environmental conditions. Because distal wing muscles are colder during flight than proximal muscles, we hypothesized that they would be less temperature sensitive to compensate for temperature effects, resulting in proximal-distal differences in temperature sensitivity that match differences in muscle operating temperature. We measured contractile rates across temperatures in the proximal pectoralis muscle and an interosseous in the handwing of
, a small neotropical fruit bat, and compared their thermal dependence with that of a forearm muscle measured in a previous study. We found that the contractile properties of the pectoralis were significantly more temperature sensitive than those of the distal muscles. This suggests that cooling of the distal wing muscles imposes a selective pressure on muscle contractile function which has led to shifts in temperature sensitivity. This study is the first to demonstrate differences in temperature sensitivity along the length of a single limb in an endotherm and suggests that temperature variation may be underappreciated as a determinant of locomotor performance in endotherms generally.
The challenges of conducting hyperacute stroke research and obtaining informed consent have been increasingly recognized within the stroke research community in recent years. Deferral of consent, in ...which a patient is enrolled in a trial and then provides consent at some point thereafter, is increasingly used to enroll patients into hyperacute stroke trials in Canada and Europe, although it is not permitted in the United States. Deferral of consent offers several potential advantages-quicker door-to-randomization, increased enrolment, decreased selection bias-but these must be balanced against the risk of enrolling patients against their wishes. We seek to minimize the attendant risks of deferral of consent by offering practical guidance regarding how to conduct acute stroke trials using deferral of consent. Building on existing guidelines and recent experiences with deferral of consent in acute stroke trials, we have developed a protocol for the use of deferral of consent that aims to maximize patient involvement while minimizing ethical and scientific risks.
The antihypertensive angiotensin receptor blockers (ARBs) and angiotensin-converting enzyme inhibitors (ACE-Is) have similar indications and mechanisms of action, but prior work suggests divergence ...in their effects on cognition.
Participants in the National Alzheimer's Coordinating Center database with a clinical diagnosis of dementia due to Alzheimer's disease (AD) using an ACE-I or an ARB at any visit were selected. The primary outcome was delayed recall memory on the Wechsler Memory Scale Revised - Logical Memory IIA. Other cognitive domains were explored, including attention and psychomotor processing speed (Trail Making Test TMT-A and Digit Symbol Substitution Test DSST), executive function (TMT-B), and language and semantic verbal fluency (Animal Naming, Vegetable Naming, and Boston Naming Tests). Random slopes mixed-effects models with inverse probability of treatment weighting were used, yielding rate ratios (RR) or regression coefficients (B), as appropriate to the distribution of the data. Apolipoprotein (APOE) ε4 status and blood-brain barrier (BBB) penetrance were investigated as effect modifiers.
Among 1689 participants with AD, ARB use (n = 578) was associated with 9.4% slower decline in delayed recall performance over a mean follow-up of 2.28 years compared with ACE-I use (n = 1111) RR = 1.094, p = 0.0327; specifically, users of BBB-crossing ARBs (RR = 1.25, p = 0.002), BBB-crossing ACE-Is (RR = 1.16, p = 0.010), and non-BBB-crossing ARBs (RR = 1.20, p = 0.005) had better delayed recall performance over time compared with non-BBB-crossing ACE-I users. An interaction with APOE ε4 status (drug × APOE × time RR = 1.196, p = 0.033) emerged; ARBs were associated with better delayed recall scores over time than ACE-Is in non-carriers (RR = 1.200, p = 0.003), but not in carriers (RR = 1.003, p = 0.957). ARB use was also associated with better performance over time on the TMT-A (B = 2.023 s, p = 0.0004) and the DSST (B = 0.573 symbols, p = 0.0485), and these differences were significant among APOE ε4 non-carriers (B = 4.066 s, p = 0.0004; and B = 0.982 symbols, p = 0.0230; respectively). Some differences were seen also in language and verbal fluency among APOE ε4 non-carriers.
Among APOE ε4 non-carriers with AD, ARB use was associated with greater preservation of memory and attention/psychomotor processing speed, particularly compared to ACE-Is that do not cross the blood-brain-barrier.
Type 2 diabetes (T2D) increases dementia risk, but clear evidence to recommend interventions that can mitigate that risk remains lacking. This population-based retrospective cohort study aimed to ...determine whether new use of sodium-glucose cotransporter 2 (SGLT2) inhibitors compared with dipeptidyl peptidase 4 (DPP-4) inhibitors was associated with lower dementia risk.
Ontario residents aged ≥66 years who were new users of an SGLT2 inhibitor or a DPP-4 inhibitor from 1 July 2016 to 31 March 2021 entered the cohort. Incident dementia was identified using a validated algorithm for Alzheimer's disease and related dementias. Propensity score-weighted Cox proportional hazards models were used to obtain adjusted hazard ratios (aHR) and CIs for time to incident dementia. To address reverse causality and disease latency, the observation window started at 1-year lag time from cohort entry. The primary analysis followed intention-to-treat exposure definition, and a secondary as-treated analysis was performed.
Among 106,903 individuals, SGLT2 inhibitors compared with DPP-4 inhibitors were associated with lower risk of dementia (14.2/1,000 person-years; aHR 0.80 95% CI 0.71-0.89) over a mean follow-up of 2.80 years from cohort entry. When stratified by different SGLT2 inhibitors, dapagliflozin exhibited the lowest risk (aHR 0.67 95% CI 0.53-0.84), followed by empagliflozin (aHR 0.78 95% CI 0.69-0.89), whereas canagliflozin showed no association (aHR 0.96 95% CI 0.80-1.16). The as-treated analysis observed a larger association (aHR 0.66 95% CI 0.57-0.76) than the intention-to-treat analysis.
SGLT2 inhibitors showed an association with lower dementia risk in older people with T2D. Randomized controlled trials are warranted.
Muscle contractile properties are dependent on temperature: cooler temperatures generally slow contractile rates. Contraction and relaxation are driven by underlying biochemical systems, which are ...inherently sensitive to temperature. Carollia perspicillata, a small Neotropical bat, experiences large temperature differentials among body regions, resulting in a steep gradient in temperature along the wing. Although the bats maintain high core body temperatures during flight, the wing muscles may operate at more than 10°C below body temperature. Partially compensating for these colder operating temperatures, distal wing muscles have lower temperature sensitivities in their contractile properties, including shortening velocity, relative to the proximal pectoralis. Shortening velocity is correlated with the activity of myosin ATPase, an enzyme that drives the cross-bridge cycle. We hypothesized that the thermal properties of myofibrillar ATPase from the pectoralis and forearm muscles of the bat wing would correlate with the temperature sensitivity of those muscles. Using myofibrillar ATPases from the proximal and distal muscles, we measured enzyme activity across a range of temperatures and enzyme thermal stability after heat incubation across a range of time points. We found that forearm muscle myofibrillar ATPase was significantly less thermally stable than pectoralis myofibrillar ATPase but that there was no significant difference in the acute temperature dependence of enzyme activity between the two muscles.
Venous thromboembolism (VTE) is a leading cause of maternal mortality. Obesity and cesarean delivery are established risk factors for pregnancy-related VTE. We identified additional risk factors ...among patients with obesity who underwent a cesarean delivery to identify those who need VTE prophylaxis. We conducted a secondary analysis of data from the Maternal-Fetal Medicine Units Network (MFMU) Cesarean Registry Database using a case-control design. Cases were identified as women with obesity having a pre-pregnancy body mass index of >30 kg/m
, who underwent cesarean delivery and subsequently developed deep venous thrombosis (DVT) or pulmonary embolism (PE). These women were compared to a control group of women with obesity who underwent cesarean delivery but did not develop DVT or PE. Analysis of risk factors associated with VTE was performed using Chi-Square test and Fisher's exact test. We identified 43 VTE cases and 172 controls in the MFMU database. Increased risk of VTE was noted in women with endometritis (OR of 4.58 95% CI: 1.86-11.2,
= .0004), receiving a blood transfusion (OR 17.07 95% CI: 4.46-65.3,
= .0001), having a coagulopathy (OR 27.73 95% CI: 3.24-237.25,
= .0003), and urinary tract infection (OR 2.39 95% CI: 1.08-5.28,
= .03). Important risk factors for VTE in women with obesity who undergo cesarean delivery include endometritis, intra- or post-operative transfusion, coagulopathy, and urinary tract infection. The presence of one or more of these factors may help guide provider decision-making regarding whether to administer thromboprophylaxis.
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