Early Experience with Modified Dose Nirmatrelvir/Ritonavir in Dialysis Patients with Coronavirus Disease 2019.

BACKGROUND: Nirmatrelvir/ritonavir was approved for use in high-risk outpatients with coronavirus disease 2019 (COVID-19). However, patients with severe CKD were excluded from the phase 3 trial, and the drug is not recommended for those with GFR <30 ml/min per 1.73 m 2 . On the basis of available pharmacological data, we developed a modified low-dose regimen of nirmatrelvir/ritonavir 300/100 mg on day 1, followed by 150/100 mg daily from day 2 to 5. In this study, we report our experience with this modified dose regimen in dialysis patients in the Canadian province of Ontario. METHODS: We included dialysis patients who developed COVID-19 and were treated with the modified dose nirmatrelvir/ritonavir regimen during a 60-day period between April 1 and May 31, 2022. Details of nirmatrelvir/ritonavir use and outcomes were captured manually, and demographic data were obtained from a provincial database. Data are presented with descriptive statistics. The principal outcomes we describe are 30-day hospitalization, 30-day mortality, and required medication changes with the modified dose regimen. RESULTS: A total of 134 dialysis patients with COVID-19 received nirmatrelvir/ritonavir during the period of study. Fifty-six percent were men, and the mean age was 64 years. Most common symptoms were cough and/or sore throat (60%). Medication interactions were common with calcium channel blockers, statins being the most frequent. Most patients (128, 96%) were able to complete the course of nirmatrelvir/ritonavir, and none of the patients who received nirmatrelvir/ritonavir died of COVID-19 in the 30 days of follow-up. CONCLUSIONS: A modified dose of nirmatrelvir/ritonavir use was found to be safe and well tolerated, with no serious adverse events being observed in a small sample of maintenance dialysis patients.

The three-dimensional shoulder pain alignment (3D-SPA) mobilization improves pain-free shoulder range, functional reach and sleep following stroke: a pilot randomized control trial.

Background and purpose: Following a stroke, three-dimensional clavicular/scapular/humeral joint rotations may become restricted and contribute to post-stroke shoulder pain. This study examined whether a treatment group provided with current standard treatment plus the proposed "Three-dimensional Shoulder Pain Alignment" mobilization protocol demonstrated improved pain-free shoulder range, functional reach and sleep compared to a control group provided with standard treatment alone.Methods: In this double-blinded parallel-group randomized control trial, treatment and control subjects with moderate/severe post-stroke upper extremity impairment and shoulder pain were treated 3x/week for 4 weeks. Outcome measures included changes in pain-free three-dimensional clavicular/scapular/humeral range (using computerized digitization), pain during sleep and functional reach (using the Pain Intensity-Numerical Rating Scale), and pain location/prognostic indicators (using the Chedoke-McMaster Stroke Assessment-Shoulder Pain Inventory).Results: Compared to controls (n = 10) the treatment group (n = 10) demonstrated significantly improved three-dimensional clavicular/scapular/humeral pain-free range during shoulder flexion and abduction (p < 0.05; Hedges g > 0.80), large effect sizes for decreased pain during sleep and functional reach to the head and back (OR range: 5.44-21.00), and moderate effect size for improved pain/prognostic indicators (OR = 3.86).Conclusions: The Three-Dimensional Shoulder Pain Alignment mobilization protocol significantly improved pain-free range of motion, functional reach and pain during sleep in shoulders with moderate/severe post-stroke upper-extremity impairment.Implications for rehabilitationAlthough three-dimensional clavicular/scapular/humeral rotations are an essential component of normal pain-free shoulder range of motion, current guidelines for treatment of post-stroke shoulder pain only includes uni-dimensional mobilizations for joint alignment and pain management.The Three-Dimensional Shoulder Pain Alignment (3D-SPA) mobilization protocol incorporates multi-dimensional mobilizations in various planes of shoulder movement.The current study results demonstrate proof-of-concept regarding the 3D-SPA mobilization, and this approach should be considered as an alternative to the uni-dimensional mobilizations currently used in clinical treatment guidelines for post-stroke shoulder pain.

Three-dimensional assessment of the asymptomatic and post-stroke shoulder: intra-rater test-retest reliability and within-subject repeatability of the palpation and digitization approach.

Purpose: Altered three-dimensional (3D) joint kinematics can contribute to shoulder pathology, including post-stroke shoulder pain. Reliable assessment methods enable comparative studies between asymptomatic shoulders of healthy subjects and painful shoulders of post-stroke subjects, and could inform treatment planning for post-stroke shoulder pain. The study purpose was to establish intra-rater test-retest reliability and within-subject repeatability of a palpation/digitization protocol, which assesses 3D clavicular/scapular/humeral rotations, in asymptomatic and painful post-stroke shoulders. Methods: Repeated measurements of 3D clavicular/scapular/humeral joint/segment rotations were obtained using palpation/digitization in 32 asymptomatic and six painful post-stroke shoulders during four reaching postures (rest/flexion/abduction/external rotation). Intra-class correlation coefficients (ICCs), standard error of the measurement and 95% confidence intervals were calculated. Results: All ICC values indicated high to very high test-retest reliability (≥0.70), with lower reliability for scapular anterior/posterior tilt during external rotation in asymptomatic subjects, and scapular medial/lateral rotation, humeral horizontal abduction/adduction and axial rotation during abduction in post-stroke subjects. All standard error of measurement values demonstrated within-subject repeatability error ≤5° for all clavicular/scapular/humeral joint/segment rotations (asymptomatic ≤3.75°; post-stroke ≤5.0°), except for humeral axial rotation (asymptomatic ≤5°; post-stroke ≤15°). Conclusions: This noninvasive, clinically feasible palpation/digitization protocol was reliable and repeatable in asymptomatic shoulders, and in a smaller sample of painful post-stroke shoulders. Implications for Rehabilitation In the clinical setting, a reliable and repeatable noninvasive method for assessment of three-dimensional (3D) clavicular/scapular/humeral joint orientation and range of motion (ROM) is currently required. The established reliability and repeatability of this proposed palpation/digitization protocol will enable comparative 3D ROM studies between asymptomatic and post-stroke shoulders, which will further inform treatment planning. Intra-rater test-retest repeatability, which is measured by the standard error of the measure, indicates the range of error associated with a single test measure. Therefore, clinicians can use the standard error of the measure to determine the "true" differences between pre-treatment and post-treatment test scores.

The Incidence of Major Cardiovascular Events in Immigrants to Ontario, Canada: The CANHEART Immigrant Study.

BACKGROUND: Immigrants from ethnic minority groups represent an increasing proportion of the population in many high-income countries but little is known about the causes and amount of variation between various immigrant groups in the incidence of major cardiovascular events. METHODS AND RESULTS: We conducted the Cardiovascular Health in Ambulatory Care Research Team (CANHEART) Immigrant study, a big data initiative, linking information from Citizenship and Immigration Canada's Permanent Resident database to nine population-based health databases. A cohort of 824 662 first-generation immigrants aged 30 to 74 as of January 2002 from eight major ethnic groups and 201 countries of birth who immigrated to Ontario, Canada between 1985 and 2000 were compared to a reference group of 5.2 million long-term residents. The overall 10-year age-standardized incidence of major cardiovascular events was 30% lower among immigrants compared with long-term residents. East Asian immigrants (predominantly ethnic Chinese) had the lowest incidence overall (2.4 in males, 1.1 in females per 1000 person-years) but this increased with greater duration of stay in Canada. South Asian immigrants, including those born in Guyana had the highest event rates (8.9 in males, 3.6 in females per 1000 person-years), along with immigrants born in Iraq and Afghanistan. Adjustment for traditional risk factors reduced but did not eliminate differences in cardiovascular risk between various ethnic groups and long-term residents. CONCLUSIONS: Striking differences in the incidence of cardiovascular events exist among immigrants to Canada from different ethnic backgrounds. Traditional risk factors explain part but not all of these differences.

The Risk of Ischemic Heart Disease and Stroke Among Immigrant Populations: A Systematic Review.

BACKGROUND: The increasing frequency of global migration to Canada and other high-income countries has highlighted the need for information on the risk of ischemic heart disease (IHD) and stroke among migrant populations. METHODS: Using the MEDLINE and EMBASE databases, we conducted an English-language literature review of articles published from 2000 to 2014 to study patterns in the incidence of IHD or stroke in migrant populations to high-income countries. Our search revealed 17 articles of interest. All studies stratified immigrants according to country or region of birth, except 2 from Canada and 1 from Denmark, in which all immigrant groups were analyzed together. RESULTS: The risk of IHD or stroke varied by country of origin, country of destination, and duration of residence. In our review we found that most migrant groups to Western Europe were at a similar or higher risk of IHD and stroke compared with the host population. Those at a higher risk included many Eastern European, Middle-Eastern, and South Asian immigrants. When duration of residence was considered, it appeared that in most migrants the risk of IHD worsened over time. In contrast, immigrants overall were at lower risk of myocardial infarction and stroke in Ontario compared with long-term residents of Canada. CONCLUSIONS: The risks of IHD and stroke vary widely in immigrant populations in Western Europe. Detailed studies of immigrants to Canada according to country of birth and duration of residence should be undertaken to guide future cardiovascular health promotion initiatives.

A three-dimensional approach to pennation angle estimation for human skeletal muscle.

Pennation angle (PA) is an important property of human skeletal muscle that plays a significant role in determining the force contribution of fascicles to skeletal movement. Two-dimensional (2D) ultrasonography is the most common approach to measure PA. However, in principle, it is challenging to infer knowledge of three-dimensional (3D) architecture from 2D assessment. Furthermore, architectural complexity and variation impose more difficulties on reliable and consistent quantification of PA. Thus, the purpose of our study is to provide accurate insight into the correspondence between 2D assessment and the underlying 3D architecture. To this end, a 3D method was developed to directly quantify PA based on 3D architectural data that were acquired from cadaveric specimens through dissection and digitization. Those data were then assessed two-dimensionally by simulating ultrasound imaging. To achieve consistency over intermuscular variation, our proposed 3D method is based on the geometric analysis of fascicle attachment. Comparative results show a wide range of differences (1.1-47.1%) between 2D and 3D measurements. That is, ultrasound can under- or over-estimate PA, depending on the architecture.