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1.
Eur J Clin Invest ; 54(2): e14106, 2024 Feb.
Article in English | MEDLINE | ID: mdl-37822060

ABSTRACT

BACKGROUND: Left ventricular stroke work index (LVSWI) and afterload-related cardiac performance (ACP) consider left ventricular (LV) afterload and could be better prognosticators in septic cardiomyopathy. However, their invasive nature prevents their routine clinical applications. This study aimed to investigate (1) whether a proposed speckle-tracking echocardiography parameter, Pressure-Strain Product (PSP), can non-invasively predict catheter-based LVSWI, ACP and serum lactate in an ovine model of septic cardiomyopathy; and (2) whether PSP can distinguish the sub-phenotypes of acute respiratory distress syndrome (ARDS) with or without sepsis-like conditions. METHODS: Sixteen sheep with ARDS were randomly assigned to either (1) sepsis-like (n = 8) or (2) non-sepsis-like (n = 8) group. Each ARDS and sepsis-like condition was induced by intravenous infusion of oleic acid and lipopolysaccharide, respectively. Pulmonary artery catheter-based LVSWI (the product of stroke work index, mean arterial pressure and .0136), ACP (the percentage of cardiac output measured to cardiac output predicted as normal) and serum lactate were measured simultaneously with transthoracic echocardiography. Two PSP indices were calculated by multiplying the mean arterial blood pressure and either global circumferential strain (PSPcirc) or radial strain (PSPrad). RESULTS: PSPcirc showed a significant correlation with LVSWI (r2 = .66, p < .001) and ACP (r2 = .82, p < .001) in the sepsis-like group. Although PSP could not distinguish subphenotypes, PSPcirc predicted LVSWI (AUC .86) and ACP (AUC .88), and PSPrad predicted serum lactate (AUC .75) better than LV ejection fraction, global circumferential and radial strain. CONCLUSIONS: A novel PSP has the potential to non-invasively predict catheter-based LVSWI and ACP, and was associated with serum lactate in septic cardiomyopathy.


Subject(s)
Cardiomyopathies , Respiratory Distress Syndrome , Sepsis , Stroke , Ventricular Dysfunction, Left , Animals , Sheep , Echocardiography , Stroke Volume , Ventricular Function, Left , Lactates , Ventricular Dysfunction, Left/diagnostic imaging
2.
Eur J Clin Invest ; : e14263, 2024 Jun 07.
Article in English | MEDLINE | ID: mdl-38849326

ABSTRACT

BACKGROUND: Left ventricular stroke work index (LVSWI) and cardiac power index (CPI) account for the haemodynamic load of the left ventricle and are promising prognostic values in cardiogenic shock. However, accurately and non-invasively measuring these parameters during veno-arterial extracorporeal membrane oxygenation (V-A ECMO) is challenging and potentially biased by the extracorporeal circulation. This study aimed to investigate, in an ovine model of cardiogenic shock, whether Pressure-Strain Product (PSP), a novel speckle-tracking echocardiography parameter, (1) can correlate with pressure-volume catheter-based LVSWI and CPI, and (2) can be load-independent during the flow modification of V-A ECMO. METHODS: Nine Dorset-cross ewes (51 ± 4 kg) were included. After cardiogenic shock was induced, full support V-A ECMO (X L/min based on 60 mL/kg/min) commenced. At seven time points during 24-h observation, echocardiographic parameters as well as pressure-volume catheter-based LVSWI and CPI were simultaneously measured with X and following X-1 L/min of ECMO flow. PSP was calculated by multiplying global circumferential strain or global radial strain, and mean arterial pressure, for PSPcirc or PSPrad, respectively. RESULTS: PSPcirc showed a stronger correlation with LVSWI (correlation coefficient, CC = .360, p < .001) and CPI (CC = .283, p < .001) than other echocardiographic parameters. The predictability of PSPcirc for pressure-volume catheter-based LVSWI (AUC .82) and CPI (AUC .80) was also higher than other echocardiographic parameters. No statistically significant differences were identified between the two ECMO flow variations in PSPcirc (p = .558). CONCLUSIONS: A novel echocardiographic parameter, PSP, may non-invasively predict pressure-volume catheter-based LVSWI and CPI in a load-independent manner in a cardiogenic shock supported by V-A ECMO.

3.
Eur J Clin Invest ; : e14259, 2024 Jun 06.
Article in English | MEDLINE | ID: mdl-38845111

ABSTRACT

BACKGROUND: The commonest echocardiographic measurement, left ventricular ejection fraction, can not necessarily predict mortality of recipients following heart transplantation potentially due to afterload dependency. Afterload-independent left ventricular stroke work index (LVSWI) is alternatively recommended by the current guideline; however, pulmonary artery catheters are rarely inserted in organ donors in most jurisdictions. We propose a novel non-invasive echocardiographic parameter, Pressure-Strain Product (PSP), as a potential surrogate of catheter-based LVSWI. This study aimed to investigate if PSP could correlate with catheter-based LVSWI in an ovine model of brain stem death (BSD) donors. The association between PSP and myocardial mitochondrial function in the post-transplant hearts was also evaluated. METHODS: Thirty-one female sheep (weight 47 ± 5 kg) were divided into two groups; BSD (n = 15), and sham neurologic injury (n = 16). Echocardiographic parameters including global circumferential strain (GCS) and global radial strain (GRS) and pulmonary artery catheter-based LVSWI were simultaneously measured at 8-timepoints during 24-h observation. PSP was calculated as a product of GCS or GRS, and mean arterial pressure for PSPcirc or PSPrad, respectively. Myocardial mitochondrial function was evaluated following 6-h observation after heart transplantation. RESULTS: In BSD donor hearts, PSPcirc (n = 96, rho = .547, p < .001) showed the best correlation with LVSWI among other echocardiographic parameters. PSPcirc returned AUC of .825 to distinguish higher values of cardiomyocyte mitochondrial function (cut-off point; mean value of complex 1,2 O2 Flux) in post-transplant hearts, which was greater than other echocardiographic parameters. CONCLUSIONS: PSPcirc could be used as a surrogate of catheter-based LVSWI reflecting mitochondrial function.

4.
J Rheumatol ; 51(5): 479-487, 2024 May 01.
Article in English | MEDLINE | ID: mdl-38359937

ABSTRACT

OBJECTIVE: Although patient outcomes in psoriatic arthritis (PsA) have improved with the advent of advanced therapies, there remains a high unmet need to treat residual disease activity. The objective of the current study was to quantify residual disease activity and burden of disease in Canadian patients with PsA. METHODS: This was a multiregion, observational, retrospective analysis of patient data extracted from the Rhumadata and the International Psoriasis and Arthritis Research Team (IPART) registries, analyzing deidentified data from patients who had initiated advanced therapy for the treatment of PsA between January 2010 and December 2019. The primary endpoint was the proportion of patients failing to achieve minimal disease activity (MDA) within 6 months; secondary endpoints included clinical and patient-reported burden of disease. Descriptive statistics included summaries by region, treatment class, and number of prior advanced therapies. RESULTS: One thousand five hundred ninety-six patients were included. The proportions of patients who failed to achieve MDA within 6 months of an advanced therapy were 64.8% in Ontario, 68.3% in Western Canada, 74.8% in Quebec, and 75% in the Atlantic/East region. Failure to achieve MDA was higher among patients receiving an IL-17i compared with a TNFi in all regions except the Atlantic/East. Between 73.2% and 78.6% of patients reported pain at 6 months, and continuing functional impairment varied from 24% in the West to 83.3% in the Atlantic/East. CONCLUSION: There is substantial burden and unmet need for improved therapies for Canadians with PsA. There is a wide regional variation in outcomes that requires further assessment.


Subject(s)
Antirheumatic Agents , Arthritis, Psoriatic , Registries , Severity of Illness Index , Humans , Arthritis, Psoriatic/drug therapy , Male , Female , Middle Aged , Canada , Retrospective Studies , Adult , Antirheumatic Agents/therapeutic use , Aged , Treatment Outcome , Cost of Illness
5.
Proc Natl Acad Sci U S A ; 118(40)2021 10 05.
Article in English | MEDLINE | ID: mdl-34599105

ABSTRACT

Although the behavior of single chains is integral to the foundation of polymer science, a clear and convincing image of single chains in the solid state has still not been captured. For bottlebrush polymers, understanding their conformation in bulk materials is especially important because their extended backbones may explain their self-assembly and mechanical properties that have been attractive for many applications. Here, single-bottlebrush chains are visualized using single-molecule localization microscopy to study their conformations in a polymer melt composed of linear polymers. By observing bottlebrush polymers with different side chain lengths and grafting densities, we observe the relationship between molecular architecture and conformation. We show that bottlebrushes are significantly more rigid in the solid state than previously measured in solution, and the scaling relationships between persistence length and side chain length deviate from those predicted by theory and simulation. We discuss these discrepancies using mechanisms inspired by polymer-grafted nanoparticles, a conceptually similar system. Our work provides a platform for visualizing single-polymer chains in an environment made up entirely of other polymers, which could answer a number of open questions in polymer science.

6.
Can Pharm J (Ott) ; 157(4): 190-199, 2024.
Article in English | MEDLINE | ID: mdl-39092087

ABSTRACT

Importance: We designed an online educational program for primary care health care providers, the Hypertension Canada Professional Certification Program (HC-PCP), based upon its 2020 guidelines. Objective: The objective was to determine the effect of the HC-PCP, taken by pharmacists, on systolic blood pressure (BP) in patients with poorly controlled hypertension. Design: Stepped wedge cluster randomized trial (unit of randomization was the pharmacy). Participants: Patients with poorly controlled hypertension (BP >140/90 mmHg or >130/80 mmHg [diabetes]) in community pharmacies in Alberta, Canada, were recruited by their pharmacist. Intervention: Pharmacists completed the HC-PCP program, then provided care to their patients with poorly controlled hypertension according to what they learned in the course. Control: Pharmacists were given a copy of the Hypertension Canada guidelines and provided their usual care to their patients prior to undertaking the HC-PCP later. Main outcome and measure: The primary outcome was a difference in change in systolic BP at 3 months between groups, while the secondary outcome was patient satisfaction with using the Consultation Satisfaction Questionnaire. Results: We enrolled 890 patients from 59 pharmacies (including 104 pharmacists). Using a linear mixed-effect model with BP reduction as the dependent variable and independent variables of treatment allocation, baseline BP, site effect and patient effect, the intervention was associated with a 4.76 mmHg (95% confidence interval, 2.02-7.50, p < 0.0001) systolic BP reduction at 3 months. Patient satisfaction with using the Consultation Satisfaction Questionnaire was high at 75.9 (/90). Conclusion and relevance: Most educational programs are not evaluated at the patient care level. The HC-PCP taken by pharmacists resulted in a 4.76 mmHg systolic BP reduction in their patients over 3 months. This would have major implications for public health, reducing heart disease, stroke and kidney failure.

7.
Methods ; 202: 31-39, 2022 06.
Article in English | MEDLINE | ID: mdl-34090971

ABSTRACT

The trendy task of digital medical image analysis has been continually evolving. It has been an area of prominent and growing importance from both research and deployment perspectives. Nonetheless, it is necessary to realize that the use of algorithms, methodology, as well as the source of medical image data, must be strictly scrutinized. As the COVID-19 pandemic has been gripping much of the world recently, there has been much efforts gone into developing affordable testing for the masses, and it has been shown that the established and widely available chest X-rays (CXR) images may be used as a screening criteria for assistive diagnosis purpose. Thanks to the dedicated work by various individuals and organizations, publicly available CXR of COVID-19 subjects are available for analytic usage. We have also provided a publicly available CXR dataset on the Kaggle platform. As a case study, this paper presents a systematic approach to learn from a typically imbalanced set of CXR images, which consists of a limited number of publicly available COVID-19 images. Our results show that we are able to outperform the top finishers in a related Kaggle multi-class CXR challenge. The proposed methodology should be able to help guide medical personnel in obtaining a robust diagnosis model to discern COVID-19 from other conditions confidently.


Subject(s)
COVID-19 , Deep Learning , COVID-19/diagnostic imaging , Humans , Pandemics , SARS-CoV-2 , Tomography, X-Ray Computed/methods , X-Rays
8.
Clin Exp Dermatol ; 48(9): 1012-1018, 2023 Aug 25.
Article in English | MEDLINE | ID: mdl-37130096

ABSTRACT

BACKGROUND: It is unclear if ambient temperature changes affect eczema. It is also unclear if people with worse disease are more susceptible to weather-related flares, or specific types of emollient offer protection. OBJECTIVES: To investigate the effect of short-term temperature variations on eczema symptoms in children. METHODS: Data from a UK cohort of 519 children with eczema were combined with data from the Hadley Centre's Integrated Surface Database. Hot and cold weeks were defined by average regional temperature > 75th or < 25th percentile, January 2018 to February 2020. Eczema flares were defined as ≥ 3-point change in Patient-Oriented Eczema Measure (POEM). Random-effects logistic regression models were used to estimate the odds ratios of flares in hot and cold weeks (reference group: temperate weeks). RESULTS: The baseline mean age was 4.9 years (SD 3.2) and the POEM score was 9.2 (SD 5.5). From the 519 participants, there were 6796 consecutively paired POEMs and 1082 flares. Seasonal variation in POEM scores was observed, suggesting symptoms worsening in winter and improving in summer. Odds ratios of flares were: 1.15 [95% confidence interval (CI) 0.96-1.39, P = 0.14] in cold weeks and 0.85 (95% CI 0.72-1.00, P = 0.05) in hot weeks. The likelihood ratio test showed no evidence of this differing by disease severity (P = 0.53) or emollient type used (P = 0.55). CONCLUSIONS: Our findings are consistent with previous studies demonstrating either improvements in eczema symptoms or reduced flares in hot weather. Worse disease and different emollient types did not increase susceptibility or provide protection against temperature changes. Further work should investigate the role of sunlight, humidity, pollution and other environmental factors.


Subject(s)
Eczema , Emollients , Child , Humans , Child, Preschool , Emollients/therapeutic use , Cohort Studies , Temperature , Eczema/epidemiology , Eczema/drug therapy , Severity of Illness Index
9.
BMC Ophthalmol ; 23(1): 71, 2023 Feb 16.
Article in English | MEDLINE | ID: mdl-36797698

ABSTRACT

BACKGROUND/AIMS: To assess the normative values and parameters of optical coherence tomography angiography (OCTA) influencing the best corrected visual acuity (BCVA) in adults aged 50 and above. METHODS: This was a prospective cross-sectional study from an eye screening programme in Hong Kong for 4188 citizens aged 50 and above. Images were analysed using a validated quantification software calculating vessel density and capillary perfusion density (CPD), along with other OCTA parameters, such as the foveal avascular zone area (FAZ) and circularity. OCTA data was collected from May 2019 to December 2020, including a total of 4188 healthy eyes from 4188 subjects. RESULTS: Mean superficial vessel density (MSVD) was 14.48 ± 3.60 mm- 1, while the mean capillary perfusion density (MCPD) was 0.41 ± 0.06. Multivariate analysis revealed ageing (ß = 0.321, p < 0.001), being male (ß=-0.089, p < 0.001), having a high body mass index (BMI) (ß = 0.039, p = 0.006), high FAZ area and low FAZ circularity (ß = 0.039 and - 0.034, p = 0.01 and 0.024 respectively), low MSVD in the outer ring (ß=-0.513, p < 0.001), specifically in the nasal and temporal outer quadrants (ß = -0.226 and - 0.259, p < 0.001 for both), and low MCPD in the outer superior quadrant (ß= -0.123, p = 0.016) being independently associated with BCVA. CONCLUSION: High FAZ area and low FAZ circularity, low MSVD in the outer ring, specifically the nasal and temporal outer quadrants, and low MCPD in the outer superior quadrant can be used as biomarkers in predicting a low visual acuity in adults aged 50 and above.


Subject(s)
Macula Lutea , Retinal Vessels , Humans , Adult , Male , Female , Cross-Sectional Studies , Fluorescein Angiography/methods , Tomography, Optical Coherence/methods , Prospective Studies , Macula Lutea/blood supply , Fundus Oculi , Biomarkers
10.
Echocardiography ; 40(11): 1251-1258, 2023 11.
Article in English | MEDLINE | ID: mdl-37855213

ABSTRACT

INTRODUCTION: Coronary computed tomography angiography (CCTA) is known to have a high negative predictive value (NPV) in identifying coronary artery disease (CAD). This study aimed to examine whether resting echocardiographic parameters could exclude significant CAD on CCTA. METHODS: We recruited 142 patients who had undergone both CCTA and echocardiography within a 3-month window. Based on the CCTA findings, patients were divided into two groups: Group A (non-significant CAD, defined as all coronary segments having <50% stenosis) and Group B (significant CAD). Resting echocardiographic parameters were compared between the two groups to identify predictors of non-significant CAD on CCTA. RESULTS: A total 92 patients (mean age, 68 ± 13 years; males, 62%) were eligible for this study; 50 in Group A and 42 in Group B. Among the various echo parameters, left atrial volume index (LAVI) and left ventricular (LV) global longitudinal strain (GLS) were significantly lower in Group A (23.5 ± 7.6 vs. 33.6 ± 7.4 mL/m2 , p < .001; -20.2 ± 1.8% vs. -16.8 ± 2.0%, p < .001, respectively). Analysis of the receiver operating characteristic curve revealed that the cutoff value to exclude significant CAD on CCTA was 29.0 mL/m2 for LAVI (NPV 80.8%) and -18.1% for GLS (NPV 80.7%). The NPV increased to 95.0% when these parameters were combined (LAVI < 29.0 mL/m2 and GLS < -18.1%). CONCLUSION: The combination of resting LAVI and GLS was clinically useful in excluding significant CAD via CCTA.


Subject(s)
Coronary Artery Disease , Coronary Stenosis , Male , Humans , Middle Aged , Aged , Aged, 80 and over , Coronary Artery Disease/diagnostic imaging , Computed Tomography Angiography , Echocardiography/methods , Tomography, X-Ray Computed/methods , Predictive Value of Tests , Coronary Angiography/methods
11.
Nano Lett ; 22(14): 5891-5897, 2022 07 27.
Article in English | MEDLINE | ID: mdl-35786930

ABSTRACT

The orientation of chains within polymeric materials influences their electrical, mechanical, and thermal properties. While many techniques can infer the orientation distribution of a bulk ensemble, it is challenging to determine this information at the single-chain level, particularly in an environment of otherwise identical polymers. Here, we use single-molecule localization microscopy (SMLM) to visualize the directions of chains within spin-coated polymer films. We find a strong relationship between shear force and the degree and direction of orientation, and additionally, we reveal the effects of chain length and solvent evaporation rate. This work utilizes single-chain resolution to observe the important, though often overlooked, property of chain orientation in the common fabrication process of spin-coating.


Subject(s)
Polymers , Solvents
12.
Medicina (Kaunas) ; 59(2)2023 Feb 16.
Article in English | MEDLINE | ID: mdl-36837589

ABSTRACT

Sodium glucose cotransporter 2 inhibitor (SGLT2i) is a class of drugs that were originally intended for decreasing blood glucose in diabetes. However, recent trials have shown that there are other beneficial effects. Major clinical trials involving SGLT2i medications from 2015 to 2022 were reviewed using PUBMED search. Recent major SGLT2i landmark trials have demonstrated benefits for cardiovascular disease (reduce major adverse cardiovascular events (heart attack, stroke, cardiovascular death), hospitalization for heart failure, all-cause death), and renal disease (delay the onset of dialysis) regardless of diabetic status. The consistent cardiorenal benefits observed in major landmark trials have resulted in the rapid adoption of SGLT2i therapy not only in diabetes guidelines but also cardiovascular and renal guidelines.


Subject(s)
Cardiovascular Diseases , Diabetes Mellitus, Type 2 , Heart Failure , Sodium-Glucose Transporter 2 Inhibitors , Humans , Sodium-Glucose Transporter 2 Inhibitors/adverse effects , Diabetes Mellitus, Type 2/drug therapy , Renal Dialysis/adverse effects , Cardiovascular Diseases/etiology , Heart Failure/complications
13.
J Med Virol ; 94(3): 1146-1153, 2022 03.
Article in English | MEDLINE | ID: mdl-34757638

ABSTRACT

Malaysia has experienced three waves of coronavirus disease 2019 (COVID-19) as of March 31, 2021. We studied the associated molecular epidemiology and SARS-CoV-2 seroprevalence during the third wave. We obtained 60 whole-genome SARS-CoV-2 sequences between October 2020 and January 2021 in Kuala Lumpur/Selangor and analyzed 989 available Malaysian sequences. We tested 653 residual serum samples collected between December 2020 to April 2021 for anti-SARS-CoV-2 total antibodies, as a proxy for population immunity. The first wave (January 2020) comprised sporadic imported cases from China of early Pango lineages A and B. The second wave (March-June 2020) was associated with lineage B.6. The ongoing third wave (from September 2020) was propagated by a state election in Sabah. It is due to lineage B.1.524 viruses containing spike mutations D614G and A701V. Lineages B.1.459, B.1.470, and B.1.466.2 were likely imported from the region and confined to Sarawak state. Direct age-standardized seroprevalence in Kuala Lumpur/Selangor was 3.0%. The second and third waves were driven by super-spreading events and different circulating lineages. Malaysia is highly susceptible to further waves, especially as alpha (B.1.1.7) and beta (B.1.351) variants of concern were first detected in December 2020/January 2021. Increased genomic surveillance is critical.


Subject(s)
COVID-19 , SARS-CoV-2 , Antibodies, Viral/genetics , COVID-19/epidemiology , Humans , Malaysia/epidemiology , Phylogeny , SARS-CoV-2/genetics , Seroepidemiologic Studies
14.
Ophthalmology ; 129(5): 552-561, 2022 05.
Article in English | MEDLINE | ID: mdl-34856231

ABSTRACT

PURPOSE: To evaluate ethnic variations, ocular and systemic determinants of retinal nerve fiber layer (RNFL) thickness, and neuroretinal rim area among Asians using a large consortium of population-based eye studies. DESIGN: Cross-sectional pooled analysis. PARTICIPANTS: Twenty-two thousand four hundred thirty-six participants (22 436 eyes) from 10 population-based studies (in China, Hong Kong, India, Japan, Russia, and Singapore) of the Asian Eye Epidemiology Consortium. METHODS: Participants 40 years of age or older without glaucoma were included. All participants underwent spectral-domain OCT imaging and systemic and ocular examinations. Data were pooled from each study. Multivariable regression was performed to evaluate interethnic differences, intermachine variations, and ocular and systemic factors associated with RNFL thickness and rim area, adjusting for age, gender, diabetes, intraocular pressure (IOP), spherical equivalent (SE), ethnicity, OCT model, and study group. When evaluating body mass index, smoking, and hypertension as exposures, these factors were additionally adjusted for in the model. MAIN OUTCOME MEASURES: Average RNFL thickness (in micrometers) and rim area (in square millimeters). RESULTS: Indian and Japanese eyes have thinner RNFLs than those of other Asian ethnicities (ß values range, 7.31-12.76 µm; P < 0.001 for all pairwise comparisons). Compared with measurements by Cirrus HD-OCT (Carl Zeiss Meditec, Inc), RNFL on average was 7.29 µm thicker when measured by Spectralis (Heidelberg Engineering), 12.85 µm thicker when measured by RS-3000 (NIDEK Co, Ltd), and 17.48 µm thicker when measured by iVue/RTVue (Optovue, Inc) devices (all P < 0.001). Additionally, older age (per decade, ß = -2.70), diabetes (ß = -0.72), higher IOP (per 1 mmHg, ß = -0.07), more myopic SE (per diopter, ß = -1.13), cardiovascular disease (ß = -0.94), and hypertension (ß = -0.68) were associated with thinner RNFL (all P ≤ 0.003). Similarly, older age (ß = -0.019), higher IOP (ß = -0.010), and more myopic SE (ß = -0.025) were associated with smaller rim area (all P < 0.001). CONCLUSIONS: In this large pooled analysis of Asian population studies, Indian and Japanese eyes were observed to have thinner RNFL profiles. These findings suggest the need for an ethnic-specific normative database to improve glaucoma detection.


Subject(s)
Glaucoma , Hypertension , Myopia , Asian People , Cross-Sectional Studies , Glaucoma/diagnosis , Glaucoma/epidemiology , Humans , Intraocular Pressure , Nerve Fibers , Retinal Ganglion Cells , Tomography, Optical Coherence/methods
15.
Cereb Cortex ; 32(1): 41-62, 2021 11 23.
Article in English | MEDLINE | ID: mdl-34255833

ABSTRACT

Cortical projections to the caudomedial frontal cortex were studied using retrograde tracers in marmosets. We tested the hypothesis that cytoarchitectural area 6M includes homologues of the supplementary and pre-supplementary motor areas (SMA and pre-SMA) of other primates. We found that, irrespective of the injection sites' location within 6M, over half of the labeled neurons were located in motor and premotor areas. Other connections originated in prefrontal area 8b, ventral anterior and posterior cingulate areas, somatosensory areas (3a and 1-2), and areas on the rostral aspect of the dorsal posterior parietal cortex. Although the origin of afferents was similar, injections in rostral 6M received higher percentages of prefrontal afferents, and fewer somatosensory afferents, compared to caudal injections, compatible with differentiation into SMA and pre-SMA. Injections rostral to 6M (area 8b) revealed a very different set of connections, with increased emphasis on prefrontal and posterior cingulate afferents, and fewer parietal afferents. The connections of 6M were also quantitatively different from those of the primary motor cortex, dorsal premotor areas, and cingulate motor area 24d. These results show that the cortical motor control circuit is conserved in simian primates, indicating that marmosets can be valuable models for studying movement planning and control.


Subject(s)
Motor Cortex , Animals , Callithrix , Gyrus Cinguli , Neural Pathways/physiology , Parietal Lobe
16.
Pediatr Crit Care Med ; 23(7): 502-513, 2022 07 01.
Article in English | MEDLINE | ID: mdl-35446796

ABSTRACT

OBJECTIVES: Fluid bolus resuscitation in African children is harmful. Little research has evaluated physiologic effects of maintenance-only fluid strategy. DESIGN: We describe the efficacy of fluid-conservative resuscitation of septic shock using case-fatality, hemodynamic, and myocardial function endpoints. SETTING: Pediatric wards of Mbale Regional Referral Hospital, Uganda, and Kilifi County Hospital, Kenya, conducted between October 2013 and July 2015. Data were analysed from August 2016 to July 2019. PATIENTS: Children (≥ 60 d to ≤ 12 yr) with severe febrile illness and clinical signs of impaired perfusion. INTERVENTIONS: IV maintenance fluid (4 mL/kg/hr) unless children had World Health Organization (WHO) defined shock (≥ 3 signs) where they received two fluid boluses (20 mL/kg) and transfusion if shock persisted. Clinical, electrocardiographic, echocardiographic, and laboratory data were collected at presentation, during resuscitation and on day 28. Outcome measures were 48-hour mortality, normalization of hemodynamics, and cardiac biomarkers. MEASUREMENT AND MAIN RESULTS: Thirty children (70% males) were recruited, six had WHO shock, all of whom died (6/6) versus three of 24 deaths in the non-WHO shock. Median fluid volume received by survivors and nonsurvivors were similar (13 [interquartile range (IQR), 9-32] vs 30 mL/kg [28-61 mL/kg], z = 1.62, p = 0.23). By 24 hours, we observed increases in median (IQR) stroke volume index (39 mL/m 2 [32-42 mL/m 2 ] to 47 mL/m 2 [41-49 mL/m 2 ]) and a measure of systolic function: fractional shortening from 30 (27-33) to 34 (31-38) from baseline including children managed with no-bolus. Children with WHO shock had a higher mean level of cardiac troponin ( t = 3.58; 95% CI, 1.24-1.43; p = 0.02) and alpha-atrial natriuretic peptide ( t = 16.5; 95% CI, 2.80-67.5; p < 0.01) at admission compared with non-WHO shock. Elevated troponin (> 0.1 µg/mL) and hyperlactatemia (> 4 mmol/L) were putative makers predicting outcome. CONCLUSIONS: Maintenance-only fluid therapy normalized clinical and myocardial perturbations in shock without compromising cardiac or hemodynamic function whereas fluid-bolus management of WHO shock resulted in high fatality. Troponin and lactate biomarkers of cardiac dysfunction could be promising outcome predictors in pediatric septic shock in resource-limited settings.


Subject(s)
Shock, Septic , Shock , Biomarkers , Child , Female , Fluid Therapy/methods , Humans , Male , Shock/therapy , Shock, Septic/therapy , Troponin , Uganda
17.
Graefes Arch Clin Exp Ophthalmol ; 260(11): 3577-3585, 2022 Nov.
Article in English | MEDLINE | ID: mdl-35524800

ABSTRACT

PURPOSE: Peripheral anterior synechiae (PAS) have been reported as a complication after argon laser trabeculoplasty, but rarely reported after selective laser trabeculoplasty (SLT). This study aims to determine the incidence and predictors of this potential complication in phakic eyes of Chinese patients. METHODS: A retrospective review of consecutive Chinese phakic patients who underwent SLT for primary open-angle glaucoma or ocular hypertension from 2011 to 2015 was analyzed for post-operative outcomes, including the development of PAS. RESULTS: There was a total of 292 patients (509 eyes) that were of Chinese ethnicity and eligible in our analysis. The 4-year incidence of PAS was 13.57% for the 221 eyes with documented gonioscopy after SLT, and the time, since first SLT, to PAS diagnosis was 5.62 years (2052 ± 75.2 days). After accounting for the inter-eye correlation by the mixed effect Cox regression model (AUC = 0.885), the predictors of earlier PAS diagnosis were baseline intraocular pressure (≥ 18 versus < 18) (HR = 4.6, p = 0.031), baseline use of bimatoprost (HR = 14.97, p = 0.006), and pre-existing hypertension (HR = 11.78, p = 0.016). There was no significant association of earlier PAS diagnosis with age (p = 0.434), baseline number of medications used (p = 0.693), and baseline use of brinzolamide (p = 0.326). CONCLUSION: PAS development after SLT appears to be more common in Chinese patients, with a presumed 4-year incidence of 13.6%, based on retrospective review of eyes with subsequent documented gonioscopy findings. TRIAL REGISTRATION: Hong Kong University Clinical Trials Registry (HKUCTR-2350).


Subject(s)
Corneal Diseases , Glaucoma, Open-Angle , Iris Diseases , Laser Therapy , Trabeculectomy , Humans , Trabeculectomy/adverse effects , Bimatoprost/therapeutic use , Argon/therapeutic use , Intraocular Pressure , Laser Therapy/adverse effects , Corneal Diseases/surgery , China/epidemiology , Lasers , Treatment Outcome
18.
Clin Exp Dermatol ; 47(8): 1502-1507, 2022 Aug.
Article in English | MEDLINE | ID: mdl-35340047

ABSTRACT

BACKGROUND: Emollients are a mainstay of treatment for dry skin conditions. In the UK, prescribers are usually expected to follow local National Health Service (NHS) formularies. A previous study in 2018 showed that the recommended emollients across England and Wales varied widely. Evidence has since emerged that bath additives provide no additional clinical benefit in eczema. AIM: To compare emollient formularies and guidelines in England. METHODS: Clinical Commissioning Group (CCG) formularies and guidelines were identified in April-May 2021, compiled and then analysed descriptively. RESULTS: In total, 105 CCGs, 72 emollient formularies and 47 emollient prescribing guidelines were identified. There were internal inconsistencies between formularies and their accompanying guidelines in 19% of cases. The majority (68%) of formularies/guidelines were organized using a ranking system. In total, 126 different leave-on emollients were named. Creams and ointments were universally available and were the most recommended first-line types. Cost was more likely than patient choice to be recommended as a criterion for selecting which emollient to prescribe. Aqueous cream was the leave-on emollient most commonly not recommended. Nearly three-quarters (74%) of formularies stated that bath additives should not be prescribed. CONCLUSION: All CCGs in England have an emollient formulary/guideline, but there is still great variability between them in their recommendations. Although the number of formularies/guidelines has reduced since 2017, there has been an increase in the total number of unique recommended leave-on emollients. Most CCGs are no longer recommending bath emollients for eczema.


Subject(s)
Eczema , Emollients , Cross-Sectional Studies , Eczema/drug therapy , Emollients/therapeutic use , England , Humans , State Medicine
19.
Am J Dermatopathol ; 44(10): 728-733, 2022 Oct 01.
Article in English | MEDLINE | ID: mdl-35925552

ABSTRACT

ABSTRACT: The aim of this study was to review the dermatopathological findings in skin biopsy specimens from pediatric oncology and hematopoietic stem cell transplantation patients over a 20-year period. Three hundred fifty-two skin biopsies from 240 patients were reviewed, and the findings were grouped into 6 categories: index neoplasms, nonindex neoplasms, infections, graft-versus-host disease, other treatment complications, and others. Among the index neoplasms identified on skin biopsy, the most common conditions were Langerhans cell histiocytosis (14 patients) and melanoma (7 patients), with other hematological malignancies and an array of soft-tissue tumors accounting for the bulk of the remainder. Neoplastic conditions common in general dermatopathological practice such as basal cell carcinoma and squamous cell carcinoma were uncommon, each being identified in only 1 patient younger than the age of 18, although basal cell carcinomas developing subsequently in young adult life were identified in 7 patients. Infections were common, with infectious agents or viral cytopathic effects (not including human papillomavirus) identified in 34 biopsies. A significant proportion (74%) represented invasive fungal infections, which are of very significant clinical importance. Biopsies performed for a clinical suspicion of graft-versus-host seldom showed histological features to suggest an alternative diagnosis, with only a single case suggesting a diagnosis of toxic erythema of chemotherapy identified.


Subject(s)
Carcinoma, Basal Cell , Graft vs Host Disease , Hematopoietic Stem Cell Transplantation , Skin Neoplasms , Biopsy , Carcinoma, Basal Cell/complications , Child , Graft vs Host Disease/pathology , Hematopoietic Stem Cell Transplantation/adverse effects , Humans , Retrospective Studies , Skin Neoplasms/etiology , Young Adult
20.
Echocardiography ; 39(1): 54-64, 2022 01.
Article in English | MEDLINE | ID: mdl-34873750

ABSTRACT

PURPOSE: Left ventricular mechanical dispersion (LVMD) is a novel speckle tracking parameter for prognostic assessment of arrhythmic risk prediction. There is growing evidence to support its use in a variety of cardiomyopathic processes. There is paucity of data addressing any presence of inter-vendor discrepancies for LVMD. The aim of this study was to assess inter-vendor variability of LVMD in vendor specific software (VSS) and vendor independent software (VIS) in subjects with preserved and reduced left ventricular function. METHODS: Fifty-nine subjects (14 normal subjects and 45 subjects with cardiac disease) were recruited and 2D speckle tracking echocardiographic images were acquired on two different ultrasound machines (GE and Philips). LVMD was measured by two different VSS (EchoPac GE and QLAB Philips) and one VIS (TomTec Arena). RESULTS: There was significant bias and wide limits of agreement (LOA) in the overall cohort observed between two different VSS (17.6 ms; LOA: -29.6 to 64.8; r: .47). There was acceptable bias and narrower LOA with good agreement for LVMD between images obtained on different vendors when performed on VIS (-3.1 ms; LOA: -27.6 to 21.4; r: .75). QLAB LVMD was consistently higher than GE LVMD and TomTec LVMD in both preserved and reduced left ventricular function. LVMD measurements have high intra-vendor reproducibility with excellent inter and intra-observer agreement. CONCLUSIONS: There was acceptable bias and narrower LOA for LVMD assessment on a VIS. Inter-vendor variability exists for LVMD assessment between VSS. Serial measurements of LVMD should be performed using a single vendor for consistent and reliable results.


Subject(s)
Echocardiography , Heart Ventricles , Echocardiography/methods , Heart Ventricles/diagnostic imaging , Humans , Reproducibility of Results , Software , Ventricular Function, Left
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