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BACKGROUND: Calciphylaxis patients historically have experienced diagnostic challenges and high morbidity; however limited data is available examining these characteristics over time. OBJECTIVE: The primary goals were to a) investigate factors associated with diagnostic delay of calciphylaxis and b) assess morbidity outcomes. The secondary goal was to provide updated mortality rates. METHODS: A retrospective review of 302 adult patients diagnosed with calciphylaxis between January 1, 2006 and December 31, 2022 was conducted. Univariate and multivariate statistical analyses were performed. RESULTS: Nonnephrogenic calciphylaxis (P = .0004) and involvement of the fingers (P = .0001) were significantly associated with an increased diagnostic delay, whereas involvement of the arms (P = .01) and genitalia (P = .022) resulted in fewer days to diagnosis. Almost all patients with genitalia, finger, or toe involvement had nephrogenic disease. The number of complications per patient decreased with time, especially for wound infections (P = .028), increase in lesion number (P = .012), and recurrent hospitalizations (P = .020). Updated 1-year mortality rates were 36.70% and 30.77% for nephrogenic and nonnephrogenic calciphylaxis, respectively. LIMITATIONS: Limitations include the retrospective nature and data from a single institution. CONCLUSION: Diagnostic delay, particularly in nonnephrogenic calciphylaxis, and complications per patient decreased with time, highlighting the importance of continued awareness to expedite diagnosis. Mortality rates have continued to improve in recent years.
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BACKGROUND: The SPAN trial (Stroke Preclinical Assessment Network) is the largest preclinical study testing acute stroke interventions in experimental focal cerebral ischemia using endovascular filament middle cerebral artery occlusion (MCAo). Besides testing interventions against controls, the prospective design captured numerous biological and procedural variables, highlighting the enormous heterogeneity introduced by the multicenter structure that might influence stroke outcomes. Here, we leveraged the unprecedented sample size achieved by the SPAN trial and the prospective design to identify the biological and procedural variables that affect experimental stroke outcomes in transient endovascular filament MCAo. METHODS: The study cohort included all mice enrolled and randomized in the SPAN trial (N=1789). Mice were subjected to 60-minute MCAo and followed for a month. Thirteen biological and procedural independent variables and 4 functional (weight loss and 4-point neuroscore on days 1 and 2, corner test on days 7 and 28, and mortality) and 3 tissue (day 2, magnetic resonance imaging infarct volumes and swelling; day 30, magnetic resonance imaging tissue loss) outcome variables were prospectively captured. Multivariable regression with stepwise elimination was used to identify the predictors and their effect sizes. RESULTS: Older age, active circadian stage at MCAo, and thinner and longer filament silicone tips predicted higher mortality. Older age, larger body weight, longer anesthesia duration, and longer filament tips predicted worse neuroscores, while high-fat diet and blood flow monitoring predicted milder neuroscores. Older age and a high-fat diet predicted worse corner test performance. While shorter filament tips predicted more ipsiversive turning, longer filament tips appeared to predict contraversive turning. Age, sex, and weight interacted when predicting the infarct volume. Older age was associated with smaller infarcts on day 2 magnetic resonance imaging, especially in animals with larger body weights; this association was most conspicuous in females. High-fat diet also predicted smaller infarcts. In contrast, the use of cerebral blood flow monitoring and more severe cerebral blood flow drop during MCAo, longer anesthesia, and longer filament tips all predicted larger infarcts. Bivariate analyses among the dependent variables highlighted a disconnect between tissue and functional outcomes. CONCLUSIONS: Our analyses identified variables affecting endovascular filament MCAo outcome, an experimental stroke model used worldwide. Multiple regression refuted some commonly reported predictors and revealed previously unrecognized associations. Given the multicenter prospective design that represents a sampling of real-world conditions, the degree of heterogeneity mimicking clinical trials, the large number of predictors adjusted for in the multivariable model, and the large sample size, we think this is the most definitive analysis of the predictors of preclinical stroke outcome to date. Future multicenter experimental stroke trials should standardize or at least ensure a balanced representation of the biological and procedural variables identified herein as potential confounders.
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Infarto da Artéria Cerebral Média , Animais , Masculino , Infarto da Artéria Cerebral Média/diagnóstico por imagem , Infarto da Artéria Cerebral Média/patologia , Camundongos , Feminino , Camundongos Endogâmicos C57BL , Modelos Animais de Doenças , Acidente Vascular Cerebral/diagnóstico por imagem , Imageamento por Ressonância Magnética , Estudos Prospectivos , AVC Isquêmico/diagnóstico por imagemRESUMO
Background: Changes in everyday functioning constitute a clinically meaningful outcome, even in the early stages of Alzheimer's disease. Performance-based assessments of everyday functioning might help uncover these early changes. We aimed to investigate how changes over time in everyday functioning relate to tau and amyloid in cognitively unimpaired older adults. Methods: Seventy-six cognitively unimpaired participants (72 ± 6 years old, 61% female) completed multiple Harvard Automated Phone Task (APT) assessments over 2.0 ± 0.9 years. The Harvard APT consists of three tasks, performed through an automated phone system, in which participants refill a prescription (APT-Script), select a new primary care physician (APT-PCP), and transfer money to pay a bill (APT-Bank). Participants underwent Pittsburgh compound-B and flortaucipir positron emission tomography scans at baseline. We computed distribution volume ratios for a cortical amyloid aggregate and standardized uptake volume ratios for medial temporal and neocortical tau regions. In separate linear mixed models, baseline amyloid by time and tau by time interactions were used to predict longitudinal changes in performance on the Harvard APT tasks. Three-way amyloid by tau by time interactions were also investigated. Lastly, we examined associations between tau and change in Harvard APT scores in exploratory voxel-wise whole-brain analyses. All models were adjusted for age, sex, and education. Results: Amyloid [unstandardized partial regression coefficient estimate (ß) = -0.007, 95% confidence interval (95% CI) = (-0.013, -0.001)], and medial temporal tau [ß = -0.013, 95% CI = (-0.022, -0.004)] were associated with change over time in years on APT-PCP only, i.e., higher baseline amyloid and higher baseline tau were associated with steeper rate of decline of APT-PCP. Voxel-wise analyses showed widespread associations between tau and change in APT-PCP scores over time. Conclusion: Even among cognitively unimpaired older adults, changes over time in the performance of cognitively complex everyday activities relate to cortical amyloid and widespread cerebral tau burden at baseline. These findings support the link between Alzheimer's disease pathology and function and highlight the importance of measuring everyday functioning in preclinical disease stages.
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BACKGROUND AND OBJECTIVES: Alzheimer disease (AD) copathologies of ß-amyloid and tau are common in the Lewy body diseases (LBD), dementia with Lewy bodies (DLB) and Parkinson disease (PD), and target distinct hippocampal subfields compared with Lewy pathology, including subiculum and CA1. We investigated the hypothesis that AD copathologies impact the pattern of hippocampal subregion volume loss and cognitive function in LBD. METHODS: This was a cross-sectional and longitudinal, single-center, observational cohort study. Participants underwent neuropsychological testing and 3T-MRI with hippocampal segmentation using FreeSurferV7. PiB-PET and flortaucipir-PET imaging of comorbid ß-amyloid (A) and tau (T) were acquired. The association of functional cognition, ß-amyloid, and tau loads with hippocampal subregion volume was assessed. The contribution of subregion volumes to the relationship of AD-related deposits on functional cognition was examined with mediation analysis. The effects of AD-related deposits on the rate of subregion atrophy were evaluated with mixed-effects models. RESULTS: Of 103 participants (mean age: 70.3 years; 37.3% female), 52 had LBD with impaired cognition (LBD-I), 26 had normal cognition (LBD-N), and 25 were A- healthy controls (HCs). Volumes of hippocampal subregions prone to AD copathologies, including subiculum (F = 6.9, p = 0.002), presubiculum (F = 7.3, p = 0.001), and parasubiculum (F = 5.9, p = 0.004), were reduced in LBD-I compared with LBD-N and HC. Volume was preserved in CA2/3, Lewy pathology susceptible subregions. In LBD-I, reduced CA1, subiculum, and presubiculum volumes were associated with greater functional cognitive impairment (all p < 0.05). Compared with HC, subiculum volume was reduced in A+T+ but not A-T- participants (F = 2.62, p = 0.043). Reduced subiculum volume mediated the effect of amyloid on functional cognition (0.12, 95% CI: 0.005 to 0.26, p = 0.040). In 26 longitudinally-evaluated participants, baseline tau deposition was associated with faster CA1 (p = 0.021) and subiculum (p = 0.002) atrophy. DISCUSSION: In LBD, volume loss in hippocampal output subregions-particularly the subiculum-is associated with functional cognition and AD-related deposits. Tau deposition appears to accelerate subiculum and CA1 atrophy, whereas Aß does not. Subiculum volume may have value as a biomarker of AD copathology-mediated neurodegeneration and disease progression.
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Peptídeos beta-Amiloides , Hipocampo , Doença por Corpos de Lewy , Tomografia por Emissão de Pósitrons , Proteínas tau , Humanos , Doença por Corpos de Lewy/metabolismo , Doença por Corpos de Lewy/diagnóstico por imagem , Doença por Corpos de Lewy/patologia , Feminino , Masculino , Idoso , Proteínas tau/metabolismo , Hipocampo/diagnóstico por imagem , Hipocampo/patologia , Hipocampo/metabolismo , Estudos Transversais , Peptídeos beta-Amiloides/metabolismo , Estudos Longitudinais , Imageamento por Ressonância Magnética , Idoso de 80 Anos ou mais , Testes Neuropsicológicos , Estudos de Coortes , Doença de Alzheimer/metabolismo , Doença de Alzheimer/diagnóstico por imagem , Doença de Alzheimer/patologia , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Nerve xenografts harvested from transgenic α1,3-galactosyltransferase knockout (GalT-KO) pigs lack the epitope responsible for hyperacute rejection in pig-to-primate transplants. It is unknown whether these cold preserved nerve grafts support axonal regeneration in another species during and after immunosuppression. In this study, we compare outcomes between autografts and cold preserved xenografts in a rat sciatic model of nerve gap repair. METHODS: Fifty male Lewis rats had a 1 cm sciatic nerve defect repaired using either: autograft and suture (n=10); 1-week or 4-week cold preserved xenograft and suture (n=10 per group); 1-week or 4-week cold preserved xenograft and photochemical tissue bonding using a human amnion wrap (PTB/HAM) (n=10 per group). Rats with xenografts were given tacrolimus until 4 months post-operatively. At 4 and 7 months, rats were euthanized and nerve sections harvested. Monthly sciatic functional index (SFI) scores were calculated. RESULTS: All groups showed increases in SFI scores by 4 and 7 months. The autograft suture group had the highest axon density at 4 and 7 months. The largest decrease in axon density from 4 to 7 months was in the 1-week cold preserved PTB/HAM group. The only significant difference between group SFI scores occurred at 5 months, when both 1-week cold preserved groups had significantly lower scores than the 4-week cold preserved suture group. CONCLUSIONS: Our results in the rat sciatic model suggest that GalT-KO nerve xenografts may be viable alternatives to autografts and demonstrate the need for further studies of long-gap repair and comparison with acellular nerve allografts. CLINICAL RELEVANCE: This proof-of-concept study in the rat sciatic model demonstrates that cold preserved GalT-KO porcine xenografts support axonal regeneration, as well as axonal viability following immunosuppression withdrawal. These results further suggest a role for both cold preservation and photochemical tissue bonding in modulating the immunological response at the nerve repair site.
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BACKGROUND: This study evaluates the association between ICUC trauma and short-form Disabilities of the Arm, Shoulder, and Hand Questionnaire (Quick DASH) scores among patients who underwent surgery for distal radius fractures. METHODS: This research gathered patient-reported outcomes (PROs) from patients registered in the ICUC database at a single trauma center. The study involved 76 adult patients who underwent surgical treatment for distal radius fractures before 2023. These patients received a volar locking plate for their distal radius fracture. The research utilized two different PROs to evaluate the patients' conditions. The ICUC trauma score measures functional impairment and pain through two 5-point scale questions, allowing patients to self-assess these aspects. The Quick DASH, comprising 11 questions, was used to evaluate symptoms and functionality of the upper extremity. RESULTS: For patients aged 55.9 ± 15.3 years and 4.6 ± 3.9 years post-op follow-up, the ICUC trauma score was 0.70 ± 0.95, and Quick DASH was 6.07 ± 10.35. A strong correlation between ICUC and Quick DASH was identified (r = 0.71, P < 0.01). The interaction between the ICUC trauma score and age at the surgery to Quick DASH revealed a significant unstandardized partial regression coefficient of 0.19 (95% confidence interval 0.08-0.31; P < 0.01). CONCLUSION: This study demonstrated a strong correlation between the ICUC trauma score and the Quick DASH among patients, especially the elderly. It was noted that an elevation in the ICUC trauma score is linked to a more marked increase in the Quick DASH score, particularly in older patients. Given its simplicity and efficacy, the ICUC trauma score may be a viable alternative to the Quick DASH for assessing the patient's clinical outcomes.
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Fraturas do Rádio , Fraturas do Punho , Adulto , Idoso , Humanos , Fraturas do Rádio/diagnóstico , Fraturas do Rádio/cirurgia , Fraturas do Rádio/etiologia , Fixação Interna de Fraturas/efeitos adversos , Mãos , Ombro , Placas Ósseas , Amplitude de Movimento Articular , Resultado do TratamentoRESUMO
Introduction: It is important to study apathy in Alzheimer's disease (AD) to better understand its underlying neurobiology and develop effective interventions. In the current study, we sought to examine the relationships between longitudinal apathy and regional tau burden in cognitively impaired older adults from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database. Methods: Three hundred and nineteen ADNI participants with mild cognitive impairment (MCI) or AD dementia underwent flortaucipir (FTP) tau positron emission tomography (PET) imaging and clinical assessment with the Neuropsychiatric Inventory (NPI) annually. Longitudinal NPI Apathy (NPI-A) scores were examined in relation to baseline tau PET signal in three a priori selected regions implicated in AD and AD-related apathy (supramarginal gyrus, entorhinal cortex [EC] and rostral anterior cingulate cortex [rACC]). Secondary models were adjusted for global cognition (Mini-Mental State Examination score) and cortical amyloid (florbetapir PET). Results: Higher baseline supramarginal gyrus and EC tau burden were each significantly associated with greater NPI-A over time, while rACC tau was associated with higher NPI-A but did not predict its trajectory over time. These results were retained for supramarginal and EC tau after adjusting models for global cognition and cortical amyloid. Discussion: Our findings suggest that baseline in vivo tau burden in parietal and temporal brain regions affected in AD, and less so in a medial frontal region involved in motivational control, is associated with increasing apathy over time in older adults with MCI and AD dementia. Future work studying emergent apathy in relation to not only core AD pathology but also circuit level dysfunction may provide additional insight into the neurobiology of apathy in AD and opportunities for intervention. Highlights: Tau (Flortaucipir PET) in regions implicated in AD was associated with increasing apathy over timeCortical amyloid was also found to be a robust predictor of the trajectory of apathyEvidence of synergy between regional tau and amyloid in overall higher levels of apathy.
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OBJECTIVES: To investigate intra-patient variability of iodine concentration (IC) between three different dual-energy CT (DECT) platforms and to test different normalization approaches. METHODS: Forty-four patients who underwent portal venous phase abdominal DECT on a dual-source (dsDECT), a rapid kVp switching (rsDECT), and a dual-layer detector platform (dlDECT) during cancer follow-up were retrospectively included. IC in the liver, pancreas, and kidneys and different normalized ICs (NICPV:portal vein; NICAA:abdominal aorta; NICALL:overall iodine load) were compared between the three DECT scanners for each patient. A longitudinal mixed effects analysis was conducted to elucidate the effect of the scanner type, scan order, inter-scan time, and contrast media amount on normalized iodine concentration. RESULTS: Variability of IC was highest in the liver (dsDECT vs. dlDECT 28.96 (14.28-46.87) %, dsDECT vs. rsDECT 29.08 (16.59-62.55) %, rsDECT vs. dlDECT 22.85 (7.52-33.49) %), and lowest in the kidneys (dsDECT vs. dlDECT 15.76 (7.03-26.1) %, dsDECT vs. rsDECT 15.67 (8.86-25.56) %, rsDECT vs. dlDECT 10.92 (4.92-22.79) %). NICALL yielded the best reduction of IC variability throughout all tissues and inter-scanner comparisons, yet did not reduce the variability between dsDECT vs. dlDECT and rsDECT, respectively, in the liver. The scanner type remained a significant determinant for NICALL in the pancreas and the liver (F-values, 12.26 and 23.78; both, p < 0.0001). CONCLUSIONS: We found tissue-specific intra-patient variability of IC across different DECT scanner types. Normalization mitigated variability by reducing physiological fluctuations in iodine distribution. After normalization, the scanner type still had a significant effect on iodine variability in the pancreas and liver. CLINICAL RELEVANCE STATEMENT: Differences in iodine quantification between dual-energy CT scanners can partly be mitigated by normalization, yet remain relevant for specific tissues and inter-scanner comparisons, which should be taken into account at clinical routine imaging. KEY POINTS: ⢠Iodine concentration showed the least variability between scanner types in the kidneys (range 10.92-15.76%) and highest variability in the liver (range 22.85-29.08%). ⢠Normalizing tissue-specific iodine concentrations against the overall iodine load yielded the greatest reduction of variability between scanner types for 2/3 inter-scanner comparisons in the liver and for all (3/3) inter-scanner comparisons in the kidneys and pancreas, respectively. ⢠However, even after normalization, the dual-energy CT scanner type was found to be the factor significantly influencing variability of iodine concentration in the liver and pancreas.
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Meios de Contraste , Iodo , Rim , Fígado , Imagem Radiográfica a Partir de Emissão de Duplo Fóton , Tomografia Computadorizada por Raios X , Humanos , Feminino , Masculino , Tomografia Computadorizada por Raios X/métodos , Pessoa de Meia-Idade , Estudos Retrospectivos , Imagem Radiográfica a Partir de Emissão de Duplo Fóton/métodos , Idoso , Rim/diagnóstico por imagem , Fígado/diagnóstico por imagem , Pâncreas/diagnóstico por imagem , AdultoRESUMO
BACKGROUND: Depression during pregnancy is increasingly recognized as a worldwide public health problem. If untreated, there can be detrimental outcomes for the mother and child. Anxiety is also often comorbid with depression. Although effective treatments exist, most women do not receive treatment. Technology is a mechanism to increase access to and engagement in mental health services. OBJECTIVE: The Guardians is a mobile app, grounded in behavioral activation principles, which seeks to leverage mobile game mechanics and in-game rewards to encourage user engagement. This study seeks to assess app satisfaction and engagement and to explore changes in clinical symptoms of depression and anxiety among a sample of pregnant women with elevated depressive symptoms. METHODS: This multimethod pilot test consisted of a single-arm, proof-of-concept trial to examine the feasibility and acceptability of The Guardians among a pregnant sample with depression (N=18). Participation included two web-based study visits: (1) a baseline assessment to collect demographic and obstetric information and to assess clinical symptoms and (2) an exit interview to administer follow-up measures and explore user experience. Participants completed biweekly questionnaires (ie, Patient Health Questionnaire-9 and Generalized Anxiety Disorder-7) during the trial to assess depression and anxiety symptom severity. App satisfaction was measured using 2 self-report scales (ie, Mobile Application Rating Scale and Player Experience of Needs Satisfaction scale). Engagement with The Guardians was captured using game interaction metric data. We used backward-eliminated mixed effects longitudinal models to examine the effects of app engagement and satisfaction and length of time in the study on symptoms of depression and anxiety. Content analysis was conducted on qualitative data from exit interviews. RESULTS: The 15-day and 30-day overall app retention rates were 26.6% and 15.1%, respectively. Mixed effects models found significant negative main effects of week in study (ß=-.35; t61=-3.05; P=.003), number of activities completed (ß=-.12; t61=-2.05; P=.04), days played (ß=-.12; t58=-2.9; P=.005), and satisfaction, according to the Mobile Application Rating Scale (ß=-3.05; t45=-2.19; P=.03) on depressive symptoms. We have reported about similar analyses for anxiety. There is preliminary evidence suggesting harder activities are associated with greater mood improvement than easier activities. Qualitative content analysis resulted in feedback falling under the following themes: activities, app design, engagement, fit of the app with lifestyle, perceived impact of the app on mood, and suggestions for app modifications. CONCLUSIONS: Preliminary results from this multimethod study of The Guardians indicate feasibility and acceptability among pregnant women with depression. Retention and engagement levels were more than double those of previous public mental health apps, and use of the app was associated with significant decrease in depressive symptom scores over the 10-week trial. The Guardians shows promise as an effective and scalable digital intervention to support women experiencing depression.
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OBJECTIVE: Late-onset GM2 gangliosidosis (LOGG) subtypes late-onset Tay-Sachs (LOTS) and Sandhoff disease (LOSD) are ultra-rare neurodegenerative lysosomal storage disorders presenting with weakness, ataxia, and neuropsychiatric symptoms. Previous studies considered LOTS and LOSD clinically indistinguishable; recent studies have challenged this. We performed a scoping review to ascertain whether imaging and clinical features may differentiate these diseases. METHODS: We examined MEDLINE/non-MEDLINE databases up to May 2022. Articles reporting brain imaging findings in genetically/enzymatically confirmed LOGG, symptom onset at age ≥ 10 years (or evaluated at least once ≥18 years) were included, yielding 170 LOGG patients (LOTS = 127, LOSD = 43) across 68 papers. We compared LOTS versus LOSD and performed regression analyses. Results were corrected for multiple comparisons. RESULTS: Age of onset was lower in LOTS versus LOSD (17.9 ± 8.2 vs. 23.9 ± 14.4 years, p = 0.017), although disease duration was similar (p = 0.34). LOTS more commonly had psychosis/bipolar symptoms (35.0% vs. 9.30%, p = 0.011) but less frequent swallowing problems (4.10% vs. 18.60%, p = 0.041). Cerebellar atrophy was more common in LOTS (89.0%) versus LOSD (60.5%), p < 0.0001, with more severe atrophy in LOTS (p = 0.0005). Brainstem atrophy was documented only in LOTS (14.2%). Independent predictors of LOTS versus LOSD (odds ratio [95% confidence interval]) included the presence of psychosis/bipolar symptoms (4.95 [1.59-19.52], p = 0.011), no swallowing symptoms (0.16 [0.036-0.64], p = 0.011), and cerebellar atrophy (5.81 [2.10-17.08], p = 0.0009). Lower age of onset (0.96 [0.93-1.00], p = 0.075) and tremor (2.50 [0.94-7.43], p = 0.078) were marginally statistically significant but felt relevant to include in the model. INTERPRETATION: These data suggest significant differences in symptomatology, disease course, and imaging findings between LOTS and LOSD.
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Gangliosidoses GM2 , Doenças Neurodegenerativas , Transtornos Psicóticos , Humanos , Criança , Progressão da Doença , Atrofia , Gangliosidoses GM2/diagnóstico por imagemRESUMO
OBJECTIVES: Increased intestinal permeability seems to be a key factor in the pathogenesis of autoimmune diseases, including celiac disease (CeD). However, it is unknown whether increased permeability precedes CeD onset. This study's objective was to determine whether intestinal permeability is altered before celiac disease autoimmunity (CDA) in at-risk children. We also examined whether environmental factors impacted zonulin, a widely used marker of gut permeability. METHODS: We evaluated 102 children in the CDGEMM study from 2014-2022. We included 51 CDA cases and matched controls, who were enrolled for 12 months or more and consumed gluten. We measured serum zonulin from age 12 months to time of CDA onset, and the corresponding time point in controls, and examined clinical factors of interest. We ran a mixed-effects longitudinal model with dependent variable zonulin. RESULTS: Children who developed CDA had a significant increase in zonulin in the 18.3 months (range 6-78) preceding CDA compared to those without CDA (slope differential = ß = 0.1277, 95% CI: 0.001, 0.255). Among metadata considered, zonulin trajectory was only influenced by increasing number of antibiotic courses, which increased the slope of trajectory of zonulin over time in CDA subjects (P = .04). CONCLUSIONS: Zonulin levels significantly rise in the months that precede CDA diagnosis. Exposure to a greater number of antibiotic courses was associated with an increase in zonulin levels in CDA subjects. This suggests zonulin may be used as a biomarker for preclinical CeD screening in at-risk children, and multiple antibiotic courses may increase their risk of CDA by increasing zonulin levels.
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Biomarcadores , Doença Celíaca , Haptoglobinas , Precursores de Proteínas , Doença Celíaca/sangue , Doença Celíaca/diagnóstico , Humanos , Lactente , Pré-Escolar , Criança , Haptoglobinas/análise , Masculino , Feminino , Antibacterianos/administração & dosagem , Precursores de Proteínas/sangueRESUMO
BACKGROUND: Calciphylaxis is a thrombotic vasculopathy characterized by painful necrotic ulcerations. There are no Food and Drug Administration approved therapies despite high mortality. OBJECTIVE: To compare mortality and wound healing outcomes in patients treated with hyperbaric oxygen therapy (HBOT) in addition to intravenous sodium thiosulfate (IV STS) versus patients who received IV STS only. Findings were stratified by dialysis status and modality. METHODS: 93 patients were included, with 57 patients in the control group (IV STS) and 36 patients in the treatment group (HBOT + IV STS). Mortality data were analyzed with traditional survival analyses and Cox proportional hazard models. Longitudinal wound outcomes were analyzed with mixed effects modeling. RESULTS: Univariate survival analyses showed that full HBOT treatment was associated with significantly (P = .016) longer survival time. Increasing number of HBOT sessions was associated with improved mortality outcomes, with 1, 5, 10 and 20 sessions yielding decreasing hazard ratios. There was also a significant (P = .042) positive association between increasing number of HBOT sessions and increased wound score. LIMITATIONS: Data collection was retrospective. CONCLUSION: HBOT may have a role in the treatment of calciphylaxis with benefits demonstrated in both mortality and wound healing. Larger prospective studies are needed to identify which patients would most benefit from this intervention.
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Calciofilaxia , Oxigenoterapia Hiperbárica , Humanos , Estudos Retrospectivos , Calciofilaxia/terapia , Calciofilaxia/tratamento farmacológico , Tiossulfatos/uso terapêuticoRESUMO
Introduction: Despite advances in the treatment of bipolar disorder (BD), most patients do not achieve complete inter-episode recovery and functional disability is common. During periods of relative remission, many patients continue to experience neurocognitive dysfunction, reduced daytime activity levels, and sleep disturbances. This 8-week, randomized, placebo-controlled pilot study evaluated the feasibility, safety and preliminary efficacy of the wake-promoting drug, modafinil (Provigil®), on neurocognitive functioning, daytime sleepiness, and sleep quality in affectively-stable BD patients. Methods: Twelve individuals with affectively-stable BD were recruited and randomized to a flexible dose of modafinil (100 to 200 mg/day) or placebo, adjunctive to a therapeutic dose of a mood stabilizer. Weekly in-person visits tracked sleep quality and daytime sleepiness as well as side effects and mood symptoms. Neurocognitive functioning was assessed at baseline, week 4, and week 8. Results: No serious adverse events were reported. Newly emergent side effects in the modafinil group included heart palpitations, itching, fatigue, and decreased energy. Two patients discontinued modafinil owing to side effects and one of these patients withdrew from the study. One patient discontinued placebo and was withdrawn from the study. Preliminary evaluations of clinical efficacy showed a marginally significant interaction between treatment group and time in two cognitive domains (speed of processing and verbal learning), indicating greater improvement in the modafinil group versus placebo. Additionally, there was a marginally significant effect of treatment group on daytime sleepiness, suggesting lower daytime sleepiness in the modafinil group versus placebo. Counterintuitively, we found a significant treatment group by time interaction effect on sleep quality, suggesting greater improvement in sleep quality in the placebo group versus the modafinil group. Discussion: Results suggest that modafinil is a relatively safe medication for affectively-stable BD patients when given with adjunctive mood stabilizers. Results are suggestive of cognitive benefit and improved daytime sleepiness, but worse sleep quality in those patients prescribed modafinil. A fully powered clinical trial is warranted with specific attention to the characteristics of patients who are most likely to benefit from treatment with modafinil and other methodological lessons learned from this pilot. Clinical trial registration: ClinicalTrials.gov, identifier NCT01965925.
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The COVID-19 pandemic and subsequent social distancing guidelines and restrictions brought on changes in the everyday experiences of older adults. It is not clear, however, to what extent the pandemic has impacted the importance of everyday preferences for persons with cognitive impairment (CI) or the proxy ratings of those preferences. The sample of this study included 27 dyads of persons with CI and their care partners. The Preferences for Everyday Living Inventory was used to assess importance of preferences among persons with CI; care partners completed concurrent proxy assessments. Mixed random and fixed effects longitudinal models were used to evaluate changes in ratings and concordance levels between persons with CI and care partners prior to and during the COVID-19 pandemic. Persons with CI rated autonomous choice preferences as significantly more important during the COVID-19 pandemic than before; there was no association between the COVID-19 pandemic and change in other everyday preferences domains or discrepancy in proxy assessments of everyday preferences. Identifying avenues to support and provide for autonomy in the decision-making of older adults with CI may offer a way forward in mitigating the psychological and behavioral impacts of the COVID-19 pandemic in this population.
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OBJECTIVE: Individuals with epilepsy often have memory difficulties, and older adults with epilepsy are especially vulnerable, due to the additive effect of aging. The goal of this study was to assess factors that are associated with 24-h memory retention in older adults with epilepsy. METHODS: Fifty-five adults with epilepsy, all aged >50 years, performed a declarative memory task involving the recall of the positions of 15 card pairs on a computer screen prior to a 24-h ambulatory electroencephalogram (EEG). We assessed the percentage of encoded card pairs that were correctly recalled after 24 h (24-h retention rate). EEGs were evaluated for the presence and frequency of scalp interictal epileptiform activity (IEA) and scored for total sleep. Global slow wave activity (SWA) power during non-rapid eye movement sleep was also calculated. RESULTS: Forty-four participants successfully completed the memory task. Two were subsequently excluded due to seizures on EEG. The final cohort (n = 42) had a mean age of 64.3 ± 7.5 years, was 52% female, and had an average 24-h retention rate of 70.9% ± 30.2%. Predictors of 24-h retention based on multivariate regression analysis when controlling for age, sex, and education included number of antiseizure medications (ß = -.20, p = .013), IEA frequency (ß = -.08, p = .0094), and SWA power (ß = +.002, p = .02). SIGNIFICANCE: In older adults with epilepsy, greater frequency of IEA, reduced SWA power, and higher burden of antiseizure medications correlated with worse 24-h memory retention. These factors represent potential treatment targets to improve memory in older adults with epilepsy.
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Epilepsia , Sono , Humanos , Feminino , Idoso , Pessoa de Meia-Idade , Masculino , Memória , Epilepsia/complicações , Convulsões , Rememoração Mental , EletroencefalografiaRESUMO
Isotretinoin is a systemic therapy approved for acne and has historically required lab monitoring in addition to adherence to the iPLEDGE Risk Evaluation and Mitigation Strategy (REMS) given the medication's teratogenic effects. The COVID-19 pandemic resulted in the expansion of telemedicine, acceptance of remote pregnancy tests, and relaxation of lab monitoring practices. A retrospective review of 142 pediatric patients was conducted, and multivariate linear regression was performed to examine differences in prescribing patterns pre-COVID and during COVID. Backward elimination identified gender and the interaction between acne severity and number of systemic treatments tried before isotretinoin as significant factors associated with increased number of visits to isotretinoin initiation, with females requiring more visits before starting isotretinoin at every acne severity level and even after accounting for systemic treatments previously tried. While the changes catalyzed by the pandemic may have improved visit-related burdens for patients and caregivers, female patients with acne continue to be delayed in receiving isotretinoin even when adjusting for acne severity and systemic treatments trialed, underscoring persistent gender disparities in prescribing practices for isotretinoin.
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Acne Vulgar , COVID-19 , Fármacos Dermatológicos , Gravidez , Humanos , Feminino , Criança , Isotretinoína/efeitos adversos , Pandemias , Acne Vulgar/tratamento farmacológico , Estudos Retrospectivos , Fármacos Dermatológicos/uso terapêuticoRESUMO
OBJECTIVE: To examine the experience of interracial anxiety among health professionals and how it may affect the quality of their interactions with patients from racially marginalized populations. We explored the influence of prior interracial exposure-specifically through childhood neighborhoods, college student bodies, and friend groups-on interracial anxiety among medical students and residents. We also examined whether levels of interracial anxiety change from medical school through residency. DATA SOURCE: Web-based longitudinal survey data from the Medical Student Cognitive Habits and Growth Evaluation Study. STUDY DESIGN: We used a retrospective longitudinal design with four observations for each trainee. The study population consisted of non-Black US medical trainees surveyed in their 1st and 4th years of medical school and 2nd and 3rd years of residency. Mixed effects longitudinal models were used to assess predictors of interracial anxiety and assess changes in interracial anxiety scores over time. PRINCIPAL FINDINGS: In total, 3155 non-Black medical trainees were followed for 7 years. Seventy-eight percent grew up in predominantly White neighborhoods. Living in predominantly White neighborhoods and having less racially diverse friends were associated with higher levels of interracial anxiety among medical trainees. Trainees' interracial anxiety scores did not substantially change over time; interracial anxiety was highest in the 1st year of medical school, lowest in the 4th year, and increased slightly during residency. CONCLUSIONS: Neighborhood and friend group composition had independent effects on interracial anxiety, indicating that premedical racial socialization may affect medical trainees' preparedness to interact effectively with diverse patient populations. Additionally, the lack of substantial change in interracial anxiety throughout medical training suggests the importance of providing curricular tools and structure (e.g., instituting interracial cooperative learning activities) to foster the development of healthy interracial relationships.
Assuntos
Internato e Residência , Estudantes de Medicina , Humanos , Criança , Amigos , Estudantes de Medicina/psicologia , Estudos Retrospectivos , Grupos Raciais , Ansiedade/epidemiologiaRESUMO
BACKGROUND: Detecting clinically meaningful changes in instrumental activities of daily living (IADL) at the earliest stages of Alzheimer's disease (AD) is critical. OBJECTIVE: The objective of this exploratory study was to examine the cross-sectional relationship between a performance-based IADL test, the Harvard Automated Phone Task (APT), and cerebral tau and amyloid burden in cognitively normal (CN) older adults. METHODS: Seventy-seven CN participants underwent flortaucipir tau and Pittsburgh Compound B amyloid PET. IADL were assessed using the three Harvard APT tasks: prescription refill (APT-Script), health insurance company call (APT-PCP), and bank transaction (APT-Bank). Linear regression models were used to determine associations between each APT task and entorhinal cortex, inferior temporal, or precuneus tau with or without an interaction with amyloid. RESULTS: Significant associations were found between APT-Bank task rate and interaction between amyloid and entorhinal cortex tau, and APT-PCP task and interactions between amyloid and inferior temporal and precuneus tau. No significant associations were found between the APT tasks and tau or amyloid alone. CONCLUSION: Our preliminary findings suggest an association between a simulated real-life IADL test and interactions of amyloid and several regions of early tau accumulation in CN older adults. However, some analyses were underpowered due to the small number of participants with elevated amyloid, and findings should be interpreted with caution. Future studies will further explore these associations cross-sectionally and longitudinally in order to determine whether the Harvard APT can serve as a reliable IADL outcome measure for preclinical AD prevention trials and ultimately in the clinic setting.
Assuntos
Doença de Alzheimer , Disfunção Cognitiva , Humanos , Idoso , Doença de Alzheimer/diagnóstico por imagem , Doença de Alzheimer/patologia , Proteínas tau/metabolismo , Atividades Cotidianas , Disfunção Cognitiva/patologia , Córtex Entorrinal/patologia , Amiloide/metabolismo , Proteínas Amiloidogênicas , Tomografia por Emissão de Pósitrons , Peptídeos beta-Amiloides/metabolismoRESUMO
The Stroke Preclinical Assessment Network (SPAN) is a multicenter preclinical trial platform using rodent models of transient focal cerebral ischemia to address translational failure in experimental stroke. In addition to centralized randomization and blinding and large samples, SPAN aimed to introduce heterogeneity to simulate the heterogeneity embodied in clinical trials for robust conclusions. Here, we report the heterogeneity introduced by allowing the 6 SPAN laboratories to vary most of the biological and experimental model variables and the impact of this heterogeneity on middle cerebral artery occlusion (MCAo) performance. We included the modified intention-to-treat population of the control mouse cohort of the first SPAN trial (n=421) and examined the biological and procedural independent variables and their covariance. We then determined their impact on the dependent variables cerebral blood flow drop during MCAo, time to achieve MCAo, and total anesthesia duration using multivariable analyses. We found heterogeneity in biological and procedural independent variables introduced mainly by the site. Consequently, all dependent variables also showed heterogeneity among the sites. Multivariable analyses with the site as a random effect variable revealed filament choice as an independent predictor of cerebral blood flow drop after MCAo. Comorbidity, sex, use of laser Doppler flow to monitor cerebral blood flow, days after trial onset, and maintaining anesthesia throughout the MCAo emerged as independent predictors of time to MCAo. Total anesthesia duration was predicted by most independent variables. We present with high granularity the heterogeneity introduced by the biological and model selections by the testing sites in the first trial of cerebroprotection in rodent transient filament MCAo by SPAN. Rather than trying to homogenize all variables across all sites, we embraced the heterogeneity to better approximate clinical trials. Awareness of the heterogeneity, its sources, and how it impacts the study performance may further improve the study design and statistical modeling for future multicenter preclinical trials.
Assuntos
Ataque Isquêmico Transitório , Acidente Vascular Cerebral , Camundongos , Animais , Modelos Animais de Doenças , Infarto da Artéria Cerebral Média , Projetos de Pesquisa , Circulação Cerebrovascular/fisiologia , Estudos Multicêntricos como AssuntoRESUMO
OBJECTIVE: Bias in surrogate decision-making can occur when proxy decision-makers overestimate the degree to which their preferences are shared by others, resulting in a projection of their beliefs onto others. The purpose of this study is to assess projection of care partners' preferences onto surrogate assessments of everyday preferences for persons with cognitive impairment (CI) and to address clinical and demographic factors as predictors of projection. METHODS: The sample included 116 dyads of persons with CI (Clinical Dementia Rating Scale score ≥ 0.5) and their care partners. The Preferences for Everyday Living Inventory (PELI) was used to assess importance of preferences among persons with CI. Care partners completed two separate PELI assessments: one from the perspective of the persons with CI (i.e., acting as a surrogate decision-maker) and one from their own perspective. To assess for projection of care partners' preferences onto surrogate assessments of preferences for persons with CI, two-step regression with multivariable-adjusted general linear models was used. RESULTS: Significant projection was noted within the PELI domains of autonomous choice, personal growth, and keeping a routine (p < 0.005). More significant cognitive impairment was associated with increased projection within the PELI domains of autonomous choice and personal growth (p < 0.05). CONCLUSION: The results of this study suggest that projection of care partners' own preferences may be a significant source of bias in proxy decision-making regarding everyday preferences for persons with CI, particularly for those with more significant CI.