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Hypertension increases the risk of cardiovascular disease in the elderly. Although treating hypertension can reduce the risk of cardiovascular disease and its related mortality, it is also challenging because these patients could have frailty, orthostatic hypotension (OH) and resistant hypertension (RHTN), which makes them more susceptible to treatment-related adverse events. Identifying such patients and tailoring the choice of drugs and blood pressure targets is crucial to balance the harms and benefits. The Clinical Frailty Scale is recommended to assess elderly patients with hypertension and frailty. For very frail patients, unnecessary medications should be deprescribed to avoid adverse events. Hypertension and OH frequently co-occur in the elderly, and recognizing and managing OH is essential to prevent falls and adverse events. The management of blood pressure in elderly patients with frailty, OH, and RHTN is complex, requiring the patients, their family and caregivers to be involved in decision-making to ensure that treatment plans are well-informed and aligned with the patient's needs.
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BACKGROUND: Spinal cord injury (SCI) is a debilitating condition that results in severe motor function impairments. Current therapeutic options remain limited, underscoring the need for novel treatments. Extracorporeal shockwave therapy (ESWT) has emerged as a promising noninvasive approach for treating musculoskeletal disorders and nerve regeneration. METHODS: This study explored the effects of low-energy ESWT on locomotor function, tissue regeneration, inflammation, and mitochondrial function in a rat SCI model. Experiments were performed using locomotor function assays, CatWalk gait analysis, histopathological examination, immunohistochemical and immunofluorescence staining. RESULTS: The findings demonstrated that low-energy ESWT had a dose-dependent effect, with three treatment sessions (ESWT3) showing superior outcomes compared to a single session. ESWT3 significantly improved motor functions (run patterns, run average speed, and maximum variation, as well as the Basso, Beattie, and Bresnahan (BBB) score) and promoted tissue regeneration while reducing inflammation. ESWT3 significantly decreased levels of IL-1ß, IL6 and macrophages (CD68) while increasing leucocyte (CD45) infiltration. Additionally, ESWT3 upregulated NueN and mitofusin 2 (MFN2), suggesting enhanced neuronal health and mitochondrial function. Moreover, ESWT3 modulated the expression of fibroblast growth factor 1 (FGF1), FGF2, their receptor FGFR1 and phosphorylation of ERK, aiding tissue repair and regeneration in SCI. CONCLUSIONS: This study highlights the potential of low-energy ESWT as an effective noninvasive treatment for SCI, demonstrating significant improvements in motor recovery, tissue regeneration, anti-inflammatory effects, and mitochondrial protection. These findings provide valuable insights into the mechanisms of ESWT and its therapeutic application for SCI recovery.
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Isoniazid is an early bactericidal anti-tuberculosis (TB) agent and isoniazid mono-resistance TB is the most prevalent drug-resistant TB worldwide. Concerns exist regarding whether resistance to isoniazid would lead to delayed culture conversion and worst outcomes. From January 2008 to November 2017, adult culture-positive pulmonary TB patients receiving isoniazid, rifampicin, pyrazinamide, and ethambutol were identified through Taiwan Center for Disease Control database and were followed until the end of 2017. Primary outcomes included time to sputum culture conversion (SCC) within two months. Secondary outcomes included death and unfavourable outcomes at the end of 2nd month. A total of 37,193 drug-susceptible and 2,832 isoniazid monoresistant pulmonary TB patients were identified. Compared with no resistance, isoniazid monoresistance was not associated with a delayed SCC (HR: 0.99, 95% CI: 0.94â1.05, p = 0.8145), a higher risk of 2-month mortality (HR: 1.19, 95% CI: 0.92â1.53, p = 0.1884), and unfavourable outcomes at 2nd month (OR: 1.05, 95% CI: 0.97â1.14, p = 0.2427). Isoniazid monoresistance was associated with delayed SCC (HR: 0.90, 95% CI: 0.83â0.98, p = 0.0099) and a higher risk of unfavourable outcomes (OR:1.18, 95% CI: 1.05â1.32, p = 0.0053) in patients aged between 20 and 65, and delayed SCC in patients without underlying comorbidities (HR: 0.90, 95% CI: 0.81â0.98, p = 0.0237). Isoniazid mono-resistant TB had a comparable outcome with drug-susceptible TB at the end of the intensive phase. Healthy, and non-elderly patients were more likely to had culture persistence, raising concerns about disease transmission in these subgroups and warranting early molecular testing for isoniazid resistance.
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Antituberculosos , Isoniazida , Mycobacterium tuberculosis , Tuberculose Pulmonar , Humanos , Isoniazida/farmacologia , Taiwan/epidemiologia , Antituberculosos/farmacologia , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Tuberculose Pulmonar/tratamento farmacológico , Tuberculose Pulmonar/microbiologia , Tuberculose Pulmonar/epidemiologia , Tuberculose Pulmonar/mortalidade , Idoso , Mycobacterium tuberculosis/efeitos dos fármacos , Mycobacterium tuberculosis/genética , Farmacorresistência Bacteriana , Populações Vulneráveis , Resultado do Tratamento , Escarro/microbiologia , Estudos Retrospectivos , Adulto Jovem , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Tuberculose Resistente a Múltiplos Medicamentos/microbiologia , Tuberculose Resistente a Múltiplos Medicamentos/epidemiologia , Rifampina/farmacologiaRESUMO
OBJECTIVE: We present low-level mosaic trisomy 21 at amniocentesis and cordocentesis in a pregnancy associated with a favorable fetal outcome and perinatal progressive decrease of the trisomy 21 cell line. CASE REPORT: A 36-year-old, primigravid woman underwent amniocentesis at 16 weeks of gestation because of advanced maternal age. This pregnancy was conceived by in vitro fertilization and embryo transfer (IVF-ET). Amniocentesis revealed a karyotype of 47,XY,+21 [3]/46,XY [17] (15% mosaicism) and simultaneous array comparative genomic hybridization (aCGH) analysis on the DNA extracted from uncultured amniocytes revealed the result of arr (21) × 2â¼3 (X,Y) × 1, consistent with 24.5% mosaicism for trisomy 21. Cordocentesis performed at 21 weeks of gestation revealed a karyotype of 47,XY,+21 [3]/46,XY [37] (6% mosaicism). She was referred for genetic counseling at 31 weeks of gestation, and continuing the pregnancy was advised. The parental karyotypes and prenatal ultrasound were normal. At 37 weeks of gestation, a phenotypically normal baby was delivered with a body weight of 2900-g. The karyotypes of cord blood, umbilical cord and placenta were 47,XY,+21 [1]/46,XY [39] (2.5% mosaicism), 47,XY,+21 [10]/46,XY [30] (25% mosaicism) and 47,XY,+21 [22]/46,XY [18] (55% mosaicism), respectively. Quantitative fluorescent polymerase chain reaction (QF-PCR) analysis on the DNA extracted from umbilical cord and parental bloods excluded uniparental disomy (UPD) 21 and revealed a maternal origin of the extra chromosome 21. When follow-up at the age of 2 months, the neonate was normal in phenotype and development. The peripheral blood had a karyotype of 47,XY,+21 [1]/46,XY [39] (2.5% mosaicism), and interphase fluorescence in situ hybridization (FISH) analysis on uncultured buccal mucosal cells revealed 4.7% (5/105 cells) mosaicism for trisomy 21, compared with 0% (5/100 cells) in the normal control. CONCLUSION: Low-level mosaic trisomy 21 at amniocentesis and cordocentesis can be associated with favorable fetal outcome and perinatal progressive decrease of the trisomy 21 cell line.
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Amniocentese , Hibridização Genômica Comparativa , Cordocentese , Síndrome de Down , Mosaicismo , Humanos , Feminino , Gravidez , Mosaicismo/embriologia , Adulto , Síndrome de Down/genética , Cordocentese/métodos , Recém-Nascido , Resultado da Gravidez , CariotipagemRESUMO
INTRODUCTION: Acute renal infarction (ARI) is a relatively rare and underdiagnosed condition. Presenting symptoms are nonspecific, and imaging is the mainstay for diagnosis. This study attempts to characterize the profile of patients with ARI and identify possible risk factors. METHODS: All inpatients admitted with diagnosis of ARI between 2010 and 2022 were included in this single-center retrospective observational study. Patients with chronic renal infarction, iatrogenic causes, and without radiographic evidence of ARI were excluded. Clinical, laboratory, and radiological findings of patients were collected. Patients were grouped into three groups based on probable etiology: cardiovascular, hypercoagulable disorders, and idiopathic, and analyzed. RESULTS: Eighty-five patients were included. Mean age of patients was 61.6 ± 17.54 years. Cardiovascular group had the highest number of patients (49.4%) of which atrial fibrillation was the most common etiology (59.5%). Malignancy was the most common etiology in the hypercoagulable disorder group (69.3%). Patients in the idiopathic group were significantly younger and had higher mean body mass index than the other 2 groups at presentation. Smokers had 9 times higher risk of renal infarction in cardiovascular group and 1.7 times higher risk in hypercoagulable when compared to the idiopathic group. 48.2% of patients developed renal infarction though they were on antiplatelets/anticoagulants. CONCLUSION: ARI is a rare and often underdiagnosed condition that can have residual renal dysfunction. It is important to consider ARI as a differential especially in young patients with risk factors even if they are on anticoagulation medication.
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BACKGROUND: Previous meta-analyses only examined the association between single or several gene polymorphisms and osteoarthritis (OA), whereas no studies have concluded that there are existing all gene loci that associate with OA. OBJECTIVE: To assess whether a definite conclusion of the association between the gene loci and OA can be drawn. METHODS: Decisive gene strategy (DGS), a literature-based approach, was used to search PubMed, Embase, and Cochrane databases for all meta-analyses that associated gene polymorphisms and OA. Trial Sequential Analysis (TSA) examined the sufficiency of the cumulative sample size. Finally, we assessed the importance of gene loci in OA based on whether there were enough sample sizes and the heterogeneity of the literatures with I2 value. RESULTS: After excluding 179 irrelevant publications, 80 meta-analysis papers were recruited. Among Caucasians, SMAD3 rs12901499 (OR = 1.20, 95% CI: 1.12-1.29) was a risk factor with validation of sufficient sample sizes through TSA model. Among Asians, there were 3 gene loci risk factors with validation of sufficient sample sizes through TSA model: ESR1 rs2228480, SMAD3 rs12901499, and MMP-1 rs1799750 (OR = 1.35, 95% CI: 1.08-1.69; OR = 1.34, 95% CI: 1.07-1.69; OR = 1.43, 95% CI: 1.18-1.74, respectively). Besides, 3 gene loci, DVWA rs7639618, GDF5 rs143383, and VDR rs7975232 (OR = 0.78, 95% CI: 0.67-0.90; OR = 0.74, 95% CI: 0.67-0.81; OR = 0.56, 95% CI: 0.35-0.90, respectively) were identified as protective factors through TSA model. CONCLUSIONS: We used DGS to identify conclusive gene loci associated with OA. These findings provide implications of precision medicine in OA and may potentially advance genetic therapy.
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Predisposição Genética para Doença , Osteoartrite , Polimorfismo de Nucleotídeo Único , Humanos , Osteoartrite/genética , Osteoartrite/terapia , Proteína Smad3/genética , Fator 5 de Diferenciação de Crescimento/genética , Metaloproteinase 1 da Matriz/genética , Receptor alfa de Estrogênio/genética , Receptores de Calcitriol/genética , Povo Asiático/genética , População Branca/genética , Fatores de RiscoAssuntos
Detecção Precoce de Câncer , Neoplasias Pulmonares , Tomografia Computadorizada por Raios X , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/diagnóstico , Tomografia Computadorizada por Raios X/métodos , Detecção Precoce de Câncer/métodosRESUMO
The redundancy present within the musculoskeletal system may offer a non-invasive source of signals for movement augmentation, where the set of muscle activations that do not produce force/torque (muscle-to-force null-space) could be controlled simultaneously to the natural limbs. Here, we investigated the viability of extracting movement augmentation control signals from the muscles of the wrist complex. Our study assessed (i) if controlled variation of the muscle activation patterns in the wrist joint's null-space is possible; and (ii) whether force and null-space cursor targets could be reached concurrently. During the null-space target reaching condition, participants used muscle-to-force null-space muscle activation to move their cursor towards a displayed target while minimising the exerted force as visualised through the cursor's size. Initial targets were positioned to require natural co-contraction in the null-space and if participants showed a consistent ability to reach for their current target, they would rotate 5 ∘ incrementally to generate muscle activation patterns further away from their natural co-contraction. In contrast, during the concurrent target reaching condition participants were required to match a target position and size, where their cursor position was instead controlled by their exerted flexion-extension and radial-ulnar deviation, while its size was changed by their natural co-contraction magnitude. The results collected from 10 participants suggest that while there was variation in each participant's co-contraction behaviour, most did not possess the ability to control this variation for muscle-to-force null-space virtual reaching. In contrast, participants did show a direction and target size dependent ability to vary isometric force and co-contraction activity concurrently. Our results indicate the limitations of using the muscle-to-force null-space activity of joints with a low level of redundancy as a possible command signal for movement augmentation.
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Contração Muscular , Músculo Esquelético , Articulação do Punho , Punho , Humanos , Músculo Esquelético/fisiologia , Masculino , Feminino , Punho/fisiologia , Adulto , Articulação do Punho/fisiologia , Contração Muscular/fisiologia , Eletromiografia , Movimento/fisiologia , Adulto Jovem , Fenômenos BiomecânicosRESUMO
OBJECTIVE: We present low-level mosaic trisomy 14 at amniocentesis. CASE REPORT: A 37-year-old, gravida 2, para 1, woman underwent amniocentesis at 18 weeks of gestation because of advanced maternal age. This pregnancy was conceived by in vitro fertilization and embryo transfer (IVF-ET). Amniocentesis revealed a karyotype of 47,XX,+14 [4]/46,XX [27], consistent with 12.9% mosaicism for trisomy 14. Simultaneous array comparative genomic hybridization (aCGH) analysis on the DNA extracted from uncultured amniocytes revealed the result of arr (1-22, X) × 2 with no genomic imbalance. Prenatal ultrasound findings were unremarkable. She was referred for genetic counseling at 21 weeks of gestation and was offered expanded non-invasive prenatal testing (NIPT) which was positive for trisomy 14. At 24 weeks of gestation, she underwent repeat amniocentesis which revealed a karyotype of 47,XX,+14 [2]/46,XX [26], consistent with 7% mosaicism for trisomy 14. The parental karyotypes were normal. Simultaneous aCGH analysis on the DNA extracted from uncultured amniocytes revealed no genomic imbalance. Polymorphic marker analysis excluded uniparental disomy (UPD) 14. Interphase fluorescence in situ hybridization (FISH) analysis on 104 uncultured amniocytes detected no trisomy 14 cell. At 35 weeks of gestation, a 2315-g phenotypically normal baby was delivered. The umbilical cord and placenta had the karyotype of 46, XX (40/40 cells). aCGH analysis on the DNA extracted from peripheral blood and buccal mucosal cells at the age of three months revealed no genomic imbalance. The neonate was normal in phenotype and development during postnatal follow-ups. CONCLUSIONS: Low-level mosaic trisomy 14 at amniocentesis can be associated with cytogenetic discrepancy between cultured amniocytes and uncultured amniocytes, perinatal progressive decrease of the trisomy 14 cell line and a favorable fetal outcome.
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Amniocentese , Cromossomos Humanos Par 14 , Hibridização Genômica Comparativa , Mosaicismo , Trissomia , Dissomia Uniparental , Humanos , Gravidez , Feminino , Mosaicismo/embriologia , Trissomia/diagnóstico , Trissomia/genética , Adulto , Dissomia Uniparental/diagnóstico , Dissomia Uniparental/genética , Cromossomos Humanos Par 14/genética , Recém-Nascido , Teste Pré-Natal não Invasivo/métodos , Nascido Vivo/genética , Âmnio/citologia , Resultado da Gravidez/genética , Cariotipagem/métodosRESUMO
OBJECTIVE: We present mosaic distal 13q duplication due to mosaic unbalanced translocation 46,XY,der(14)t(13;14)(q32.2;p13)/46,XY at amniocentesis in a pregnancy associated with a favorable fetal outcome. CASE REPORT: A 37-year-old, gravida 2, para 0, woman underwent amniocentesis at 17 weeks of gestation because of advanced maternal age. Amniocentesis revealed a karyotype of 46,XY, add(14) (p13)[17]/46,XY[13] (56.6% mosaicism). Array comparative genomic hybridization (aCGH) analysis on the DNA extracted from cultured amniocytes revealed arr 13q32.2q34 × 2â¼3, consistent with 45% mosaicism for distal 13q duplication. Repeat amniocentesis at 24 weeks of gestation revealed a karyotype of 46,XY,der(14)t(13;14)(q32.2;p13)[14]/46,XY[16] (46.6% mosaicism). The parental karyotypes were normal. aCGH analysis on the DNA extracted from uncultured amniocytes revealed arr 13q32.2q34 × 2.38, consistent with 30-40% mosaicism for distal 13q duplication. Interphase fluorescence in situ hybridization (FISH) analysis on uncultured amniocytes detected 22.8% (23/101 cells) mosaicism for distal 13q duplication. Prenatal ultrasound findings were unremarkable. At 39 weeks of gestation, a 3616-g phenotypically normal baby was delivered. The karyotypes of cord blood, umbilical cord and placenta were 46,XY,der(14)t(13;14)(q32.2;p13)[20]/46,XY[20] (50% mosaicism), 46,XY,der(14)t(13;14)(q32.2;p13)[14]/46,XY[26] (35% mosaicism) and 46,XY (40/40 cells) (0% mosaicism), respectively. When follow-ups at the age of 4½ months and the age of one year, the peripheral blood had the karyotype of 46,XY,der(14)t(13;14)(q32.2;p13)[18]/46,XY[22] (45% mosaicism). Interphase FISH analysis on buccal mucosal cells at the age of 4½ months revealed 2.7% (3/110 cells) mosaicism for distal 13q duplication, compared with 1% (1/100 cells) in the normal control. The neonate was normal in phenotype and development. CONCLUSIONS: Mosaic unbalanced translocation at amniocentesis can be associated with a favorable fetal outcome, perinatal progressive decrease of the aneuploid cell line and cytogenetic discrepancy between cultured amniocytes and uncultured amniocytes.
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Amniocentese , Cromossomos Humanos Par 13 , Mosaicismo , Translocação Genética , Humanos , Feminino , Gravidez , Mosaicismo/embriologia , Adulto , Translocação Genética/genética , Cromossomos Humanos Par 13/genética , Hibridização Genômica Comparativa , Cromossomos Humanos Par 14/genética , Cariotipagem , Aneuploidia , Trissomia/genética , Cariótipo , Resultado da Gravidez/genética , Duplicação Cromossômica/genética , Hibridização in Situ FluorescenteRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Periostracum Cicadae (PC), the molted exoskeleton of the cicada Cryptotympana pustulata Fabricius, is frequently employed in Chinese herbal medicine. Based on traditional therapies and pharmacological studies, PC appears to have immunomodulatory activity. However, the specific impact of PC on immunomodulation, particularly its effect on dendritic cells (DCs), remains unknown. DCs act professionally as antigen-presenting cells that trigger adaptive immune responses, making them critical for immunomodulation. MATERIALS AND METHODS: The DCs derived from mouse bone marrow were used to examine the suppressive effect of PC extract on DC activation and maturation. The in vivo suppressive effect was evaluated using a mouse model of contact hypersensitivity (CHS) responses. The determination of the substances in the sample was performed by Liquid chromatography-mass spectrometry/mass spectrometry. RESULTS: The ethyl acetate extract of PC (PCEA) significantly decreased the expressions of proinflammatory cytokines (IL-12, interleukin [IL]-6, as well as tumor necrosis factor [TNF]-α) and surface markers CD80 and CD86 in lipopolysaccharide-stimulated DCs. In the 2,4-dinitro-1-fluorobenzene-induced CHS mouse model, PCEA treatment dramatically attenuated the severity of symptoms. This was evidenced by the alleviation of ear swelling and a reduction in the count of infiltrating CD3+ T cells in the tested ears. In addition, N-acetyldopamine dimer and trimer were identified as major components. CONCLUSION: This study is the first to show that components derived from PCEA inhibit the activation and maturation of DCs as well as CHS responses, indicating they have the potential for treating delayed-type hypersensitivity or DC-related immune disorders.
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The fallopian tubes play key roles in processes from pregnancy to ovarian cancer where three-dimensional (3D) cellular and extracellular interactions are important to their pathophysiology. Here, we develop a 3D multicompartment assembloid model of the fallopian tube that molecularly, functionally, and architecturally resembles the organ. Global label-free proteomics, innovative assays capturing physiological functions of the fallopian tube (i.e., oocyte transport), and whole-organ single-cell resolution mapping are used to validate these assembloids through a multifaceted platform with direct comparisons to fallopian tube tissue. These techniques converge at a unique combination of assembloid parameters with the highest similarity to the reference fallopian tube. This work establishes (i) an optimized model of the human fallopian tubes for in vitro studies of their pathophysiology and (ii) an iterative platform for customized 3D in vitro models of human organs that are molecularly, functionally, and microanatomically accurate by combining tunable assembloid and tissue mapping methods.
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Tubas Uterinas , Humanos , Feminino , Tubas Uterinas/anatomia & histologia , Tubas Uterinas/metabolismo , Imageamento Tridimensional/métodos , Proteômica/métodos , Modelos Biológicos , Análise de Célula Única/métodosRESUMO
OBJECTIVE: We present prenatal diagnosis of familial 3p26.3p25.3 deletion in a pregnancy associated with a favorable fetal outcome and asymptomatic carrier parent and family members in three generations. CASE REPORT: A 35-year-old, gravida 2, para 1, woman underwent amniocentesis at 17 weeks of gestation because of advanced maternal age and the carrier of distal 3p deletion. She was phenotypically normal, and there was no family history of congenital anomalies. Amniocentesis revealed a karyotype of 46,XY,del(3)(p26.1). Repeat amniocentesis at 21 weeks of gestation revealed a karyotype of 46,XY,del(3)(p25.3). Simultaneous array comparative genomic hybridization (aCGH) analysis on the DNA extracted from uncultured amniocytes showed the result of arr 3p26.3p25.3 (117,735-8,709,972) × 1.0 [GRCh37 (hg19)] with an 8.59-Mb deletion of 3p26.3p25.3 encompassing 14 OMIM genes of CHL1, CNTN6, CNTN4, IL5RA, TRNT1, CRBN, SETMAR, SUMF1, ITPR1, BHLHE40, ARL8B, GRM7, LMCD1 and SSUH2. Cytogenetic analysis of parental bloods revealed a karyotype of 46,XX,del (3) (p25.3) in the mother and 46,XY in the father. The woman's 69-year-old mother and her 2-year-old elder son carried the same aberrant chromosome of 3p25.3âp26.3 deletion by conventional cytogenetic analysis but manifested no phenotypic abnormality. aCGH analysis of the peripheral bloods showed that the woman's mother and her elder son had the same 8.59-Mb deletion of 3p26.3p25.3. The woman was advised to continue the pregnancy. At 39 weeks of gestation, a 3040-g healthy male baby was delivered. When follow-up at age 2½ years, the neonate was normal in development and showed no apparent phenotypic abnormality. CONCLUSION: Distal 3p deletion of 3p26.3p25.3 involving the OMIM genes from CHL1 to SSUH2 can be associated with no apparent phenotypic abnormality.
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Amniocentese , Deleção Cromossômica , Cromossomos Humanos Par 3 , Hibridização Genômica Comparativa , Linhagem , Humanos , Feminino , Gravidez , Cromossomos Humanos Par 3/genética , Adulto , Masculino , Heterozigoto , Recém-NascidoRESUMO
BACKGROUND: Although elevated heart rate is a risk factor for cardiovascular morbidity and mortality in healthy people, the association between resting heart rate and major cardiovascular risk in patients after acute ischemic stroke remains debated. This study evaluated the association between heart rate and major adverse cardiovascular events after ischemic stroke. METHODS: We conducted a retrospective cohort study analyzing data from the Chang Gung Research Database for 21,655 patients with recent ischemic stroke enrolled between January 1, 2010, and September 30, 2018. Initial in-hospital heart rates were averaged and categorized into 10-beats per minute (bpm) increments. The primary outcome was the composite of hospitalization for recurrent ischemic stroke, myocardial infarction, or all-cause mortality. Secondary outcomes were hospitalization for recurrent ischemic stroke, myocardial infarction, and heart failure. Hazard ratios and 95% confidence intervals (CIs) were estimated using Cox proportional hazards models, using the heart rate < 60 bpm subgroup as the reference. RESULTS: After a median follow-up of 3.2 years, the adjusted hazard ratios for the primary outcome were 1.13 (95% CI: 1.01 to 1.26) for heart rate 60-69 bpm, 1.35 (95% CI: 1.22 to 1.50) for heart rate 70-79 bpm, 1.64 (95% CI: 1.47 to 1.83) for heart rate 80-89 bpm, and 2.08 (95% CI: 1.85 to 2.34) for heart rate ≥ 90 bpm compared with the reference group. Heart rate ≥ 70 bpm was associated with increased risk of all secondary outcomes compared with the reference group except heart failure. CONCLUSIONS: Heart rate is a simple measurement with important prognostic implications. In patients with ischemic stroke, initial in-hospital heart rate was associated with major adverse cardiovascular events.
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Frequência Cardíaca , AVC Isquêmico , Humanos , Masculino , Feminino , Estudos Retrospectivos , AVC Isquêmico/fisiopatologia , AVC Isquêmico/epidemiologia , AVC Isquêmico/complicações , Frequência Cardíaca/fisiologia , Idoso , Pessoa de Meia-Idade , Infarto do Miocárdio/epidemiologia , Infarto do Miocárdio/fisiopatologia , Infarto do Miocárdio/complicações , Fatores de Risco , Insuficiência Cardíaca/fisiopatologia , Insuficiência Cardíaca/epidemiologia , Insuficiência Cardíaca/complicações , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/fisiopatologia , Idoso de 80 Anos ou maisRESUMO
OBJECTIVES: The weekly rifapentine plus isoniazid for 3 months (3HP) improves completion rate of latent tuberculosis infection treatment, but flu-like symptoms are common. The novel 1HP regimen, involving daily rifapentine plus isoniazid for 28 days, has demonstrated low toxicity in HIV-infected populations. We aimed to investigate whether 1HP has a lower incidence rate of systemic drug reaction (SDR) compared with 3HP during treatment in non-HIV populations. METHODS: This randomized, multicentre trial compared the completion rate and risks of SDRs of 1HP and 3HP in aged ≥13 years non-HIV subjects with latent tuberculosis infection between September 2019 and September 2023 (ClinicalTrials.gov: NCT04094012). We also investigated associations between SDRs and plasma levels of drugs and their metabolites. RESULTS: A total of 251 and 239 individuals were randomly assigned to 1HP and 3HP groups, respectively, with completion rates of 82.9% (208/251) and 84.5% (202/239), respectively. Among them, 12.7% (32/251) and 10.9% (26/239) of 1HP and 3HP groups experienced SDRs, respectively (p 0.522), predominantly urticaria in 1HP group (59.4% [19/32]) and flu-like syndrome in 3HP group (80.8% [21/26]). Among participants experiencing SDRs, 43.8% (14/32) and 34.6% (9/26) in 1HP and 3HP groups, respectively, completed treatment (p 0.470). Cutaneous reactions were more common in 1HP than 3HP group (32.7% [82/251] vs. 13.0% [31/239], p < 0.001). In 1HP group, urticaria was associated with a higher plasma desacetyl-rifapentine level (ug/mL) at both 2 (median [interquartile range]: 36.06 [17.46-50.79] vs. 22.94 [14.67-31.65], p 0.018) and 6 hours (26.13 [15.80-53.06] vs. 29.83 [18.13-34.01], p 0.047) after dosing. DISCUSSION: In non-HIV population, the incidence rate of SDR under 1HP is not lower than 3HP. Notably, urticaria, rather than flu-like syndrome, was the predominant SDR associated 1HP. The findings of this study underscore the feasibility of 1HP regimen in non-HIV populations with a high-completion rate exceeding 80%.
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Antituberculosos , Isoniazida , Tuberculose Latente , Rifampina , Humanos , Isoniazida/administração & dosagem , Isoniazida/uso terapêutico , Isoniazida/efeitos adversos , Masculino , Feminino , Tuberculose Latente/tratamento farmacológico , Rifampina/análogos & derivados , Rifampina/administração & dosagem , Rifampina/uso terapêutico , Rifampina/efeitos adversos , Adulto , Antituberculosos/efeitos adversos , Antituberculosos/administração & dosagem , Antituberculosos/uso terapêutico , Pessoa de Meia-Idade , Quimioterapia Combinada , Esquema de Medicação , Adulto Jovem , AdolescenteRESUMO
BACKGROUND: Stroke risks associated with rapid climate change remain controversial due to a paucity of evidence. AIMS: To examine the risk of subarachnoid hemorrhage (SAH), intracranial hemorrhage (ICH), and ischemic stroke (IS) associated with meteorological parameters. METHODS: In this time-stratified case-crossover study, adult patients hospitalized for their first stroke between 2011 and 2020 from the insurance claims data in Taiwan were identified. The hospitalization day was designated as the case period, and three or four control periods were matched by the same day of the week and month of each case period. Daily mean and 24-h variations in ambient temperature, relative humidity, air pressure, and apparent temperature were measured. Conditional logistic regression models were applied to assess the risk of stroke associated with exposure to weather variables, using the third quintile as a reference, controlling for air pollutant levels. RESULTS: There were 7161 patients with SAH, 40,426 patients with ICH, and 107,550 patients with IS. There was an inverse linear relationship between mean daily temperature and apparent temperature with ICH. Elevated mean daily atmospheric pressure was associated with an increased risk of ICH. A greater decrease in apparent temperature over a 24-h period was associated with increased risk of ICH but decreased risk of IS (odds ratio (95% confidence interval) for the first vs. third quintile of changes in apparent temperature, 1.141 (1.053-1.237) and 0.946 (0.899-0.996), respectively). CONCLUSIONS: There were considerable differences in short-term associations between meteorological parameters and three main pathological types of strokes. DATA ACCESS STATEMENT: The authors have no permission to share the data.
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BACKGROUND: The effectiveness of fish oil in preventing cardiovascular events is still debating. Some studies indicate a correlation between the use of fish oil supplements and reduced mortality or decreased incidence of stroke. However, other studies show no significant association between fish oil intake and stroke prevention, indicating an ongoing debate. This study aimed at exploring which subjects may benefit more from fish oil supplementation. METHODS: This study utilized the data obtained through face-to-face interview from the Taiwan Longitudinal Study in Aging (TLSA). A total of 3,652 participants were included from the 2003 baseline data, after excluding patients with pre-existing ischemic heart disease or stroke. Participants were divided into two groups based on whether taking fish oil supplement or not. Participants were followed until 2015, estimating and comparing the all-cause mortality and cumulative incidence rate of stroke between both groups. RESULTS: The results of the 12-year longitudinal study showed that the cumulative incidence rate of stroke in the fish oil supplementation group was 5.7%, compared to 7.7% in the non-supplemented group (P < 0.05). Additionally, the crude hazard ratio for stroke was significantly lower in the fish oil supplementation group (HR = 0.686;95% CI 0.476-0.987). However, after adjusting potential confounders, the adjusted risk of stroke was lower only for the diabetic patients supplemented with fish oil (aHR = 0.123; 95% CI 0.016-0.930) compared to non-diabetic patients (aHR = 0.917; 95% CI 0.616-1.364). CONCLUSION: This study suggests that there is an association between fish oil supplementation and a lower cumulative incidence rate of subsequent stroke among diabetic patients.