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1.
J Craniovertebr Junction Spine ; 15(2): 178-184, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38957772

RESUMO

Objective: The authors report the results of "only-fixation" of the affected spinal segment without any decompression of the bones or soft tissue or manipulation of the cyst wall or contents in eight cases having lumbar parafacetal cyst (LPFC). This surgical strategy was based on the concept that LPFCs are secondary to spinal instability, has a protective or adaptive role, and is reversible following stabilization. Materials and Methods: During the period from January 2018 to January 2023, eight consecutive patients having LPFC were surgically treated. There were 5 males and 3 females, and their ages ranged from 48 to 72 years (average 63 years). Seven patients had a single cyst and one patient had multiple cysts. The patients presented with symptoms classically attributed to lumbar canal stenosis. Apart from the cyst-affected spinal segment, degenerative alterations were observed in adjoining spinal segments in six out of seven patients having a single cyst. All patients underwent "only fixation" of the unstable spinal segments without any kind of bone or soft-tissue resection and without any manipulation or handling of the cyst wall or contents. Results: During the follow-up period that ranged from 12 to 57 months (average 29 months), all patients improved from their symptoms. The recovery was observed in the immediate postoperative period and was lasting. Conclusions: LPFCs are one of the several secondary alterations observed in spinal degeneration. Identification of unstable spinal segments and their fixation constitutes rational treatment of lumbar parafacetal cysts. Direct handling and resection of cysts are unnecessary.

2.
Kidney Med ; 6(6): 100832, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38873241

RESUMO

Rationale & Objective: The Advancing Americans Kidney Health Executive order has directed substantial increases in home dialysis use for incident kidney replacement therapy (KRT). Clinical guidelines recommend patients' self-selection of KRT modality through a shared decision-making process, which, at the minimum, requires predialysis nephrology care and KRT-directed comprehensive prekidney failure patient education (CoPE). The current state of these essential services among Americans with advanced (stages 4 and 5) chronic kidney disease (CKD) and their informed preferences for home dialysis are unknown. Study Design: We conducted a community-based, cross-sectional, observational cohort study across a large regional Veteran Healthcare System from October 1, 2020, to September 30, 2021. Setting & Participants: Of the 928 Veterans with advanced CKD, 287 (30.9%) were invited for needs assessment evaluations. Of the 218 (76% of invited cohort) responding, 178 (81.6%) were receiving nephrology care, with approximately half of those (43.6%) receiving such care from non-Veterans Affairs providers. Outcomes: The study was targeted to assess the prevalent state of ongoing nephrology care and KRT-directed pre-kidney failure education among Veterans with advanced CKD. The secondary outcome included evaluation of dialysis decision-making state among Veterans with advanced CKD. Analytical Approach: Veterans with advanced CKD with 2 sustained estimated glomerular filtration rates <30 mL/min/1.73 m2 were identified through an electronic database query, and a randomly selected cohort was invited for their current state of and outstanding needs for predialysis nephrology care and CoPE, essential for informed KRT selection. Results: Basic awareness of kidney disease was high (92.2%) among Veterans with advanced CKD, although only 38.5% were aware of the severity of their CKD. KRT-directed education during clinical care was reported by 46.8% of Veterans, of which 21.1% reported having received targeted CoPE classes. Three-quarters (74.3%) of Veterans expressed interest in receiving CoPE services. Overall, awareness of CKD and its severity and receipt of KRT-directed education were significantly higher among Veterans with nephrology care than among those without. Of the 61 Veterans providing their KRT preferences, overall decision making was poor, with three-quarters (73.8%) of the cohort unable to choose any KRT modality, irrespective of ongoing nephrology care. Only 8 (13%) felt confident choosing home KRT modalities. Limitations: The study results are primarily applicable to the Veterans with advanced CKD. Furthermore, a limited numbers of respondents provided data on their KRT decision-making state, prohibiting broad generalizations. Conclusions: In a first-of-its-kind community-based needs assessment evaluation among Veterans with advanced CKD, we found that awareness of kidney disease is positively associated with nephrology care; however, the informed KRT selection capabilities are universally poor, irrespective of nephrology care. Our results demonstrate a critical gap between the recommended and prevalent nephrology practices such as KRT-directed education and targeted CoPE classes required for informed patient-centered home dialysis selection in advanced CKD.


The Advancing American Kidney Health Executive Order recommended substantial, potentially unrealistic increases in societal home dialysis use. Unfortunately, we have not examined patient preferences for these targets to guide health care policies. Conducting a community-level needs assessment study among Veterans with advanced kidney disease, we found significant deficits in basic clinical care, namely the specialty nephrology care and dialysis-directed patient education services essential for informed patient-centered dialysis selection. This was expectedly associated with a suboptimal state of dialysis decision making, with about three-quarters of those surveyed being unable to select any dialysis modality. Our results show a critical need for provider and system-level efforts to ensure universal availability of specialty kidney care and targeted education for all patients with advanced chronic kidney disease.

4.
World Neurosurg ; 2024 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-38759781

RESUMO

BACKGROUND: This is a report of a series of 14 patients who presented with a range of "atypical" cranial, spinal, and systemic symptoms that started after they suffered a relatively severe injury to the head and/or neck several months or years before surgical treatment. The implications of diagnosing and treating central or axial atlantoaxial dislocation (CAAD) is discussed. Also, the role of dynamic rotatory and lateral head tilt imaging in the diagnosis and treatment is analyzed. METHODS: Of the 14 patients, 7 were men and 7 were women, with an age range of 21-64 years (average, 42 years). Due to the severity of the presenting neurological and non-neurological symptoms, all the patients had lost their occupation and were heavily dependent on painkillers and/or antidepressant drugs. In addition to other characteristic clinical and radiological evidence, CAAD was diagnosed made based on the facet alignments on lateral profile imaging in the neutral head position. Dynamic head flexion-extension, lateral head tilt, and neck rotation imaging findings confirmed and subclassified CAAD. All 14 patients underwent atlantoaxial fixation surgery. RESULT: A personalized self-assessment clinical scoring parameter and the World Health Organization Disability Assessment Schedule 2.0 was used to evaluate the outcome. One patient did not follow-up after surgery. At a minimum follow-up of 6 months after atlantoaxial fixation surgery, the remaining 13 patients experienced relief from all major symptoms. CONCLUSIONS: Diagnosing and treating CAAD can have major therapeutic implications for patients presenting with progressively worsening disabling clinical symptoms following relatively severe head and/or neck trauma.

5.
Neurosurg Rev ; 47(1): 224, 2024 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-38767778

RESUMO

OBJECTIVE: The article analyzes the clinical features, morphological characteristics, surgical subtleties and long-term outcome of surgery in 89 cases of 'large' sized AVMs. MATERIALS AND METHODS: During the period 2004 to 2022, 89 cases of 'large' arteriovenous malformations were operated in the neurosurgery departments of the authors. Large AVMs were defined as those that were more than 4 cm on either lateral or antero-posterior view of digital subtraction angiogram. The factors that determined the extent of surgical difficulties included site and eloquence of the area, number of feeding vascular territories and draining veins, degree and rate of flow, presence of flow-related aneurysms, and the physical nature of the arteriovenous malformation. RESULTS: There were 59 males and 30 females and the average age was 32 years. Headache, giddiness and convulsions were the common presenting complaints. Six patients were unconscious after surgery. Of these, five patients died in the immediate post-operative period and one patient gradually recovered. Additionally, seven patients developed unilateral limb weakness that included hemiplegia (4 patients) and hemiparesis (3 patients) following surgery. Clinical follow-up ranged from 6 months to 18 years (average 43 months). All surviving patients are leading normal and essentially symptom free life and have recovered from their symptoms of headache, convulsions and giddiness. CONCLUSIONS: Large AVMs are amenable to 'curative' surgery with 'acceptable' results. The surgery can be challenging and appropriate case selection that is based on the surgeons experience is vital and decisive.


Assuntos
Malformações Arteriovenosas Intracranianas , Humanos , Feminino , Masculino , Adulto , Malformações Arteriovenosas Intracranianas/cirurgia , Pessoa de Meia-Idade , Resultado do Tratamento , Adolescente , Adulto Jovem , Criança , Procedimentos Neurocirúrgicos/métodos , Angiografia Digital , Complicações Pós-Operatórias/epidemiologia , Angiografia Cerebral , Idoso , Seguimentos , Estudos Retrospectivos
6.
Clin Pharmacol Ther ; 116(1): 217-224, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38629679

RESUMO

Both short-acting (epoetin alfa or beta) and long-acting (darbepoetin alfa or PEG-epoetin) erythropoiesis-stimulating agents (ESAs) are commonly prescribed for patients with kidney failure undergoing maintenance hemodialysis. We compared the risks of major adverse cardiovascular events (MACE) and of all-cause mortality associated with receipt of short- vs. long-acting ESAs. This retrospective cohort analysis included Medicare hemodialysis beneficiaries aged ≥ 18 years in the United States Renal Data System from January 2015 to December 2017. We included adults who survived > 90 days after initiating hemodialysis and received either short- or long-acting ESAs. Outcomes were MACE (first occurrence of stroke, acute myocardial infarction, or cardiovascular-related mortality) and all-cause mortality. After stabilized inverse probability of treatment weighting, Cox proportional hazards regression models were used to estimate the hazard ratio (HR) and 95% confidence interval (CI) for each outcome. Of 68,607 patients (mean age: 65 years, 45% females), 33,658 (49%) received long-acting ESAs and 34,949 (51%) received short-acting ESAs. There was no difference in the risk of MACE associated with receipt of short- vs. long-acting ESAs (HR: 1.02 (95% CI: 0.98-1.08)). However, long-acting (vs. short-acting) ESA receipt was associated with a lower risk of all-cause mortality (HR: 0.91 (95% CI: 0.87-0.96)). Compared with short-acting ESAs, long-acting ESAs were associated with a lower risk of all-cause mortality, with no difference in the risk of MACE. Future studies with a longer follow-up are needed to confirm these findings.


Assuntos
Darbepoetina alfa , Hematínicos , Diálise Renal , Humanos , Diálise Renal/efeitos adversos , Hematínicos/efeitos adversos , Hematínicos/uso terapêutico , Hematínicos/administração & dosagem , Feminino , Masculino , Estudos Retrospectivos , Idoso , Pessoa de Meia-Idade , Darbepoetina alfa/uso terapêutico , Darbepoetina alfa/efeitos adversos , Darbepoetina alfa/administração & dosagem , Estados Unidos/epidemiologia , Doenças Cardiovasculares/mortalidade , Epoetina alfa/uso terapêutico , Epoetina alfa/efeitos adversos , Falência Renal Crônica/terapia , Falência Renal Crônica/mortalidade , Falência Renal Crônica/complicações , Anemia/tratamento farmacológico , Medicare , Preparações de Ação Retardada , Idoso de 80 Anos ou mais , Eritropoetina , Proteínas Recombinantes
7.
J Craniovertebr Junction Spine ; 15(1): 74-82, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38644907

RESUMO

Aim: The authors analyze their published work and update their experience with 374 cases of cervical radiculopathy and/or myelopathy related to spinal degeneration that includes ossification of the posterior longitudinal ligament (OPLL). The role of atlantoaxial and subaxial spinal instability as the nodal point of pathogenesis and focused target of surgical treatment is analyzed. Materials and Methods: During the period from June 2012 to November 2022, 374 patients presented with acute or chronic symptoms related to radiculopathy and/or myelopathy that were attributed to degenerative cervical spondylotic changes or due to OPLL. There were 339 males and 35 females, and their ages ranged from 39 to 77 years (average 62 years). All patients were treated for subaxial spinal stabilization by Camille's transarticular technique with the aim of arthrodesis of the treated segments. Atlantoaxial stabilization was done in 128 cases by adopting direct atlantoaxial fixation in 55 cases or a modified technique of indirect atlantoaxial fixation in 73 patients. Decompression by laminectomy, laminoplasty, corpectomy, discoidectomy, osteophyte resection, or manipulation of OPLL was not done in any case. Standard monitoring parameters, video recordings, and patient self-assessment scores formed the basis of clinical evaluation. Results: During the follow-up period that ranged from 3 to 125 months (average: 59 months), all patients had clinical improvement. Of 130 patients who had clinical evidences of severe myelopathy and were either wheelchair or bed bound, 116 patients walked aided (23 patients), or unaided (93 patients) at the last follow-up. One patient in the series was operated on 24 months after the first surgery by anterior cervical route for "adjacent segment" disc herniation. No other patient in the entire series needed any kind of repeat or additional surgery for persistent, recurrent, increased, or additional related symptoms. None of the screws at any level backed out or broke. There were no implant-related infections. Spontaneous regression of the size of osteophytes was observed in 259 patients where a postoperative imaging was possible after at least 12 months of surgery. Conclusions: Our successful experience with only spinal fixation without any kind of "decompression" identifies the defining role of "instability" in the pathogenesis of spinal degeneration and its related symptoms. OPLL appears to be a secondary manifestation of chronic or longstanding spinal instability.

8.
Physiol Plant ; 176(2): e14276, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38566244

RESUMO

The leaf-specific Catharanthus roseus alkaloid, vindoline, is the major bottleneck precursor in the production of scarce and costly anticancer bisindoles (vincristine and vinblastine). The final steps of its biosynthesis and storage occur in the laticifers. Earlier, we have shown that vindoline content is directly related to laticifer number. Pectin remodeling enzymes, like pectin methylesterase (PME), are known to be involved in laticifer development. A search in the croFGD yielded a leaf-abundant CrPME isoform that co-expressed with a few vindoline biosynthetic genes. Full-length cloning, tissue-specific expression profiling, and in silico analysis of CrPME were carried out. It was found to possess all the specific characteristics of a typical plant PME. Transient silencing (through VIGS) and overexpression of CrPME in C. roseus indicated a direct relationship between its expression and vindoline content. Comparative analysis of transcript abundance and enzyme activity in three familial C. roseus genotypes differing significantly in their vindoline content and laticifer count (CIM-Sushil > Dhawal > Nirmal) also corroborated the positive relationship of CrPME expression with vindoline content. This study highlights the possible role of CrPME, a cell wall remodeling enzyme, in modulating laticifer-associated secondary metabolism.


Assuntos
Catharanthus , Vimblastina , Vimblastina/análogos & derivados , Vimblastina/metabolismo , Catharanthus/genética , Catharanthus/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo
9.
Viruses ; 16(2)2024 02 13.
Artigo em Inglês | MEDLINE | ID: mdl-38400062

RESUMO

HIV-1 latency remains a barrier to a functional cure because of the ability of virtually silent yet inducible proviruses within reservoir cells to transcriptionally reactivate upon cell stimulation. HIV-1 reactivation occurs through the sequential action of host transcription factors (TFs) during the "host phase" and the viral TF Tat during the "viral phase", which together facilitate the positive feedback loop required for exponential transcription, replication, and pathogenesis. The sequential action of these TFs poses a challenge to precisely delineate the contributions of the host and viral phases of the transcriptional program to guide future mechanistic and therapeutic studies. To address this limitation, we devised a genome engineering approach to mutate tat and create a genetically matched pair of Jurkat T cell clones harboring HIV-1 at the same integration site with and without Tat expression. By comparing the transcriptional profile of both clones, the transition point between the host and viral phases was defined, providing a system that enables the temporal mechanistic interrogation of HIV-1 transcription prior to and after Tat synthesis. Importantly, this CRISPR method is broadly applicable to knockout individual viral proteins or genomic regulatory elements to delineate their contributions to various aspects of the viral life cycle and ultimately may facilitate therapeutic approaches in our race towards achieving a functional cure.


Assuntos
Infecções por HIV , HIV-1 , Humanos , Provírus/genética , Sistemas CRISPR-Cas , HIV-1/genética , Latência Viral/genética
10.
JAMA Intern Med ; 184(4): 451-452, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38372980
11.
Mol Biol Rep ; 51(1): 202, 2024 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-38270668

RESUMO

BACKGROUND: Achyranthes aspera L. (family Amaranthaceae) is a plant species valued in Ayurveda for the treatment of respiratory ailments. Scientific validation of its antiallergic potential was aimed. METHODS AND RESULTS: Three extracts of A. aspera [aqueous (AaAq), hydroalcoholic (AaHA), ethanolic (AaEt)] were evaluated for their potency against C48/80-induced anaphylaxis in mice at 200 mg/kg BW oral dose. The effective dose of the most potent extract was determined through its effect on C48/80-induced anaphylaxis, and was further analyzed through its effect on mast cell degranulation, histamine-induced bronchospasm and ovalbumin (OVA)-induced asthma in a murine model. Among the three extracts, AaAq was found to be most potent at 200 mg/kg BW. AaAq 400 (400 mg/kg BW) was found to be the most effective dose in terms of inhibition of mortality and histamine level. AaAq 400 prevented the peritoneal and mesenteric mast cells from undergoing morphological changes due to degranulation induced by C48/80. Further, AaAq 400 delayed pre-convulsive time in histamine-induced bronchospasm. In the OVA-induced asthma model, AaAq 400 inhibited the level of inflammatory cell count in blood, bronchoalveolar lavage fluid and peritoneal fluid of mice. The Th2 cytokines (IL-4, IL-5, IL-13), TGF-ß and OVA-specific IgE were also reduced as evaluated by ELISA. Also, significant reduction in IL-5 (an eosinophilia indicator) transcript abundance and lung inflammatory score was observed. AaAq was safe up to 4000 mg/kg BW. CONCLUSIONS: Thus AaAq 400 possesses significant antiallergic potential and acts via attenuation of C48/80-induced anaphylaxis and inhibition of mast cell degranulation. It reduces pre-convulsive dyspnea in histamine-induced bronchospasm and Th2 cytokines in asthmatic mice.


Assuntos
Achyranthes , Anafilaxia , Antialérgicos , Asma , Espasmo Brônquico , Animais , Camundongos , Ovalbumina , Histamina , p-Metoxi-N-metilfenetilamina , Modelos Animais de Doenças , Interleucina-5 , Asma/induzido quimicamente , Asma/tratamento farmacológico , Citocinas
12.
Sci Total Environ ; 912: 168655, 2024 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-37992837

RESUMO

Delhi, among the world's most polluted megacities, is a hotspot of particulate matter emissions, with high contribution from organic aerosol (OA), affecting health and climate in the entire northern India. While the primary organic aerosol (POA) sources can be effectively identified, an incomplete source apportionment of secondary organic aerosol (SOA) causes significant ambiguity in the management of air quality and the assessment of climate change. Present study uses positive matrix factorization analysis on the water-soluble organic aerosol (WSOA) data from the offline-aerosol mass spectrometry (AMS). It revealed POA as the dominant source of WSOA, with biomass-burning OA (31-34 %) and solid fuel combustion OA (∼21 %) being two major contributors. Here we use water-solubility fingerprints to track the SOA precursors, such as oxalates or organic nitrates, instead of identifying them based on their O:C ratio. Non-fossil precursors dominate in more oxidized oxygenated organic carbon (MO-OOC) (∼90 %), a proxy for aged secondary organic carbon (SOC), by coupling offline-AMS with 14C measurements. On the contrary, the oxidation of fossil fuel emissions produces a large quantity of fresh fossil SOC, which accounts for ∼75 % of less oxidized oxygenated organic carbon (LO-OOC). Our study reveals that apart from major POA contributions, large fractions of fossil (10-14 %) and biomass-derived SOA (23-30 %) contribute significantly to the total WSOA load, having impact on climate and air quality of the Delhi megacity. Our study reveals that large-scale unregulated biomass burning was not only found to dominate in POA but was also observed to be a significant contributor to SOA with implications on human health, highlighting the need for effective control strategies.

13.
Gene ; 893: 147958, 2024 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-37923095

RESUMO

Several covalent modifications are found associated with the transcriptionally active chromatin regions constituted by the genes transcribed by RNA polymerase (pol) II. Pol III-transcribed genes code for the small, stable RNA species, which participate in many cellular processes, essential for survival. Pol III transcription is repressed under most of the stress conditions by its negative regulator Maf1. We found that most of the histone acetylations increase with starvation-induced repression on several genes transcribed by the yeast pol III. On one of these genes, SNR6 (coding for the U6snRNA), a strongly positioned nucleosome in the gene upstream region plays regulatory role under repression. On this nucleosome, the changes in H3K9 and H3K14 acetylations show different dynamics. During repression, acetylation levels on H3K9 show steady increase whereas H3K14 acetylation increases with a peak at 40 min after which levels reduce. Both the levels settle by 2 hr to a level higher than the active state, which revert to normal levels with nutrient repletion. The increase in H3 acetylations is seen in the mutants reported to show reduced SNR6 transcription but not in the maf1Δ cells. This increase on a regulatory nucleosome may be part of the signaling mechanisms, which prepare cells for the stress-related quick repression as well as reactivation. The contrasting association of the histone acetylations with pol II and pol III transcription may be an important consideration to make in research studies focused on drug developments targeting histone modifications.


Assuntos
Nucleossomos , Transcrição Gênica , Nucleossomos/genética , Histonas/genética , Histonas/metabolismo , RNA Polimerase III/genética , RNA Polimerase III/metabolismo , Acetilação , RNA Polimerase II/genética , RNA Polimerase II/metabolismo , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo
14.
Physiol Plant ; 175(5): e13994, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37882277

RESUMO

Plant lipocalins perform diverse functions. Recently, allene oxide cyclase, a lipocalin family member, has been shown to co-express with vindoline pathway genes in Catharanthus roseus under various biotic/abiotic stresses. This brought focus to another family member, a temperature-induced lipocalin (CrTIL), which was selected for full-length cloning, tissue-specific expression profiling, in silico characterization, and upstream genomic region analysis for cis-regulatory elements. Stress-mediated variations in CrTIL expression were reflected as disturbances in cell membrane integrity, assayed through measurement of electrolyte leakage and lipid peroxidation product, MDA, which implicated the role of CrTIL in maintaining cell membrane integrity. For ascertaining the function of CrTIL in maintaining membrane stability and elucidating the relationship between CrTIL expression and vindoline content, if any, a direct approach was adopted, whereby CrTIL was transiently silenced and overexpressed in C. roseus. CrTIL silencing and overexpression confirmed its role in the maintenance of membrane integrity and indicated an inverse relationship of its expression with vindoline content. GFP fusion-based subcellular localization indicated membrane localization of CrTIL, which was in agreement with its role in maintaining membrane integrity. Altogether, the role of CrTIL in maintaining membrane structure has possible implications for the intracellular sequestration, storage, and viability of vindoline.


Assuntos
Catharanthus , Catharanthus/genética , Catharanthus/metabolismo , Temperatura , Vimblastina/química , Vimblastina/metabolismo , Lipocalinas/metabolismo , Folhas de Planta/genética , Folhas de Planta/metabolismo
15.
Drugs R D ; 23(4): 301-329, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37606750

RESUMO

Calcineurin inhibitors such as cyclosporine and tacrolimus are immunosuppressant drugs that are known to induce tremors. Non-calcineurin inhibitors such as sirolimus and everolimus have also reportedly been accompanied by tremors, albeit less likely. However, the prevalence rates reported in the literature are notably wide, and the risk profiles for these drug-induced tremors are less understood. We searched PubMed to extract data on the risk of tremors with these drugs when prescribed for various transplant and non-transplant indications. We ascertained whether the risk of drug-induced tremor is influenced by the underlying diagnosis, dosing formulations, drug concentrations, and blood monitoring. We extracted data on treatment strategies and outcomes for tremors. Articles were primarily screened based on English language publications, abstracts, and studies with n ≥ 5, which included case series, retrospective studies, case-controlled studies, and prospective studies. We found 81 eligible studies comprising 33 cyclosporine, 43 tacrolimus, 6 sirolimus, and 1 everolimus that discussed tremor as an adverse event. In the pooled analysis of studies with n > 100, the incidence of tremor was 17% with cyclosporine, 21.5% with tacrolimus, and 7.8% with sirolimus and everolimus together. Regarding the underlying diagnosis, tremor was more frequently reported in kidney transplant (cyclosporine 28%, tacrolimus 30.1%) and bone marrow transplant (cyclosporine 40%, tacrolimus 41.9%) patients compared with liver transplant (cyclosporine 9%, tacrolimus 11.5%) and nontransplant indications (cyclosporine 21.5%, tacrolimus 11.3%). Most studies did not report whether the risk of tremors correlated with drug concentrations in the blood. The prevalence of tremors when using the twice-daily formulation of tacrolimus was nearly the same as the once-daily formulation (17% vs 18%). Data on individual-level risk factors for tremors were lacking. Except for three studies that found some benefit to maintaining magnesium levels, there were minimal data on treatments and outcomes. A large body of data supports a substantive and wide prevalence of tremor resulting from tacrolimus use followed by cyclosporine, especially in patients receiving a kidney transplant. However, there is little reporting on the patient-related risk factors for tremor, risk relationship with drug concentrations, treatment strategies, and outcomes.


Assuntos
Ciclosporina , Tacrolimo , Humanos , Ciclosporina/efeitos adversos , Tacrolimo/efeitos adversos , Everolimo/efeitos adversos , Sirolimo/uso terapêutico , Tremor/induzido quimicamente , Tremor/epidemiologia , Tremor/tratamento farmacológico , Estudos Prospectivos , Estudos Retrospectivos , Imunossupressores , Inibidores de Calcineurina/efeitos adversos
16.
Interact J Med Res ; 12: e43384, 2023 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-37486757

RESUMO

BACKGROUND: Identifying advanced (stages 4 and 5) chronic kidney disease (CKD) cohorts in clinical databases is complicated and often unreliable. Accurately identifying these patients can allow targeting this population for their specialized clinical and research needs. OBJECTIVE: This study was conducted as a system-based strategy to identify all prevalent Veterans with advanced CKD for subsequent enrollment in a clinical trial. We aimed to examine the prevalence and accuracy of conventionally used diagnosis codes and estimated glomerular filtration rate (eGFR)-based phenotypes for advanced CKD in an electronic health record (EHR) database. We sought to develop a pragmatic EHR phenotype capable of improving the real-time identification of advanced CKD cohorts in a regional Veterans health care system. METHODS: Using the Veterans Affairs Informatics and Computing Infrastructure services, we extracted the source cohort of Veterans with advanced CKD based on a combination of the latest eGFR value ≤30 ml·min-1·1.73 m-2 or existing International Classification of Diseases (ICD)-10 diagnosis codes for advanced CKD (N18.4 and N18.5) in the last 12 months. We estimated the prevalence of advanced CKD using various prior published EHR phenotypes (ie, advanced CKD diagnosis codes, using the latest single eGFR <30 ml·min-1·1.73 m-2, utilizing two eGFR values) and our operational EHR phenotypes of a high-, intermediate-, and low-risk advanced CKD cohort. We evaluated the accuracy of these phenotypes by examining the likelihood of a sustained reduction of eGFR <30 ml·min-1·1.73 m-2 over a 6-month follow-up period. RESULTS: Of the 133,756 active Veteran enrollees at North Florida/South Georgia Veterans Health System (NF/SG VHS), we identified a source cohort of 1759 Veterans with advanced nondialysis CKD. Among these, 1102 (62.9%) Veterans had diagnosis codes for advanced CKD; 1391(79.1%) had the index eGFR <30 ml·min-1·1.73 m-2; and 928 (52.7%), 480 (27.2%), and 315 (17.9%) Veterans had high-, intermediate-, and low-risk advanced CKD, respectively. The prevalence of advanced CKD among Veterans at NF/SG VHS varied between 1% and 1.5% depending on the EHR phenotype. At the 6-month follow-up, the probability of Veterans remaining in the advanced CKD stage was 65.3% in the group defined by the ICD-10 codes and 90% in the groups defined by eGFR values. Based on our phenotype, 94.2% of high-risk, 71% of intermediate-risk, and 16.1% of low-risk groups remained in the advanced CKD category. CONCLUSIONS: While the prevalence of advanced CKD has limited variation between different EHR phenotypes, the accuracy can be improved by utilizing two eGFR values in a stratified manner. We report the development of a pragmatic EHR-based model to identify advanced CKD within a regional Veterans health care system in real time with a tiered approach that allows targeting the needs of the groups at risk of progression to end-stage kidney disease.

17.
Opt Lett ; 48(11): 2937-2940, 2023 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-37262248

RESUMO

Deterministic optical manipulation of fluorescent nanodiamonds (FNDs) in fluids has emerged as an experimental challenge in multimodal biological imaging. Designing and developing nano-optical trapping strategies to serve this purpose is an important task. In this Letter, we show how chemically prepared gold nanoparticles and silver nanowires can facilitate an opto-thermoelectric force to trap individual entities of FNDs using a long working distance lens, low power-density illumination (532-nm laser, 12 µW/µm2). Our trapping configuration combines the thermoplasmonic fields generated by individual plasmonic nanoparticles and the opto-thermoelectric effect facilitated by the surfactant to realize a nano-optical trap down to a single FND that is 120 nm in diameter. We use the same trapping excitation source to capture the spectral signatures of single FNDs and track their position. By tracking the FND, we observe the differences in the dynamics of the FND around different plasmonic structures. We envisage that our drop-casting platform can be extrapolated to perform targeted, low-power trapping, manipulation, and multimodal imaging of FNDs inside biological systems such as cells.

18.
J Ren Nutr ; 33(5): 682-690, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37315706

RESUMO

OBJECTIVES: The objectives of this study were: (1) investigate hemodialysis (HD)/peritoneal dialysis (PD) patients' barriers to dietary adherence, (2) identify strategies to overcome these barriers, and (3) examine dialysis providers' perceptions toward patients' barriers to dietary adherence and strategies to overcome these barriers. METHODS: A qualitative descriptive approach was conducted from February-May 2022. A total of 21 HD/PD participants and 11 health care providers participated in individual interviews. HD/PD participants also responded to a 57-item food frequency questionnaire. Six months of serum laboratory values were obtained from the medical charts. Content analysis methodology was used to identify themes. Mann-Whitney U tests were conducted to examine diet quality and laboratory values of the HD and PD participants using SPSS v.27 with statistical significance of P < .05. RESULTS: The median (interquartile range) diet quality score for HD/PD patients was 36 (26-43) with no differences observed between the patient populations. Mann-Whitney U tests showed no differences between serum laboratory values between the patient populations. Barriers identified by the HD/PD patients were communication/patient education and dietary habits. Barriers identified by the health care providers were communication/patient education and socioeconomic status. Strategies to overcome these barriers were enhancing communication between all parties involved in the care and tailoring educational information to the patient's background. CONCLUSIONS: Communication and patient education were themes identified among both health care providers and patients. Therefore, open communication among the patients and providers and enhancement of the nutrition education handouts may improve dietary adherence.


Assuntos
Falência Renal Crônica , Diálise Peritoneal , Humanos , Falência Renal Crônica/terapia , Diálise Renal , Diálise Peritoneal/métodos , Dieta , Pessoal de Saúde
19.
Clin J Am Soc Nephrol ; 18(9): 1234-1243, 2023 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-37150877

RESUMO

Kidney health advocacy organizations and leaders in the nephrology community have repeatedly emphasized the need to increase home dialysis utilization in the United States. Limited awareness and understanding of options for the management of kidney failure among patients living with advanced CKD is a significant barrier to increasing the selection and use of home dialysis. Studies have shown that providing targeted comprehensive patient education before the onset of kidney failure can improve patients' awareness of kidney disease and substantially increase the informed utilization of home dialysis. Unfortunately, in the absence of validated evidence-based education protocols, outcomes associated with home dialysis use vary widely among published studies, potentially affecting the routine implementation and reporting of these services among patients with advanced CKD. This review provides pragmatic guidance on establishing effective patient-centered education programs to empower patients to make informed decisions about their KRT and, in turn, increase home dialysis use.


Assuntos
Insuficiência Renal Crônica , Insuficiência Renal , Humanos , Estados Unidos , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/terapia , Hemodiálise no Domicílio/educação , Padrões de Referência
20.
Fed Pract ; 40(4): 116-122b, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37223661

RESUMO

Background: Home dialysis utilization is lower among veterans than in the general US population. Several sociodemographic factors and comorbidities contribute to peritoneal dialysis (PD) underutilization. In 2019, the Veterans Health Administration (VHA) Kidney Disease Program Office convened a PD workgroup to address this concern. Observations: The PD workgroup was explicitly concerned by the limited availability of PD within the VHA, which frequently requires veterans to transition kidney disease care from US Department of Veterans Affairs medical centers (VAMCs) to non-VHA facilities when they progress from chronic kidney disease to end-stage kidney disease, causing fragmentation of care. Since the administrative requirements and infrastructure of VAMCs vary, the workgroup focused its deliberations on synthesizing a standard process for evaluating the feasibility and establishing a new PD program within any individual VAMC. A 3-phased approach was envisioned, beginning with ascertainment of prerequisites, leading to an examination of the clinical and financial feasibility through the process of data gathering and synthesis, culminating in a business plan that translates the previous 2 steps into an administrative document necessary for obtaining VHA approvals. Conclusions: VAMCs can use the guide presented here to improve therapeutic options for veterans with kidney failure by establishing a new or restructured PD program.

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