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3.
J Prev Alzheimers Dis ; 11(2): 402-413, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38374746

RESUMEN

Dementia is from an economic perspective a main challenge for economies worldwide because of increasing costs. Since there is no cure in sight, prevention seems the most promising approach for reducing health care cost due to Dementia. On the contrary, approximately 40% of dementias is attributable to modifiable risk factors and first studies showed that multidomain interventions may be effective for preventing dementia. Considering the increasing economic burden, for many health administrations worldwide, cost-effectiveness plays a mayor role. This scoping review wants to bring evidence to the question if prevention for people at risk may be cost-effective. Therefore, the four databases Medline (via Pubmed), CINHAL (via EBSCO), Business Source Complete (via EBSCO), and the Health Economic Evaluation database (HEED) were used to conduct a scoping review using PICO and a systematic search string. 3,629 studies were identified and seven met all inclusion criteria. The included studies showed clear cost-effectiveness for most multidomain interventions. The gained QALYs at mean were 0.08 (SD=0.08) and the intervention average costs 472.20 EUR per Person (SD=74.06 EUR). The Incremental Cost-Effectiveness Ratios varied between -80,427.97 and 104,189.82 EUR per QALY. The three core results are (i) prevention programs focusing on people at risk may be cost-effective and cost-efficient, (ii) multimodal prevention reveal cost saving potential, when the people at risk are defined well, (iii prevention in middle-aged cohorts may be also cost-effective if life-style related risk factors are addressed.


Asunto(s)
Demencia , Costos de la Atención en Salud , Persona de Mediana Edad , Humanos , Análisis Costo-Beneficio , Factores de Riesgo , Demencia/prevención & control
4.
Clin Res Cardiol ; 113(5): 737-749, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38224373

RESUMEN

BACKGROUND: Despite progress in diagnosis and therapy of heart failure (HF), etiology and risk stratification remain elusive in many patients. METHODS: The My Biopsy HF Study (German clinical trials register number: DRKS22178) is a retrospective monocentric study investigating an all-comer population of patients with unexplained HF based on a thorough workup including endomyocardial biopsy (EMB). RESULTS: 655 patients (70.9% men, median age 55 [45/66] years) with non-ischemic, non-valvular HF were included in the analyses. 489 patients were diagnosed with HF with reduced ejection fraction (HFrEF), 52 patients with HF with mildly reduced ejection fraction (HFmrEF) and 114 patients with HF with preserved ejection fraction (HFpEF). After a median follow-up of 4.6 (2.5/6.6) years, 94 deaths were enumerated (HFrEF: 68; HFmrEF: 8; HFpEF: 18), equating to mortality rates of 3.3% and 11.6% for patients with HFrEF, 7.7% and 15.4% for patients with HFmrEF and 5.3% and 11.4% for patients with HFpEF after 1 and 5 years, respectively. In EMB, we detected a variety of putative etiologies of HF, including incidental cardiac amyloidosis (CA, 5.8%). In multivariate logistic regression analysis adjusting for age, sex and comorbidities only CA, age and NYHA functional class III + IV remained independently associated with all-cause mortality (CA: HRperui 3.13, 95% CI 1.5-6.51; p = 0.002). CONCLUSIONS: In an all-comer population of patients presenting with HF of unknown etiology, incidental finding of CA stands out to be independently associated with all-cause mortality. Our findings suggest that prospective trials would be helpful to test the added value of a systematic and holistic work-up of HF of unknown etiology.


Asunto(s)
Insuficiencia Cardíaca , Disfunción Ventricular Izquierda , Masculino , Humanos , Persona de Mediana Edad , Femenino , Volumen Sistólico , Estudios Retrospectivos , Estudios Prospectivos , Pronóstico
5.
Urology ; 182: 161-167, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37689247

RESUMEN

OBJECTIVE: To understand the relationship between common urologic medications phosphodiesterase-5 inhibitors (PDE5i) and anticholinergics (AC) and risk of dementia onset in men who underwent different primary treatments for prostate cancer. MATERIALS AND METHODS: Patients (>50years) with prostate cancer (1998-2022) without Alzheimer's disease or related dementias were selected from Cancer of the Prostatic Strategic Urologic Research Endeavor Registry. Minimum medication use was 3months. Fine-Gray regression was performed to determine the association between medication exposure and dementia onset ≥12months after primary treatment in men matched on age, race, comorbid conditions, smoking, and type of clinical site, with competing risk of death. RESULTS: Among 5937 men (53% PDE5i; 14% AC), PDE5i users were younger (63 vs 70, P < .01) with less CAD, CVA, DM (all P < .01); AC users were older (68 vs 66, P < .01) with higher incidence of comorbidities (P < .01). Median months of use was 24.3 (IQR 12.1, 48.7) for PDE5i and 12.2 (IQR 6.1, 24.3) for AC users. Cumulative incidence of Alzheimer's disease or related dementias was 6.5% at 15years. PDE5i (P = .07) and AC (P = .06) were not associated with dementia regardless of primary treatment modality. CONCLUSION: In this retrospective cohort study, PDE5i and AC use do not appear independently associated with risk of dementia. Notably, our cohort was generally healthy and younger which may limit our ability to detect significance. We recommend prospective investigation into association between PDE5i and dementia and advise continued judicious stewardship of AC in older patient populations.


Asunto(s)
Enfermedad de Alzheimer , Neoplasias de la Próstata , Masculino , Humanos , Anciano , Enfermedad de Alzheimer/complicaciones , Enfermedad de Alzheimer/epidemiología , Enfermedad de Alzheimer/inducido químicamente , Estudios Retrospectivos , Estudios Prospectivos , Neoplasias de la Próstata/complicaciones , Neoplasias de la Próstata/tratamiento farmacológico , Próstata , Inhibidores de Fosfodiesterasa 5/uso terapéutico
6.
Urology ; 180: 242-248, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37442296

RESUMEN

OBJECTIVE: To characterize the incidence of stress urinary incontinence (SUI) after radical prostatectomy (RP), its treatment, and impact on quality of life (QoL) and work status 1year after RP. MATERIALS AND METHODS: Prostate cancer patients treated by RP (1998-2016) were selected from CaPSURE. SUI was defined as any pads per day (ppd) 1 year after RP. SUI procedures were tracked by CPT codes (sling and artificial sphincter). Patients reported work status (full-time, part-time, unpaid), UCLA PCa Index urinary function (UF) and bother (UB) and SF36 Index physical function (PF). Associations of incontinence with UF, UB, and PF and work status changes were assessed (ANOVA). Lifetable estimates and Cox proportional hazards regression evaluated risk of undergoing SUI procedures. RESULTS: 664/2989 (22%) men treated with RP reported SUI at 1 year. More men with SUI had ≥GG2, intermediate to high-risk disease and non-nerve-sparing surgery (all P < .01). Cumulative incidence of SUI procedures was 1.4% at 10years after RP. Age (HR 2.68 per 10years, 95% CI 1.41-5.08) and number of ppd at 1 year (HR 3.20, 95% CI 2.27-4.50) were associated with undergoing SUI procedures. UF declined at 1year after RP, while UB and PF remained stable. UF, UB, and PF were inversely associated with number of ppd (all P < .01). Change in work status was not associated with incontinence or QoL scores. CONCLUSION: Incontinence affected QoL without impacting work status, suggesting that men with SUI after RP may continue working and go under-treated despite impact on QoL.

7.
Anim Cogn ; 26(4): 1353-1368, 2023 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-37219737

RESUMEN

Comparing oneself to others is a key process in humans that allows individuals to gauge their performances and abilities and thus develop and calibrate their self-image. Little is known about its evolutionary foundations. A key feature of social comparison is the sensitivity to other individuals' performance. Recent studies on primates produced equivocal results, leading us to distinguish between a 'strong' variant of the social comparison hypothesis formulated for humans and a 'weak' variant found in non-human primates that would comprise some elements of human social comparison. Here, we focus on corvids that are distantly related to primates and renowned for their socio-cognitive skills. We were interested in whether crows' task performances were influenced (i) by the presence of a conspecific co-actor performing the same discrimination task and (ii) by the simulated acoustic cues of a putative co-actor performing better or worse than themselves. Crows reached a learning criterion quicker when tested simultaneously as compared to when tested alone, indicating a facilitating effect of social context. The performance of a putative co-actor influenced their performance: crows were better at discriminating familiar images when their co-actor was better than they were. Standard extremity (how pronounced the difference was between the performance of the subject and that of the co-actor), and category membership (affiliation status and sex), of the putative co-actors had no effect on their performance. Our findings are in line with the 'weak' variant of social comparison and indicate that elements of human social comparison can be found outside of primates.


Asunto(s)
Cuervos , Humanos , Animales , Comparación Social , Señales (Psicología) , Evolución Biológica , Primates
8.
Pain Res Manag ; 2022: 1217717, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36247103

RESUMEN

There is no approved drug for fibromyalgia syndrome (FMS) in Europe. In the German S3 guideline, amitriptyline, duloxetine, and pregabalin are recommended for temporary use. The aim of this study was to cross-sectionally investigate the current practice of medication in FMS patients in Germany. We systematically interviewed 156 patients with FMS, while they were participating in a larger study. The patients had been stratified into subgroups with and without a decrease in intraepidermal nerve fiber density. The drugs most commonly used to treat FMS pain were nonsteroidal anti-inflammatory drugs (NSAIDs) (41.0% of all patients), metamizole (22.4%), and amitriptyline (12.8%). The most frequent analgesic treatment regimen was "on demand" (53.9%), during pain attacks, while 35.1% of the drugs were administered daily and the remaining in other regimens. Median pain relief as self-rated by the patients on a numerical rating scale (0-10) was 2 points for NSAIDS, 2 for metamizole, and 1 for amitriptyline. Drugs that were discontinued due to lack of efficacy rather than side effects were acetaminophen, flupirtine, and selective serotonin reuptake inhibitors. Reduction in pain severity was best achieved by NSAIDs and metamizole. Our hypothesis that a decrease in intraepidermal nerve fiber density might represent a neuropathic subtype of FMS, which would be associated with better effectiveness of drugs targeting neuropathic pain, could not be confirmed in this cohort. Many FMS patients take "on-demand" medication that is not in line with current guidelines. More randomized clinical trials are needed to assess drug effects in FMS subgroups.


Asunto(s)
Fibromialgia , Neuralgia , Acetaminofén/uso terapéutico , Amitriptilina/uso terapéutico , Analgésicos/uso terapéutico , Antiinflamatorios/uso terapéutico , Antiinflamatorios no Esteroideos/uso terapéutico , Estudios Transversales , Dipirona/uso terapéutico , Clorhidrato de Duloxetina/uso terapéutico , Fibromialgia/tratamiento farmacológico , Humanos , Neuralgia/tratamiento farmacológico , Pregabalina/uso terapéutico , Inhibidores Selectivos de la Recaptación de Serotonina/uso terapéutico
9.
World J Biol Psychiatry ; 23(3): 219-227, 2022 03.
Artículo en Inglés | MEDLINE | ID: mdl-34449294

RESUMEN

OBJECTIVES: Genome-Wide Association Studies (GWAS) of Schizophrenia (SCZ) have provided new biological insights; however, most cohorts are of European ancestry. As a result, derived polygenic risk scores (PRS) show decreased predictive power when applied to populations of different ancestries. We aimed to assess the feasibility of a large-scale data collection in Hanoi, Vietnam, contribute to international efforts to diversify ancestry in SCZ genetic research and examine the transferability of SCZ-PRS to individuals of Vietnamese Kinh ancestry. METHODS: In a pilot study, 368 individuals (including 190 SCZ cases) were recruited at the Hanoi Medical University's associated psychiatric hospitals and outpatient facilities. Data collection included sociodemographic data, baseline clinical data, clinical interviews assessing symptom severity and genome-wide SNP genotyping. SCZ-PRS were generated using different training data sets: (i) European, (ii) East-Asian and (iii) trans-ancestry GWAS summary statistics from the latest SCZ GWAS meta-analysis. RESULTS: SCZ-PRS significantly predicted case status in Vietnamese individuals using mixed-ancestry (R2 liability = 4.9%, p = 6.83 × 10-8), East-Asian (R2 liability = 4.5%, p = 2.73 × 10-7) and European (R2 liability = 3.8%, p = 1.79 × 10-6) discovery samples. DISCUSSION: Our results corroborate previous findings of reduced PRS predictive power across populations, highlighting the importance of ancestral diversity in GWA studies.


Asunto(s)
Esquizofrenia , Humanos , Esquizofrenia/genética , Estudio de Asociación del Genoma Completo , Proyectos Piloto , Predisposición Genética a la Enfermedad , Vietnam , Herencia Multifactorial
10.
Int J Tuberc Lung Dis ; 24(12): 1234-1240, 2020 12 01.
Artículo en Inglés | MEDLINE | ID: mdl-33317665

RESUMEN

OBJECTIVE: 1) To determine the prevalence of diabetes mellitus and impaired fasting glucose (IFG) in patients with TB and HIV co-infection, and 2) to investigate the effect of fasting plasma glucose (FPG) on rifampicin (RIF) and isoniazid (INH) serum concentrations.DESIGN: Retrospective data analysis of a cohort of HIV-infected adults with newly diagnosed pulmonary TB. Plasma glucose and TB drug levels were obtained at Week 0, 2, 8 and 24 of TB treatment.RESULTS: A total of 107 patients were included in this analysis. Random plasma glucose ≥200 mg/dL was found in 1/53 (2%) participant at Week 0. The prevalence of FPG ≥ 126 mg/dL decreased from 8/41 (20%) at Week 2 to 3/89 (3%) at Week 24. IFG (100-125 mg/dL) was observed in 23/41 (56%) participants at Week 2, and 39/89 (44%) at Week 24. FPG was inversely correlated with lower area under the curve (AUC0-24h) for RIF (c = -0.52; 95%CI -0.84 to -0.21; P = 0.001). FPG was not associated with lower INH AUC0-24h.CONCLUSION: We found a high prevalence of FPG ≥ 126 mg/dL, which decreased significantly during treatment, and a high proportion of IFG at the end of TB treatment. Higher FPG was associated with lower AUC for RIF.


Asunto(s)
Infecciones por VIH , Hiperglucemia , Isoniazida , Rifampin , Tuberculosis , Adulto , Humanos , Glucemia , Coinfección/epidemiología , Ayuno , Infecciones por VIH/complicaciones , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/epidemiología , Hiperglucemia/epidemiología , Isoniazida/farmacocinética , Estudios Retrospectivos , Rifampin/farmacocinética , Uganda/epidemiología , Tuberculosis/tratamiento farmacológico
11.
Ned Tijdschr Tandheelkd ; 127(5): 292-301, 2020 May.
Artículo en Holandés | MEDLINE | ID: mdl-32609100

RESUMEN

It is estimated that, in the Netherlands, 20-30% of 18-year-olds have suffered some form of dental trauma. A third of them must bear the consequences for the rest of their lives. Adequate care and treatment can make a difference and considerably improve the prognosis of a traumatised tooth. Knowledge about the various types of injuries, forms the basis of optimal treatment. Based on the literature currently available, this article provides an overview of the ways in which details in clinical research can be helpful in more effectively estimating the risk of losing teeth and thus in determining treatment options, in such a way that they are immediately applicable in daily practice.


Asunto(s)
Traumatismos de los Dientes , Humanos , Países Bajos , Pronóstico , Factores de Tiempo
12.
Ned Tijdschr Tandheelkd ; 127(5): 302-308, 2020 May.
Artículo en Holandés | MEDLINE | ID: mdl-32609101

RESUMEN

In dental trauma, the first thought is often: 'Where is that tooth?' And, of course, it is certainly true that fast repositioning is beneficial for the prognosis of the tooth. Nevertheless, it is extremely important to focus on the condition of the patient before focussing on the treatment. A structured approach is mandatory for optimal diagnosis and treatment. This includes possible concomitant injuries such as neurotrauma. The principle of initial screening of the severity of the injury is called triage. There is a clear difference in the severity of injuries of patients with dental trauma presenting themselves in hospital or the dental practice. In hospital there are protocols for primary care; these principles can be applied in the dental practice as well.


Asunto(s)
Triaje , Humanos , Pronóstico
13.
Tech Coloproctol ; 23(10): 957-963, 2019 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-31368009

RESUMEN

BACKGROUND: Endoscopic full-thickness resection (EFTR) significantly expands the spectrum of endoscopic colorectal resection methods for lesions that show no lifting sign, submucosal lesions and mucosal carcinomas. The aim of our study was to evaluate the efficacy and safety of EFTR using a commercially available full thickness resection device (FTRD) by assessing the completeness of the full-thickness resection, the technical success, as well as complications in a cohort of patients from three referral centers in Germany. Another aim was to determine which patient subpopulations benefit most in clinical practice. METHODS: This retrospective multicenter study was conducted on consecutive patients who were admitted to three referral centers in Germany between November 2014 and December 2017. The EFTR was conducted according to the standard indications using the FTRD System (OVESCO, Tübingen, Germany). Data were obtained from prospectively maintained institutional databases. RESULTS: There were 70 patients, 42 males and 25 females with a mean age of 79.5 years (range 25-89 years) who had colonoscopy for EFTR. In three patients EFTR was not feasible because the lesions were too large. Of the remaining 67 patients, 52 had recurrent adenomas, 10 had high-grade intraepithelial neoplasia or mucosal carcinoma and five had a subepithelial lesion. Resection was technically successful in 65 patients (97.0%). Histologically complete resection (R0) was achieved in 59/65 patients (90.8%). The R0 resection rate was lower for lesions > 20 mm (86.5%) versus lesions ≤ 20 mm (92.9%). The total complication rate was 14.9%: there was one major complication (perforation of sigmoid colon), while all other complications were minor. CONCLUSIONS: EFTR yields excellent resection rates for benign recurrent adenomas with non-lifting sign, advanced histopathological findings or submucosal lesions when the procedure is performed in experienced hands and for the correct indication. Thus, surgery can be avoided in many cases. For all lesions the risk of R1 resection goes up with the size of the lesion and careful patient selection is mandatory.


Asunto(s)
Adenoma/cirugía , Carcinoma/cirugía , Colonoscopía/instrumentación , Neoplasias Colorrectales/cirugía , Resección Endoscópica de la Mucosa/instrumentación , Adulto , Anciano , Anciano de 80 o más Años , Colonoscopía/métodos , Resección Endoscópica de la Mucosa/métodos , Femenino , Alemania , Humanos , Tracto Gastrointestinal Inferior/cirugía , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Resultado del Tratamiento
14.
Internist (Berl) ; 59(5): 505-513, 2018 May.
Artículo en Alemán | MEDLINE | ID: mdl-29536125

RESUMEN

The incidence of clostridium difficile infections (CDI) remains on a high level globally. In Germany, the number of severe or even lethal cases continues to increase. The main risk factor for the development of CDI is exposure to broad spectrum antibiotics, which disturb the physiological microbiome and therefore enable colonization with C. difficile. According to the updated US and European guidelines, orally administered vancomycin is the treatment of choice. Fidaxomicin is as effective as vancomycin but has the advantage of a lower rate of recurrence. Furthermore, recent clinical studies were able to demonstrate that significantly fewer recurrences occurred in patients who additionally received the monoclonal antibody bezlotoxumab. In recent years, several new antibiotics with narrow-spectrum acitivity and low intestinal resorption have been developed for the treatment of CDI, including surotomycin, cadazolid, and ridinilazol. Novel toxoid vaccines are expected to become an efficacious tool in the prevention of CDI; however, pivotal clinical trials have so far not been completed.


Asunto(s)
Clostridioides difficile , Infecciones por Clostridium , Antibacterianos/uso terapéutico , Infecciones por Clostridium/tratamiento farmacológico , Alemania , Humanos , Vancomicina/uso terapéutico
15.
Leukemia ; 32(2): 364-375, 2018 02.
Artículo en Inglés | MEDLINE | ID: mdl-28804121

RESUMEN

Somatic hypermutation (SHM) is a pivotal process in adaptive immunity that occurs in the germinal centre and allows B cells to change their primary DNA sequence and diversify their antigen receptors. Here, we report that genome binding of Lamin B1, a component of the nuclear envelope involved in epigenetic chromatin regulation, is reduced during B-cell activation and formation of lymphoid germinal centres. Chromatin immunoprecipitation-Seq analysis showed that kappa and heavy variable immunoglobulin domains were released from the Lamin B1 suppressive environment when SHM was induced in B cells. RNA interference-mediated reduction of Lamin B1 resulted in spontaneous SHM as well as kappa-light chain aberrant surface expression. Finally, Lamin B1 expression level correlated with progression-free and overall survival in chronic lymphocytic leukaemia, and was strongly involved in the transformation of follicular lymphoma. In summary, here we report that Lamin B1 is a negative epigenetic regulator of SHM in normal B-cells and a 'mutational gatekeeper', suppressing the aberrant mutations that drive lymphoid malignancy.


Asunto(s)
Linfocitos B/patología , Lamina Tipo B/genética , Leucemia Linfocítica Crónica de Células B/genética , Leucemia Linfocítica Crónica de Células B/patología , Hipermutación Somática de Inmunoglobulina/genética , Línea Celular Tumoral , Inmunoprecipitación de Cromatina/métodos , Progresión de la Enfermedad , Humanos , Cadenas Pesadas de Inmunoglobulina/genética , Región Variable de Inmunoglobulina/genética , Linfoma Folicular/genética , Linfoma Folicular/patología
16.
Neurogastroenterol Motil ; 30(5): e13261, 2018 05.
Artículo en Inglés | MEDLINE | ID: mdl-29193461

RESUMEN

BACKGROUND: Alterations of site-specific gene expression profiles in disease-relevant networks within the different layers of the intestinal wall may contribute to the onset and clinical course of gastrointestinal disorders. To date, no systematic analysis has assessed and compared sub-regional gene expression patterns in all distinct layers of the gut using fresh frozen human samples. Our aim was to establish an optimized protocol for site-specific RNA isolation in order to achieve maximum RNA quality and amount for subsequent gene expression analysis combining laser-capture microdissection (LCM) with a probe-based technology, the NanoString nCounter Analysis system. METHODS: Four full-thickness colon samples from patients who underwent surgery due to pathological conditions were processed and separated into epithelium, lamina propria, myenteric plexus, submucosa, and tunica muscularis by LCM. Site-specific marker expression by nCounter technology was performed on total RNA from each sub-region, respectively. KEY RESULTS: Collecting ~10 mm² (~100 000-250 000 cells) of tissue from the epithelial layer, lamina propria, and myenteric plexus provided sufficient amounts of RNA of appropriate quality for subsequent analyses. In contrast, ~40 mm² (~250 000-650 000 cells) of tissue were dissected from the less cell-rich submucosal and tunica muscularis layer. nCounter analysis revealed a site-specific expression pattern of marker genes in the different layers of the colonic wall which were highly correlating (r > .9). CONCLUSIONS AND INFERENCES: LCM in combination with nCounter expression analysis enables site-specific, sensitive, reliable detection, and quantification of mRNA from histologically heterogeneous tissues.


Asunto(s)
Colon/metabolismo , Expresión Génica , Perfilación de la Expresión Génica , Humanos , Captura por Microdisección con Láser , Plexo Mientérico/metabolismo
17.
J Antimicrob Chemother ; 72(4): 1172-1177, 2017 04 01.
Artículo en Inglés | MEDLINE | ID: mdl-28108678

RESUMEN

Background: Toxicities due to anti-TB treatment frequently occur among TB/HIV-coinfected patients. Objectives: To determine the association between anti-TB drug concentrations and the occurrence of hepatotoxicity and peripheral neuropathy among TB/HIV-coinfected patients. Methods: TB/HIV-coinfected patients were started on standard dose anti-TB treatment according to WHO guidelines. Anti-TB drug concentrations were measured using HPLC 1, 2 and 4 h after drug intake at 2, 8 and 24 weeks following initiation of TB treatment. Participants were assessed for hepatotoxicity using Division of AIDS toxicity tables and for peripheral neuropathy using clinical assessment of tendon reflexes, vibration sensation or symptoms. Cox regression was used to determine the association between toxicities and drug concentrations. Results: Of the 268 patients enrolled, 58% were male with a median age of 34 years. Participants with no hepatotoxicity or mild, moderate and severe hepatotoxicity had a median C max of 6.57 (IQR 4.83-9.41) µg/mL, 7.39 (IQR 5.10-10.20) µg/mL, 7.00 (IQR 6.05-10.95) µg/mL and 3.86 (IQR 2.81-14.24) µg/mL, respectively. There was no difference in the median C max of rifampicin among those who had hepatotoxicity and those who did not ( P = 0.322). There was no difference in the isoniazid median C max among those who had peripheral neuropathy 2.34 (1.52-3.23) µg/mL and those who did not 2.21 (1.45-3.11) µg/mL ( P = 0.49). Conclusions: There was no association between rifampicin concentrations and hepatotoxicity or isoniazid concentrations and peripheral neuropathy among TB/HIV-coinfected patients.


Asunto(s)
Antituberculosos/efectos adversos , Antituberculosos/sangre , Coinfección/microbiología , Coinfección/virología , Tuberculosis/tratamiento farmacológico , Adulto , Antituberculosos/uso terapéutico , Enfermedad Hepática Inducida por Sustancias y Drogas/epidemiología , Enfermedad Hepática Inducida por Sustancias y Drogas/etiología , Coinfección/tratamiento farmacológico , Coinfección/epidemiología , Femenino , Infecciones por VIH/complicaciones , Infecciones por VIH/epidemiología , Humanos , Isoniazida/administración & dosificación , Isoniazida/efectos adversos , Isoniazida/uso terapéutico , Masculino , Persona de Mediana Edad , Enfermedades del Sistema Nervioso Periférico/epidemiología , Enfermedades del Sistema Nervioso Periférico/etiología , Estudios Prospectivos , Análisis de Regresión , Rifampin/efectos adversos , Rifampin/sangre , Rifampin/uso terapéutico , Tuberculosis/complicaciones , Tuberculosis/epidemiología , Tuberculosis/microbiología , Tuberculosis Pulmonar/tratamiento farmacológico , Adulto Joven
18.
Rep Prog Phys ; 80(5): 054401, 2017 05.
Artículo en Inglés | MEDLINE | ID: mdl-28059773

RESUMEN

Recently two emerging areas of research, attosecond and nanoscale physics, have started to come together. Attosecond physics deals with phenomena occurring when ultrashort laser pulses, with duration on the femto- and sub-femtosecond time scales, interact with atoms, molecules or solids. The laser-induced electron dynamics occurs natively on a timescale down to a few hundred or even tens of attoseconds (1 attosecond = 1 as = 10-18 s), which is comparable with the optical field. For comparison, the revolution of an electron on a 1s orbital of a hydrogen atom is ∼152 as. On the other hand, the second branch involves the manipulation and engineering of mesoscopic systems, such as solids, metals and dielectrics, with nanometric precision. Although nano-engineering is a vast and well-established research field on its own, the merger with intense laser physics is relatively recent. In this report on progress we present a comprehensive experimental and theoretical overview of physics that takes place when short and intense laser pulses interact with nanosystems, such as metallic and dielectric nanostructures. In particular we elucidate how the spatially inhomogeneous laser induced fields at a nanometer scale modify the laser-driven electron dynamics. Consequently, this has important impact on pivotal processes such as above-threshold ionization and high-order harmonic generation. The deep understanding of the coupled dynamics between these spatially inhomogeneous fields and matter configures a promising way to new avenues of research and applications. Thanks to the maturity that attosecond physics has reached, together with the tremendous advance in material engineering and manipulation techniques, the age of atto-nanophysics has begun, but it is in the initial stage. We present thus some of the open questions, challenges and prospects for experimental confirmation of theoretical predictions, as well as experiments aimed at characterizing the induced fields and the unique electron dynamics initiated by them with high temporal and spatial resolution.

19.
Doc Ophthalmol ; 133(2): 81-90, 2016 10.
Artículo en Inglés | MEDLINE | ID: mdl-27510912

RESUMEN

PURPOSE: The subretinal Alpha IMS visual implant is a CE-approved medical device for restoration of visual functions in blind patients with end-stage outer retina degeneration. We present a method to test the function of the implant objectively in vivo using standard electroretinographic equipment and to assess the devices' parameter range for an optimal perception. METHODS: Subretinal implant Alpha IMS (Retina Implant AG, Reutlingen, Germany) consists of 1500 photodiode-amplifier-electrode units and is implanted surgically into the subretinal space in blind retinitis pigmentosa patients. The voltages that regulate the amplifiers' sensitivity (V gl) and gain (V bias), related to the perception of contrast and brightness, respectively, are adjusted manually on a handheld power supply device. Corneally recorded implant responses (CRIR) to full-field illumination with long duration flashes in various implant settings for brightness gain (V bias) and amplifiers' sensitivity (V gl) are measured using electroretinographic setup with a Ganzfeld bowl in a protocol of increasing stimulus luminances up to 1000 cd/m2. RESULTS: CRIRs are a meaningful tool for assessing the transfer characteristic curves of the electronic implant in vivo monitoring the implants' voltage output as a function of log luminance in a sigmoidal shape. Changing the amplifiers' sensitivity (V gl) shifts the curve left or right along the log luminance axis. Adjustment of the gain (V bias) changes the maximal output. Contrast perception is only possible within the luminance range of the increasing slope of the function. CONCLUSIONS: The technical function of subretinal visual implants can be measured objectively using a standard electroretinographic setup. CRIRs help the patient to optimise the perception by adjusting the gain and luminance range of the device and are a useful tool for clinicians to objectively assess the function of subretinal visual implants in vivo.


Asunto(s)
Ceguera/rehabilitación , Córnea/fisiología , Electrodos Implantados , Electrorretinografía/métodos , Degeneración Retiniana/complicaciones , Visión Ocular/fisiología , Adulto , Ceguera/etiología , Ceguera/fisiopatología , Humanos , Estimulación Luminosa , Retina/fisiopatología , Degeneración Retiniana/fisiopatología
20.
BMC Hematol ; 16: 16, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-27274846

RESUMEN

BACKGROUND: Tuberculosis (TB) and HIV are among the risk factors for deep vein thrombosis (DVT). There are several challenges in the management of DVT patients with TB-HIV co-infection including drug-drug interactions and non-adherence due to pill burden. METHODS: HIV infected patients starting treatment for TB were identified and followed up two weekly. Cases of DVT were diagnosed with Doppler ultrasound and patients were initiated on oral anticoagulation with warfarin and followed up with repeated INR measurements and warfarin dose adjustment. RESULTS: We describe 7 cases of TB and HIV-infected patients in Uganda diagnosed with DVT and started on anticoagulation therapy. Their median age was 30 (IQR: 27-39) years and 86 % were male. All patients had co-medication with cotrimoxazole, tenofovir, lamivudine and efavirenz and some were on fluconazole. The therapeutic range of the International Normalization Ratio (INR) was difficult to attain and unpredictable with some patients being under-anticoagulated and others over-anticoagulated. The mean Time in Therapeutic Range (TTR) for patients who had all scheduled INR measurements in the first 12 weeks was 33.3 %. Only one patient among those with all the scheduled INR measurements had achieved a therapeutic INR by 2 weeks. Four out of seven (57 %) of the patients had at least one INR above the therapeutic range which required treatment interruption. None of the patients had major bleeding. CONCLUSION: We recommend more frequent monitoring and timely dose adjustment of the INR, as well as studies on alternative strategies for the treatment of DVT in TB-HIV co-infected patients.

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