Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 492
Filtrar
1.
Qual Life Res ; 2021 Jan 02.
Artículo en Inglés | MEDLINE | ID: mdl-33387288

RESUMEN

PURPOSE: To validate the Impact Index, a short, publicly available scale that measures the extent to which a respondent's health problem adversely impacts their quality of life. METHODS: Secondary analysis of patients with hip or knee osteoarthritis surveyed after visiting a surgeon at baseline (N = 322) and about 6 months after the visit (N = 283). Patients responded to the Impact Index and previously validated questionnaires about overall health, pain, and function. The Impact Index includes four questions that ask how much the respondent is bothered, worried, limited, or in pain due to their health condition over the past 30 days. Total scores range from 0 to 12; higher scores indicate more deleterious impact. RESULTS: Patients were mostly female (55%), majority white (95%), had an average age of 65 (SD = 9), and most had surgery (64%). The baseline Impact Index score was 9.48 (SD = 2.63); at follow up 4.75 (SD = 3.54). Impact Index was related to overall health at baseline (r = - 0.49). For knee patients at baseline, Impact Index was negatively related to their knee symptoms (r = - 0.49) and knee pain (r = - 0.67). For hip patients at baseline, Impact Index was negatively related to the Harris Hip score (r = - 0.62). Scale directions varied; however, the signs of all correlations were as hypothesized. The Impact Index was predictive of surgical choice (p < .001, OR = 1.45), however, overall health (p = .88) and comorbidity (p = .24) measures were not. Reliability was acceptable (α = 0.85). Responsiveness statistics suggested overall health, pain, function, and Impact Index measures reflected improvement patients experienced from surgery. The Impact Index had the largest effect sizes (> - 3.4) and Guyatt Responsiveness Statistics (> - 2.3). CONCLUSIONS: The Impact Index demonstrated strong evidence of validity, reliability, and responsiveness in hip or knee osteoarthritis patients.

3.
JAMA ; 324(20): 2069-2075, 2020 Nov 24.
Artículo en Inglés | MEDLINE | ID: mdl-33231670

RESUMEN

Importance: Cardiovascular disease (CVD) is a leading cause of death in the US. Known modifiable risk factors for CVD include smoking, overweight and obesity, diabetes, elevated blood pressure or hypertension, dyslipidemia, lack of physical activity, and unhealthy diet. Adults who adhere to national guidelines for a healthy diet and physical activity have lower cardiovascular morbidity and mortality than those who do not. All persons, regardless of their CVD risk status, benefit from healthy eating behaviors and appropriate physical activity. Objective: To update its 2014 recommendation, the USPSTF commissioned a review of the evidence on behavioral counseling to promote a healthy diet and physical activity for CVD prevention in adults with cardiovascular risk factors. Population: This recommendation statement applies to adults 18 years or older with known hypertension or elevated blood pressure, those with dyslipidemia, or those who have mixed or multiple risk factors such as metabolic syndrome or an estimated 10-year CVD risk of 7.5% or greater. Adults with other known modifiable cardiovascular risk factors such as abnormal blood glucose levels, obesity, and smoking are not included in this recommendation. Evidence Assessment: The USPSTF concludes with moderate certainty that behavioral counseling interventions have a moderate net benefit on CVD risk in adults at increased risk for CVD. Recommendation: The USPSTF recommends offering or referring adults with CVD risk factors to behavioral counseling interventions to promote a healthy diet and physical activity. (B recommendation).

4.
BMJ Open ; 10(11): e040806, 2020 Nov 14.
Artículo en Inglés | MEDLINE | ID: mdl-33191267

RESUMEN

OBJECTIVES: To determine the use and expenditure associated with cystic fibrosis (CF) modulator therapies in Ireland since their reimbursement in 2013. DESIGN: A retrospective analysis of a national drug claims database. SETTING: The data included in this study are nationally representative (Ireland). PARTICIPANTS: Data on all persons receiving CF modulator therapies were included. METHODS: We obtained national claims data for CF therapies from the Health Service Executive's Primary Care Reimbursement Service. We determined the use and expenditure associated with CF therapies from January 2012 to March 2020. RESULTS: The increased prescribing of CF modulator therapies was associated with an approximate fivefold increase in expenditure from €23 million in 2013 to €113 million in 2019. Many patients who initiated lumacaftor/ivacaftor in 2017 went on to receive symptomatic therapies, and subsequently initiated tezacaftor/ivacaftor in 2019. CONCLUSION: Despite none of these modulator therapies demonstrating value for money when subjected to health technology assessment, the associated Irish expenditure reached €113 million in 2019 alone.

5.
JAMA ; 324(18): 1878-1883, 2020 Nov 10.
Artículo en Inglés | MEDLINE | ID: mdl-33170248

RESUMEN

Importance: Prevalence of hypertension (both primary and secondary) in children and adolescents in the US ranges from 3% to 4%. Primary hypertension in children and adolescents occurs primarily in children older than 13 years and has no known cause but is associated with several risk factors, including family history and higher body mass index. Secondary hypertension occurs primarily in younger children and is most commonly caused by genetic disorders, renal disease, endocrine disorders, or cardiovascular abnormalities. Objective: To update its 2013 recommendation, the USPSTF commissioned a review of the evidence on the benefits and harms of screening, test accuracy, the effectiveness and harms of treatment, and the association between hypertension and markers of cardiovascular disease in childhood and adulthood. Population: This recommendation statement applies to children and adolescents aged 3 to 18 years not known to have hypertension or who are asymptomatic. Evidence Assessment: The USPSTF concludes that the evidence to support screening for high blood pressure in children and adolescents is insufficient and that the balance of benefits and harms cannot be determined. Recommendation: The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of screening for high blood pressure in children and adolescents. (I statement).


Asunto(s)
Hipertensión/diagnóstico , Tamizaje Masivo , Adolescente , Determinación de la Presión Sanguínea/instrumentación , Enfermedades Cardiovasculares/prevención & control , Niño , Preescolar , Reacciones Falso Positivas , Femenino , Humanos , Hipertensión/terapia , Masculino , Tamizaje Masivo/efectos adversos , Servicios Preventivos de Salud , Valores de Referencia
6.
Ann Surg ; 2020 Nov 16.
Artículo en Inglés | MEDLINE | ID: mdl-33201091

RESUMEN

OBJECTIVE: To develop and validate a short measure of trust in the surgical decision making process. SUMMARY OF BACKGROUND DATA: Having a reliable and valid measure of trust is important to assess the quality of the patient-surgeon relationship when decisions about surgical procedures are made. METHODS: A previously published 10-item trust scale was qualitatively tested with patients, and a revised set of 14 items was tested using a web-based survey of 300 people who had hip, knee or back surgery in the past 2 years. The 14 items were evaluated using patterns of correlations and relevance to medical decision making to create a 5-item version. A 5-item subset was compared to the 14-item version to assess reliability and validity of patient's trust in the surgical decision making process. RESULTS: Of the 300 participants, 32% had hip surgery, 33% had knee surgery, and 34% back surgery. Mean age was 53 years, 45% female, 80% White, and 36% had a high school degree or less. The item intercorrelations for the 14 items were 0.43-0.72 and 0.58-0.71 for the 5 items. Correlation between the versions was 0.96 (P < 0.01). The 14- and 5-item versions were positively correlated with participants' shared decision making process scores (0.42 and 0.41, both P = 0.01), internal consistency reliability scores were 0.95 and 0.89, respectively, and were negatively correlated with their Decision Regret scores (-0.51 and -0.48, both P = 0.01). CONCLUSION: The 5-item Trust in the Surgical Decision Scale has strong evidence of validity and reliability for patients who underwent common orthopedic procedures.

7.
Transl Vis Sci Technol ; 9(12): 27, 2020 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-33244447

RESUMEN

Purpose: At present, Argus II is the only retinal prosthesis approved by the US Food and Drug Administration that induces visual percepts in people who are blind from end-stage outer retinal degenerations such as retinitis pigmentosa. It has been shown to work well in sparse, high-contrast settings, but in daily practice visual performance with the device is likely to be hampered by the cognitive load presented by a cluttered real-world environment. In this study, we investigated the effect of a stereo-disparity-based distance-filtering system on four experienced Argus II users for a range of tasks: object localization, depth discrimination, orientation and size discrimination, and people detection and direction of motion. Methods: Functional vision was assessed in a semicontrolled setup using unfiltered (normal camera) and distance-filtered (stereo camera) imagery. All tasks were forced choice designs and an extension of signal detection theory to latent (unobservable) variables was used to analyze the data, allowing estimation of person ability (person measures) and task difficulty (item measures) on the same axis. Results: All subjects performed better with the distance filter compared with the unfiltered image (P  < 0.001 on all tasks except localization). Conclusions: Our results show that depth filtering using a disparity-based algorithm has significant benefits for people with Argus II implants. Translational Relevance: The improvement in functional vision with the distance filter found in this study may have an important impact on vision rehabilitation and quality of life for people with visual prostheses and ultra low vision.

8.
Value Health ; 23(11): 1423-1426, 2020 11.
Artículo en Inglés | MEDLINE | ID: mdl-33127011

RESUMEN

It is expected that the coronavirus disease 2019 (COVID-19) pandemic will leave large deficits in the budgets of many jurisdictions. Funding for other treatments, in particular new treatments, may become more constrained than previously expected. Therefore, a robust health technology assessment (HTA) system is vital. Many clinical trials carried out during the pandemic may have been temporarily halted, while others may have had to change their protocols. Even trials that continue as normal may experience external changes as other aspects of the healthcare service may not be available to the patients in the trial, or the patients themselves may contract COVID-19. Consequently, many limitations are likely to arise in the provision of robust HTAs, which could have profound consequences on the availability of new treatments. Therefore, the National Centre for Pharmacoeconomics Review Group wishes to discuss these issues and make recommendations for applicants submitting to HTA agencies, in ample time for these HTAs to be prepared and assessed. We discuss how the pandemic may affect the estimation of the treatment effect, costs, life-years, utilities, discontinuation rates, and methods of evidence synthesis and extrapolation. In particular, we note that trials conducted during the pandemic will be subject to a higher degree of uncertainty than before. It is vital that applicants clearly identify any parameters that may be affected by the pandemic. These parameters will require considerably more scenario and sensitivity analyses to account for this increase in uncertainty.


Asunto(s)
Comités Consultivos , Infecciones por Coronavirus , Pandemias , Neumonía Viral , Evaluación de la Tecnología Biomédica , Betacoronavirus , Presupuestos , Infecciones por Coronavirus/tratamiento farmacológico , Economía Farmacéutica , Humanos , Neumonía Viral/tratamiento farmacológico , Calidad de Vida , Resultado del Tratamiento , Privación de Tratamiento
9.
Annu Int Conf IEEE Eng Med Biol Soc ; 2020: 3323-3326, 2020 07.
Artículo en Inglés | MEDLINE | ID: mdl-33018715

RESUMEN

Tracking the eye of a blind patient can enhance the usability of an artificial vision system. In systems where the sensing element, i.e. the scene camera that captures the visual information, is mounted on the patient's head, the user must use head scanning in order to steer the line of sight of the implant to the region of interest. Integrating an eye tracker in the prosthesis will enable scanning using eye movements. The eye position will set the region of interest within the wide field-of-view of the scene camera. An essential requirement of an eye tracker is the need to calibrate it. Obviously, off-the-shelf calibration methods that require looking at known points in space cannot be used with blind users.Here we tested the feasibility of calibrating the eye-tracker based on pupil position and the location of the percept reported by the implant recipient, using a handheld marker. Pupil positions were extracted using custom image processing in a field-programmable-gate-array built into a glasses-mounted eye tracker. In the calibration process, electrodes were directly stimulated and the subject reported the location of the percept using a handheld marker. Linear regression was used to extract the transfer function from pupil position to gaze direction in the coordinates of the scene camera.In using the eye tracker with the proposed calibration method, patients demonstrated improved precision on a localization task with corresponding reduction of head movements.


Asunto(s)
Movimientos Oculares , Personas con Daño Visual , Ceguera , Movimientos de la Cabeza , Humanos , Procesamiento de Imagen Asistido por Computador
10.
BMC Health Serv Res ; 20(1): 851, 2020 Sep 10.
Artículo en Inglés | MEDLINE | ID: mdl-32912191

RESUMEN

BACKGROUND: Obtaining a sample that is representative of the group of interest is of utmost importance in questionnaire studies. In a survey using a state authorized web-portal for citizen communication with authorities, we wanted to investigate the view of adult men on patient involvement in health care decision-making regarding Prostate-Specific Antigen test for prostatic cancer. In this paper, we report on sample characteristics and representativeness of our sample in terms of personality and baseline involvement preferences. METHODS: We compared personality profiles (BFI-10) and baseline healthcare decision-making preferences (CPS) in our sample (n = 6756) to internationally available datasets. Pooled data from a) US, UK, Canada, Australia, and New Zealand (n = 1512), b) Germany, Netherlands, Switzerland, and Belgium (n = 1136), and c) Norway, Sweden, Finland, and Denmark (n = 1313) were used for BFI-10 comparisons. Regarding CPS, we compared our sample with three previous datasets relating to decision-making in cancer (n = 425, 387, and 199). RESULTS: Although statistically significant differences particularly appeared in large dataset comparisons, sample BFI-10 and CPS profiles mostly were within the range of those previously reported. Similarity was greatest in BFI-10 comparisons with group a) where no statistically significant difference could be established in factors 'agreeableness' and 'neuroticism' (p = .095 and .578, respectively). CONCLUSION: Despite some variation, our sample displays personality and baseline preference profiles that are generally similar to those described in previous international studies. For example, this was the case with the BFI-10 'agreeableness' measure (incl. trust and fault-finding items), an important factor in healthcare decision-making.

11.
Expert Rev Pharmacoecon Outcomes Res ; 20(5): 431-436, 2020 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-32909850

RESUMEN

INTRODUCTION: Health technology assessment (HTA) is a widely used process to systematically evaluate the properties, effects, and impacts of health technology, with the main purpose of informing policymaking in healthcare. However, to ensure optimal use of scarce healthcare budgets, there is a need to look beyond HTA - to post-reimbursement health technology management (HTM). AREAS COVERED: This review aims to describe the significant impact HTA, in combination with HTM, has made to the cost-effective prescribing and cost-containment in Ireland. This review will cover a number of specific examples, such as; specific reimbursement criteria for sacubitril/valsartan (Entresto®) and evolocumab (Repatha®), the introduction of a reimbursement application system for lidocaine 5% medicated plaster (Versatis®), and the introduction of 'preferred' biosimilars for patent-expired biologic medicines. EXPERT OPINION: Healthcare payers are increasingly recognizing the benefits of HTM particularly when used in conjunction with HTA. This review highlights several examples whereby significant cost-savings can be made through HTM of not only new drugs but also drugs which are already available on the market.

12.
JAMA ; 324(7): 674-681, 2020 08 18.
Artículo en Inglés | MEDLINE | ID: mdl-32809008

RESUMEN

Importance: Approximately 20 million new cases of bacterial or viral sexually transmitted infections (STIs) occur each year in the US, and about one-half of these cases occur in persons aged 15 to 24 years. Rates of chlamydial, gonococcal, and syphilis infection continue to increase in all regions. Sexually transmitted infections are frequently asymptomatic, which may delay diagnosis and treatment and lead persons to unknowingly transmit STIs to others. Serious consequences of STIs include pelvic inflammatory disease, infertility, cancer, and AIDS. Objective: To update its 2014 recommendation, the US Preventive Services Task Force (USPSTF) commissioned a review of the evidence on the benefits and harms of behavioral counseling interventions for preventing STI acquisition. Population: This recommendation statement applies to all sexually active adolescents and to adults at increased risk for STIs. Evidence Assessment: The USPSTF concludes with moderate certainty that behavioral counseling interventions reduce the likelihood of acquiring STIs in sexually active adolescents and in adults at increased risk, including for example, those who have a current STI, do not use condoms, or have multiple partners, resulting in a moderate net benefit. Recommendation: The USPSTF recommends behavioral counseling for all sexually active adolescents and for adults at increased risk for STIs. (B recommendation).


Asunto(s)
Terapia Conductista , Consejo , Conducta Sexual , Enfermedades de Transmisión Sexual/prevención & control , Adolescente , Adulto , Terapia Conductista/métodos , Consejo/métodos , Femenino , Humanos , Masculino , Atención Primaria de Salud , Conducta de Reducción del Riesgo
13.
BMC Med Inform Decis Mak ; 20(1): 187, 2020 08 12.
Artículo en Inglés | MEDLINE | ID: mdl-32787849

RESUMEN

BACKGROUND: Determining the primary indication of a surgical procedure can be useful in identifying patients undergoing elective surgery where shared decision-making is recommended. The purpose of this study was to develop and validate an algorithm to identify patients receiving the following combinations of surgical procedure and primary indication as part of a study to promote shared decision-making: (1) knee arthroplasty to treat knee osteoarthritis (KOA); (2) hip arthroplasty to treat hip osteoarthritis (HOA); (3) spinal surgery to treat lumbar spinal stenosis (SpS); and (4) spinal surgery to treat lumbar herniated disc (HD). METHODS: Consecutive surgical procedures performed by participating spine, hip, and knee surgeons at four sites within an integrated care network were included. Study staff reviewed electronic medical records to ascertain a "gold standard" determination of the procedure and primary indication status. Electronic algorithms consisting of ICD-10 and CPT codes for each combination of procedure and indication were then applied to records for each case. The primary measures of validity for the algorithms were the sensitivity and specificity relative to the gold standard review. RESULTS: Participating surgeons performed 790 procedures included in this study. The sensitivity of the algorithms in determining whether a surgical case represented one of the combinations of procedure and primary indication ranged from 0.70 (HD) to 0.92 (KOA). The specificity ranged from 0.94 (SpS) to 0.99 (HOA, KOA). CONCLUSION: The electronic algorithm was able to identify all four procedure/primary indication combinations of interest with high specificity. Additionally, the sensitivity for the KOA cases was reasonably high. For HOA and the spine conditions, additional work is needed to improve the sensitivity of the algorithm to identify the primary indication for each case.

14.
Vaccines (Basel) ; 8(3)2020 Aug 22.
Artículo en Inglés | MEDLINE | ID: mdl-32842679

RESUMEN

Clostridium difficile causes nearly 500,000 infections and nearly 30,000 deaths each year in the U.S., which is estimated to cost $4.8 billion. C. difficile infection (CDI) arises from bacteria colonizing the large intestine and releasing two toxins, toxin A (TcdA) and toxin B (TcdB). Generating humoral immunity against C. difficile's toxins provides protection against primary infection and recurrence. Thus, a vaccine may offer the best opportunity for sustained, long-term protection. We developed a novel single-cycle adenovirus (SC-Ad) vaccine against C. difficile expressing the receptor-binding domains from TcdA and TcdB. The single immunization of mice generated sustained toxin-binding antibody responses and protected them from lethal toxin challenge for up to 38 weeks. Immunized Syrian hamsters produced significant toxin-neutralizing antibodies that increased over 36 weeks. Single intramuscular immunization provided complete protection against lethal BI/NAP1/027 spore challenge 45 weeks later. These data suggest that this replicating vaccine may prove useful against CDI in humans.

15.
J Med Internet Res ; 22(9): e19517, 2020 09 02.
Artículo en Inglés | MEDLINE | ID: mdl-32663149

RESUMEN

BACKGROUND: Being able to generalize research findings to a broader population outside of the study sample is an important goal in surveys on the internet. We conducted a nationwide, cross-sectional, web-based survey with vignettes illustrating different levels of patient involvement to investigate men's preferences regarding participation in health care decision-making. Following randomization into vignette variants, we distributed the survey among men aged 45 to 70 years through the state-authorized digital mailbox provided by the Danish authorities for secure communication with citizens. OBJECTIVE: This study aimed to investigate the sociodemographic representativeness of our sample of men obtained in a nationwide web-based survey using the digital mailbox. METHODS: Response rate estimates were established, and comparisons were made between responders and nonresponders in terms of age profiles (eg, average age) and municipality-level information on sociodemographic characteristics. RESULTS: Among 22,288 men invited during two waves, a total of 6756 (30.31%) participants responded to the survey. In adjusted analyses, responders' characteristics mostly resembled those of nonresponders. Response rates, however, were significantly higher in older men (odds ratio [OR] 2.83 for responses among those aged 65-70 years compared with those aged 45-49 years, 95% CI 2.58-3.11; P<.001) and in rural areas (OR 1.10 compared with urban areas, 95% CI 1.03-1.18; P=.005). Furthermore, response rates appeared lower in areas with a higher tax base (OR 0.89 in the highest tertile, 95% CI 0.81-0.98; P=.02). CONCLUSIONS: Overall, the general population of men aged 45 to 70 years was represented very well by the responders to our web-based survey. However, the imbalances identified highlight the importance of supplementing survey findings with studies of the representativeness of other characteristics of the sample like trait and preference features, so that proper statistical corrections can be made in upcoming analyses of survey responses whenever needed.

16.
J Patient Rep Outcomes ; 4(1): 57, 2020 Jul 14.
Artículo en Inglés | MEDLINE | ID: mdl-32666381

RESUMEN

BACKGROUND: Patients' behaviors play a key role in chronic disease management, but how effective they are may depend on how engaged they feel. The objective was to develop a short measure of how much patients felt engaged in self-managing a chronic condition. Online test of a three-question series followed by a survey of physicians and their eligible diabetic patients. Physicians answered: 1) how well the physician thought the patient was managing his/her diabetes, and 2) how much effort the physician thought the patient was putting in. Each patient was mailed a survey that included three questions on self-management. Six hundred six patients from a national online consumer panel with diabetes or obesity, and 35 physicians from 3 primary care practices and a sample of 243 of their diabetic patients. Respondents were asked three questions about how much they thought their behavior could affect their health condition, how confident they were that they could do what was needed, and how involved they were in decisions about managing their condition. These items were summed to create a WELL score. Descriptive statistics and correlation coefficients were used to describe item relationships. Generalized Estimating Equations were used to predict how well the physician thought the patient was managing their diabetes and patient effort. RESULTS: Correlations among the three patient-reported items ranged from - 0.01 to 0.45. The WELL score was correlated with an existing measure of patient activation commitment (r = .43, p < 0.001) and found to be a significant predictor of physicians' ratings of how much effort patients devoted to condition management (b = 0.02, p = 0.001, OR = 1.02) after adjusting for confounders. The WELL score didn't predict physicians' ratings of how effective patients were (b = 0.003, p = .526, OR = 1.004) after their A1c score had been taken into account. CONCLUSION: Patients' WELL scores predicted physicians' ratings of patient effort in diabetes self-management.

17.
JAMA ; 323(22): 2301-2309, 2020 Jun 09.
Artículo en Inglés | MEDLINE | ID: mdl-32515821

RESUMEN

Importance: An estimated 12% of adults 18 years or older and 8% of adolescents aged 12 to 17 years report unhealthy use of prescription or illegal drugs in the US. Objective: To update its 2008 recommendation, the USPSTF commissioned reviews of the evidence on screening by asking questions about drug use and interventions for unhealthy drug use in adults and adolescents. Population: This recommendation statement applies to adults 18 years or older, including pregnant and postpartum persons, and adolescents aged 12 to 17 years in primary care settings. This statement does not apply to adolescents or adults who have a currently diagnosed drug use disorder or are currently undergoing or have been referred for drug use treatment. This statement applies to settings and populations for which services for accurate diagnosis, effective treatment, and appropriate care can be offered or referred. Evidence Assessment: In adults, the USPSTF concludes with moderate certainty that screening by asking questions about unhealthy drug use has moderate net benefit when services for accurate diagnosis of unhealthy drug use or drug use disorders, effective treatment, and appropriate care can be offered or referred. In adolescents, because of the lack of evidence, the USPSTF concludes that the benefits and harms of screening for unhealthy drug use are uncertain and that the balance of benefits and harms cannot be determined. Recommendation: The USPSTF recommends screening by asking questions about unhealthy drug use in adults 18 years or older. Screening should be implemented when services for accurate diagnosis, effective treatment, and appropriate care can be offered or referred. (Screening refers to asking questions about unhealthy drug use, not testing biological specimens.) (B recommendation) The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of screening for unhealthy drug use in adolescents. (I statement).


Asunto(s)
Tamizaje Masivo/normas , Antagonistas de Narcóticos/uso terapéutico , Psicoterapia , Detección de Abuso de Sustancias/normas , Trastornos Relacionados con Sustancias/diagnóstico , Adolescente , Adulto , Humanos , Tamizaje Masivo/efectos adversos , Tamizaje Masivo/métodos , Antagonistas de Narcóticos/efectos adversos , Sensibilidad y Especificidad , Detección de Abuso de Sustancias/métodos , Trastornos Relacionados con Sustancias/tratamiento farmacológico , Trastornos Relacionados con Sustancias/terapia , Encuestas y Cuestionarios
18.
Gastroenterology ; 159(4): 1487-1503.e17, 2020 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-32574624

RESUMEN

BACKGROUND & AIMS: Endoplasmic reticulum to nucleus signaling 1 (ERN1, also called IRE1A) is a sensor of the unfolded protein response that is activated in the livers of patients with nonalcoholic steatohepatitis (NASH). Hepatocytes release ceramide-enriched inflammatory extracellular vesicles (EVs) after activation of IRE1A. We studied the effects of inhibiting IRE1A on release of inflammatory EVs in mice with diet-induced steatohepatitis. METHODS: C57BL/6J mice and mice with hepatocyte-specific disruption of Ire1a (IRE1αΔhep) were fed a diet high in fat, fructose, and cholesterol to induce development of steatohepatitis or a standard chow diet (controls). Some mice were given intraperitoneal injections of the IRE1A inhibitor 4µ8C. Mouse liver and primary hepatocytes were transduced with adenovirus or adeno-associated virus that expressed IRE1A. Livers were collected from mice and analyzed by quantitative polymerase chain reaction and chromatin immunoprecipitation assays; plasma samples were analyzed by enzyme-linked immunosorbent assay. EVs were derived from hepatocytes and injected intravenously into mice. Plasma EVs were characterized by nanoparticle-tracking analysis, electron microscopy, immunoblots, and nanoscale flow cytometry; we used a membrane-tagged reporter mouse to detect hepatocyte-derived EVs. Plasma and liver tissues from patients with NASH and without NASH (controls) were analyzed for EV concentration and by RNAscope and gene expression analyses. RESULTS: Disruption of Ire1a in hepatocytes or inhibition of IRE1A reduced the release of EVs and liver injury, inflammation, and accumulation of macrophages in mice on the diet high in fat, fructose, and cholesterol. Activation of IRE1A, in the livers of mice, stimulated release of hepatocyte-derived EVs, and also from cultured primary hepatocytes. Mice given intravenous injections of IRE1A-stimulated, hepatocyte-derived EVs accumulated monocyte-derived macrophages in the liver. IRE1A-stimulated EVs were enriched in ceramides. Chromatin immunoprecipitation showed that IRE1A activated X-box binding protein 1 (XBP1) to increase transcription of serine palmitoyltransferase genes, which encode the rate-limiting enzyme for ceramide biosynthesis. Administration of a pharmacologic inhibitor of serine palmitoyltransferase to mice reduced the release of EVs. Levels of XBP1 and serine palmitoyltransferase were increased in liver tissues, and numbers of EVs were increased in plasma, from patients with NASH compared with control samples and correlated with the histologic features of inflammation. CONCLUSIONS: In mouse hepatocytes, activated IRE1A promotes transcription of serine palmitoyltransferase genes via XBP1, resulting in ceramide biosynthesis and release of EVs. The EVs recruit monocyte-derived macrophages to the liver, resulting in inflammation and injury in mice with diet-induced steatohepatitis. Levels of XBP1, serine palmitoyltransferase, and EVs are all increased in liver tissues from patients with NASH. Strategies to block this pathway might be developed to reduce liver inflammation in patients with NASH.

19.
Br J Nutr ; 124(7): 693-700, 2020 Oct 14.
Artículo en Inglés | MEDLINE | ID: mdl-32406341

RESUMEN

Although lignin has been negatively correlated with neutral-detergent fibre (NDF) digestibility (NDFD) in ruminants and used to predict potential extent of NDF digestion of forages, selection of an analysis, Klason lignin (KL) or acid-detergent lignin (ADL), to describe that the nutritionally relevant lignin has not been resolved. Dismissed as an artifact is the difference between KL and ADL (ΔL). A question is whether ΔL influences NDFD. We evaluated the relationships of ΔL, KL and ADL with NDFD in order to determine the nutritionally homogeneous or heterogeneous nature of KL. Data sets from two laboratories (DS1 and DS2) were used that included ADL, KL and in vitro NDFD at 48 h (NDFD48). DS1 contained seven C3 grasses, seventeen C4 maize forages and nineteen alfalfas, and DS2 had fifteen C3 grasses, eight C4 forages and six alfalfas. Mean ΔL was greater than ADL in C3 and C4 samples and less in alfalfas. Within forage type and laboratory, ΔL was not correlated with NDFD48 (r -0·34-0·49; all P > 0·17). ADL was more consistently correlated with NDFD48 (r -0·47--0·95; P < 0·01-0·21) than with KL (r 0·03--0·91; P < 0·01-0·94). ΔL as a proportion of KL was correlated with NDFD48 in C3 and C4 samples (r 0·44-0·76; P < 0·01-0·08). The differing behaviours of ΔL and ADL relative to NDFD48 indicate that KL is a nutritionally heterogeneous fraction, the behaviour of which may vary by forage type and ratios of ADL and ΔL present.

20.
Br J Clin Pharmacol ; 2020 May 29.
Artículo en Inglés | MEDLINE | ID: mdl-32470158

RESUMEN

AIMS: Entresto (sacubitril/valsartan) is used to treat symptomatic chronic heart failure with reduced ejection fraction. Given its high potential budget impact, the Health Services Executive introduced a reimbursement application system (RAS) to ensure its appropriate use. The aim of this study was to evaluate the utilisation of Entresto in Ireland and compare patient characteristics to those of the pivotal PARADIGM-HF trial. METHODS: We used dispensed claims data from the Primary Care Reimbursement Services, clinical data obtained from the RAS, and data from published studies of Entresto utilisation. Differences in the baseline characteristics in the study populations vs the Entresto arm of the PARADIGM-HF trial were analysed. We also investigated cardiovascular medication use in the 6 months pre- and post-Entresto initiation. RESULTS: In 2018, there were 1043 individuals receiving Entresto, corresponding to an expenditure of €1.2 million. Patients prescribed Entresto in Ireland were older, had lower left ventricular ejection fraction and were more symptomatic than those in the PARADIGM-HF trial. Irish patient characteristics were reflective of Entresto-treated populations in other real-world studies. More than 63% of patients were commenced on the lowest Entresto dose. Entresto initiation was associated with a reduction in the use of other medications for heart failure. CONCLUSION: The utilisation of Entresto has been steadily increasing in Ireland since its reimbursement approval. The expenditure in the first year was substantially lower than predicted, and the RAS is an example of how health technology management can facilitate appropriate and cost-effective use of medicines.

SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA