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1.
Cancer ; 130(6): 901-912, 2024 03 15.
Artículo en Inglés | MEDLINE | ID: mdl-38180788

RESUMEN

BACKGROUND: Colorectal cancer (CRC) incidence at ages <50 years is increasing worldwide. Screening initiation was lowered to 45 years in the United States. The cost-effectiveness of initiating CRC screening at 45 years in Israel was assessed with the aim of informing national policy and addressing internationally relevant questions. METHODS: A validated CRC screening model was calibrated to Israeli data and examined annual fecal immunochemical testing (FIT) or colonoscopy every 10 years from 45 to 74 years (FIT45-74 or Colo45-74) versus from 50 to 74 years (FIT50-74 or Colo50-74). The addition of a fourth colonoscopy at 75 years was explored, subanalyses were performed by sex/ethnicity, and resource demands were estimated. RESULTS: FIT50-74 and Colo50-74 reduced CRC incidence by 57% and 70% and mortality by 70% and 77%, respectively, versus no screening, with greater absolute impact in Jews/Other versus Arabs but comparable relative impact. FIT45-74 further reduced CRC incidence and mortality by an absolute 3% and 2%, respectively. With Colo45-74 versus Colo50-74, CRC cases and deaths increased slightly as three colonoscopies per lifetime shifted to 5 years earlier but mean quality-adjusted life-years gained (QALYGs) per person increased. FIT45-74 and Colo45-74 cost 23,800-53,900 new Israeli shekels (NIS)/QALYG and 110,600-162,700 NIS/QALYG, with the lowest and highest values among Jewish/Other men and Arab women, respectively. A fourth lifetime colonoscopy cost 48,700 NIS/QALYG. Lowering FIT initiation to 45 years with modest participation required 19,300 additional colonoscopies in the first 3 years. CONCLUSIONS: Beginning CRC screening at 45 years in Israel is projected to yield modest clinical benefits at acceptable costs per QALYG. Despite different estimates by sex/ethnicity, a uniform national policy is favored. These findings can inform Israeli guidelines and serve as a case study internationally.


Asunto(s)
Neoplasias Colorrectales , Detección Precoz del Cáncer , Masculino , Humanos , Femenino , Estados Unidos , Persona de Mediana Edad , Israel/epidemiología , Análisis Costo-Beneficio , Colonoscopía , Neoplasias Colorrectales/diagnóstico , Neoplasias Colorrectales/epidemiología , Sangre Oculta , Tamizaje Masivo
2.
Cancer ; 130(2): 256-266, 2024 01.
Artículo en Inglés | MEDLINE | ID: mdl-37861363

RESUMEN

BACKGROUND: Surveillance of high-risk individuals for pancreatic ductal adenocarcinoma (PDAC) is recommended. This study aimed to determine the prevalence and outcomes of PDAC and its precursor lesions in BRCA1/2 pathogenic variants (PVs) carriers undergoing pancreatic surveillance. METHODS: A retrospective multicenter cohort study of pancreatic surveillance outcomes in Israeli BRCA1/2 carriers preferably with a family history of PDAC. RESULTS: A total of 180 asymptomatic carriers participated in the screening programs, including 57 (31.7%) with BRCA1 PVs, 121 (67.2%) with BRCA2 PVs, and 12 (6.6%) with PVs in BRCA1/2 and other genes, for a median follow-up period of 4 years. Ninety-one individuals (50.5%) fulfilled the International Cancer of the Pancreas Screening (CAPS) criteria for surveillance whereas 116 (64.4%) fulfilled the American College of Gastroenterology (ACG) criteria. There were four cases of adenocarcinoma and four cases of grade 1-neuroendocrine tumor (G1-NET). All were BRCA2 carriers, and two had no family history of PDAC. Three cancer patients were at resectable stages (IA, IIA, IIB) whereas one had a stage IIIB tumor. Of the G1-NET cases, one had surgery and the others were only followed. Success rate for detection of confined pancreatic carcinoma was thus 1.6% (three of 180) in the whole cohort, 1.6% (two of 116) among individuals who fulfilled ACG criteria and 2.2% (two of 91) in those fulfilling CAPS criteria for surveillance. CONCLUSIONS: Despite the low detection rate of PDAC and its' high-risk neoplastic precursor lesions among BRCA1/2 carriers undergoing pancreatic surveillance, 75% of cancer cases were detected at a resectable stage.


Asunto(s)
Adenocarcinoma , Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Humanos , Proteína BRCA1/genética , Estudios de Cohortes , Proteína BRCA2/genética , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/epidemiología , Neoplasias Pancreáticas/genética , Carcinoma Ductal Pancreático/diagnóstico , Carcinoma Ductal Pancreático/epidemiología , Carcinoma Ductal Pancreático/genética , Adenocarcinoma/diagnóstico , Adenocarcinoma/epidemiología , Adenocarcinoma/genética , Células Germinativas , Predisposición Genética a la Enfermedad
3.
Hered Cancer Clin Pract ; 21(1): 19, 2023 Oct 11.
Artículo en Inglés | MEDLINE | ID: mdl-37821984

RESUMEN

The recognition of dominantly inherited micro-satellite instable (MSI) cancers caused by pathogenic variants in one of the four mismatch repair (MMR) genes MSH2, MLH1, MSH6 and PMS2 has modified our understanding of carcinogenesis. Inherited loss of function variants in each of these MMR genes cause four dominantly inherited cancer syndromes with different penetrance and expressivities: the four Lynch syndromes. No person has an "average sex "or a pathogenic variant in an "average Lynch syndrome gene" and results that are not stratified by gene and sex will be valid for no one. Carcinogenesis may be a linear process from increased cellular division to localized cancer to metastasis. In addition, in the Lynch syndromes (LS) we now recognize a dynamic balance between two stochastic processes: MSI producing abnormal cells, and the host's adaptive immune system's ability to remove them. The latter may explain why colonoscopy surveillance does not reduce the incidence of colorectal cancer in LS, while it may improve the prognosis. Most early onset colon, endometrial and ovarian cancers in LS are now cured and most cancer related deaths are after subsequent cancers in other organs. Aspirin reduces the incidence of colorectal and other cancers in LS. Immunotherapy increases the host immune system's capability to destroy MSI cancers. Colonoscopy surveillance, aspirin prevention and immunotherapy represent major steps forward in personalized precision medicine to prevent and cure inherited MSI cancer.

4.
Aging Clin Exp Res ; 34(9): 2217-2223, 2022 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-35670959

RESUMEN

BACKGROUND: Liver cirrhosis (LC) is a common disease diagnosed in all ages. With the increasing population age, LC is noticeable more in the clinics. AIM: To distinguish the clinical characteristics, complications, and survival of patients with liver cirrhosis. METHODS: A retrospective study enrolled patients diagnosed with liver cirrhosis at Soroka University Medical Center. Patients with cirrhosis diagnosed at an age older than 65 years (group 1) were compared with patients diagnosed at an age younger than 65 years (group 2). RESULTS: We included 1046 patients; 411 (39.3%) in group 1 and 635 (60.7%) in group 2. Fatty liver and cryptogenic liver disease were found to cause cirrhosis at a significantly higher rate in the elderly (23.4% vs. 13.9%, p < 0.001, 15.3% vs. 6.3%, p < 0.001, respectively). A higher rate of non-hepatocellular carcinoma cancers and mortality (17.5% vs. 9.1%, p < 0.001, 76.6% vs. 57%, respectively) was found among cirrhotic elderly patients, but a lower rate of oesophageal varices (47.7% vs. 60.1%, p = 0.002). Twenty-year follow-up Kaplan-Meier survival analysis for mortality estimated poor survival in the elderly (log-rank p < 0.001). The adjusted Cox proportional hazards regression model showed an association of age > 65 with an all-cause mortality hazard ratio of 2.26 (95% CI 1.89-2.69). CONCLUSION: Higher rates of fatty liver, cryptogenic cirrhosis, non-HCC cancers, and mortality were found among patients diagnosed with cirrhosis in the elderly.


Asunto(s)
Carcinoma Hepatocelular , Hígado Graso , Neoplasias Hepáticas , Anciano , Carcinoma Hepatocelular/patología , Hígado Graso/complicaciones , Humanos , Cirrosis Hepática/complicaciones , Cirrosis Hepática/diagnóstico , Cirrosis Hepática/patología , Neoplasias Hepáticas/patología , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Factores de Riesgo , Análisis de Supervivencia
5.
Hered Cancer Clin Pract ; 20(1): 36, 2022 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-36182917

RESUMEN

OBJECTIVE: To compare colorectal cancer (CRC) incidences in carriers of pathogenic variants of the MMR genes in the PLSD and IMRC cohorts, of which only the former included mandatory colonoscopy surveillance for all participants. METHODS: CRC incidences were calculated in an intervention group comprising a cohort of confirmed carriers of pathogenic or likely pathogenic variants in mismatch repair genes (path_MMR) followed prospectively by the Prospective Lynch Syndrome Database (PLSD). All had colonoscopy surveillance, with polypectomy when polyps were identified. Comparison was made with a retrospective cohort reported by the International Mismatch Repair Consortium (IMRC). This comprised confirmed and inferred path_MMR carriers who were first- or second-degree relatives of Lynch syndrome probands. RESULTS: In the PLSD, 8,153 subjects had follow-up colonoscopy surveillance for a total of 67,604 years and 578 carriers had CRC diagnosed. Average cumulative incidences of CRC in path_MLH1 carriers at 70 years of age were 52% in males and 41% in females; for path_MSH2 50% and 39%; for path_MSH6 13% and 17% and for path_PMS2 11% and 8%. In contrast, in the IMRC cohort, corresponding cumulative incidences were 40% and 27%; 34% and 23%; 16% and 8% and 7% and 6%. Comparing just the European carriers in the two series gave similar findings. Numbers in the PLSD series did not allow comparisons of carriers from other continents separately. Cumulative incidences at 25 years were < 1% in all retrospective groups. CONCLUSIONS: Prospectively observed CRC incidences (PLSD) in path_MLH1 and path_MSH2 carriers undergoing colonoscopy surveillance and polypectomy were higher than in the retrospective (IMRC) series, and were not reduced in path_MSH6 carriers. These findings were the opposite to those expected. CRC point incidence before 50 years of age was reduced in path_PMS2 carriers subjected to colonoscopy, but not significantly so.

6.
Cancer Invest ; 39(9): 690-695, 2021 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-33784229

RESUMEN

We investigated whether maternal hepatitis B virus (HBV) or hepatitis C virus (HCV) carrier status increases the risk for long-term oncologic morbidity of their offspring up to the age of 18 years. A population-based cohort study was conducted, including all singleton deliveries between the years 1991 and 2014 at a tertiary medical center. Our study included: HBV carriers (n = 588), HCV carriers (n = 183) and non-carriers (n = 241,570. No significant differences regarding oncologic morbidity were found between offspring of HBV carriers (0.2%), HCV carriers (0%) and non-carriers (0.6%; p = 0.216, respectively). To conclude: maternal HBV or HCV carrier status is not a risk factor for long-term oncologic morbidity of the offspring.


Asunto(s)
Hepatitis B/epidemiología , Hepatitis C/epidemiología , Neoplasias/epidemiología , Complicaciones Infecciosas del Embarazo/epidemiología , Efectos Tardíos de la Exposición Prenatal/epidemiología , Adolescente , Adulto , Portador Sano/epidemiología , Estudios de Cohortes , Femenino , Humanos , Incidencia , Masculino , Edad Materna , Morbilidad , Vigilancia de la Población/métodos , Embarazo , Complicaciones Infecciosas del Embarazo/virología , Factores de Riesgo , Adulto Joven
7.
J Viral Hepat ; 27(8): 794-799, 2020 08.
Artículo en Inglés | MEDLINE | ID: mdl-32274882

RESUMEN

The objective of the study was to investigate the long-term effects of maternal hepatitis B virus (HBV) or hepatitis C virus (HCV) carrier status on the long-term infectious morbidity of their offspring. A population-based cohort study was conducted, including all singleton deliveries between the years 1991 and 2014 at a tertiary medical centre. The mothers were subdivided into three groups: HBV carriers, HCV carriers and non-carriers. Data on demographics, maternal, perinatal and long-term hospitalization for infectious morbidity were compared between the groups. During the study period, 242 905 (99.7%) non-carrier mothers, 591 (0.2%) HBV carriers and 186 (0.1%) HCV carriers were observed. Hospitalizations related to infectious morbidity was significantly higher in the offspring of HBV carriers compared with HCV and non-carriers (15.6% vs 11.3% vs 11.0%; P = .002, respectively; Kaplan-Meier, log-rank P < .001). Specifically, a significantly higher rate of hospitalizations gastrointestinal infectious morbidity was noted among the offspring of HBV carrier mothers (3.6% in the HBV carrier group, 1.6% in the HCV carrier group and 1.6% in the non-carrier group [P = .001]). There was a respiratory infectious morbidity of 8.1% among the offspring of HBV carriers, 8.6% among HCV carriers and 5.5% in non-carriers (P = .005). Using a Cox multivariable model, controlling for confounding variables, maternal HBV carrier status was associated with a significantly increased long-term infectious morbidity of the offspring, with an adjusted HR of 1.7 (95% CI, 1.388-2.077, P < .001). Maternal HBV carrier status is an independent risk factor for long-term infectious morbidity of the offspring, particularly for gastrointestinal and respiratory infections.


Asunto(s)
Hepatitis B , Hepatitis C , Complicaciones Infecciosas del Embarazo/virología , Efectos Tardíos de la Exposición Prenatal/virología , Portador Sano/virología , Estudios de Cohortes , Femenino , Hepacivirus , Hepatitis B/epidemiología , Virus de la Hepatitis B , Hepatitis C/epidemiología , Humanos , Incidencia , Morbilidad , Embarazo , Factores de Riesgo
8.
Liver Int ; 39(11): 2046-2051, 2019 11.
Artículo en Inglés | MEDLINE | ID: mdl-31319010

RESUMEN

BACKGROUND: More than 360 million people have chronic hepatitis B or C (HBV/HCV) infection worldwide, many of which are women at childbearing age. While the risk of perinatal HBV/HCV has been well established, the long-term implications on offspring health, have been less studied. We aimed to evaluate the association between maternal HBV/HCV carrier status and long-term gastrointestinal (GI) morbidities in offspring. AIMS & METHODS: A population-based cohort analysis compared the risk for long-term childhood GI morbidities in children born to HBV/HCV carrier mothers vs the risk in those who were born to noncarriers. Childhood GI morbidities were predefined based on ICD-9 codes, as recorded in hospital medical files. Children with congenital malformations and multiple gestations were excluded from the analysis. A Kaplan-Meier survival curve was constructed to compare the cumulative GI morbidities over time, and a Cox proportional hazards model was used to control for confounders. RESULTS: During the study period (1991-2014), 242 342 newborns met the inclusion criteria: 771 (0.3%) were born to HBV/HCV mothers and 241 571 (99.7%) were not. The median follow-up was 10.51 years (0-18 years). Offspring to HBV/HCV mothers had a higher incidence of GI diseases (9.3% vs 5.4%, OR = 1.82; 95% CI 1.43-2.32; Kaplan-Meier log-rank = 0.001). The increased risk remained significant in the Cox proportional hazards models, which adjusted for gestational age, mode of delivery and pregnancy complications (adjusted HR = 2.26, 95% CI: 1.79-2.85; P < .001). CONCLUSION: Maternal HBV or HCV carrier status is an independent risk factor for long-term the GI morbidity of offspring.


Asunto(s)
Enfermedades Gastrointestinales/epidemiología , Hepatitis B/epidemiología , Hepatitis C/epidemiología , Complicaciones Infecciosas del Embarazo/epidemiología , Efectos Tardíos de la Exposición Prenatal/epidemiología , Adolescente , Adulto , Portador Sano , Niño , Preescolar , Estudios de Cohortes , Femenino , Edad Gestacional , Humanos , Incidencia , Lactante , Recién Nacido , Israel/epidemiología , Estimación de Kaplan-Meier , Masculino , Embarazo , Modelos de Riesgos Proporcionales , Factores de Riesgo , Adulto Joven
9.
Harefuah ; 158(8): 523-528, 2019 Aug.
Artículo en Hebreo | MEDLINE | ID: mdl-31407542

RESUMEN

INTRODUCTION: Colorectal cancer (CRC) is the second most common cancer in Israel, with about 3,100 new cases annually. The available screening methods are occult fecal blood testing, stool DNA, sigmoidoscopy, colonoscopy and virtual colonoscopy. Each modality has different sensitivity, specificity, participation rates, complications, availability and mortality reduction rate. In Israel, the fecal immunochemical testing (FIT) is available for populations aged 50-74 years. However, many of the patients are still diagnosed with CRC at stages 2-4. A new standard of care modality should be established with the objective of reducing CRC incidence and mortality. Colonoscopy is currently the most successful modality that reduces CRC incidence. Cost, limited availability and participation rates should be considered as challenging factors in establishing colonoscopy for primary screening. However, a plan to gradually implement a national colonoscopy screening program in parallel to FIT testing before phasing out of the current dominating modalities will be successful and cost effective in the long term. Such a program will be cost effective because early detection and thus lowering its incidence prevents the need for highly expensive therapies associated with more progressive disease. Although colonoscopy is very effective, a new technology of capsule endoscopy may be a more favorable screening option in case it does not require bowel preparation. When such capsule endoscopy becomes available, the medical community will likely change its approach and use colonoscopy for therapeutic purposes. Conclusion: A national program using colonoscopy as the main component of CRC screening should be implemented gradually to increase early detection and lower incidence rate.


Asunto(s)
Colonoscopía , Neoplasias Colorrectales , Detección Precoz del Cáncer , Anciano , Humanos , Israel , Persona de Mediana Edad , Sangre Oculta
10.
BMC Gastroenterol ; 18(1): 153, 2018 Oct 20.
Artículo en Inglés | MEDLINE | ID: mdl-30342474

RESUMEN

BACKGROUND: Serological markers used for diagnostic purposes and disease stratification in inflammatory bowel disease. We aimed to investigate the frequency of ASCA and ANCA among Arab Bedouin IBD patients and its relationship to disease phenotype and course. METHODS: From cohort of 68, 25 Crohn's disease (CD) and 25 Ulcerative colitis (UC) patients were recruited (72%). ASCA IgG was determined by ELISA assay. Immunofluorescence analysis of ANCA was performed. RESULTS: The IgG ASCA was detected in 13 (52%) of the CD patients and in three (12%) UC patients. The prevalence of ANCA among UC patients was positive with 76%, sub-grouped, atypical ANCA in 9 patients (36%), pANCA in six patients (24%) and cANCA in 4 patients (16%). The detection of ASCA among CD patients was found not to be a reliable predictor of young age at diagnosis, gender, ileal involvement, anti-TNF treatment or surgery. UC patients with positive ANCA were younger, mean age 40.2 ± 11.9 compared with 57.3 ± 21.2 (p = 0.03), and diagnosed at a younger age, 29.2 ± 11.8 compared with 43.5 ± 15.3 (p = 0.05). CONCLUSION: The frequency of ASCA among Bedouin CD patients and ANCA among UC patients was high, however ASCA was not found to have a predictive value for disease phenotype or course. Positive ANCA in UC patients was predictive for younger age and age at diagnosis.


Asunto(s)
Anticuerpos Anticitoplasma de Neutrófilos/sangre , Árabes , Colitis Ulcerosa/etnología , Colitis Ulcerosa/inmunología , Enfermedad de Crohn/etnología , Enfermedad de Crohn/inmunología , Inmunoglobulina G/sangre , Saccharomyces cerevisiae/inmunología , Adulto , Biomarcadores/sangre , Colitis Ulcerosa/diagnóstico , Enfermedad de Crohn/diagnóstico , Femenino , Humanos , Masculino , Persona de Mediana Edad , Fenotipo
11.
Isr Med Assoc J ; 20(11): 695-699, 2018 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-30430799

RESUMEN

BACKGROUND: Inflammatory bowel disease (IBD) prevalence is increasing among Bedouin Arabs in Israel. This population is known to have a high rate of consanguinity. NOD2/CARD15 mutations are well-studied in IBD. OBJECTIVES: To investigate the frequency of NOD2/CARD15 mutations in IBD Bedouin patients and their relevance to disease phenotype. METHODS: The IBD-Arab cohort in southern Israel included 68 patients, of which 25 Crohn's disease (CD) patients and 25 ulcerative colitis (UC) patients consented to participate (72%). Blood samples were obtained from all participants who were genotyped for NOD2/CARD15 variants Arg702Trp, Gly908Arg, and Leu1007fsinsC. RESULTS: The NOD2/CARD15 mutation frequency was higher in Crohn's disease than in ulcerative colitis patients. Carrier frequency for the Gly908Arg mutation in CD and UC patients was 8/25 (32%) and 3/25 (12%), respectively (P = 0.08). Neither the Arg702Trp nor Leu1007fsinsC mutation was found in our cohort. No homozygous/compound heterozygote mutations were found. Genotype-phenotype analysis revealed that CD patients carrying the Gly908Arg mutation were younger at diagnosis, 22.8 ± 4.5 vs. 28.82 ± 9.1 years (P = 0.04). All carriers were males, compared with 41.2% in non-carriers (P = 0.005). NOD2/CARD15 mutation carriers with UC were older, 67.0 ± 24.5 years compared with 41.2 ± 12.3 years (P = 0.006). No other associations regarding disease localization or other clinical parameter were found. CONCLUSIONS: The frequency of NOD2/CARD15 gene mutations is high in CD and UC among Bedouin Arab IBD patients and is associated with younger age at onset in CD and male gender.


Asunto(s)
Árabes/genética , Colitis Ulcerosa/genética , Enfermedad de Crohn/genética , Proteína Adaptadora de Señalización NOD2/genética , Adulto , Edad de Inicio , Estudios de Cohortes , Colitis Ulcerosa/diagnóstico , Colitis Ulcerosa/epidemiología , Enfermedad de Crohn/diagnóstico , Enfermedad de Crohn/epidemiología , Femenino , Predisposición Genética a la Enfermedad , Genotipo , Humanos , Israel , Masculino , Persona de Mediana Edad , Mutación , Fenotipo , Factores Sexuales , Adulto Joven
12.
Harefuah ; 155(5): 272-5, 324, 323, 2016 05.
Artículo en Hebreo | MEDLINE | ID: mdl-27526553

RESUMEN

BACKGROUND: For the last decade the backbone of hepatitis C (HCV) treatment was the pan-genotyping dual therapy with pegylated interferon alfa in combination with Ribavirin. This regimen was limited in achieving sustained virological response (SVR) and accompanied by serious adverse events. In 2010 there was overwhelming progress in the treatment options for HCV. This change began with the introduction of the first generation specific Direct Antiviral Agents (DAA's) that inhibit the viral protease, agents used in combination with the dual protocol for genotype 1 (triple therapy). In 2014 this revolution continued with the introduction of advanced DAA's targeting different non-structural viral proteins. These DAA's achieve an all oral regimen shorter in duration with outstanding SVR rates and mild side effects. Our liver clinic manages the treatment and follow-up of the vast majority of patients with HCV in southern Israel. As part of the unprecedented advance in the treatment regimen for HCV with the introduction of the first generation DAA's and especially after they were included by the national health care as an option for treatment, we started to treat HCV genotype 1 patients with the triple regimen. Now, in the era of advanced DAA's regimens, we look back, retrospectively, analyze and conclude our experience with a regimen that changed the conception of eradication for HCV by combining immune activation and specific inhibition of functional viral proteins. This was conducted in the hope that it will inspire the development of revolutionary regimens for eradication in other viral diseases. METHODS: During the period between September 2011 to November 2013, 55 patients infected with HCV genotype 1 were treated in our outpatient liver clinic with the triple regimen. These patients finished a 6 month period of post-treatment follow-up allowing the evaluation of their viral PCR status at the latest in May 2014. The data were collected from the patient's computerized file and were statistically analyzed by the SMC clinical research center. RESULTS: Out of the 55 patients, 39 received Telaprevir as the protease inhibitor and 16 were treated with Boceprevir. Of all the treated patients 34 achieved SVR; 47% of patients with genotype 1A reached SVR, whereas 71% of those with genotype 1B reached that endpoint. A total of 63.6% of patients with mild or no fibrosis (F 0-2) achieved SVR compared to 63% in patients with advanced fibrosis (F 3-4]. There were 6 patients with no METAVIR evaluation. A total of 57% of naïve patients, 83.3% of prior relapsers and 57.1% of previous non-responders reached SVR at 6 months in current triple therapy. There was no significant response difference in any sub-group when the two first generation PI's were compared. CONCLUSIONS: In our experience with first generation PI based triple regiment for HCV genotype 1, though more effective than previous dual treatment, it was still limited in its effectiveness, while creating some major safety issues. In light of this new era where much more effective and safe DAA's emerged and are now in routine use, the triple therapy in our view should be reviewed as a transitional phase that changed forever the concept of eradicating HCV and aimed at specific viral sites. This regimen paved the way for advanced DAA protocols achieving cures in overwhelming unprecedented rates.


Asunto(s)
ADN Viral , Hepacivirus , Hepatitis C , Interferón-alfa , Oligopéptidos , Polietilenglicoles , Prolina/análogos & derivados , Ribavirina , Adulto , Antivirales/administración & dosificación , Antivirales/efectos adversos , Portadores de Fármacos , Quimioterapia Combinada , Femenino , Hepacivirus/efectos de los fármacos , Hepacivirus/enzimología , Hepacivirus/genética , Hepatitis C/tratamiento farmacológico , Hepatitis C/fisiopatología , Hepatitis C/virología , Humanos , Interferón alfa-2 , Interferón-alfa/administración & dosificación , Interferón-alfa/efectos adversos , Israel , Masculino , Oligopéptidos/administración & dosificación , Oligopéptidos/efectos adversos , Polietilenglicoles/administración & dosificación , Polietilenglicoles/efectos adversos , Prolina/administración & dosificación , Prolina/efectos adversos , Inhibidores de Proteasas/administración & dosificación , Inhibidores de Proteasas/efectos adversos , Proteínas Recombinantes/administración & dosificación , Proteínas Recombinantes/efectos adversos , Estudios Retrospectivos , Ribavirina/administración & dosificación , Ribavirina/efectos adversos , Resultado del Tratamiento
13.
Isr Med Assoc J ; 17(5): 277-81, 2015 May.
Artículo en Inglés | MEDLINE | ID: mdl-26137652

RESUMEN

BACKGROUND: The impact of admission glycated hemoglobin (HbA1c) on hospital outcome is controversial. OBJECTIVES: To evaluate the association between admission glucose and HbA1c levels and mortality 1 year after hospitalization in the internal medicine ward. METHODS: HbA1c level of consecutive patients was measured during the first 24 hours of admission to the internal medicine ward and divided at the cutoff point of 6.5%. Three groups of patients were prospectively identified: patients with preexisting diabetes mellitus (DM), patients with glucose > 140 mg/dl (hyperglycemia) on admission and no known diabetes (H), and patients without diabetes or hyperglycemia (NDM). The primary end-point was 1 year all-cause mortality. RESULTS: A total of 1024 patients were enrolled, 592 (57.8%) belonged to the DM group, 119 (11.6/6) to the H group and 313 (30.6%) to the NDM group. At 1 year, death occurred in 70 (11.9%) in the DM group, 12 (10.0%) in the H group and 15 (4.8%) in the NDM group (P = 0.002). Elevated admission glucose levels did not influence outcome in any of the groups. HbA1c levels were similar for survivors and non-survivors (P = 0.60). Within-group multivariate analysis adjusted for comorbidities and age showed that in the H group HbA1C levels of 6.5% or above were associated with increased mortality risk [hazard ratio (HR) 8.25, 95% confidence interval (CI) 1.93-35.21]. In the DM group, HbA1c levels below 6.5% were associated with increased mortality risk (HR = 2.05, 95% CI 1.25-3.36). CONCLUSIONS: Glucose levels upon admission did not affect mortality. However, HbA1c levels below 6.5% had opposite effects on 1 year mortality in diabetes patients and patients with hyperglycemia.


Asunto(s)
Diabetes Mellitus , Hemoglobina Glucada/análisis , Hiperglucemia , Adulto , Anciano , Diabetes Mellitus/sangre , Diabetes Mellitus/diagnóstico , Diabetes Mellitus/mortalidad , Pruebas Diagnósticas de Rutina/métodos , Pruebas Diagnósticas de Rutina/estadística & datos numéricos , Femenino , Estudios de Seguimiento , Humanos , Hiperglucemia/diagnóstico , Hiperglucemia/mortalidad , Medicina Interna/métodos , Israel/epidemiología , Masculino , Persona de Mediana Edad , Alta del Paciente/estadística & datos numéricos , Valor Predictivo de las Pruebas , Pronóstico , Modelos de Riesgos Proporcionales , Medición de Riesgo , Factores de Riesgo
14.
Artículo en Inglés | MEDLINE | ID: mdl-38767740

RESUMEN

Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease. We aimed to investigate the potential similarities and differences regarding the disease among Arabs and Jews. Retrospective study included all patients older than 18 years with NAFLD diagnosis according to ICD-10 codes. Data regarding demographics, comorbidities, and outcomes were retrieved using the MdClone platform from "Clalit" in Israel. Data concerning 34,090 Arab patients and 173,500 Jewish patients with NAFLD were included. Arab patients were significantly younger at diagnosis (35.0 ± 13 years vs. 43.6 ± 15 years, p < 0.001) and had higher rates of obesity and diabetes mellitus (69.5% vs. 56.5% and 27.0% vs. 22.7%, p < 0.001, respectively). Arab patients had higher rates of cirrhosis and portal hypertension-related complications (2.5% vs. 2.0%, p < 0.001), esophageal varices (0.9% vs. 0.5%, p < 0.001), spontaneous bacterial peritonitis (0.3% vs. 0.1%, p < 0.001), and hepatorenal syndrome (0.3% vs. 0.1%, p < 0.001). There was no significant difference in the prevalence of hepatocellular carcinoma between study groups (0.4% vs. 0.5%, p = 0.156). Liver transplantation was performed in 0.2% of Arab NAFLD patients compared to 0.07% of Jewish NAFLD patients (p < 0.001). Lower rates of all-cause mortality were found among the Arab NAFLD patients versus Jewish NAFLD patients (7.7% versus 11.5%, p < 0.001). According to the Cox regression model, Arab ethnicity is a risk factor for death with OR of 1.36. Significant differences regarding comorbidities, complications, liver transplantations rates, and all-cause mortality were found among NAFLD patients of different ethnicities, hence specific population need specific consideration in prevention, early diagnosis and follow up.

15.
Eur J Investig Health Psychol Educ ; 14(6): 1688-1699, 2024 Jun 09.
Artículo en Inglés | MEDLINE | ID: mdl-38921077

RESUMEN

The study aimed to explore patients' experiences and perceptions throughout the various stages of endoscopic procedures and examine the association between patient-centered communication and the patient's experience. A total of 191 patients responded to pre- and post-procedure surveys that inquired about fear and pain, patients' satisfaction regarding the information provided to them, perceptions and experience. Pain was associated with post-procedure fear (r = 0.63, p < 0.01) and negatively associated with reported patient experience at the end of the visit (r = -0.17, p < 0.01). Significant positive associations were found between patient experience and satisfaction from the information provided before (r = 0.47, p < 0.01) and the information provided after the procedure (r = 0.51, p < 0.001). A predictive model found that perceptions toward the physicians, satisfaction from information provided before discharge, and feelings of trust are predictors of the patient experience (F = 44.9, R2 = 0.61, p < 0.001). Patients' satisfaction with information provided before and after the procedure can positively affect the patients' experience, leading to a decrease in fear and anxiety and increasing compliance with medical recommendations. Strategies for PCC with endoscopic patients should be developed and designed in a participatory manner, taking into account the various aspects associated with the patient experience.

16.
Viruses ; 15(7)2023 06 22.
Artículo en Inglés | MEDLINE | ID: mdl-37515101

RESUMEN

Hepatitis C Virus (HCV) infection is a leading etiology of liver cirrhosis and its associated complications, namely, decompensated cirrhosis. As such, hepatitis C potentially necessitates liver transplantation and may result in death. Recently, HCV treatment has evolved. Current HCV treatment is effective in curing HCV; some of the agents are pan-genotypic. Numerous countries have adopted an initiative to eliminate HCV. Achieving elimination poses many challenges; it requires improved availability and accessibility of pan-genotypic therapy. Barriers exist at the level of the collective healthcare system and at the level of the individual healthcare providers and patients. Therefore, organized national and local efforts are needed. Surmounting these barriers calls for interventions concerning screening, linkage to care, and treatment delivery. Pertinent barriers include inadequate availability of screening, ill-equipped laboratory testing before treatment, and insufficient access to treatment. Interventions should seek to decentralize laboratory testing and treatment provision, increase funding for resources and personnel, and spread awareness. Special consideration should be allocated to at-risk populations, such as intravenous drug users, refugees, and prisoners. Computerized medical filing and telemedicine have the potential to refine HCV management by enhancing detection, availability, accessibility, and cost-effectiveness.


Asunto(s)
Hepatitis C , Trasplante de Hígado , Humanos , Hepacivirus/genética , Antivirales/uso terapéutico , Hepatitis C/diagnóstico , Hepatitis C/tratamiento farmacológico , Hepatitis C/epidemiología , Trasplante de Hígado/efectos adversos , Factores de Riesgo
17.
J Pers Med ; 13(6)2023 Jun 17.
Artículo en Inglés | MEDLINE | ID: mdl-37373997

RESUMEN

Inflammatory bowel diseases are increasing among different ethnic groups. We aimed to compare the clinical characteristics, complications, and outcomes among Arab and Jewish people sharing the same healthcare system. All patients older than 18 years with a diagnosis of Crohn's disease (CD) or ulcerative colitis (UC) between the years 2000 and 2021 were included. Data regarding demographics, disease characteristics, extraintestinal manifestation, treatment, comorbidities, and mortality were retrieved. A total of 1263 (9.8%) Arab CD patients were compared with 11,625 Jewish CD patients, and 1461 (11.8%) Arab UC patients were compared to 10,920 Jewish patients. Arab CD patients were younger at diagnosis, 36.11 ± 16.7 compared to 39.98 ± 19.4 years, p < 0.001, 59.5% males compared to 48.7%, p < 0.001; in addition, Arab CD patients had a higher rate of anal fissure, perianal abscess, erythema nodosum, diabetes mellitus, obesity, liver cirrhosis, and male infertility. Arab CD patients were less frequently treated with azathioprine or mercaptopurine compared with Jewish patients. No significant difference was found in the rate of anti-TNF treatment, but a higher rate of steroids treatment was found. The all-cause mortality of CD patients was lower among Arab patients (8.4% vs. 10.2%, p = 0.039). Significant differences were found regarding disease characteristics, course, comorbidities, and treatment among Arab and Jewish patients with IBD.

18.
Biomedicines ; 11(4)2023 Apr 06.
Artículo en Inglés | MEDLINE | ID: mdl-37189727

RESUMEN

(1) Background: Non-alcoholic fatty liver disease (NAFLD) is a common liver disease. Aims: We aimed to investigate the frequency of comorbidities and malignancies among NAFLD patients compared to the general population. (2) Methods: A retrospective study included adult patients with a NAFLD diagnosis. A control group was matched for age and gender. Demographics, comorbidities, malignancies, and mortality were collected and compared. (3) Results: 211,955 NAFLD patients were analyzed in comparison to 452,012 matched general population controls. Significantly higher rates of diabetes mellitus (23.2% vs. 13.3%), obesity (58.8% vs. 27.8%), hypertension (57.2% vs. 39.9%), chronic ischemic heart disease (24.7% vs. 17.3%), and CVA (3.2% vs. 2.8%) were found among NAFLD patients. Patients with NAFLD had significantly higher rates of the following malignancies: prostate cancer (1.6% vs. 1.2%), breast cancer (2.6% vs. 1.9%), colorectal cancer (1.8% vs. 1.4%), uterine cancer (0.4 vs. 0.2%), kidney cancer (0.8% vs. 0.5%), but a lower rate of lung cancer (0.9% vs. 1.2%) and stomach cancer (0.3% vs. 0.4%). The all-cause mortality rate among NAFLD patients was significantly lower in comparison to the general population (10.8% vs. 14.7%, p < 0.001). (4) Conclusions: Higher rates of comorbidities and malignancies among NAFLD patients were observed, but a lower rate of all-cause mortality was found.

19.
Life (Basel) ; 13(9)2023 Sep 05.
Artículo en Inglés | MEDLINE | ID: mdl-37763276

RESUMEN

There is accumulating evidence that treatment of chronic hepatitis C (HCV) leads to improvements in liver fibrosis. We aimed to investigate the improvement in fibrosis stage following treatment with direct-acting antivirals (DAAs) and factors associated with fibrosis regression. Fibroscan® was performed for patients treated with DAAs, at least 3 years post-HCV eradication. The fibrosis stage at the onset of treatment was compared with the current fibrosis stage. A total of 209 patients were enrolled in this study (56% males; age 58.8 ± 13.3 years; age at treatment 54 ± 10.9 years). Genotype subgrouping was as follows: 1a (16%), 1b (58%), 2a (4%), 3 (18%), and 4a (2%). Overall, 71% of patients were considered treatment-naïve, with a mean follow-up time of 4.5 ± 1.3 years. Fibrosis improvement was observed among 57% of patients; fibrosis progression was seen among 7% of patients and no change was seen in 36% of patients. Moreover, 28% of these patients regressed from F3/F4 to F2 or less. In our multivariable analysis, the age at treatment and advanced fibrosis stage were found to be factors significantly associated with fibrosis regression. In conclusion, fibrosis improvement was observed among 57% of HCV patients after treatment with DAAs. Age and advanced fibrosis at baseline were found to be factors associated with fibrosis regression.

20.
Front Med (Lausanne) ; 10: 1225616, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37614949

RESUMEN

Background: Colorectal cancer (CRC) is a feared complication of inflammatory bowel disease (IBD). We aimed to investigate the prevalence and risk factors of CRC among a large cohort of IBD patients. Methods: Data on IBD patients free of CRC at baseline was extracted using the MDClone platform of the Clalit health maintenance organization in Israel. We investigated the frequency rate of CRC among IBD patients compared to a control group without IBD. Possible risk factors, including comorbidities and IBD-related medications, were investigated in a multivariate analysis. Results: During a follow-up of 139,448 years among Crohn's disease (CD) patients and 139,533 years among ulcerative colitis (UC) patients, a frequency rate of CRC was 1.5% (191) among 12,888 CD patients and 2.1% (261) among 12,381 UC patients compared to 1.2% among 57,334 controls. In a multivariate analysis of UC patients, age at diagnosis (OR 1.030, p < 0.001), primary sclerosing cholangitis (OR 2.487, p = 0.005), diabetes mellitus (OR 2.01, p < 0.001), and glucocorticoids treatment (OR 1.465, p = 0.008) were found to be predictors of CRC. For CD patients, age at diagnosis (OR 1.035, p < 0.001), primary sclerosing cholangitis (OR 2.25, p = 0.029), and glucocorticoids treatment (OR 2.07, p < 0.001) were found to be predictors for CRC, but not diabetes mellitus. Conclusion: Despite the continuously decreasing rates of CRC among IBD patients, these are still higher in IBD patients compared to the general population. IBD patients, particularly those with risk factors, require special consideration in follow-up for CRC.

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