Efficacy of a referral center for patient-centered care in multiple myeloma: a cohort study.

BACKGROUND: Within the Brazilian Unified Health System (SUS), Referral Centers (RCs) are care facilities that provide specialized services. The objective of this study was to evaluate the efficacy of care provided to patients with multiple myeloma (MM) at a specialized RC (Hospital de Clínicas de Porto Alegre Referral Center for Multiple Myeloma, CRMM-HCPA) and to compare quality of life between patients with MM treated at CRMM-HCPA and those treated at non-RC facilities. METHODS: A 6-month cohort study was conducted in patients with MM receiving thalidomide from the Rio Grande do Sul State Health Department and treated at CRMM-HCPA and patients receiving treatment at other, non-RC care facilities. Thirty-two patients were included in the study, 19 from CRMM-HCPA and 13 from other institutions. To analyze the efficacy of care provided at CRMM-HCPA, the main outcome measure was the time from diagnosis to referral for autologous hematopoietic stem cell transplantation (HSCT). This outcome measure was assessed using questionnaires specifically designed for this study. Quality of life was also assessed, using the SF-36 questionnaire. RESULTS: Time from MM diagnosis to referral for autologous HSCT in each group was measured only in patients aged ≤ 65 years (n = 25); of these, 15 were recruited from CRMM-HCPA and 10 from other institutions. In this analysis, there was a significant difference (p = 0.036) in time elapsed between diagnosis and referral for autologous HSCT, which was significantly shorter for patients treated at CRMM-HCPA (median, 9 months; IQR, 8.5-14.5) than for those treated elsewhere (median, 24 months; IQR, 16-24). On quality of life analysis, there was a significant difference in the Social Functioning domain of the SF-36 questionnaire, which relates to performance of social activities (p = 0.02). CONCLUSIONS: The Referral Center model provided seems to be a more efficient treatment strategy as compared with other health care facilities, as it enabled a reduction in time to transplantation. Patients treated at CRMM-HCPA demonstrated greater ease in performing social activities, with less interference from physical or emotional problems.

Comparison of clinical outcomes in patients undergoing mitral valve replacement with mechanical or biological substitutes: a 20 years cohort.

BACKGROUND: The choice of prosthesis for mitral valve replacement still remains controversial. This study assessed mortality, bleeding events and reoperation in patients who underwent mitral valve replacement surgery with biological or mechanical substitutes. METHODS: A total of 352 patients who underwent mitral valve replacement surgery between 1990 and 2008 with 5 to 23 years of follow-up were retrospectively evaluated in a cohort study. RESULTS: The 5, 10, 15 and 20 year survival rates after surgery using a mechanical substitute were 87.7%, 74.2%, 69.3% and 69.3%, respectively, while after surgery with a biological substitute, they were 87.6%, 71.0%, 64.2% and 56.6%, respectively. There was no significant difference between the two groups (p = 0.38). In the multivariate analysis, the factors associated with death were age, bleeding events and renal failure. The probabilities of remaining free of reoperation at 5, 10, 15 and 20 years after surgery using a mechanical substitute were 94.4%, 92.7%, 92.7% and 92.7%; after surgery with a bioprosthesis, they were 95.9%, 86.4%, 81.2% and 76.5%, respectively (p = 0.073). There was a significantly higher incidence of reoperation for the bioprosthetic valve replacement group (p = 0.008). The probabilities of remaining free of bleeding events at 5, 10, 15 and 20 years after surgery using a mechanical substitute were 95.0%, 91.0%, 89.6% and 89.6%, respectively, while after surgery with a bioprosthesis, they were 96.9%, 94.0%, 94.0% and 94.0%, (p = 0.267). CONCLUSIONS: The authors concluded that: 1) mortality during follow-up was statistically similar for both groups; 2) there was a greater tendency to reoperation in the bioprosthesis group; 3) the probability of remaining free from reoperation remained unchanged after 10 years' follow-up for patients with mechanical substitute valves; 4) the probability of remaining fee from bleeding events remained unchanged after 10 years' follow-up for patients given bioprostheses; 5) the baseline characteristics of patients were the greatest determinants of later mortality after surgery; 6) the type of prosthesis was not an independent predictive factor of any of the outcomes tested in the multivariate analysis.

Tumour necrosis factor -308 and -238 promoter polymorphisms are predictors of a null virological response in the treatment of Brazilian hepatitis C patients.

Certain host single nucleotide polymorphisms (SNPs) affect the likelihood of a sustained virological response (SVR) to treatment in subjects infected with hepatitis C virus (HCV). SNPs in the promoters of interleukin (IL)-10 (-1082 A/G, rs1800896), myxovirus resistance protein 1 (-123 C/A, rs17000900 and -88 G/T, rs2071430) and tumour necrosis factor (TNF) (-308 G/A, rs1800629 and -238 G/A, rs361525) genes and the outcome of PEGylated α-interferon plus ribavirin therapy were investigated. This analysis was performed in 114 Brazilian, HCV genotype 1-infected patients who had a SVR and in 85 non-responders and 64 relapsers. A significantly increased risk of having a null virological response was observed in patients carrying at least one A allele at positions -308 [odds ratios (OR) = 2.58, 95% confidence intervals (CI) = 1.44-4.63, p = 0.001] or -238 (OR = 7.33, 95% CI = 3.59-14.93, p < 0.001) in the TNF promoter. The risk of relapsing was also elevated (-308: OR = 2.87, 95% CI = 1.51-5.44, p = 0.001; -238: OR = 4.20, 95% CI = 1.93-9.10, p < 0.001). Multiple logistic regression of TNF diplotypes showed that patients with at least two copies of the A allele had an even higher risk of having a null virological response (OR = 16.43, 95% CI = 5.70-47.34, p < 0.001) or relapsing (OR = 6.71, 95% CI = 2.18-20.66, p = 0.001). No statistically significant association was found between the other SNPs under study and anti-HCV therapy response.

C-reactive protein and cognition are unrelated to leukoaraiosis.

Elevated serum levels of C-reactive protein (CRP) have been associated with leukoaraiosis in elderly brain. However, several studies indicate that leukoaraiosis is associated with an increased risk of cognitive impairment. It is unknown how the effect of CRP on cognition is mediated by leukoaraiosis. The purpose of this study is to assess the relationship between serum levels of CRP, the presence of leukoaraiosis, and cognitive impairment in a population of coronary patients over 50 years old. CRP levels explained 7.18% (P: 0.002) of the variance of the MMSE. The adjustment for the presence of leukoaraiosis little changed this variance (5.98%, P: 0.005), indicating that only a small portion of the CRP influence on cognition was mediated via leukoaraiosis. Patients with CRP levels ≥ 5.0 had 2.9 (95% CI: 1.26-6.44) times more chance to present cognitive impairment (P: 0.012). We found that elevated serum levels of CRP were associated with increased risk of cognitive impairment in elderly and it was not mediated by presence of leukoaraiosis.

Symptomatic treatment of the common cold with a fixed-dose combination of paracetamol, chlorphenamine and phenylephrine: a randomized, placebo-controlled trial.

BACKGROUND: The common cold and other viral airway infections are highly prevalent in the population, and their treatment often requires the use of medications for symptomatic relief. Paracetamol is as an analgesic and antipyretic; chlorphenamine is an antihistamine; and phenylephrine, a vasoconstrictor and decongestant. This randomized, double-blind, placebo-controlled trial sought to evaluate the efficacy and safety of a fixed-dose combination of paracetamol, chlorphenamine and phenylephrine in the symptomatic treatment of the common cold and flu-like syndrome in adults. METHODS: This study enrolled 146 individuals aged 18 to 60 years who had moderate to severe flu-like syndrome or common cold. After clinical examination and laboratory tests, individuals were randomly assigned to receive the fixed-dose combination (73) or placebo (73), five capsules per day for 48 to 72 hours. The primary efficacy endpoint was the sum of the scores of 10 symptoms on a four-point Likert-type scale. To evaluate treatment safety, the occurrence of adverse events was also measured. RESULTS: Mean age was 33.5 (±9.5) years in the placebo group and 33.8 (±11.5) in the treatment group. There were 55 women and 18 men in the placebo group, and 46 women and 27 men in the treatment group. Comparison of overall symptom scores in the two groups revealed a significantly greater reduction in the treatment group than in the placebo group (p = 0.015). Analysis at the first 13 dose intervals (± 66 h of treatment) showed a greater reduction of symptom scores in the treatment group than in the placebo group (p < 0.05). The number and distribution of adverse events were similar in both groups. CONCLUSION: A fixed-dose combination of paracetamol, chlorphenamine and phenylephrine was safe and more effective than placebo in the symptomatic treatment of the common cold or flu-like syndrome in adults. TRIAL REGISTRATION: NCT01389518.

National guidelines for high-cost drugs in Brazil: achievements and constraints of an innovative national evidence-based public health policy.

INTRODUCTION: The translation of best evidence into practice has become an important purpose of policy making in health care. In Brazil, a country of continental dimensions with widespread regional and social inequalities, the dissemination and use of the best-evidence in policy making is a critical issue for the healthcare system. OBJECTIVES: The main purpose of this study is to describe an evidence-based public health policy with special emphasis on guidelines creation for high-cost medicines. We also describe how that strategy was diffused to the judiciary system and to other parts of the healthcare system. RESULTS: We present an 11-year follow-up of a national project for creating and updating guidelines for high-cost medicines in Brazil. A total of 109 national guidelines were published (new or updated versions) for 66 selected diseases, the first such effort in Brazilian history. The project influenced the Brazilian legislature, which has recently established a Federal Law requiring national guidelines for any new technology listed for payment by the Brazilian public healthcare system. CONCLUSION: We were able to involve many different stakeholders in a partnership between academia and policy makers, which made possible the widespread dissemination of the clinical practice guidelines. Problems and constraints were also encountered. This evolving public health strategy might be useful for other developing countries.

Response to treatment in Brazilian patients with chronic hepatitis C is associated with a single-nucleotide polymorphism near the interleukin-28B gene.

A single-nucleotide polymorphism (SNP) upstream of interleukin (IL)28B was recently identified as an important predictor of the outcome of chronic hepatitis C patients treated with pegylated interferon plus ribavirin (PEG-IFN/RBV). The aim of this study was to investigate the association between the IL28B gene polymorphism (rs12979860) and virological response in chronic hepatitis C patients. Brazilian patients (n = 263) who were infected with hepatitis C virus (HCV) genotype 1 and were receiving PEG-IFN/RBV were genotyped. Early virological response (EVR) (12 weeks), end-of-treatment response (EOTR) (48 weeks), sustained virological response (SVR) (72 weeks) and relapse were evaluated using conventional and quantitative polymerase chain reaction (PCR) assays. The frequency of the C allele in the population was 39%. Overall, 43% of patients experienced SVR. The IL28B CC genotype was significantly associated with higher treatment response rates and a lower relapse rate compared to the other genotypes [84% vs. 58% EVR, 92% vs. 63% EOTR, 76% vs. 38% SVR and 17% vs. 40% relapse rate in CC vs. other genotypes (CT and TT), respectively]. Thus, the IL28B genotype appears to be a strong predictor of SVR following PEG-IFN/RBV therapy in treatment-naïve Brazilian patients infected with HCV genotype 1. This study, together with similar research examining other SNPs, should help to define adequate protocols for the treatment of patients infected with HCV genotype 1, especially those with a poor prognosis.

Disparity in the use of Alzheimer's disease treatment in Southern Brazil.

Alzheimer's disease (AD) treatment is freely available in the Brazilian public health system. However, the prescription pattern and its associated factors have been poorly studied in our country. We reviewed all granted requests for AD treatment in the public health system in October 2021 in the Rio Grande do Sul (RS) state, Southern Brazil. We performed a spatial autocorrelation analysis with the population-adjusted patients receiving any AD medication as the outcome and correlated it with several socioeconomic variables. 2382 patients with AD were being treated during the period analyzed. The distribution of the outcome variable was not random (Moran's I 0.17562, P <.0001), with the most developed regions having a higher number of patients/100,000 receiving any AD medication. We show that although AD medications are available through the public health system, there is a clear disparity between regions of RS state. Factors related to socioeconomic development partly explain this finding.

The effectiveness of retreatment with peginterferon alfa and ribavirin in patients with chronic viral hepatitis C genotype 2 and 3: a prospective cohort study in Brazil.

BACKGROUND: More than 50% of patients infected with chronic hepatitis C virus (HCV) do not respond to treatment with conventional interferon (IFN) combined with ribavirin (RBV). The aim of our study was to evaluate the effectiveness of retreatment with peginterferon alfa-2a or 2b (PEG-IFN 2a or 2b) concomitantly with RBV in patients with HCV genotype 2 and 3, which were non-responders or relapsers to initial treatment with IFN / RBV and to identify possible predictors of sustained virological response (SVR). METHODS: From September 2003 to March 2009 a cohort of 216 patients who had previously failed therapy with a regimen of standard interferon and ribavirin, were followed in a specialized service implemented in the Brazilian Unified Health System, Rio Grande do Sul. All patients were retreated with PEG-IFN 2a or 2b per week, associated with RBV, through oral route, with doses determined according to weight (1,000 mg if weight ≤ 75 Kg and 1,250 mg if ≥ 75 Kg) per day for 48 weeks. The HCV-RNA was tested by Polymerase Chain Reaction (PCR). Virological Response (VR) within 48 weeks and SVR in the 72 weeks was considered for evaluation of treatment efficacy. Analyses were performed in patients who received at least one dose of PEG-IFN. RESULTS: The SVR rate for non-responders to previous treatment was 34.4% and for relapsers was 50% (p = 0.031). As predictive factors that contribute to improve SVR, were identified the age (p = 0.005), to be relapsers to previous treatment (p = 0.023) and present liver biopsy examination Metavir F0-F2 (p = 0.004). In assessing the safety profile, 51 patients (23.6%) discontinued treatment prematurely. CONCLUSIONS: This alternative retreatment for patients who have failed prior therapies for anti-HCV, has demonstrated promising SVR rate, provided that it includes a careful selection of patients with predictors of response and adverse events monitored.

Hypoglycemia frequency and treatment satisfaction in patients receiving insulin analogues for treatment of type 1 diabetes mellitus.

OBJECTIVE: The aim of this study was to evaluate the frequency of hypoglycemia and the treatment satisfaction in patients with type 1 diabetes (T1D) using insulin analogues. METHODS: This observational retrospective study included 516 adult patients with T1D from 38 cities in Southern Brazil. Demographics and clinical data were collected using a self-report questionnaire. Hypoglycemia was defined as an event based on either symptoms or self-monitored blood glucose < 70 mg/dL. Treatment satisfaction was evaluated using the Diabetes Treatment Satisfaction Questionnaire status version (DTSQs) and with a specific question with scores ranging from 0-10. Common mental disorders were assessed using the General Health Questionnaire (GHQ-12). RESULTS: Overall, the mean age was 38 ± 14 years and 52% of the participants were women. The median diabetes duration was 18 years. The scores for insulin analogue treatment satisfaction were higher than those for previous treatments. DTSQ scores had a median value of 32 (interquartile range 29-35) and remained unchanged over time. The percentage of patients with hypoglycemia (including severe and nocturnal) was comparable across groups divided according to duration of use of insulin analogues. Most patients (n=395, 77%) screened positive for common mental disorders. CONCLUSION: Patient satisfaction with insulin analogue treatment was high and remained unchanged with time. Episodes of hypoglycemia also remained unchanged over time among patients using insulin analogues.

Evaluation of severe hypoglycemia and common mental disorders in patients receiving insulin analogues for treatment of type 1 diabetes.

This is a retrospective report of the frequency of severe hypoglycemia and the association between common mental disorders and type 1 diabetes mellitus treated with insulin analogues. Patients with severe hypoglycemia compared with those without this complication had a higher prevalence of positive screening for common mental disorders (88% vs. 77%, respectively, p = 0.03).

Interferon-lambda 3 and 4 Polymorphisms Increase Sustained Virological Responses and Regulate Innate Immunity in Antiviral Therapy With Pegylated Interferon-Alpha.

Sustained virologic response (SVR) in chronic hepatitis C (CHC) treatment denotes that the host genetics controls the immune response and unequivocally contribute to viral clearance or disease severity. In this context, single nucleotide polymorphisms (SNPs) in the locus of interferon lambda 3 and 4 genes (IFNL3/4) have been important genetic markers of responsiveness to CHC as prognostic markers for the pegylated-Interferon-alpha/ribavirin (Peg-IFN-α/RBV). Here, we analyzed 12 SNPs at the IFNL3/4 region in 740 treatment-naïve patients with CHC infected with hepatitis C virus (HCV) genotypes 1, 2, or 3 treated with Peg-IFN-α/RBV. Individually, rs12979860-CC, rs8109886-CC, or rs8099917-TT were predictive markers of SVR, while rs12979860-CC demonstrated the stronger effect. Besides, the genotypic combination of these three predictors' genotypes, CC/CC/TT, increased the rate of SVR. Serum levels of cytokines and gene expression analysis on the genes IFNL3, IFNL4, IFNA1, and some of the IFN-stimulated genes (ISGs) were measured in a subgroup of 24 treated patients and 24 healthy volunteers. An antagonist effect was highlighted between the expression of IFNL3/4 and IFNA1 mRNA among patients. Besides, a prominent production of the pro-inflammatory chemokines CCL4 and CXCL10 was observed at a 12-week treatment follow-up. Lower serum levels of these chemokines were detected in patients with an rs12979860-CC genotype associated with the better treatment outcome. Also, lower expression levels of the IFI6, IFI16, IRF9 genes were observed among rs12979860-CC individuals. In conclusion, a combination of the genotypes at the IFNL3/4 locus can act as a better marker for the prognosis for virological responses in an admixed Brazilian population presenting the modulating effect over innate immunity and inflammation that are controlling the outcome of the viral infection, but also other infectious diseases. This study is registered on the ClinicalTrials.gov platform (accession number NCT01889849 and NCT01623336).

Increasing rational use of cholinesterase inhibitors for Alzheimer's disease in Brazil: public health strategy combining guideline with peer-review of prescriptions.

OBJECTIVES: Since 2002, the treatment with cholinesterase inhibitors (CHEIs) for Alzheimer's disease (AD) has been paid for by the public health system of the Brazilian Ministry of Health for any patient that fulfills clinical criteria established by an evidence-based guideline developed and published by the Ministry. The aim of this study was to evaluate compliance of prescription patterns to the national guideline for use of CHEIs' in the southern Brazilian state of Rio Grande do Sul. METHODS: We created a regional expert-committee reference center to review all prescriptions of CHEIs and to send feedback to physicians whenever prescriptions without compliance to the guideline were noted. One thousand three hundred ninety-nine (1,399) CHEI prescriptions presented to the public health system from 2005 to 2007 were evaluated by an expert team of neurologists and psychiatrists. Clinical history, performance on mental status screening by Mini Mental State Examination (MMSE), Clinical Dementia Rating scale (CDR), laboratory results, and neuroimaging findings were evaluated in relation to the adherence to the national guideline's recommendations. If the prescription was rejected because of lack of adherence to the criteria of the guideline, a written response was sent by the expert committee to physicians concerning the request. RESULTS: The majority of the requests (n = 1,044; 75 percent) did not meet the AD guideline's criteria, either for diagnosis or for treatment, and were not granted. A diagnostic mistake was evident in 64.3 percent of cases. Findings of vascular or Parkinson's dementia or severe AD were the main reasons for rejection. Rivastigmine was the most prescribed cholinesterase inhibitor, used in 86 percent of cases. Of note was the reduction in the number of CHEIs prescriptions in the years following this intervention. CONCLUSIONS: The public health strategy of using expert-review of prescriptions and their compliance to national guideline revealed a low rate of rational use of CHEIs for dementia. Such a strategy is relevant for protecting patients from unproven medical interventions and for reducing waste of resources.

Randomized clinical trial of a phytotherapic compound containing Pimpinella anisum, Foeniculum vulgare, Sambucus nigra, and Cassia augustifolia for chronic constipation.

BACKGROUND: A phytotherapic compound containing Pimpinella anisum L., Foeniculum vulgare Miller, Sambucus nigra L., and Cassia augustifolia is largely used in Brazil for the treatment of constipation. However, the laxative efficacy of the compound has never been tested in a randomized clinical trial. The aim of this study was to evaluate the efficacy and safety of the product. METHODS: This randomized, crossover, placebo-controlled, single-blinded trial included 20 patients presenting with chronic constipation according to the criteria of the American Association of Gastroenterology. The order of treatments was counterbalanced across subjects: half of the subjects received the phytotherapic compound for a 5-day period, whereas the other half received placebo for the same period. Both treatment periods were separated by a 9-day washout period followed by the reverse treatment for another 5-day period. The primary endpoint was colonic transit time (CTT), measured radiologically. Secondary endpoints included number of evacuations per day, perception of bowel function, adverse effects, and quality of life. RESULTS: Mean CTT assessed by X ray was 15.7 hours (95%CI 11.1-20.2) in the active treatment period and 42.3 hours (95%CI 33.5-51.1) during the placebo treatment (p < 0.001). Number of evacuations per day increased during the use of active tea; significant differences were observed as of the second day of treatment (p < 0.001). Patient perception of bowel function was improved (p < 0.01), but quality of life did not show significant differences among the study periods. Except for a small reduction in serum potassium levels during the active treatment, no significant differences were observed in terms of adverse effects throughout the study period. CONCLUSIONS: The findings of this randomized controlled trial allow to conclude that the phytotherapic compound assessed has laxative efficacy and is a safe alternative option for the treatment of constipation. TRIAL REGISTRATION: ClinicalTrial.gov NCT00872430.

Treatment of hepatitis C with peginterferon and ribavirin in a public health program.

BACKGROUND/AIMS: In hepatitis C treatment, literature is limited with regard to independent studies developed outside the context of clinical assays. To evaluate the sustained virological response to the treatment of patients with chronic hepatitis C genotype 1 in a public program in the south of Brazil. METHODOLOGY: It is a mixed cohort, the data of all patients with chronic hepatitis C treated with peginterferon associated with ribavirin for 48 weeks were collected. If there was no early virological response on week 12 the treatment was discontinued. The significance level adopted in the statistical analysis was micro = 0.05. RESULTS: The cohort was comprised of 323 individuals. The treatment was completed in 215 (66.6%) patients. With the intention to treat analysis, the sustained virological response was obtained in 114 (35.3%) patients. The factors predictive of the response were lower age (below 40 years) and minor fibrosis (< F3 according METAVIR score), as well as viral load less than 600,000 IU/ml and the absence of hepatitis C virus viremia on 12th week of treatment. CONCLUSION: The sustained virological response in patients with chronic hepatitis C genotype 1 treated with peginterferon and ribavirin in a public health system did not reproduce the results obtained in the major clinical trials.

A population-based study of tuberculosis incidence among rheumatic disease patients under anti-TNF treatment.

INTRODUCTION: Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis. The advent of immunobiologic therapy with TNF inhibitors agents, has been associated with a significant increase in incident cases of tuberculosis in this population. OBJECTIVE: To estimate the incidence of tuberculosis in patients receiving TNF inhibitors therapy for rheumatic diseases. As secondary objectives, we sought to evaluate mortality and the clinical impact of screening for latent tuberculosis infection. METHODS: This retrospective study included patients with rheumatic diseases of Public Health System from the Brazilian state, a high TB incidence area, who received prescriptions of TNF inhibitors agents between 2006 and 2016. RESULTS: A total of 5853 rheumatic disease patients were included. Patients were predominantly women (68.7%) aged 49.5 (± 14.7) years old. Forty-three cases of TB were found (2.86 cases per 1000 person-years; 18 times higher than in the general population). Adalimumab and certolizumab users presented a higher risk for TB development compared to etanercept users (RR: 3.11, 95%CI 1.16-8.35; 7.47, 95%CI 1.39-40.0, respectively). In a subgroup of patients, screening for latent tuberculosis infection was performed in 86% of patients, and 30.2% had a positive tuberculin skin test. Despite latent TB treatment, TB was diagnosed in 2 out of 74 (2.7%) patients. Overall, TB diagnosis did not increase mortality. CONCLUSION: In this population-based study of rheumatic disease patients from a high incident area, TNF inhibitor exposure was associated with an 18-time increased TB incidence. Adalimumab and certolizumab were associated with greater and earlier TB diagnosis compared to etanercept.

Pharmacokinetics comparison of two pegylated interferon alfa formulations in healthy volunteers.

BACKGROUND: Several countries have used pegylation technology to improve the pharmacokinetic properties of essential drugs. Recently, a novel interferon alfa-2b protein conjugated to four-branched 12 kDa polyethylene glycol molecules was developed jointly between Cuba and Brazil. The aim of this study was to compare the pharmacokinetic properties of BIP48 (pegylated interferon alfa-2b from Bio-Manguinhos/Fiocruz, Brazil) to those of PEGASYS® (commercially available pegylated interferon alfa-2a from Roche Pharmaceutical). METHODS: This phase I, single-centre, randomized, double-blind crossover trial enrolled 31 healthy male volunteers aged 19 to 35 who were allocated to two stages, either side of a 5-week wash-out period, with each arm lasting 14 consecutive days after subcutaneous administration of 180 µg of one formulation or the other (study or comparator). The main outcome variable was serum pegylated interferon concentrations in 15 samples collected during the course of the study and tested using an enzyme immunoassay. RESULTS: There were no differences between formulations in terms of magnitude or absorption parameters. Analysis of time parameters revealed that BIP48 remained in the body significantly longer than PEGASYS® (Tmax: 73 vs. 54 h [p = 0.0010]; MRT: 133 vs. 115 h [p = 0.0324]; ke: 0.011 vs. 0.013 h(-1) [p = 0.0153]; t1/2: 192 vs. 108 h [p = 0.0218]). CONCLUSION: BIP48 showed the expected pharmacokinetic profile for a pegylated product with a branched molecular structure. Compared to PEGASYS®, the magnitude absorption was similar, but time parameters were consistent with slower elimination. Further studies should be conducted to evaluate the clinical implications of these findings. A phase II-III repeated-dose clinical trial is ongoing to study these findings in patients with chronic hepatitis C virus infection. TRIAL REGISTRATION: This study is registered on the ClinicalTrials.gov platform (accession number NCT01889849 ). This trial was retrospectively registered in June 2013.

A double-blind, randomized, crossover study of prosigne versus botox in patients with blepharospasm and hemifacial spasm.

There is a lack of evidence on the clinical efficacy and safety of the recently released Chinese botulinum toxin serotype A (Prosigne) for the treatment of focal dystonias and hemifacial spasm. Determining a more precise role of Prosigne in the treatment of such conditions is of paramount importance, because botulinum toxin type A treatments have a huge economic implication in health services, especially in developing countries. The aim of our study was to compare the efficacy and safety of Prosigne in the treatment of blepharospasm and hemifacial spasm in comparison to Botox. We performed a double-blind, randomized, crossover study enrolling 26 patients. There were no significant differences between Prosigne and Botox regarding subjective global improvement, response onset, efficacy duration, and incidence and severity of adverse events. Our results suggest that Prosigne and Botox are comparable with respect to efficacy and safety for the short-term treatment of blepharospasm and hemifacial spasm.

Prediction of Sustained Virological Response to Peginterferon-based Therapy for Chronic Hepatitis C: Regression Analysis of a Cohort from Rio Grande do Sul, Brazil.

AIM: Peginterferon plus ribavirin (peg-IFN/RBV) is still the standard of care for treatment of hepatitis C virus (HCV) in many countries. Given the high toxicity of this regimen, our study aimed to develop a prediction tool that can identify which patients are unlikely to benefit from peg-IFN/RBV and could thus postpone treatment in favor of new-generation direct-acting antivirals. MATERIALS AND METHODS: Binary regression was performed using demographic, clinical, and laboratory covariates and sustained virological response (SVR) outcomes from a prospective cohort of individuals referred for therapy from 2003 to 2008 in a public HCV treatment center in Rio Grande do Sul, Brazil. RESULTS: Of the 743 participants analyzed, 489 completed 48 weeks of treatment (65.8%). A total of 202 of those who completed peg-IFN/RBV therapy achieved SVR (27.2% responders), 196 did not (26.4%), and 91 had missing viral load (VL) at week 72 (12.2% loss to follow-up). The remainder discontinued therapy (n = 254 [34.2%]), 78 (30.7%) doing so due to adverse effects. Baseline covariates included in the regression model were sex, age, human immunodeficiency virus, infection status, aspartate transaminase, alanine transaminase, hemoglobin, platelets, serum creatinine, prothrombin time, pretreatment VL, cirrhosis on liver biopsy, and treatment naivety. A predicted SVR of 17.9% had 90.0% sensitivity for detecting true nonresponders. The negative likelihood ratio at a predicted SVR of 17.9% was 0.16, and the negative predictive value was 92.6%. CONCLUSION: Easily obtainable variables can identify patients that will likely not benefit from peg-IFN-based therapy. This prediction model might be useful to clinicians. CLINICAL SIGNIFICANCE: To our knowledge, this is the only prediction tool that can reliably help clinicians to postpone peg-IFN/RBV therapy for HCV genotype 1 patients.How to cite this article: Picon RV, Fendt L, Amaral K, Picon PD. Prediction of Sustained Virological Response to Peginterferon-based Therapy for Chronic Hepatitis C: Regression Analysis of a Cohort from Rio Grande do Sul, Brazil. Euroasian J Hepato-Gastroenterol 2017;7(1):27-33.