Percentage Of Non-responders Research Articles

Homotoxicological remedies versus desmopressin versus placebo in the treatment of enuresis: a randomised, double-blind, controlled trial

The aim of this trial was to compare the safety and efficacy of homotoxicological remedies versus placebo and versus desmopressin (dDAVP) in the treatment of monosymptomatic nocturnal enuresis (MNE). We conducted a randomised, double-blind, double-dummy, controlled trial in which 151 children with MNE were randomly assigned to receive oral homotoxicological remedies (n = 50), dDAVP (n = 50) or placebo (n = 51). The primary outcomes were: the reduction of wet nights per week after 3 months of therapy; the evaluation of the numbers and percentages of non-responders and responders; the number of children relapsing after initial response and the number of children attaining 14 consecutive dry nights during the treatment. The secondary outcome was the detection of adverse effects. Baseline clinical characteristics were similar in the three groups of patients. After the 3 months of therapy there was a significant difference between the three groups (P < 0.001) in the mean number of wet nights per week. The daily dose of dDAVP produced a statistically significant decrease (62.9%) in wet nights compared to placebo (2.4%) (P < 0.001) and compared to homotoxicological remedies (30.0%) (P < 0.001). There was a significant decrease in wet nights among the group treated with homotoxicological medications if compared with placebo (P < 0.001). The full response achieved with homotoxicological remedies (20%) was superior if compared with placebo (0%) (P < 0.001). Homotoxicology was superior to placebo (P < 0.001) with regard to the number of children attaining 14 consecutive dry nights during treatment. Our study demonstrates that homotoxicology is safe and effective when compared with placebo, even if it is significantly less effective than dDAVP in this clinical condition.

Efetividade das vacinas anti-VHB (DNA-recombinante) em doadores de sangue de uma região endêmica para hepatite B no sul do Brasil

The objective of this work was to estimate the effectiveness of DNA recombinant anti-HBV vaccines in a retrospective cohort study of 1,012 Brazilian blood donors who completed the vaccination schedule (3 doses + booster of antibody titer < 10IU/L) during the period 1998-2002. The results showed that seroconversion rates were significantly lower among the donors whose antibody titers was measured six months after completing the vaccination scheme and among older donors, particularly those aged over 50. Overall vaccine effectiveness was 88.7%, ranging from 80.6% in the oldest (50 years or over) to 91.4% among the youngest (18-30 years) donors. The booster regimen was effective at reducing the percentage of non-responders. We conclude that vaccine effectiveness was significantly better in younger blood donors and that the anti-HBs testing interval influenced the vaccine effectiveness.

The Use of Echocardiography for the Evaluation of Dyssynchrony

Tissue Doppler imaging (TDI), is a new imaging tool that allows measurement of dyssynchrony. In several small studies, TDI predicted clinical response and reverse remodeling after cardiac resynchronization therapy (CRT). Moreover, it allowed detection of mechanical dyssynchrony in heart failure patients with narrow QRS. Using TDI, the selection criteria for CRT might be changed to include heart failure patients with narrow QRS. Furthermore, it will help predict responders to this therapy, hence decreasing the percentage of nonresponders and allowing a more cost-effective use of this new technology.

Histological response to interferon alfa-based therapies in hepatitis C.

Histological response is defined as an improvement in the severity of liver inflammation with or without an improvement in fibrosis in patients following treatment for an acute or chronic liver disorder. Histological response occurs in patients with chronic hepatitis C virus (HCV) infection who have had a sustained virological response following treatment with interferon (IFN) therapy and in a percentage of nonresponders. Continuing IFN long term as maintenance therapy has been shown to prevent histological progression in patients who had both a marked decline in serum HCV RNA level during treatment and a histological response on repeat histological analysis. Prospective controlled trials are currently evaluating the benefits of low-dose maintenance therapy with pegylated IFN in HCV patients who have failed to achieve sustained virological response. In the future, the development of serum markers of fibrosis may allow for monitoring of hepatic fibrosis and histological response to therapy without the need to perform repeat liver biopsy.

Impact of CYP2D6 genotype on postoperative tramadol analgesia

Genetic polymorphisms result in absent enzyme activity of CYP2D6 (poor metabolizers, PM) in about 10% of the Caucasian population. This study investigates whether the PM genotype has an impact on the response to tramadol analgesia in postoperative patients. A prospective study design was used and 300 patients recovering from abdominal surgery were enrolled. After titration of an individual loading dose, patients could self-administer 1 ml bolus doses of the drug combination tramadol 20 mg/ml, dipyrone 200 mg/ml and metoclopramide 0.4 mg/ml via patient-controlled analgesia (PCA). Patients' genotype was analyzed considering the most prevalent PM associated CYP2D6 mutations using a real-time PCR and hybridization based genotyping method. Demographic data, surgery related variables, pain scores, analgesic consumption and need for rescue medication were compared between extensive metabolizers (EM) and PM. The primary outcome criterion ‘response’ was defined as responder or non-responder status by the need for rescue medication and patients' satisfaction at the final interview. Demographic and surgery related data were comparable between EM ( n=241) and PM ( n=30). The percentage of non-responders was significantly higher in the PM group (46.7%) compared with the EM group (21.6%; p=0.005). Tramadol loading dose amounted to 108.2±56.9 and 144.7±22.6 mg ( p<0.001) in EM and PM, respectively. More patients displaying the PM genotype needed rescue medication in the recovery room and during PCA period than patients with at least one wild type allele (21.6 versus 43.3%, p=0.02). PM for CYP2D6 showed a lower response rate to postoperative tramadol analgesia than EM. Therefore, CYP2D6 genotype has an impact on analgesia with tramadol. Pharmacogenetics may explain some of the varying response to pain medication in postoperative patients.

A report of the Osteoarthritis Research Society International Standing Committee for Clinical Trials Response Criteria Initiative

Background The domains of pain, function and patient's global assessment are identified as core variables and frequently measured in clinical trials of patients with osteoarthritis (OA) of the hip and knee.Objective To develop response criteria for OA of hip and knee based on the domains of pain, function and patient's global assessment.Methods A methodology was developed by an interaction of the Osteoarthritis Research Society International Standing Committee on Clinical Trials, biostatisticians, pharmaceutical company representatives and health agency representatives. Data from previously conducted placebo-controlled clinical trials were normalized and collated. Data were subset by location of OA (knee, hip), active agent used in the clinical trial (non-steroidal anti-inflammatory drug, other agent) and route of administration (oral, intra-articular). Statistical analysis identified response criteria which best discriminate active agent from placebo.Results Based on the analysis of data from 14 studies (totaling 1886 patients) and consensus opinion, the optimal responder criteria set differed for location of OA, active agent to be used, and route of administration. Because of nearly identical statistical results, two sets of responder criteria are proposed: (1) ‘high’ pain response or, alternatively, a ‘moderate’ response for at least two of three domains: pain, function and patient's global assessment; (2) ‘high’ response for either pain or function or, alternatively, a ‘moderate’ response for at least two of three domains: pain, function and patient's global assessment. The sensitivity (i.e., the percentage of responders in the active group) ranged from 52 to 96% and the specificity (i.e., the percentage of nonresponders in the control group) from 47 to 73%.Conclusion Based on data from clinical trials, two sets of responder criteria have been developed that can categorize an individual's responses to treatment in a clinical trial. These responder criteria require validation in additional datasets.

Evaluation of short-term nonpharmacological treatment of insomnia in a clinical setting

Of the 86 chronic insomnia patients we treated with nonpharmacological means, 74 improved considerably. The subjective improvement was confirmed by the outcome of the sleep logs registered after 4 weeks of treatment (decrease in sleep-onset latency, wake after sleep onset, and an increase of sleep efficiency). Of the 49 patients who had used hypnotics at intake, 18 discontinued their medication and 19 considerably reduced theirs after therapy. The investigated population was characterized by high scores for anxiety, depression, and somaticization; the depression and anxiety scores were significantly higher for the hypnotics users. The percentage of nonresponders (patients who were unaffected by the treatment) was highest for the group of homemakers and for the group of patients with a low level of education. Significantly less of the nonresponders had received cognitive therapy compared with responders. The value of nonpharmacological treatment lies in the fact that it leads to a subjective improvement of sleep and to increased control over the sleep problem that the patient was experiencing. Helping the patients to obtain control over their sleep problems was our main therapeutic goal.

Association between alcohol consumption and mortality, myocardial infarction, and stroke in 25 year follow up of 49 618 young Swedish men

Several epidemiological studies have shown that moderate alcohol consumption is associated with reduced mortality from cardiovascular diseases in middle aged and elderly subjects,1 but its effect in younger people is...

Immunoglobulin A antibodies against Pseudomonas aeruginosa in the tear fluid of contact lens wearers

Purpose. Pseudomonas aeruginosa is the most important cause of contact lens-associated ulcerative keratitis, especially for those who use extended-wear lenses. Until now, the presence of specific anti-P. aeruginosa immunoglobulin A (IgA) antibodies in the tears of contact lens wearers has not been investigated and is the purpose of the current study. Methods. The levels of specific IgA antibodies against P. aeruginosa and total secretory IgA (sIgA) concentrations were measured in tears of various groups of contact lens and non-contact lens wearers using enzyme-linked immunosorbent assays. Contact lens groups were divided into the following categories: daily-wear rigid gas-permeable lenses (n = 23), daily-wear soft lenses (n = 22), extended-wear soft lenses (n = 17), and non-contact lens wearers (n = 23). As a positive control group, we tested tears obtained from patients with cystic fibrosis (n = 5) because the respiratory tract of these persons often are colonized by P. aeruginosa. Results. The percentage of nonresponders (<15 U/ml) varied between 9% in daily-wear rigid gas-permeable contact lens users to 23% in daily-wear soft contact lens users. The percentage of nonresponders in controls was 13%. The frequency of nonresponders was not significantly different among the different groups tested. All patients with cystic fibrosis showed a very high anti-P. aeruginosa IgA response in their tears. When analyzing the mean anti-P. aeruginosa IgA response, a significandy lower level was found in extended-wear contact lens users (38 U/ml) compared to non-contact lens wearers (82 U/ml). Total s-IgA levels in die tears of the various groups tested were not significandy different. Conclusions. A substantial number of persons in the population of contact lens wearers tested lack detectable IgA antibodies against P. aeruginosa in their tears and may be susceptible to P. aeruginosa keratitis if die physiological condition of dieir cornea is compromised. Invest Ophthalmol Vis Sci. 1996; 37:2081-2088.

Response to the hepatitis B virus vaccine in haemodialysis patients: influence of malnutrition and its importance as a risk factor for morbidity and mortality

To assess if malnutrition influences the response to the hepatitis B virus vaccine in haemodialysis patients and whether this correlates with morbidity and mortality in these patients. A 4-year prospective open study. Haemodialysis unit of a 434-bed University Hospital. Sixty-four patients with end-stage chronic renal failure on maintenance haemodialysis. Three-dose vaccination series with recombinant hepatitis B virus vaccine. Antibody formation against the vaccine, predialysis serum urea, serum albumin and prealbumin, dialysis efficacy (Kt/V), protein catabolic rate (PCR), arm muscle circumference, triceps skinfold, serum parathyroid hormone concentration, mortality and morbidity (hospital days per year of dialysis). Increase in age negatively influences the formation of antibodies (P = 0.01), whereas serum albumin (P = 0.008) and predialysis blood urea concentration (P = 0.004) are positively correlated with the formation of antibodies. Responders had significantly higher levels of serum albumin and prealbumin and predialysis blood urea than non-responders. The percentage of non-responders was higher (70%) in the group with predialysis blood urea concentration between 90 and 125 mg/dl than in those with predialysis blood urea concentrations between 176 and 225 mg/dl (14.2%). Patients with serum albumin levels between 3 and 3.5 g/dl were non-responders in a higher percentage (87.5%) than those with serum albumin levels between 4.5 and 5 g/dl (18.8%). After a 4-year follow-up, survival was 20% higher in the responder group (P < 0.05). Morbidity, expressed as hospital days per year of haemodialysis, was markedly lower in the responder group (10.4 +/- 2 versus 32 +/- 14 days, P = 0.03). Malnutrition negatively influences the response to the hepatitis B virus vaccine in haemodialysis patients. Non-responders have higher morbidity and mortality than responders, and therefore the absence of response to the hepatitis B vaccine can be considered as a risk factor in the haemodialysis population.

Effect of therapy with combined interferon and tauroursodeoxycholic acid in chronic hepatitis C: Biochemical and virologic evaluation

Sixty men and women with biopsy-proven chronic hepatitis C were randomized to receive interferon (IFN) subcutaneously 3 million units three times a week (n=30) or 3 million units three times a week with tauroursodeoxycholic acid (TUDCA) 250 mg BID (n=30) for 6 months. A follow-up period of 3 months at the end of therapy was scheduled. Thirty-four patients (56.7%) had normalized serum alanine aminotransferase levels at the end of therapy; 16 received IFN alone and 18 received IFN plus TUDCA. Sixteen of these 34 patients (47.1%) relapsed in the follow-up period. No significant difference in relapse rate was observed between the two treatment groups. The overall percentage of nonresponders was 36.6%. Treatment was discontinued for noncompliance and/or side effects in four patients (6.7%), two in the IFN group and two in the IFN plus TUDCA group. Hepatitis C virus-ribonucleic acid was evident at the start of treatment in all patients and became undetectable in almost all responders. In some cases there was no correlation between viremia and biochemical signs of liver disease. No virologic differences were found between treatment groups. The tendency toward a reduced, but not significant, relapse rate in patients treated with IFN plus TUDCA must be confirmed in studies using a larger sample size.

Alternating sequential endocrine therapy: Tamoxifen and medroxyprogesterone acetate versus tamoxifen in postmenopausal advanced breast cancer patients

The effects of tamoxifen (TAM) versus the alternating sequential combination of TAM plus medroxy-progesterone acetate (MPA) has been evaluated in 20 postmenopausal patients with advanced breast cancer in a randomized controlled trial. In the TAM arm, patients received 20 mg b.i.d. of TAM. In the TAM-MPA arm, patients received only 20 mg b.i.d. of TAM for 7 days and, on the following 7 days. TAM plus an oral daily dose of 500 mg of MPA, in alternating sequence. Objective tumor reduction was achieved in 22 (41%) of the 54 patients in the TAM arm and in 25 (43%) of the 58 patients in the TAM-MPA arm. With regard to the stabilization of disease, a significant difference was observed between patients treated with the TAM-MPA combination and those treated with TAM alone (47% vs 22%). The percentage of nonresponders was also significantly higher in the TAM group (37%) than in the TAM-MPA group (10%). The time to progression was significantly shorter for the TAM arm than for the TAM-MPA arm (median, 7 vs 15 months), but the duration of remission was not significantly different for either treatment.

Prevalence of HBV Markers in the Italian Armed Forces and HBV Vaccination

Hepatitis B (HBV) markers were studied in 710 subjects who had been on active duty for over 6 months in the Italian Armed Forces. The prevalence of HBsAg carriers was found to be 4.4%, while 31.6% of the subjects were positive for various HBV antibodies. A total of 137 subjects were vaccinated with an anti-HBV vaccine (HB-VAX, MSD). The percentages of non-responders and low responders were 13.86% and 13.14%, respectively. Boosters administered 3 months post-vaccination schedule, with or without immunostimulatory treatment, resulted in seroconversions and/or substantial increases in HBsAb levels in 50% of these subjects.

Effects of imipramine on the autonomie responses of obsessive-compulsives to auditory tones

It has been argued that a mechanism of clomipramine's efficacy for obsessive-compulsive disorder is its reduction of excessive autonomie reactivity. The present study evaluated this proposed mechanism of action by assessing the effect on autonomic responding of imipramine, which is structurally similar to clomipramine, but lacks therapeutic efficacy for obsessive-compulsives. Twenty-three obsessive-compulsive patients received three sessions of 20 unsignalled 1000-Hz, 100-dB tones of 1-sec duration and 100-msec risetime. Skin conductance level, response frequency and magnitude, and heart rate were scored for an adaptation period and for each tone onset. Six weeks after the first tone session, during which half of the subjects received imipramine while the remainder received placebo, the second tone assessment was performed. A third tone assessment was performed after an additional 4 weeks of medication. Percentage of nonresponders was also evaluated for each group. Imipramine reduced electrodermal activity and increased heart rate. Skin conductance level and both number and amplitude of responses decreased significantly after 6 weeks of imipramine, compared with placebo, with further attenuation of electrodermal activity after 10 weeks of the drug. Electrodermal nonresponding increased dramatically for the imipramine group as compared to the nondrug group. These results reveal effects of imipramine on autonomie responding, and cast doubt on the hypothesis that a mechanism for successful drug treatment of obsessivecompulsive disorder is decreased autonomie reactivity.

Lymphocyte proliferative response to mitogenic monoclonal antibodies in systemic sclerosis. Evidence for unresponsiveness to murine monoclonal antibodies of IgG1 isotype.

Proliferative response of peripheral blood mononuclear cells to phitohemoagglutinin and anti-CD3 mitogenic monoclonal antibodies (MoAbs) of the IgG2a (OKT3) and IgG1 (PanT2, CLB T3/4.1) isotypes was studied in 39 patients with systemic sclerosis (SSc) and in 82 control subjects. The effect of IL-2 on this response was also investigated. No difference in the response to PHA and to IgG2a anti-CD3 MoAb OKT3 was seen between scleroderma patients and controls. Both the patient and control groups contained responders and non-responders to IgG1 anti-CD3 MoAbs. The percentage of non-responders was significantly higher in scleroderma patients than in controls. When purified lymphocytes from non-responder scleroderma patients were cultured with monocytes from control responders, proliferative response to IgG1 MoAbs was restored. Our results show that monocytes from patients with systemic sclerosis bear a defect leading to IgG1 unresponsiveness by T lymphocytes.

RBC-choline: changes by lithium and relation to prophylactic response.

Red blood cell (RBC)- and plasma-choline levels were measured in patients on lithium (n = 96), antidepressants (n = 32) and neuroleptics (n = 51), and in 25 healthy drug-free controls. Lithium patients exhibited highly increased RBC- and slightly increased plasma-choline levels compared with controls (P less than 0.001 and P less than 0.05, respectively); the choline ratio (RBC-/plasma-choline) was elevated almost to the same extent as RBC-choline (P less than 0.001). With antidepressants RBC-choline and choline ratios were slightly reduced (P less than 0.05), whereas neuroleptics showed no effect on choline levels. 79% of lithium patients were responders (reduction in hospitalizations with lithium), 21% were non-responders (no reduction or increase in hospitalizations). Choline ratio exhibited a significant relation to prophylactic lithium response, but lithium ratio did not. The percentage of non-responders was significantly higher in patients with a choline ratio exceeding 100 than in patients with a choline ratio below this cut-off (P less than 0.01). Thus, the increase of RBC-choline and choline ratios appears to be an effect specific for lithium and might be related to the outcome of lithium prophylaxis.

Blood Pressure Control in a Middle‐Aged Male Population

A health examination survey comprising 2 322 men born in 1920-24 was carried out in 1970-73 at the University Hospital, Uppsala. Untreated subjects with a diastolic BP greater than or equal to 105 mmHg and those already on treatment for hypertension were considered hypertensives. If a BP elevation was verified at a second screening and the patient had no established contact with a physician, he was offered treatment. Thus, 83 men have been followed up for at least 6 years. The overall reduction in SBP after 6 years was 29.0 mmHg and in DBP 19.6 mmHg. Six men have died, four of them from myocardial infarction, five have dropped out for other reasons. The percentage of non-responders (DBP greater than or equal to 105 mmHg) 1, 2, 3, 4 and 5 years +/- 3 months after the start of treatment was high, about 20% on the average. On the other hand, when the mean BP for the non-responders at all visits to the hypertension clinic was compared with their pretreatment value, a reduction of 29.3 mmHg in SBP and 17.0 mmHg in DBP was achieved. The results with regard to compliance and BP reduction are encouraging and would seem to justify more widespread screening and treatment.