Single- or multiple-session viscosupplementation protocols for temporomandibular joint degenerative disorders: a randomized clinical trial.

The aim of the study was to compare the effectiveness of two single-session protocols, either adopting high- (protocol A) or medium-molecular weight hyaluronic acid (protocol B), with the reference five-session protocol of temporomandibular joint (TMJ) lavage plus viscosupplementation (protocol C) in the management of chronic TMJ degenerative disorders. A randomized clinical trial (RCT) with ten participants per treatment group was designed, with multiple observation points, ending at 6 months after treatment. Pain levels on a 10-point VAS scale were selected as the primary outcome variable to rate treatment effectiveness, along with a number of secondary outcome parameters. Findings showed that Group C patients had the highest decrease in pain levels. Nonparametric permutation analyses revealed that the global effect of treatment was significantly different between the three protocols (P = 0·024). Pairwise comparisons showed that the differences of treatment effect between the two single-session interventions were negligible (global P-value = 0·93). On the contrary, the five-session protocol was significantly superior to both single-session protocols (global P-values ranging from 0·003 to 0·012). In conclusion, in a population of age-, sex-, and psychosocial aspects-matched study groups, the standard of reference five-session protocol proved to be superior at 6 months as far as the decrease in pain levels was concerned, whilst there were no differences between the two single-session interventions. The absence of differences in treatment effect as for some other secondary clinical outcome variables may suggest that there is further space for future investigations attempting to reduce the number of multiple interventions for TMJ viscosupplementation.

The clinical use of statistical permutation test methodology: a tool for identifying predictive variables of outcome.

OBJECTIVES: To identify the predictive variables affecting the outcome after radical surgery for bladder cancer by a newer statistical methodology, i.e. nonparametric combination (NPC). METHODS: A multicenter study enrolled 1,312 patients who had undergone radical cystectomy for bladder cancer in 11 Italian oncological centers from January 1982 to December 2002. A statistical analysis of their medical history and diagnostic, pathological and postoperative variables was performed using a NPC test. The patients were included in a comprehensive database with medical history and clinical and pathological data. Five-year survival was used as the dependent variable, and p values were corrected for multiplicity using a closed testing procedure. The newer nonparametric approach was used to evaluate the prognostic importance of the variables. All of the analyses were performed using routines developed in MATLAB© and the significance level was set at α = 0.05. RESULTS: A significant prognostic predictive value (p < 0.01) for tumor clinical staging, hydronephrosis, tumor pathological staging, grading, presence of concomitant carcinoma in situ, regional lymph node involvement, corpora cavernosa invasion, microvascular invasion, lymphatic invasion and prostatic stroma involvement was found. CONCLUSIONS: The NPC test could handle any type of variable (categorical and quantitative) and take into account the multivariate relation among variables. This newer methodology offers a significant contribution in biomedical studies with several endpoints and is recommended in presence of non-normal data and missing values, as well as solving high-dimensional data and problems relating to small sample sizes.

Temporomandibular joint osteoarthritis: an open label trial of 76 patients treated with arthrocentesis plus hyaluronic acid injections.

This study is an open-label trial on a sample of 76 consecutive patients with temporomandibular joint (TMJ) osteoarthritis treated with a cycle of five weekly arthrocenteses plus hyaluronic acid injections. Patients had a diagnosis of osteoarthritis according to the Research Diagnostic Criteria for Temporomandibular Disorders (RDC/TMD Axis I Group IIIb). They underwent a cycle of five arthrocenteses with injections (1 per week) of 1ml hyaluronic acid and four follow-up assessments after the end of the treatment (at 1 week, 1 month, 3 months, 6 months). At each appointment, several subjective and objective outcome variables were assessed to test the efficacy of the treatment protocol. Marked improvements were reported for all variables during the treatment phase. The improvements were maintained over the 6-month follow-up period. The p-value of the multivariate permutation test for the efficacy of the treatment over time (with Tippett's combination) was 0.001, and significant changes at the end of the follow-up period were detected for almost all the outcome variables. Data from this study lend further support to the usefulness of serial hyaluronic acid injections performed after arthrocentesis for the treatment of TMJ osteoarthritis and for the maintenance of improvements over a 6-month follow-up period.

Pharmacosurveillance and quality of care of thalassaemic patients. A large scale epidemiological survey.

OBJECTIVE: For adolescent thalassaemic patients, parenteral iron-chelation therapy is still a burden and a major reason for unsatisfactory compliance. The introduction of a new pharmaceutical preparation of deferoxamine (Desferal) claimed to be better tolerated was accompanied by an epidemiological study on the quality of care and life of the Italian thalassaemic population and on the acceptability and safety profile of the new preparation compared with the old one. METHODS: This was a two-period prospective survey of 867 patients (12% of the registered thalassaemic patient population) in a sample of centres representative of the different contexts of care. RESULTS: The majority of patients (81%) reported an overall positive opinion about the quality of care (median satisfaction score 7.4). Judgement was more critical among patients over 15 years, unemployed, less compliant with chelation treatment and with higher mean serum ferritin levels. The co-morbidity profile did not appear to influence patients' satisfaction scores, but 21% of respondents associated great discomfort with the use of Desferal, which appeared in a multivariate analysis to be a strong predictor [odds ratio (OR) 2.15, 95% confidence interval (CI) 1.20-3.83] of negative perception. Quality of life was reported as fair or poor (score below 6) by 21% of patients. Over a total of 29,066 infusions included in the comparison of the safety of the new versus the old preparation, the reported incidences of any adverse event (AE) were 51% versus 57%, respectively, and 8.2% versus 9.3% for severe AEs. Comparing the new with the old preparation, the adjusted relative risk of severe AEs was 0.79 (95% CI 0.65-0.96). CONCLUSION: While oral chelation therapies are still under evaluation, the overall quality of care and perceived quality of life of a representative sample of the Italian population of thalassaemic patients show that room for improvement depends more on the contexts of life and care than on strictly medical conditions. Comprehensive epidemiological surveillance is needed as a routine component of the care of this highly morbidity-burdened population to ensure timely appreciation of unmet needs and to assess the yield of innovative treatment schedules.

Polymorphisms in the coagulation factor VII gene and the risk of myocardial infarction.

BACKGROUND: High blood levels of coagulation factor VII are associated with a risk of ischemic vascular disease. Although factor VII levels may be genetically determined, the relation between genetic polymorphisms of factor VII, factor VII blood levels, and the risk of myocardial infarction has not been established. METHODS: We performed a case-control study of 165 patients with familial myocardial infarction (mean [+/-SD] age, 55+/-9 years) and 225 controls without a personal or family history of cardiovascular disease (mean age, 56+/-8 years). The polymorphisms involving R353Q and hypervariable region 4 of the factor VII gene were studied. Factor VII clotting activity and antigen levels were also measured. RESULTS: Patients with the QQ or H7H7 genotype had a decreased risk of myocardial infarction (odds ratios, 0.08 [95 percent confidence interval, 0.01 to 0.9] and 0.22 [95 percent confidence interval, 0.08 to 0.63], respectively). For the R353Q polymorphism, the RR genotype was associated with the highest risk, followed by the RQ genotype and then by the QQ genotype (P<0.001). For the polymorphism involving hypervariable region 4, the combined H7H5 and H6H5 genotypes were associated with the highest risk, followed in descending order by the H6H6, H6H7, and H7H7 genotypes (P<0.001). Patients with the QQ or H7H7 genotype had lower levels of both factor VII antigen and factor VII clotting activity than those with the RR or H6H6 genotype. Patients with the lowest level of factor VII clotting activity had a lower risk of myocardial infarction than those with the highest level (odds ratio, 0.13; 95 percent confidence interval, 0.05 to 0.34). CONCLUSIONS: Our findings suggest that certain polymorphisms of the factor VII gene may influence the risk of myocardial infarction. It is possible that this effect may be mediated by alterations in factor VII levels.