Pedram Sendi

Long-term effectiveness of potent antiretroviral therapy in preventing AIDS and death: a prospective cohort study

BACKGROUND Evidence on the effectiveness of highly active antiretroviral therapy (HAART) for HIV-infected individuals is limited. Most clinical trials examined surrogate endpoints over short periods of follow-up and there has been no placebo-controlled randomised trial of HAART. Estimation of treatment effects in observational studies is problematic, because of confounding by indication. We aimed to use novel methodology to overcome this problem in the Swiss HIV Cohort Study. METHODS Patients were included if they had been examined after January 1996, when HAART became available in Switzerland, were not on HAART, and were free of AIDS at baseline. Cox regression models were weighted to create a statistical population in which the probability of being treated at each time point was unrelated to prognostic factors. RESULTS Low CD4 counts and increasing HIV-1 viral load were associated with increased probability of starting HAART. Overall hazard ratios were 0.14 (95% CI 0.07-0.29) for HAART compared with no treatment, and 0.49 (0.31-0.79) compared with dual therapy. Compared with no treatment, HAART became more beneficial with increasing time since initiation but was less beneficial for patients whose presumed mode of transmission was via intravenous drug use (hazard ratio 0.27, 0.12-0.61) than for other patients (0.08, 0.03-0.19). INTERPRETATION Our results, which are appropriately controlled for confounding by indication, are consistent with reported declines in rates of AIDS and death in developed countries, and provide a context in which to consider adverse effects of HAART.

Immune Reconstitution in HIV-Infected Patients

The prognosis of patients infected with human immunodeficiency virus (HIV) type 1 has dramatically improved since the advent of potent antiretroviral therapies (ARTs), which have enabled sustained suppression of HIV replication and recovery of CD4 T cell counts. Knowledge of the function of CD4 T cells in immune reconstitution was derived from large clinical studies demonstrating that primary and secondary prophylaxis against infectious agents, such as Pneumocystis jirovecii (Pneumocystis carinii), Mycobacterium avium complex, cytomegalovirus, and other pathogens, can be discontinued safely once CD4 T cell counts have increased beyond pathogen-specific threshold levels (usually >200 CD4 T cells/mm3) for 3-6 months. The downside of immune reconstitution is an inflammatory syndrome occurring days to months after the start of ART, with outcomes ranging from minimal morbidity to fatal progression. This syndrome can be elicited by infectious and noninfectious antigens. Microbiologically, the possible pathogenic pathways involve recognition of antigens associated with ongoing infection or recognition of persisting antigens associated with past (nonreplicating) infection. Specific antimicrobial therapy, nonsteroidal anti-inflammatory drugs, and/or steroids for managing immune reconstitution syndrome should be considered.

Isoniazid prophylaxis for tuberculosis in HIV infection: a meta-analysis of randomized controlled trials.

OBJECTIVES To evaluate the efficacy of isoniazid for the prevention of tuberculosis in tuberculin skin test-positive and negative individuals with HIV infection. DESIGN Meta-analysis of randomized controlled trials. SETTING Seven trials from Mexico, Haiti, the United States, Zambia, Uganda and Kenya. PATIENTS Individuals free from tuberculosis, 2367 persons in the intervention and 2162 in the control groups. INTERVENTION Comparison of isoniazid with placebo or no prophylaxis. METHODS A systematic search of the literature was carried out from 1985 to October 1997 for randomized controlled trials of isoniazid prophylaxis in HIV-infected persons. Two reviewers evaluated the relevance of each candidate study and the validity of eligible trials. Studies were pooled using a random effect model, conducting secondary analyses for tuberculin skin test-positive and negative persons. RESULTS Mean follow-up in trials varied between 0.4 and 3.2 years. Pooling all seven trials, a risk ratio was found for persons treated with isoniazid for developing tuberculosis of 0.58 [95% confidence interval (CI), 0.43-0.80] and 0.94 (95% CI, 0.83-1.07) for death. In groups of tuberculin skin test-positive and negative persons, the risk ratio of tuberculosis was 0.40 (95% CI, 0.24-0.65) and 0.84 (95% CI, 0.54-1.30), respectively, and the difference in the effectiveness of isoniazid versus placebo between these groups was statistically significant (P = 0.03, for the difference of summary estimates). Consistency of results was found across trials (P > 0.10, heterogeneity value) for all comparisons. CONCLUSIONS Prophylaxis with isoniazid reduces the risk of tuberculosis in persons with HIV infection. The effect is restricted to tuberculin skin test-positive persons.

Highly active antiretroviral therapy : Pharmacoeconomic issues in the management of HIV infection

The advent of highly active antiretroviral therapy (HAART), including protease inhibitors and/or non-nucleoside reverse transcriptase inhibitors, for the treatment of HIV infection has led to a dramatic decline of morbidity and mortality. The acquisition costs of HAART are substantial. However, these costs are partially offset by reduced inpatient care for opportunistic infections and other AIDS-related diseases. Furthermore, job productivity in patients infected with HIV is increased under HAART. In developed countries with a low unemployment rate, the discounted value of savings caused by increased productivity in earlier years exceeds the discounted value of later increases in costs resulting from morbidity. Therefore, HAART represents a very efficient treatment strategy that leads to overall cost savings when taking a societal perspective.

Comparison of Periapical Radiography and Limited Cone-Beam Computed Tomography in Mandibular Molars for Analysis of Anatomical Landmarks before Apical Surgery

INTRODUCTION The purpose of the present study was to evaluate the detectability and dimensions of periapical lesions, the relationship of the mandibular canal to the roots of the respective teeth, and the dimension of the buccal bone by using limited cone-beam computed tomography (CBCT) in comparison to conventional periapical (PA) radiographs for evaluation of mandibular molars before apical surgery. METHODS The study comprised 38 molars with 75 roots. The type of PA lesion as diagnosed on PA radiographs was compared with the type of lesion seen on sagittal and coronal CBCT sections. The distances of the apices of the first mandibular molars and basal border of the PA lesion to the coronal lining of the mandibular canal were assessed with PA radiographs and corresponding sagittal and coronal CBCT images. Furthermore, coronal CBCT images were used to measure the distance from the apices to the buccal bone surface and the corresponding width of the cortical bone plate. RESULTS Of 58 detected PA lesions, 15 (25.9%) lesions diagnosed with sagittal CBCT slices were missed with PA radiography. The distance between the apices and the upper border of the mandibular canal was only measurable in 24 of 68 radiographs (35.3%) by using PA images. The cortical bone wall had a mean thickness of 1.7 mm, whereas the total buccal bone wall (cortical and spongious) measured 5.3 mm on average. CONCLUSIONS The present study highlights the advantages of using limited CBCT for treatment planning in mandibular molars before apical surgery.

Comparison of intraoral radiography and limited cone beam computed tomography for the assessment of root‐fractured permanent teeth

AIM To compare intraoral occlusal (OC) and periapical (PA) radiographs vs. limited cone beam computed tomography (CBCT) in diagnosing root-fractured permanent teeth. MATERIAL AND METHODS In 38 patients (mean age 24 years, range 8-52 years) with 44 permanent teeth with horizontal root fractures, intraoral radiographs (PA and OC) and limited CBCT were used to evaluate the location (apical, middle, cervical third of the root) and angulation of the fracture line. Furthermore, the conventional radiographs and CBCT images were compared for concordance of fracture location. RESULTS In the PA and OC radiographs, 28 fractures (63.6%) were located in the middle third of the root, 11 (25.0%) in the apical third and 5 (11.4%) in the cervical third. The PA/OC radiographs and the sagittal CBCT images (facial aspect) yielded the same level of root fracture in 70.5% of cases (31 teeth; 95% CI: 54.1-82.7%). The PA/OC radiographs and sagittal CBCT images (palatal aspect) showed the same level of root fracture in 31.8% of cases. There was a statistically significant association between the angle at which the root fracture line intersected the axis of the tooth and the level of root fracture in the facial aspect of the sagittal CBCT images. CONCLUSIONS The diagnosis of the location and angulation of root fractures based on limited CBCT imaging differs significantly from diagnostic procedures based on intraoral radiographs (PA/OC) alone. The clinical significance for treatment strategies and for the prognosis of root-fractured teeth has to be addressed in future studies.

Characteristics and dimensions of the Schneiderian membrane: a radiographic analysis using cone beam computed tomography in patients referred for dental implant surgery in the posterior maxilla.

OBJECTIVES To determine the dimensions of the Schneiderian membrane using limited cone beam computed tomography (CBCT) in individuals referred for dental implant surgery, and to determine factors influencing the mucosal thickness. MATERIAL AND METHODS The study included 143 consecutive patients referred for dental implant placement in the posterior maxilla. A total of 168 CBCT images were taken using a limited field of view of 4 × 4 cm, 6 × 6 cm, or 8 × 8 cm. Reformatted coronal CBCT slices were analyzed with regard to the thickness and characteristics of the Schneiderian membrane in nine standardized points of reference. Factors such as age, gender, or status of the remaining dentition that could influence the dimensions of the Schneiderian membrane were evaluated using univariate and multivariate linear regression models. RESULTS The thickness of the Schneiderian membrane exhibited a wide range, with a minimum value of 0.16 mm and a maximum value of 34.61 mm. The highest mean values, ranging from 2.16 to 3.11 mm, were found for the mucosa located in the mid-sagittal regions of the maxillary sinus. The most frequent mucosal findings diagnosed were flat thickenings of the Schneiderian membrane (62 positive findings, 37%). For the multivariate linear regression model, only gender had a statistically significant influence on the mean overall and mid-sagittal thickness of the sinus mucosa. CONCLUSION There is great interindividual variability in the thickness of the Schneiderian membrane. Gender seems to be the most important parameter influencing mucosal thickness in asymptomatic patients. Future studies are needed to assess the therapeutic and prognostic consequences of mucosal alterations in the maxillary sinus.

Morphology of the nasopalatine canal and dental implant surgery: a radiographic analysis of 100 consecutive patients using limited cone-beam computed tomography

OBJECTIVES To analyze the dimensions and anatomic characteristics of the nasopalatine canal and the corresponding buccal bone plate of the alveolar process, using limited cone-beam computed tomography (CBCT) imaging. MATERIAL AND METHODS Partially edentulous patients scheduled for CBCT imaging for further radiographic evaluation of a prospective implant recipient site in the anterior maxilla were consecutively enrolled in this study. For all CBCT images, a limited field of view (FOV) of 4 × 4 cm, 6 × 6 cm or 8 × 8 cm was selected. Reformatted sagittal and coronal slices were analyzed with regard to dimensions and anatomic characteristics of the nasopalatine canal as well as the dimensions of the buccal bone wall. Factors influencing these parameters were evaluated using univariate and multivariate linear regression models. RESULTS The study population comprised 44 men and 56 women with a mean age of 43.09 years. Gender of the included patients had a statistically significant influence on the dimensions of the buccal bone plate, the mean values being generally higher for male subjects. In the multivariate linear regression model, the status of the central maxillary incisors (both present, one missing, and both missing) and the time elapsed since loss of the central incisors (<1 year vs. >1 year) were independently associated with buccal bone wall measurements, adjusted for age and sex. CONCLUSION The present study demonstrates decreasing values for the coronal width of the buccal bone wall in patients with missing central incisors and a time span since tooth loss of over 1 year. The age of the patients had a significant influence only on the length of the nasopalatine canal, with the mean values generally decreasing with an increasing age. The limited CBCT scans with FOVs varying between 4 × 4 and 8 × 8 cm are a valid diagnostic alternative to cross-sectional imaging in the anterior maxilla for dental implant treatment planning.

Optimizing a portfolio of health care programs in the presence of uncertainty and constrained resources.

Much research has been devoted to handling uncertainty in cost-effectiveness analysis. The current literature suggests summarizing uncertainty in cost-effectiveness analysis using acceptability curves or net health benefits. These approaches, however, focus only on uncertainty associated with costs and effects of the programs under consideration. In the real world, most decision-makers have to fund a portfolio of health care programs. Therefore, a more comprehensive approach would include in the analysis the uncertainty of costs and effects of all programs supported by the fixed budget. This paper extends the decision rule described by Birch and Gafni (J. Health Econ. 11(3) (1992) 279) within the context of a portfolio of programs when costs and effects are uncertain and resources constrained.

Radiographic Study of the Mandibular Retromolar Canal: An Anatomic Structure with Clinical Importance

INTRODUCTION The retromolar canal is an anatomic structure of the mandible with clinical importance. This canal branches off from the mandibular canal behind the third molar and travels to the retromolar foramen in the retromolar fossa. The retromolar canal might conduct accessory innervation to the mandibular molars or contain an aberrant buccal nerve. METHODS Patients referred for panoramic radiography were consecutively enrolled, provided a limited cone-beam computed tomography (CBCT) scan had also been taken in the area of interest. Radiographs were retrospectively screened for the presence of a retromolar canal, and linear measurements (distance to second molar, height, width) were taken. RESULTS One hundred twenty-one sides in 100 patients were evaluated (100 unilateral and 21 bilateral cases). A total of 31 retromolar canals were identified with CBCT (25.6%). Only 7 of these canals were also seen on the corresponding panoramic radiographs. The existence of a retromolar canal was not statistically related to gender or side. With regard to the linear measurements, the mean distance from the retromolar canal to the second molar was 15.16 mm (±2.39 mm), the mean height of the canal was 11.34 mm (±2.36 mm), and the mean width was 0.99 mm (±0.31 mm). CONCLUSIONS This radiographic study documents a frequency of 25% for the presence of a retromolar canal. The clinician is advised to preserve this anatomic variation when performing surgery in the retromolar area and to consider additional locoregional anesthesia in the case of failed mandibular block anesthesia.