Vaccine trials in the developing world: operational lessons learnt from a phase IV poliomyelitis vaccine trial in South Africa.

BACKGROUND: Conducting vaccine trials in developing nations is necessary but operationally complex. We describe operational lessons learnt from a phase IV poliomyelitis vaccine trial in a semi-rural region of South Africa. METHODS: We reviewed operational data collected over the duration of the trial with respect to staff recruitment and training, participant recruitment and retention, and cold chain maintenance. RESULTS-LESSONS LEARNT: The recruitment model we used that relied on the 24h physical presence of a team member in the birthing unit was expensive and challenging to manage. Forecasting of enrolment rates was complicated by incomplete baseline data and by the linear nature of forecasts that do not take into account changing variables. We found that analyzing key operational data to monitor progress of the trial enabled us to identify problem areas timeously, and to facilitate a collegial problem-solving process by the extended trial team. Pro-actively nurturing a working relationship with the public sector health care system and the community was critical to our success. Despite the wide geographical area and lack of fixed addresses, we maintained an excellent retention rate through community assistance and the use of descriptive residential information. Training needs of team members were ongoing and dynamic and we discovered that these needs that were best met by an in-house, targeted and systemized training programme. The use of vaccine refrigerators instead of standard frost-free refrigerators is cost-effective and necessary to maintain the cold-chain. CONCLUSION: Operational challenges of a vaccine trial in developing world populations include inexperienced staff, the close liaison required between researchers and public health care services, impoverished participants that require complex recruitment and retention strategies, and challenges of distance and access. These challenges can be overcome by innovative strategies that allow for the unique characteristics of the setting, trial population, and trial team.

Chronic oral inflammation and the progression of periodontal pathology in the third molar region.

PURPOSE: To assess the association between risk markers of chronic oral inflammation and changes over time in periodontal probing depth (PD) in the third molar region, the distal of a second molar, or around a third molar. SUBJECTS AND METHODS: The data from these analyses are part of a study of subjects enrolled with 4 asymptomatic third molars with adjacent second molars in an institutional review board-approved longitudinal trial. Full-mouth periodontal probing was conducted at enrollment and follow-up. Enrollment levels of periodontal pathogens and gingival crevicular fluid inflammatory mediators were assayed as indicators of the degree of oral inflammation. Subjects were categorized as those who had at least a 2 mm change in periodontal PD between baseline and follow-up in the third molar region and those who did not. The relationship between aggregated subject baseline PD, levels of periodontal pathogens, and gingival crevicular fluid IL-1 beta, and the proportion of subjects with changes in PD >or=2 mm versus those with PD <2 mm were compared with Cochran-Mantel-Haenzsel statistics. Level of significance was set at 0.05. Risk assessment models for a change in PD >or=2 mm were developed using logistic regression analysis. RESULTS: Twenty-four percent of 254 subjects exhibited a change in PD from baseline to follow-up of >or=2 mm in the third molar region. Of these, 95% had a baseline PD of >or=4 mm. Both high (>or=10(5)) "orange" and "red" complex bacteria and PD of >or=4 mm detected at enrollment were significantly associated with a change in PD >or=2 mm. Odds of a change in PD >or=2 mm were increased if baseline pathogen levels were >or=10(5) or a PD of >or=4 mm was detected at enrollment. CONCLUSION: Our findings are consistent with chronic oral inflammation leading to a progression of periodontal disease in the third molar region.

Progression of periodontal disease in the second/third molar region in subjects with asymptomatic third molars.

PURPOSE: To assess the change in periodontal status over time by periodontal probing depth (PD) in the third molar region. SUBJECTS AND METHODS: The data for these analyses are part of a study of subjects enrolled with 4 asymptomatic third molars with adjacent second molars in an institutional review board-approved longitudinal trial. Full mouth periodontal probing was conducted to determine periodontal status at baseline and follow-up. Panoramic radiographs were analyzed for angulation and degree of eruption of third molars. Subjects were categorized as those who exhibited at least a 2 mm change in periodontal PD between baseline and follow-up in the third molar region, the distal of a second molar or around a third molar, and those who did not exhibit a 2 mm or greater change. Subjects with and without changes in PD were compared with Cochran-Mantel-Haenzsel statistics. Level of significance was set at 0.05. RESULTS: Data from 254 subjects with at least 2 annual follow-up visits were available for analysis. Mean age at baseline was 27.5 years. Median follow-up from baseline to the second follow-up visit was 2.2 years (interquartile range 2.0, 2.6). At enrollment, 59% of the subjects had at least 1 PD > or =4 mm in the third molar region, one quarter had a PD > or =5 mm. Twenty-four percent of the subjects had at least 1 tooth that had an increased PD > or =2 mm in the third molar region at follow-up. If subjects had at least 1 PD > or =4 mm at baseline, 38% had at least 1 PD deepen by 2 mm or more at follow-up. Only 3% of those who had all teeth with a PD of less than 4 mm at baseline exhibited a change of > or =2 mm (P < .001). CONCLUSION: Increased periodontal PDs > or =2 mm were often found in the third molar region for asymptomatic subjects with at least 1 PD > or =4 mm at enrollment, clinical measures that indicated increased periodontal pathology, and a deteriorating periodontal condition.

Incidence of occlusal dental caries in asymptomatic third molars.

PURPOSE: We sought to determine the incidence of caries experience on the occlusal surface of asymptomatic third molars erupted to the occlusal plane and to examine the association between the prevalence of caries experience in third molars and other molars. PATIENTS AND METHODS: Clinical data were collected from healthy patients (ASA Class I, II) with asymptomatic third molars enrolled at 2 clinical centers in an institutional review board-approved clinical trial. All patients with at least one third molar at the occlusal plane and with data at baseline and from the most recent of at least 2 follow-up visits were compared in the analysis. At each visit, the presence or absence of caries experience on the occlusal surface of third molars and on any surface of the first and second molars was recorded during clinical and radiographic examinations. RESULTS: Median time between baseline and the most recent follow-up examination was 2.9 years (interquartile range, 1.6 to 4.0 years). Patients (N = 211) were more often female (55%) and white (79%). Median age at baseline was 26.6 years (interquartile range, 22.7 to 32.6 years). At baseline, 29% of patients were affected by third molar occlusal caries, increasing to 33% at follow-up. Older patients at baseline had more caries in a third molar than those younger than 25 years (43% versus 9%). However, patients who were younger at baseline were more likely to develop caries in third molars at follow-up (9% versus 19%). Mandibular third molars were affected more often than maxillary third molars: 25% versus 19% at baseline and 29% versus 22% at follow-up. At baseline and at follow-up, nearly all patients with third molar caries, 98% and 99%, also had caries in first/second molars. CONCLUSIONS: The 3-year caries incidence in third molars erupted to the occlusal plane was highest among younger patients and mandibular teeth. The presence of caries in first/second molars at baseline was highly predictive of the development of third molar caries during the ensuing 3 years.

Occlusal caries experience in patients with asymptomatic third molars.

PURPOSE: Our goals were to determine the prevalence of caries experience, carious lesions, or restorations on the occlusal surface, in asymptomatic third molars erupted to the occlusal plane, and to examine the association between caries experience in other molars and third molars within the same mouth and quadrant. PATIENTS AND METHODS: Clinical data assessing oral health were collected from healthy patients (ASA I, II). The presence or absence of caries experience on the occlusal surface of third molars and on any surface of the first and second molars was recorded during clinical and radiographic examinations. The occurrence of caries experience for younger and older subjects was compared using the general association Cochran-Mantel-Haenszel statistic and the association of occurrence in the maxilla and mandible by the McNemar test. The association between caries experience in a third molar and caries experience in first and second molars also was assessed. RESULTS: Overall, 28% of the 303 patients with at least 1 third molar at the occlusal plane were affected by third molar caries. Patients 25 years or older had more caries experience in a third molar than those younger than 25 years, 39% versus 11% (P <.0001). Mandibular third molars were affected more often than maxillary third molars, 24% versus 18% (P <.0001). Nearly all patients, 76 of 80 (95%), with third molar caries experience also had caries experience in first/second molars, but only 80 of 223 (36%) of patients with first/second molar caries experience had a history of third molar caries. CONCLUSIONS: The prevalence of caries in third molars erupted to the occlusal plane in these young patients was high, but not unique to third molars, particularly in those 25 years of age and older. Although these results provide a baseline description of the association between caries experience in first/second molars and associated third molars, data are needed from longitudinal studies to determine the value of first/second molar caries experience in predicting the risk of caries in third molars.

Comprehension and production of gestures by children with normal and impaired language at ages 4, 5, and 6.

12 children with normal verbal language, ages 4, 5, and 6, were matched with 12 children with impaired verbal language. When the two groups were compared for comprehension and production of nonverbal gestures as well as verbal language, the latter group scored more poorly in both areas. Implications for speech-language pathologists and other professionals in the assessment and remediation of language in language-impaired children are mentioned.

Comparison of outcome in patients with acute myocardial infarction aged > 75 years with that in younger patients.

Despite the advancements in reperfusion therapy, elderly patients with acute myocardial infarction (AMI) continue to have higher mortality and complication rates than younger patients. To evaluate this group we reviewed 994 consecutive patients with AMI at our hospital during a 24-month period. There were 307 patients aged > 75 years and 687 younger patients. Demographic analysis of the 2 groups showed that the elderly had a higher proportion of women (56% vs 31%, p < 0.01), more previous AMI (32% vs 23%, p < 0.01), and a higher incidence of bundle branch block (18% vs 8%, p < 0.01). Only 8% of the elderly and 36% of the younger patients were considered eligible for thrombolysis (p < 0.01). In the elderly, risk of bleeding and late presentation were the most common reasons for exclusion from treatment with thrombolytic therapy. Despite a higher proportion of non-Q-wave AMI (56% vs 44%, p < 0.01) in the elderly, the incidence of congestive heart failure (47% vs 23%, p < 0.001) and death (28% vs 11%, p = 0.001) was greater. Causes of death were not significantly different. Increased mortality in the elderly was not due to multisystem failure but to impaired myocardial reserve, suggesting that more aggressive reperfusion strategies may improve prognosis.