Economic evaluation of school-based caries preventive programs: A systematic review.

OBJECTIVE: Assess interventions and health outcomes in studies giving data on economic evaluation (EE) of school-based caries prevention. BASIC RESEARCH DESIGN: Systematic review. Both partial EE that included cost description, cost-outcome description, cost analysis and full EE that included both cost and outcome of at least 2 interventions were included. Quality assessment used the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) guidelines. RESULTS: An electronic search of 6 databases identified 558 titles and abstracts. Paper eligibility screening identified 32 full papers which met the inclusion criteria. Most were conducted in the United States and cost effectiveness analysis was the most common type of EE. Nine were model-based studies and 17 derived their data from single studies. Sealants were most frequently evaluated followed by fluoride mouthrinse. Many CHEERS criteria were not met in the included studies. The following were found to be cost-effective: school-based, under general supervision, longer duration of program and targeting high caries risk groups. CONCLUSIONS: The deficiencies in the existing studies warrant more investigations of the economic aspects of school-based activities interventions to prevent caries.

Plasmid CDS5 influences infectivity and virulence in a mouse model of Chlamydia trachomatis urogenital infection.

The native plasmid of both Chlamydia muridarum and Chlamydia trachomatis has been shown to control virulence and infectivity in mice and in lower primates. We recently described the development of a plasmid-based genetic transformation protocol for Chlamydia trachomatis that for the first time provides a platform for the molecular dissection of the function of the chlamydial plasmid and its individual genes or coding sequences (CDS). In the present study, we transformed a plasmid-free lymphogranuloma venereum isolate of C. trachomatis, serovar L2, with either the original shuttle vector (pGFP::SW2) or a derivative of pGFP::SW2 carrying a deletion of the plasmid CDS5 gene (pCDS5KO). Female mice were inoculated with these strains either intravaginally or transcervically. We found that transformation of the plasmid-free isolate with the intact pGFP::SW2 vector significantly enhanced infectivity and induction of host inflammatory responses compared to the plasmid-free parental isolate. Transformation with pCDS5KO resulted in infection courses and inflammatory responses not significantly different from those observed in mice infected with the plasmid-free isolate. These results indicate a critical role of plasmid CDS5 in in vivo fitness and in induction of inflammatory responses. To our knowledge, these are the first in vivo observations ascribing infectivity and virulence to a specific plasmid gene.

Prevalence of clinical consequences of untreated dental caries and its relation to dental fear among 12-15-year-old schoolchildren in Bangalore city, India.

PURPOSE: To investigate the prevalence of clinical consequences of untreated dental caries and its relation to dental fear among public schoolchildren in India. METHOD: A cross-sectional study of 1,452 schoolchildren aged 12-15-years in Bangalore city using a three-stage stratified random sample was conducted. Caries was scored by WHO (World Health Organisation) criteria (1997) and clinical consequences of untreated dental caries using the PUFA index. Dental fear was assessed by a single item dental fear questionnaire. RESULTS: The overall prevalence of caries was 57.9% and of untreated dental caries was 19.4%. Children with high dental fear had 2.05 times the risk of untreated caries as compared to children with low fear. CONCLUSIONS: This study showed that the prevalence of clinical consequences of untreated dental caries was low, and dental fear was shown to be a significant determinant of clinical consequences of untreated dental caries.

Dental trauma in children with disabilities in India: a comparative study.

AIM: To investigate and describe the characteristics of traumatic dental injury (TDI) in children with disabilities attending special schools in Bangalore, India and to compare these with a matched group of healthy children. METHODS: The sample included 231 children with disabilities aged 6-16 years and 231 age- and sex-matched healthy children. Data were collected through clinical examinations according to the modified Ellis classification of TDI. RESULTS: All the dental injuries involved maxillary incisor teeth, and trauma was noted in 12.1 % of disabled children as compared to 6.9 % among the control group which showed statistical significance. There was no difference in the distribution of traumatic injuries between the genders and no difference in the mean age was found between the study and the control groups. Simple fractures involving little or no dentine were the most frequent type of injury. CONCLUSIONS: The data suggest that the TDI prevalence in children with disability was higher than that of non-disabled children.

Mast cell/IL-4 control of Francisella tularensis replication and host cell death is associated with increased ATP production and phagosomal acidification.

Mast cells are now recognized as effective modulators of innate immunity. We recently reported that mast cells and secreted interleukin-4 (IL-4) effectively control intramacrophage replication of Francisella tularensis Live Vaccine Strain (LVS), and that mice deficient in mast cells or IL-4 receptor (IL-4R(-/-)) exhibit greater susceptibility to pulmonary challenge. In this study, we further evaluated the mechanism(s) by which mast cells/IL-4 control intramacrophage bacterial replication and host cell death, and found that IL-4R(-/-) mice exhibited significantly greater induction of active caspase-3 within lung macrophages than wild-type animals following intranasal challenge with either LVS or the human virulent type A strain SCHU S4. Treatment of LVS-infected bone-marrow-derived macrophages with a pancaspase inhibitor (zVAD) did not alter bacterial replication, but minimized active caspase-3 and other markers (Annexin V and propidium iodide) of cell death, whereas treatment with both rIL-4 and zVAD resulted in concomitant reduction of both parameters, suggesting that inhibition of bacterial replication by IL-4 was independent of caspase activation. Interestingly, IL-4-treated infected macrophages exhibited significantly increased ATP production and phagolysosomal acidification, as well as enhanced mannose receptor upregulation and increased internalization with acidification, which correlated with observations in mast cell-macrophage co-cultures, with resultant decreases in F. tularensis replication.

Donepezil treatment of patients with MCI: a 48-week randomized, placebo-controlled trial.

BACKGROUND: Treatment of mild cognitive impairment (MCI) with cholinesterase inhibitors may improve symptoms. METHODS: In this multicenter, randomized, placebo-controlled trial, subjects with MCI entered a 3-week placebo run-in period followed by 48 weeks of double-blind donepezil (5 mg/day for 6 weeks, then 10 mg/day for 42 weeks) or placebo treatment. Primary efficacy variables included change from baseline in the modified Alzheimer Disease Assessment Scale-cognitive subscale (ADAS-Cog) and Clinical Dementia Rating Scale-sum of boxes (CDR-SB) after 48 weeks of treatment (modified intention-to-treat analysis). Secondary efficacy measures evaluated cognition, behavior, and function. RESULTS: The dual primary efficacy endpoint was not reached. We noted a small, but significant, decrease in modified ADAS-Cog scores in favor of donepezil at study endpoint. Little change from baseline in CDR-SB and secondary variables was observed for either group. Patient Global Assessment scores favored donepezil at all time points except week 12 (p < or = 0.05). Perceived Deficits Questionnaire scores favored donepezil at week 24 (p = 0.05). Clinical Global Impression of Change-MCI scores favored donepezil only at week 6 (p = 0.04). Adverse events were generally mild or moderate. More donepezil-treated subjects (18.4%) discontinued treatment due to adverse events than placebo-treated subjects (8.3%). CONCLUSIONS: Donepezil demonstrated small but significant improvement on the primary measure of cognition but there was no change on the primary measure of global function. Most other measures of global impairment, cognition, and function were not improved, possibly because these measures are insensitive to change in MCI. Responses on subjective measures suggest subjects perceived benefits with donepezil treatment.

Seed Transmission of Indian Peanut Clump Virus (IPCV) in Peanut and Millets.

An enzyme-linked immunosorbent assay (ELISA) procedure was developed to test peanut seed for Indian peanut clump virus (IPCV). A double antibody sandwich form of ELISA detected the Hyderabad isolate (IPCV-H) in seed of peanut. Correlation was established between the results from ELISA performed on cotyledons of peanut seed and grow-out tests. Seed transmission in the field-infected peanut plants ranged from 3.5 to 17%, depending on the genotype. The transmission frequency was 48 to 55% in seed collected from plants infected through seed. Because testae of all seed contained viral antigen, their removal was essential for the determination of frequency of seed transmission. Apparently the virus present only in cotyledons and embryo contributed to the seed transmission. For the first time, IPCV-H was shown to be seed transmitted in finger millet (Eleusine coracana), foxtail millet (Setaria italica), and pearl millet (Pennisetum glaucum) at frequencies of 5.2, 9.7, and 0.9%, respectively. Seed transmission was not observed in sorghum (Sorghum bicolor). Significance of seed transmission in millet crops is discussed.

Concomitant cisplatin/5-FU infusion and radiotherapy in advanced head and neck cancer: 8-year analysis of results.

BACKGROUND: The purpose of this study was to analyze long-term follow-up of a single institution's experience with a regimen of concomitant cisplatin/fluorouracil (5-FU) infusion and radiation given every other week. This analysis was stimulated by results of a randomized trial showing superiority for this regimen over induction cisplatin/5-FU chemotherapy followed by radiotherapy, especially in regional disease control. METHODS: All patients with stage III/IV disease who were referred by surgeons for nonoperative therapy and had a follow-up of at least 2 years were included. Concomitant chemoradiotherapy was administered days 1-5 of a 2-week treatment cycle, for a total of 7 cycles, with cisplatin 60 mg/m2 day 1, 5-FU 800 mg/m2 given over 24 hours days 1-5, and radiation 2 Gy days 1-5. RESULTS: Seventy-eight patients with stage III (n = 16) or IV (n = 62) were treated and followed for a median of 8 years. Six patients died during treatment, of aspiration pneumonia, sudden death, gastrointestinal bleeding, and stroke. When assessed 6 weeks after the end of treatment, 45 patients (63%) had no clinical evidence of disease, whereas 27 (37%) still had some persistent abnormality. However, 17 of these "partial responders" have not recurred. In all, 24 patients (31%) have recurred or progressed, 13 at the primary site, 5 after 3 years. None of 16 stage III and 24 (39%) of 62 stage IV patients ever progressed. Tongue and glottic larynx did best, with only 1 of 22 patients ever failing (none locally). Supraglottic and oral cavity cancers other than tongue had the worst failure rates. Nineteen patients (24%) died of other causes (DOC), tumor-free. Patients who DOC correlated strongly with T stage (p < .002) but not with N stage or with AJC stage. The 5-year progression-free survival was 60% (confidence interval [CI] = 49% to 72%), and overall survival was 43% (CI = 33% to 56%). CONCLUSIONS: Disease control for this advanced head and neck cancer population was excellent. This regimen was especially effective in advanced tongue and glottic cancers and all stage III disease sites. Advanced supraglottic and hypopharynx cancers are problematic. These, and especially T4 lesions, are associated with high DOC rates, possibly in part related to swallowing malfunction. Nevertheless, the long-term survival without surgical intervention was high with this regimen.

Integration of surgery in multimodality therapy for esophageal cancer.

BACKGROUND: While adding chemotherapy to radiation for the treatment of esophageal cancers has been shown to be beneficial, surgery usually follows treatment or is omitted. In either case, regional control remains problematic. The purpose of this study was to test the feasibility of using chemotherapy and radiation following surgery in the treatment of of esophageal cancer and to assess the impact of this approach on regional control and survival. PATIENTS AND METHODS: Twenty-five patients with esophageal cancer were treated in a phase I pilot protocol consisting of initial esophagectomy with gastroesophagostomy and subsequent combined chemotherapy and radiation. Chemotherapy consisted of cisplatin given on day 1 and 5-fluorouracil (FU) on days 1-5 by continuous infusion. Radiation therapy was administered in varying fractionation schedules of once or twice daily concomitantly with the chemotherapy. Treatment was repeated every other week for two to four cycles. Median follow-up was 42 months. RESULTS: Acute toxicities (mucositis and cytopenias) were common but not worse than grade 3. Higher doses of 50 Gy with 2 Gy b.i.d. hyperfractionation caused late complications in four of 10 patients, (two lethal). Control of local disease for all patients was excellent with only two known and two possible local recurrences (16%) but distant metastases were common (46%). Disease-free survival was 58 and 30% at 1 and 2 years, respectively. Survival was 58 and 32% at 1 and 2 years, respectively (median survival, 19 months). CONCLUSION: The local control rate and survival were better than those in our historical experience with cisplatin and 5-FU chemotherapy and radiation given prior to surgery. A dose-fractionation schedule of < 2 Gy up to a total of 50 Gy b.i.d. is recommended to avoid late adverse effects. The role of surgery will be defined by randomized studies. Better systemic therapy is needed to impact on systemic failure.

Delaying the initiation of intact breast irradiation for patients with lymph node positive breast cancer increases the risk of local recurrence.

BACKGROUND: The impact of delaying irradiation to the intact breast for patients receiving chemotherapy for lymph node positive breast cancer is controversial. METHODS: From 1974 to 1989, 474 patients underwent lumpectomy and intact breast irradiation for early stage invasive breast cancer. Chemotherapy was administered to 84 patients (1 patient with bilateral breast cancer) because of positive axillary lymph nodes. Time from definitive breast surgery (lumpectomy or reexcision) to the initiation of breast irradiation was 21-314 days, with a median of 124 days. Forty-two patients began receiving radiation therapy before 120 days (early) and 42 more than 120 days after surgery (delayed). In the early group, cyclophosphamide/methotrexate/5-fluorouracil (CMF) was administered to 32 patients, doxorubicin, cyclophosphamide or cyclophosphamide, doxorubicin, 5-fluorouracil (AC or CAF) to 6 patients, and other regimens to 4 patients; in the delayed group, CMF was given to 29 patients, CAF to 12 patients, and L-PAM/5-fluorouracil to 1 patient. RESULTS: Median follow-up was 62 months. There was one breast recurrence in the early group, compared with six in the patients receiving delayed irradiation. The actuarial relapse rates for these groups at 5 years were 2% and 14%, respectively (P = 0.05). Survival and distant disease free survival were not significantly different between the two groups. CONCLUSIONS: Delays in the initiation of irradiation are associated with increased risk of relapse in the breast. When possible, the interval between definitive breast surgery (lumpectomy or reexcision) and the initiation of radiation therapy should be fewer than 120 days.

Should multicentric disease be an absolute contraindication to the use of breast-conserving therapy?

PURPOSE: Multicentric cancer is present in a large proportion of mastectomies performed as treatment of breast cancer; it has been considered a contraindication to breast conservation. METHODS AND MATERIALS: We reviewed the records of our patients with Stage I or II breast cancer treated with breast conserving surgery and radiation therapy over a 13-year period. Twenty-seven patients had two or more nodules of grossly visible cancer separated by histologically normal breast tissue. All patients had grossly negative margins of excision; however, four patients had microscopically positive margins. Nine patients had positive axillary nodes. All patients received radiation therapy to the breast postoperatively, with a median dose of 50.4 Gy in 28 fractions; 11 patients also received a boost dose of 6-20 Gy to the tumor bed. Eleven patients were given adjuvant chemotherapy and one patient was given adjuvant tamoxifen. RESULTS: With a median follow-up of 53 months, only one patient has relapsed in the breast (3.7%); that patient relapsed in multiple distant sites at the same time. Three patients have died of disseminated disease; the actuarial survival and disease-free survival rates at 4 years are 89%. CONCLUSION: Breast conservation may be considered for patients with multicentric breast cancer discovered at the time of histologic examination. For patients with multicentric disease detected prior to surgery, breast conserving therapy may be appropriate as long as: (1) all clinically and radiographically apparent abnormalities are removed, (2) clear margins of resection are achieved, and (3) there is no extensive intraductal component.

Pilot study for the evaluation of simultaneous cisplatin/5-fluorouracil infusion and limited radiation therapy in regionally recurrent head and neck cancer (EST P-C385).

From 1981 to 1989, 21 patients with heavily pretreated head and neck cancers were retreated with combined chemotherapy (CT) and irradiation (RT). All patients had previously received radiation therapy with doses of 50-70 Gy. Metastatic disease to lungs and/or osseous sites occurred in 4 patients. Treatment consisted of simultaneous cisplatin, 5-fluorouracil, and external beam radiation therapy, with planned doses of 20 to 70 Gy. The RT+CT was given over 5 consecutive days every 2 weeks. Four patients did not complete treatment due to toxicity (2 patients) or disease progression (2 patients). All patients developed grade 2-3 mucositis. Because of toxicity, 11 patients required treatment delays of 1 to 3 weeks. Clinically complete responses were noted in 10 patients (48%), with partial responses occurring in 5 patients (24%). Of the 21 patients, 18 have died: 13 had local and/or regional recurrence, 2 died of treatment toxicity and 3 died of intercurrent disease. Median time to progression was 5 months (range: 1-15 months). Three patients remain alive with no evidence of disease at 44, 86, and 88 months after retreatment.

Randomized comparison of neoadjuvant cisplatin and fluorouracil infusion followed by radiation versus concomitant treatment in advanced head and neck cancer.

PURPOSE: To compare two published schedules of cisplatin plus fluorouracil (5-FU) infusion and radiation as either sequential or concomitant treatment for toxicity and efficacy in patients with unresectable head and neck cancer. PATIENTS AND METHODS: This was a randomized trial between cisplatin 100 mg/m2 over 15 minutes on day 1 plus 5-FU 1.0 g/m2 by continuous infusion on days 1 to 5, repeated every 3 weeks for three cycles, followed by 70 Gy of radiation in 7 to 8 weeks, versus cisplatin 60 mg/m2 over 15 minutes on day 1 plus 5-FU 800 mg/m2 by continuous infusion on days 1 to 5 plus radiation 2 Gy on days 1 to 5, repeated every other week for seven cycles. Unresectable head and neck squamous cancer patients not previously treated with radiation or chemotherapy and with a performance status of 0 to 2 were stratified by tumor (T) and node (N) groupings and performance status and randomized. RESULTS: Two hundred fifteen patients were entered and 214 analyzed, 107 on each arm. After all treatment, overall response rates were different (P = .003), with similar complete response rates, but more partial responses and fewer patients with no change or progression with concomitant treatment. Cox regression analysis for progression-free survival identified concomitant treatment (P = .003), Radiation Therapy Oncology Group (RTOG) stage III grouping (P < .0001), performance status (P = .0002), concomitant treatment (P = .003), and treating institution (P = .006) as significant. The sequential and concomitant treatments showed similar distant failure patterns (10% and 7%, respectively), but divergent regional failure rates (55% and 39%). Severe and worse toxic events were similar between the treatment programs, but radiation-induced mucositis combined with cisplatin-induced water-losing nephropathy, in the concomitant arm only, demanded more supportive care. Survival duration was similar between the treatment arms, but significantly more patients in the sequential arm died of their cancer (P = .011). CONCLUSION: Concomitant treatment offered improved disease control, predominantly of regional disease, but benefit was dependent on the experience of the treating institution. Translation of this benefit into improved survival is not yet evident, with an excess of deaths from other causes in the concomitant arm.

Endodermal sinus tumor: report of 12 cases.

Twelve cases of endodermal sinus tumor were reviewed. There were 10 females and 2 males with a median age at presentation of 3 years. The primary site was sacrococcygeal in 4 patients, vaginal in 3, retroperitoneal in 2, and testicular, ovarian and left chest wall in one each. The diagnosis rested on histopathological examination and elevation of serum alfa feto protein levels (median 46,200 ng/ml). Two patients had Stage I disease, 9 had Stage III and one had Stage IV disease. Patients were managed by surgery and chemotherapy (BVP regime). All patients on BVP (even those lost at later stages), had achieved clinical remission with the first cycle of treatment.

Long-term results of curative irradiation in pathologically staged IA and IIA Hodgkin disease.

One hundred seventy-six patients with pathologically staged IA and IIA Hodgkin disease (HD) treated with irradiation alone were evaluated for long-term survival and freedom from relapse (FFR). Most of the patients received treatment to mantle and paraaortic fields; chemotherapy was not given except as salvage therapy. For pathologically staged IA disease, the 5-, 10-, and 15-year survival rates were 94%; the corresponding FFR rates were 96%, 93%, and 93%. For pathologically staged IIA disease, respective survival rates were 93%, 89%, and 80%, with FFR rates of 86%, 84%, and 84%. Twenty-one patients (12%) had relapse of HD; salvage therapy was successful in 11 of these patients. Pelvic recurrence was uncommon (three of 176 cases [2%]). No patient developed leukemia, and only two patients developed second malignancies (lung cancer in both cases). The authors conclude that radiation therapy is effective in treatment of early-stage HD.

Concomitant chemotherapy and split-course radiation for cure and preservation of speech and swallowing in head and neck cancer.

To assess the ability of simultaneous cisplatin, 5-Fluorouracil, and radiation to substitute for surgery and radiation in advanced head and neck cancer, we have retrospectively selected from our phase II study a subgroup of 29 patients having primary disease requiring either more than a hemiglossectomy or a laryngectomy for control. Patients included 22 with stage IV and 7 with stage III disease, 12 tongue, 10 hypopharynx, and 7 larynx primaries. The treatment consisted of concurrent cisplatin, 5-Fluorouracil, and split-course radiation every other week for a total of 7 cycles within 13 weeks. With a median follow-up of 5 years, 86% of patients had preservation of speech and/or swallowing function. Median survival was 45 months, with 14 (48%) patients currently alive and disease free, 11 (38%) dead from their cancer, and 4 (14%) dead of other causes. The overall failure rate was 38%. Advanced-stage presence of N3 nodal disease and fewer than 7 cycles of chemotherapy received were significantly associated with increasing failure rates. This program of concomitant cisplatin, 5-Fluorouracil, and radiation produced control rates quite competitive with surgery and radiation and is appropriate for definitive testing in a randomized trial.

Peripheral nerve sheath tumours: an ultrastructural study of 30 cases.

This report deals with the ultrastructural observations of 30 peripheral nerve sheath tumours [PNST], which include 25 schwannomas of acoustic nerve, one schwannoma of cauda equina, one neurofibroma from a case of Von Recklinghausen's disease, one pigmented neurofibroma of spinal nerve root and a malignant schwannoma of frontal region. Interdigitating slender cytoplasmic processes covered with a continuous layer of basal lamina constitute the single most important ultrastructural attribute of Schwann cells. Myelin formation was encountered in the cell processes of four out of 25 acoustic schwannomas. In four cases Microtubular arrays identical to that in an axon were seen in Schwann cells. These two observations require further support by additional cases of PNST studies by electron microscopy. The neurofibroma consisted only of Schwann cells and no ultrastructurally identifiable perineurial cells or fibroblasts were detected. The cells in the pigmented neurofibroma revealed submicroscopic features of both Schwann cell and melanocyte, indicating their common ancestry. A unique case of malignant schwannoma arising from frontal meninges is illustrated and it is emphasized that electron microscopy is mandatory for a correct histogenetic diagnosis of malignant tumours which occur at unexpected anatomical sites.