Antonis Valachis

Obstetric outcomes after treatment of periodontal disease during pregnancy: systematic review and meta-analysis

Objective To examine whether treatment of periodontal disease with scaling and root planing during pregnancy is associated with a reduction in the preterm birth rate. Design Systematic review and meta-analysis of randomised controlled trials. Data sources Cochrane Central Trials Registry, ISI Web of Science, Medline, and reference lists of relevant studies to July 2010; hand searches in key journals. Study selection Randomised controlled trials including pregnant women with documented periodontal disease randomised to either treatment with scaling and root planing or no treatment. Data extraction Data were extracted by two independent investigators, and a consensus was reached with the involvement a third. Methodological quality of the studies was assessed with the Cochrane’s risk of bias tool, and trials were considered either high or low quality. The primary outcome was preterm birth (<37 weeks). Secondary outcomes were low birthweight infants (<2500 g), spontaneous abortions/stillbirths, and overall adverse pregnancy outcome (preterm birth <37 weeks and spontaneous abortions/stillbirths). Results 11 trials (with 6558 women) were included. Five trials were considered to be of high methodological quality (low risk of bias), whereas the rest were low quality (high or unclear risk of bias). Results among low and high quality trials were consistently diverse; low quality trials supported a beneficial effect of treatment, and high quality trials provided clear evidence that no such effect exists. Among high quality studies, treatment had no significant effect on the overall rate of preterm birth (odds ratio 1.15, 95% confidence interval 0.95 to 1.40; P=0.15). Furthermore, treatment did not reduce the rate of low birthweight infants (odds ratio 1.07, 0.85 to 1.36; P=0.55), spontaneous abortions/stillbirths (0.79, 0.51 to 1.22; P=0.28), or overall adverse pregnancy outcome (preterm births <37 weeks and spontaneous abortions/stillbirths) (1.09, 0.91 to 1.30; P=0.34). Conclusion Treatment of periodontal disease with scaling and root planing cannot be considered to be an efficient way of reducing the incidence of preterm birth. Women may be advised to have periodical dental examinations during pregnancy to test their dental status and may have treatment for periodontal disease. However, they should be told that such treatment during pregnancy is unlikely to reduce the risk of preterm birth or low birthweight infants.

Overall survival benefit for weekly vs three-weekly taxanes regimens in advanced breast cancer: a meta-analysis

BACKGROUND Taxanes have been extensively tested in patients with advanced breast cancer, but it is unclear whether their weekly use might offer any benefits against standard every three weeks administration. We therefore performed a meta-analysis of randomized controlled trials that compared weekly and every three weeks taxanes regimens in advanced breast cancer. METHODS The endpoints that we assessed were objective response rate, progression free survival (PFS) and overall survival. Efficacy data for paclitaxel and docetaxel were separately analyzed. Trials were located through PubMed and Cochrane Library searches and abstracts of major international conferences. RESULTS Omicronbjective response rate was notably better when paclitaxel was used as every three weeks regimen (7 studies, 1772 patients, fixed effect model pooled RR 1.20 95%CI 1.08-1.32 p<0.001). No difference were found for PFS (6 studies, 1610 patients, random effect model HR 1.02, 95%CI 0.81-1.30 p=0.860); while OS was statistically higher among patients receiving weekly paclitaxel (5 studies, 1471 patients, fixed effect model pooled HR 0.78, 95%CI 0.67-0.89 p=0.001). No differences were observed for the weekly compared to the every three weeks use of docetaxel either for objective response, PFS and OS. Overall, the incidence of serious adverse events, neutropenia, neutropenic fever, and peripheral neuropathy were significantly lower in weekly taxanes schedules. The incidence of nail changes and epiphora were significantly lower in the every three weeks docetaxel regimens. CONCLUSIONS Use of paclitaxel in weekly regimen give overall survival advantages compared with the standard every three weeks regimen. The observed survival benefit does not seem to stem from an increased potency of the drug with weekly regimens. The use of weekly paclitaxel regimens is therefore recommended for the treatment of locally advanced/metastatic breast cancer.

The role of aerosolized colistin in the treatment of ventilator-associated pneumonia: a systematic review and metaanalysis.

Objectives:The present meta-analysis and systematic review evaluated the efficacy and safety of aerosolized colistin as adjunctive therapy to IV antimicrobials or as monotherapy in the treatment of ventilator-associated pneumonia. Design:The databases of MEDLINE and Cochrane Library up to June 2013 and all reference lists of the included studies and relevant reviews were searched. Studies were eligible if the efficacy and safety of aerosolized colistin in the treatment of ventilator-associated pneumonia was evaluated. An overall effect estimate for all dichotomous data as an odds ratio with 95% CI was calculated by the Mantel-Haenszel or the DerSimonian and Laird method depending on the statistical heterogeneity. The Grading of Recommendations Assessment, Development, and Evaluation approach was used to interpret the findings. Interventions:None. Measurements and Main Results:Sixteen studies fulfilled the inclusion criteria: eight were comparing adjunctive aerosolized versus IV colistin (seven observational cohort or case-control studies and one randomized trial) and were meta-analyzed, and eight were single arm and were only systematically reviewed. The Grading of Recommendations Assessment, Development, and Evaluation approach showed limitations of the study design and presence of inconsistency in most of the outcomes, but no obvious indirectness or imprecision of results reporting. Based on the above assessments, the quality of evidence presented for each outcome ranged from “very low” to “low.” A significant improvement in clinical response (odds ratio, 1.57; 95% CI, 1.14–2.15; p = 0.006; I2 = 37%), microbiological eradication (odds ratio, 1.61; 95% CI, 1.11–2.35; p = 0.01; I2 = 0%), and infection-related mortality (odds ratio, 0.58; 95% CI, 0.34–0.96; p = 0.04; I2 = 46%) was observed with the addition of aerosolized colistin to IV treatment, whereas the addition of aerosolized colistin did not affect overall mortality (odds ratio, 0.74; 95% CI, 0.54–1.01; p = 0.06; I2 = 25%) or nephrotoxicity (odds ratio, 1.18; 95% CI, 0.76–1.83; p = 0.45; I2 = 0%). Conclusion:Based on the present results and awaiting further evidence from randomized trials, aerosolized colistin is associated with improved outcome in the treatment of ventilator-associated pneumonia although the level of evidence was low.

Trastuzumab combined to neoadjuvant chemotherapy in patients with HER2-positive breast cancer: A systematic review and meta-analysis

PURPOSE To perform a meta-analysis in order to quantify the actual cumulative randomized evidence for the benefit and toxicity of trastuzumab combined with neoadjuvant chemotherapy in HER2-positive breast cancer. METHODS Potentially eligible trials were located through PubMed and Cochrane Library searches and abstracts of major international conferences. The endpoints that we assessed were pathologic complete response (pCR) rate, breast-conserving surgery (BCS) rate and toxicity. RESULTS Five trials were identified with 515 eligible patients. The probability to achieve pCR was higher for the trastuzumab plus chemotherapy arm (RR 1.85, 95% CI: 1.39-2.46; p-value < 0.001). No significant difference in terms of breast-conserving surgery between the two treatment arms was observed (OR: 0.98, 95% CI: 0.80-1.19, p-value = 0.82). Regarding toxicity, the addition of trastuzumab did not increase the incidence of neutropenia, neutropenic fever, and cardiac adverse events. CONCLUSION The addition of trastuzumab in HER2-positive breast cancer in the neoadjuvant setting improves the probability of achieving higher pCR with no additional toxicity. Based on the available evidence, the use of trastuzumab combined with neoadjuvant chemothetherapy in patients with HER2-positive breast cancer seems to offer substantial benefit in terms of pCR.

Safety of Pregnancy After Primary Breast Carcinoma in Young Women: A Meta-Analysis to Overcome Bias of Healthy Mother Effect Studies

Background: An increased number of women are expected to conceive after the diagnosis of early breast cancer. Most physicians recommend that pregnancy be delayed by 2 to 3 years after diagnosis of early breast cancer, but this recommendation is based on data from trials with small patient cohorts. Furthermore, a healthy mother effect (HME) selection bias may be operative in most of these studies, because women undergoing childbearing after treatment were healthier when compared with the control group. Aim: To perform a systematic review and meta-analysis of published trials corrected for HME bias so as to assess the effect of pregnancy (at least 10 months after diagnosis) versus no pregnancy on overall survival of primary breast cancer patients less than 45 years. Methods: We searched MEDLINE and Thomson Reuters (ISI) Web of Knowledge for eligible studies. From each study we extracted the relative hazard ratio or, if not provided, all the necessary data to impute it. In cases where the duration from diagnosis to pregnancy was not reported, we extracted relevant data to estimate it. Results: Our electronic search strategy yielded 1623 hits pertaining to 20 potentially eligible studies involving 49,370 premenopausal breast cancer patients. Ten studies were eligible after considering HME potential bias in matching controls. Among these, 9 studies (pregnant 1089, matched-controls 13051) contained data appropriate for analysis. Overall survival was statistically higher among patients who became pregnant compared to controls: fixed effect model estimated pooled hazard ratio for death 0.51 (95% confidence interval: 0.42–0.62). No study heterogeneity was observed: Q = 10.4, P = 0.17; I2 = 48%. Conclusion: The pooled available evidence indicates that in early breast cancer patients, pregnancy that occurs at least 10 months after diagnosis does not jeopardize prognosis and may actually confer significant survival benefit. Target Audience: Obstetricians & Gynecologists, Family Physicians Learning Objectives: After completing this CME activity, physicians should be better able to assess the effect pregnancy has on long-term survival in primary breast cancer patients under age 45; counsel patients on the safety of pregnancy after breast cancer diagnosis and treatment; and interpret how pregnancy may be associated with improved breast cancer survival.

Partial breast irradiation or whole breast radiotherapy for early breast cancer: a meta-analysis of randomized controlled trials.

Abstract:  The purpose of the study was to compare treatment outcomes in patients with breast cancer treated with partial breast irradiation (PBI) and of those treated with whole breast‐radiation therapy (WBRT). We conducted a systematic review and meta‐analysis of published randomized clinical trials comparing PBI versus WBRT. Primary outcome was overall survival and secondary outcomes were locally, axillary, supraclavicular, and distant recurrences. A search of the literature identified three trials with pooled total of 1,140 patients. We found no statistically significant difference between partial and whole breast radiation arms associated with death (OR 0.912, 95% CI 0.674–1.234, p = 0.550), distant metastasis (OR 0.740, 95% CI, 0.506–1.082, p = 0.120), or supraclavicular recurrences (pooled OR 1.415, 95% CI 0.278–7.202, p = 0.560). However, PBI was statistically significantly associated with an increased risk of both local (pooled OR 2.150, 95% CI, 1.396–3.312; p = 0.001) and axillary recurrences (pooled OR 3.430, 95% CI, 2.058–5.715; p < 0.0001) compared with whole breast‐radiation. Partial breast irradiation does not seem to jeopardize survival and may be used as an alternative to whole breast‐radiation. Nevertheless the issue of loco‐regional recurrence needs to be further addressed.

Adjuvant Therapy With Zoledronic Acid in Patients With Breast Cancer: A Systematic Review and Meta-Analysis

BACKGROUND The purpose of the study was to estimate the impact on survival and fracture rates of the use of zoledronic acid versus no use (or delayed use) in the adjuvant treatment of patients with early-stage (stages I-III) breast cancer. MATERIALS AND METHODS We performed a systematic review and meta-analysis of randomized clinical trials. Trials were located through PubMed, ISI, Cochrane Library, and major cancer scientific meeting searches. All trials that randomized patients with primary breast cancer to undergo adjuvant treatment with zoledronic acid versus nonuse, placebo, or delayed use of zoledronic acid as treatment to individuals who develop osteoporosis were considered eligible. Standard meta-analytic procedures were used to analyze the study outcomes. RESULTS Fifteen studies were considered eligible and were further analyzed. The use of zoledronic acid resulted in a statistically significant better overall survival outcome (five studies, 6,414 patients; hazard ratio [HR], 0.81; 95% confidence interval [CI], 0.70-0.94). No significant differences were found for the disease-free survival outcome (seven studies, 7,541 patients; HR, 0.86; 95% CI, 0.70-1.06) or incidence of bone metastases (seven studies, 7,543 patients; odds ratio [OR], 0.94; 95% CI, 0.64-1.37). Treatment with zoledronic acid led to a significantly lower overall fracture rate (OR, 0.78; 95% CI, 0.63-0.96). Finally, the rate of osteonecrosis of the jaw was 0.52%. CONCLUSION Zoledronic acid as adjuvant therapy in breast cancer patients appears to not only reduce the fracture risk but also offer a survival benefit over placebo or no treatment.

Intraperitoneal dissemination of endometrial cancer cells after hysteroscopy: a systematic review and meta-analysis

Introduction: Hysteroscopy is a diagnostic procedure with a high accuracy in diagnosing endometrial cancer. Because of the increase of intrauterine pressure during distention media inflation, several retrospective studies postulated that it may result in cancer cell dissemination within the peritoneal cavity through the fallopian tubes. We therefore set to estimate whether hysteroscopy increases the risk for intraperitoneal cancer cell dissemination in patients with endometrial cancer and the risk of disease upstaging in patients with clinically early-stage disease. Methods: We searched the PubMed, the ISI Web of Science, and the Cochrane Library through July 2009. Eligible trials were all controlled clinical trials in which patients were allocated to hysteroscopy (alone or after other diagnostic procedure, eg, dilation and curettage and biopsy) versus any other diagnostic procedure except hysteroscopy or no procedure before surgery for endometrial carcinoma. Results: Nine trials were included in our analysis. One thousand fifteen patients with histologically proven endometrial carcinoma were allocated to hysteroscopy or no hysteroscopy before surgery. Hysteroscopy resulted in a significantly higher rate of malignant peritoneal cytology (odds ratio [OR], 1.78; 95% confidence interval [CI], 1.13-2.79; P = 0.013) and significantly higher disease upstaging owing solely to the presence of malignant cells in the peritoneal cavity (OR, 2.61; 95% CI, 1.47-4.63; P = 0.001) compared with no hysteroscopy. When isotonic sodium chloride was used as distention medium, hysteroscopy resulted in a statistically significant higher rate of malignant peritoneal cytology (OR, 2.89; 95% CI, 1.48-5.64; P = 0.002), whereas a nonsignificant trend for higher malignant cells was observed in patients allocated to the hysteroscopy group (OR, 3.23; 95% CI, 0.94-11.09; P = 0.062) when inflated media pressure reached or exceeded 100 mm Hg. Conclusions: Hysteroscopy in patients with endometrial cancer hints a risk for cancer cell dissemination within the peritoneal cavity. Prospective and sufficiently powered trials are needed to clarify whether the risk of cancer cell spreading is correlated with worse prognosis.

Financial Relationships in Economic Analyses of Targeted Therapies in Oncology

PURPOSE A potential financial relationship between investigators and pharmaceutical manufacturers has been associated with an increased likelihood of reporting favorable conclusions about a sponsors proprietary agent in pharmacoeconomic studies. The purpose of this study is to investigate whether there is an association between financial relationships and outcome in economic analyses of new targeted therapies in oncology. MATERIALS AND METHODS We searched PubMed (last update June 2011) for economic analyses of targeted therapies (including monoclonal antibodies, tyrosine-kinase inhibitors, and mammalian target of rapamycin inhibitors) in oncology. The trials were qualitatively rated regarding the cost assessment as favorable, neutral, or unfavorable on the basis of prespecified criteria. RESULTS Overall, 81 eligible studies were identified. Economic analyses that were funded by pharmaceutical companies were more likely to report favorable qualitative cost estimates (28 [82%] of 34 v 21 [45%] of 47; P = .003). The presence of an author affiliated with manufacturer was not associated with study outcome. Furthermore, if only studies including a conflict of interest statement were included (66 of 81), studies that reported any financial relationship with manufacturers (author affiliation and/or funding and/or other financial relationship) were more likely to report favorable results of targeted therapies compared with studies without financial relationship (32 [71%] of 45 v nine [43%] of 21; P = .025). CONCLUSION Our study reveals a potential threat for industry-related bias in economic analyses of targeted therapies in oncology in favor of analyses with financial relationships between authors and manufacturers. A more balanced funding of economic analyses from other sources may allow greater confidence in the interpretation of their results.

Lack of evidence for fracture prevention in early breast cancer bisphosphonate trials: A meta-analysis

OBJECTIVES Recent data suggest that fractures might affect quality of life and survival in early breast cancer patients. Bisphosphonates are effective in treatment and prevention of cancer treatment-induced bone loss, but their value in the prevention of fractures is still investigational. Our aim was to evaluate the fracture rate in breast cancer patients receiving adjuvant bisphosphonates compared with those receiving no treatment or placebo. METHODS Our study is a systematic review and meta-analysis of randomized clinical trials. Trials were located through PubMed, ISI, Cochrane Library and major cancer scientific meetings searches. We identified 21 potentially eligible trials. Of these, 14 studies reported fracture data and were included in the analyses. Overall, 7461 early breast cancer patients were randomized, 3691 received bisphosphonates and 3770 received either placebo or no treatment. RESULTS Adjuvant breast cancer treatment with bisphosphonates did not reduce the fracture rate compared to placebo or no use either in intent to treat analysis (12 trials, OR=0.99, 95% CI=0.73-1.34, p=0.932) and in comprehensive analysis (all 14 trials included, OR=0.84, 95% CI=0.65-1.09 p=0.197). Treatment with bisphosphonates was not beneficial in postmenopausal patients (7 trials, OR=0.82, 95% CI=0.55-1.20 p=0.298) and in patients receiving aromatase inhibitors (6 trials, OR=0.79, 95% CI=0.53-1.17 p=0.242). CONCLUSION Our meta-analysis provides substantial evidence that bisphosphonates in the adjuvant setting among women with breast cancer do not decrease the number of fractures compared with placebo or no treatment.