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OBJECTIVES: Patterns of disease recurrence on poly(ADP-ribose) polymerase inhibitor maintenance therapy are unclear and may affect subsequent treatment. This ad hoc subgroup analysis of the phase 3 PRIMA/ENGOT-OV26/GOG-3012 study evaluated patterns of initial recurrence in patients with advanced ovarian cancer (AOC). METHODS: PRIMA included participants at high risk for disease progression. This ad hoc analysis only evaluated participants randomized to niraparib maintenance without evidence of disease at baseline. The number and site(s) of initial recurrent lesions at investigator-assessed progressive disease (PD) were evaluated. RESULTS: Of the 314 niraparib-treated patients analyzed, 190 developed ≥1 new lesion (median number of new lesions, 1.0; interquartile range, 1-2). In total, 93.2% (177/190) of patients developed 1-3 lesions at first disease progression. The most common sites of recurrence were the peritoneum (30.0% [57/190]), lymph nodes (26.3% [50/190]), and liver (20.5% [39/190]). Similar results were observed when patients with PD were stratified by biomarker status, disease stage at diagnosis, and type of debulking surgery. Patients with homologous recombination-proficient tumors, stage III disease, or a history of primary debulking developed a median of 2.0 new lesions at first progression; patients with homologous recombination-deficient tumors, stage IV disease, or a history of interval debulking developed a median of 1.0 new lesion. CONCLUSIONS: Many patients with AOC without lesions at first-line maintenance treatment initiation develop oligometastatic disease at first recurrence. Prospective evaluation is required to determine whether these patients have improved outcomes when local therapies are combined with continuous, systemic, targeted maintenance therapy.
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OBJECTIVE: To evaluate the impact of age on the efficacy and safety of niraparib first-line maintenance therapy in patients with newly diagnosed advanced ovarian cancer with a complete/partial response to first-line platinum-based chemotherapy. METHODS: Post hoc analysis of the phase 3 PRIMA/ENGOT-OV26/GOG-3012 study (NCT02655016). Patients in the intent-to-treat population were categorized according to age at baseline (<65 years vs ≥65 years), and progression-free survival (PFS), safety, and health-related quality of life (HRQOL) were evaluated for each age subgroup (clinical cutoff date, May 17, 2019). Safety findings were also evaluated according to a fixed starting dose (FSD) or an individualized starting dose (ISD). RESULTS: Of 733 randomized patients, 289 (39.4%) were ≥65 years (190 niraparib, 99 placebo) at baseline. Median PFS (niraparib vs placebo) and hazard ratios (95% CI) were similar in patients aged <65 years (13.9 vs 8.2 months; HR, 0.61 [0.47-0.81]) and ≥65 years (13.7 vs 8.1 months; HR, 0.53 [0.39-0.74]). The incidences of any-grade and grade ≥3 treatment-emergent adverse events (TEAEs) were similar across age subgroups; in the niraparib arm, TEAEs leading to dose discontinuation occurred in 7.8% of patients <65 years and 18.4% of patients ≥65 years. ISD use lowered the incidence of grade ≥3 thrombocytopenia events in niraparib-treated patients compared with the FSD (<65 years: 42.8% vs 18.0%; ≥65 years 57.0% vs 26.1%). HRQOL was comparable across age subgroups. CONCLUSION: Niraparib efficacy, safety, and HRQOL were generally comparable across age subgroups, although patients ≥65 years had a higher rate of discontinuations due to TEAEs. ISD use reduced grade ≥3 thrombocytopenia events regardless of age.
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Indazóis , Neoplasias Ovarianas , Piperidinas , Inibidores de Poli(ADP-Ribose) Polimerases , Intervalo Livre de Progressão , Qualidade de Vida , Humanos , Indazóis/efeitos adversos , Indazóis/administração & dosagem , Indazóis/uso terapêutico , Feminino , Piperidinas/efeitos adversos , Piperidinas/administração & dosagem , Piperidinas/uso terapêutico , Idoso , Neoplasias Ovarianas/tratamento farmacológico , Pessoa de Meia-Idade , Inibidores de Poli(ADP-Ribose) Polimerases/efeitos adversos , Inibidores de Poli(ADP-Ribose) Polimerases/administração & dosagem , Inibidores de Poli(ADP-Ribose) Polimerases/uso terapêutico , Idoso de 80 Anos ou mais , Fatores Etários , Adulto , Método Duplo-Cego , Carcinoma Epitelial do Ovário/tratamento farmacológico , Quimioterapia de Manutenção/métodosRESUMO
OBJECTIVE: To identify characteristics associated with long-term progression-free survival (≥2 years) in patients with advanced ovarian cancer treated with niraparib first-line maintenance therapy in the phase III PRIMA/ENGOT-OV26/GOG-3012 study. METHODS: In this post hoc analysis of PRIMA, patients randomized to niraparib were grouped based on investigator-assessed progression-free survival (progressive disease/censoring <2 years or ≥2 years after randomization). Variables assessed for predictive value were Eastern Cooperative Oncology Group performance status, International Federation of Gynecology and Obstetrics (FIGO) stage at diagnosis, clinical response to platinum-based chemotherapy, number of prior chemotherapy cycles, primary tumor location, body mass index, categorical age, debulking surgery type, number of baseline target lesions, number of baseline non-target lesions, BRCA/homologous recombination-deficiency status, residual disease status, and duration from end of chemotherapy to randomization. Logistic regression modeling using backward elimination (significance level=0.15) identified covariates associated with long-term progression-free survival (clinical cut-off date November 17, 2021). RESULTS: Of 487 patients randomized to niraparib, 152 (31%) had progressive disease/censoring ≥2 years after randomization. Multivariable logistic regression modeling using backward elimination identified BRCA1/2 mutation/homologous recombination deficiency status (p<0.0001), FIGO stage (p=0.041), primary tumor location (p=0.095), and number of baseline non-target lesions (p=0.0001) to be associated with long-term progression-free survival. Patients significantly more likely to achieve progression-free survival of ≥2 years in the final model were those with BRCA1- and BRCA2-mutated/homologous recombination-deficient tumors or BRCA wild-type/not determined/homologous recombination-deficient tumors (vs BRCA wild-type/homologous recombination-proficient/not determined tumors), FIGO stage III (vs IV), and 0 or 1 baseline non-target lesions (vs ≥2 baseline non-target lesions). CONCLUSIONS: The hypothesis-generating results of this analysis suggest that BRCA1/2 mutation/homologous recombination-deficiency status, FIGO stage, and number of baseline non-target lesions may predict progression-free survival of ≥2 years in patients with advanced ovarian cancer receiving niraparib first-line maintenance therapy. TRIAL REGISTRATION NUMBER: NCT02655016.
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Indazóis , Neoplasias Ovarianas , Piperidinas , Intervalo Livre de Progressão , Humanos , Feminino , Indazóis/uso terapêutico , Indazóis/administração & dosagem , Piperidinas/uso terapêutico , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/mortalidade , Pessoa de Meia-Idade , Inibidores de Poli(ADP-Ribose) Polimerases/uso terapêutico , Adulto , IdosoRESUMO
BACKGROUND: Niraparib, an inhibitor of poly(adenosine diphosphate [ADP]-ribose) polymerase (PARP), has been associated with significantly increased progression-free survival among patients with recurrent ovarian cancer after platinum-based chemotherapy, regardless of the presence or absence of BRCA mutations. The efficacy of niraparib in patients with newly diagnosed advanced ovarian cancer after a response to first-line platinum-based chemotherapy is unknown. METHODS: In this randomized, double-blind, phase 3 trial, we randomly assigned patients with newly diagnosed advanced ovarian cancer in a 2:1 ratio to receive niraparib or placebo once daily after a response to platinum-based chemotherapy. The primary end point was progression-free survival in patients who had tumors with homologous-recombination deficiency and in those in the overall population, as determined on hierarchical testing. A prespecified interim analysis for overall survival was conducted at the time of the primary analysis of progression-free survival. RESULTS: Of the 733 patients who underwent randomization, 373 (50.9%) had tumors with homologous-recombination deficiency. Among the patients in this category, the median progression-free survival was significantly longer in the niraparib group than in the placebo group (21.9 months vs. 10.4 months; hazard ratio for disease progression or death, 0.43; 95% confidence interval [CI], 0.31 to 0.59; P<0.001). In the overall population, the corresponding progression-free survival was 13.8 months and 8.2 months (hazard ratio, 0.62; 95% CI, 0.50 to 0.76; P<0.001). At the 24-month interim analysis, the rate of overall survival was 84% in the niraparib group and 77% in the placebo group (hazard ratio, 0.70; 95% CI, 0.44 to 1.11). The most common adverse events of grade 3 or higher were anemia (in 31.0% of the patients), thrombocytopenia (in 28.7%), and neutropenia (in 12.8%). No treatment-related deaths occurred. CONCLUSIONS: Among patients with newly diagnosed advanced ovarian cancer who had a response to platinum-based chemotherapy, those who received niraparib had significantly longer progression-free survival than those who received placebo, regardless of the presence or absence of homologous-recombination deficiency. (Funded by GlaxoSmithKline; PRIMA/ENGOT-OV26/GOG-3012 ClinicalTrials.gov number, NCT02655016.).
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Indazóis/uso terapêutico , Neoplasias Ovarianas/tratamento farmacológico , Piperidinas/uso terapêutico , Inibidores de Poli(ADP-Ribose) Polimerases/uso terapêutico , Administração Oral , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/uso terapêutico , Terapia Combinada , Método Duplo-Cego , Feminino , Humanos , Indazóis/efeitos adversos , Quimioterapia de Manutenção , Pessoa de Meia-Idade , Náusea/induzido quimicamente , Neoplasias Ovarianas/mortalidade , Neoplasias Ovarianas/cirurgia , Piperidinas/efeitos adversos , Inibidores de Poli(ADP-Ribose) Polimerases/efeitos adversos , Intervalo Livre de Progressão , Qualidade de Vida , Análise de SobrevidaRESUMO
OBJECTIVE: Olaparib treatment resulted in significant improvement in objective response rates (ORRs) and progression-free survival (PFS) over nonplatinum chemotherapy in patients with BRCA1/BRCA2-mutated (BRCAm) platinum-sensitive relapsed ovarian cancer (PSROC) and ≥2 prior lines of platinum-based chemotherapy in the phase III SOLO3 study. LIGHT (NCT02983799) prospectively evaluated olaparib treatment for patients with PSROC and known BRCAm and homologous recombination deficiency (HRD) status. METHODS: In this phase II open-label multicenter study, patients with PSROC and ≥1 prior line of platinum-based chemotherapy were assigned to cohorts by presence of germline BRCAm (gBRCAm), somatic BRCAm (sBRCAm), HRD-positive tumors without BRCAm, or HRD-negative tumors. The primary endpoint was investigator-assessed ORR. Secondary endpoints included disease control rate (DCR) and PFS. Tumors were analyzed using Myriad BRACAnalysis CDx and myChoice HRD assays; HRD-positive tumors were defined using a genomic instability score of ≥42. RESULTS: Of 272 enrolled patients, 271 received olaparib and 270 were included in efficacy analyses. At data cut-off, ORRs in the gBRCAm, sBRCAm, HRD-positive, and HRD-negative cohorts were 69.3%, 64.0%, 29.4%, and 10.1%, respectively. DCRs were 96.0%, 100.0%, 79.4%, and 75.3% in each cohort, respectively. Median PFS was 11.0, 10.8, 7.2, and 5.4 months, respectively. The most common (≥ 20%) treatment-emergent adverse events included nausea, fatigue/asthenia, vomiting, anemia, constipation, diarrhea, and decreased appetite. CONCLUSIONS: Olaparib treatment demonstrated activity across all cohorts. The greatest efficacy was observed in the BRCAm cohorts, regardless of gBRCAm/sBRCAm. For patients without a BRCAm, greater efficacy was observed in the HRD-positive than the HRD-negative cohorts. The safety profile was consistent with that established in previous olaparib studies.
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Neoplasias Ovarianas , Proteína BRCA1/genética , Proteína BRCA2/genética , Carcinoma Epitelial do Ovário/tratamento farmacológico , Carcinoma Epitelial do Ovário/genética , Feminino , Recombinação Homóloga , Humanos , Mutação , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/genética , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/patologia , Ftalazinas , PiperazinasRESUMO
OBJECTIVE: To evaluate the association between surgical timing and postoperative residual disease status on the efficacy of niraparib first-line maintenance therapy in patients with newly diagnosed advanced ovarian cancer at high risk of recurrence. METHODS: Post hoc analysis of the phase 3 PRIMA/ENGOT-OV26/GOG-3012 (NCT02655016) study of niraparib in patients with newly diagnosed primary advanced ovarian, primary peritoneal, or fallopian tube cancer with a complete/partial response to first-line platinum-based chemotherapy. Progression-free survival (PFS) was assessed by surgical status (primary debulking surgery [PDS] vs neoadjuvant chemotherapy/interval debulking surgery [NACT/IDS]) and postoperative residual disease status (no visible residual disease [NVRD] vs visible residual disease [VRD]) in the intent-to-treat population. RESULTS: In PRIMA (N = 733), 236 (32.2%) patients underwent PDS, and 481 (65.6%) received NACT/IDS before enrollment. Median PFS (niraparib vs placebo) and hazard ratios (95% CI) for progression were similar in PDS (13.7 vs 8.2 months; HR, 0.67 [0.47-0.96]) and NACT/IDS (14.2 vs 8.2 months; HR, 0.57 [0.44-0.73]) subgroups. In patients who received NACT/IDS and had NVRD (n = 304), the hazard ratio (95% CI) for progression was 0.65 (0.46-0.91). In patients with VRD following PDS (n = 183) or NACT/IDS (n = 149), the hazard ratios (95% CI) for progression were 0.58 (0.39-0.86) and 0.41 (0.27-0.62), respectively. PFS was not evaluable for patients with PDS and NVRD because of sample size (n = 37). CONCLUSIONS: In this post hoc analysis, niraparib efficacy was similar across PDS and NACT/IDS subgroups. Patients who had NACT/IDS and VRD had the highest reduction in the risk of progression with niraparib maintenance.
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Neoplasias Ovarianas , Carcinoma Epitelial do Ovário/tratamento farmacológico , Carcinoma Epitelial do Ovário/cirurgia , Quimioterapia Adjuvante , Procedimentos Cirúrgicos de Citorredução , Feminino , Humanos , Indazóis/uso terapêutico , Terapia Neoadjuvante , Estadiamento de Neoplasias , Neoplasia Residual , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/cirurgia , PiperidinasRESUMO
What is this summary about? This PLSP provides a short summary of an original scientific article that presented results from the PRIMA study after 3.5 years of follow-up time. The original article was published in the European Journal of Cancer in 2023.The PRIMA study included adult patients with newly diagnosed advanced high-risk ovarian cancer whose tumors shrunk or became undetectable after treatment with chemotherapy with or without surgery. The PRIMA study evaluated how well the drug niraparib, also known as Zejula, worked at delaying or preventing ovarian cancer from coming back (recurring) or getting worse (progressing) compared with placebo (a substance with no effects that a doctor gives to a patient instead of a drug). The first results from the PRIMA study were published in 2019, when patients had participated in the PRIMA study for about 1.2 years.The article this PLSP is based on reports longer-term data from the PRIMA study, when patients had participated in the PRIMA study for about 3.5 years. Patients were monitored (or followed) for a longer time to understand how well niraparib continued to work and to evaluate whether the safety of niraparib changed with additional time being monitored.What were the results? Patients who took niraparib had more time before their cancer came back or got worse than patients who took placebo. In terms of safety, no new types of side effects with niraparib treatment were observed with additional time being monitored as part of the PRIMA study.What do the results mean? These results support that niraparib remains an important treatment option to help delay the cancer from coming back or getting worse in patients with newly diagnosed advanced ovarian cancer that responded to initial treatment.Clinical Trial Registration: NCT02655016 (PRIMA study) (ClinicalTrials.gov).
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PURPOSE: To report updated long-term efficacy and safety from the double-blind, placebo-controlled, phase 3 PRIMA/ENGOT-OV26/GOG-3012 study (NCT02655016). METHODS: Patients with newly diagnosed advanced ovarian cancer with complete or partial response (CR or PR) to first-line platinum-based chemotherapy received niraparib or placebo once daily (2:1 ratio). Stratification factors were best response to first-line chemotherapy regimen (CR/PR), receipt of neoadjuvant chemotherapy (yes/no), and homologous recombination deficiency (HRD) status (deficient [HRd]/proficient [HRp] or not determined). Updated (ad hoc) progression-free survival (PFS) data (as of November 17, 2021) by investigator assessment (INV) are reported. RESULTS: In 733 randomised patients (niraparib, 487; placebo, 246), median PFS follow-up was 3.5years. Median INV-PFS was 24.5 versus 11.2months (hazard ratio, 0.52; 95% confidence interval [CI], 0.40-0.68) in the HRd population and 13.8 versus 8.2months (hazard ratio, 0.66; 95% CI, 0.56-0.79) in the overall population for niraparib and placebo, respectively. In the HRp population, median INV-PFS was 8.4 versus 5.4months (hazard ratio, 0.65; 95% CI, 0.49-0.87), respectively. Results were concordant with the primary analysis. Niraparib-treated patients were more likely to be free of progression or death at 4years than placebo-treated patients (HRd, 38% versus 17%; overall, 24% versus 14%). The most common grade ≥ 3 treatment-emergent adverse events in niraparib patients were thrombocytopenia (39.7%), anaemia (31.6%), and neutropenia (21.3%). Myelodysplastic syndromes/acute myeloid leukaemia incidence rate (1.2%) was the same for niraparib- and placebo-treated patients. Overall survival remained immature. CONCLUSIONS: Niraparib maintained clinically significant improvements in PFS with 3.5years of follow-up in patients with newly diagnosed advanced ovarian cancer at high risk of progression irrespective of HRD status. No new safety signals were identified.
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Neoplasias Ovarianas , Humanos , Feminino , Intervalo Livre de Progressão , Neoplasias Ovarianas/tratamento farmacológico , Carcinoma Epitelial do Ovário/tratamento farmacológico , Indazóis/efeitos adversos , Quimioterapia de Manutenção/métodosRESUMO
OBJECTIVE: To update the state of evidence on the efficacy of metformin, used either alone or in combination with clomiphene citrate in women with polycystic ovary syndrome, by examining three outcomes: ovulation, pregnancy, and live birth. Sources of heterogeneity among the published randomized controlled trials are systematically assessed. DATA SOURCES: An electronic literature search was performed using MEDLINE, EMBASE, SCOPUS, CENTRAL, Cochrane, and U.S. Food and Drug Administration databases, restricted to studies conducted on humans and published in English. METHODS OF STUDY SELECTION: Of the 406 potentially relevant articles identified, 17 met criteria for inclusion in the meta-analysis, rendering a total sample of 1,639 women. Study quality was examined in terms of randomization scheme, masking process, adequacy of allocation concealment, statistical power, and loss to follow-up; publication bias was also assessed. Meta-analytic procedures were used to compare metformin with placebo, and metformin plus clomiphene with clomiphene alone, for all study outcomes. Exploratory analyses were conducted to assess differences in treatment effects between clomiphene-resistant and nonresistant patients, obese and nonobese patients, and trials with long and short durations of follow-up. TABULATION, INTEGRATION, AND RESULTS: Metformin improved the odds of ovulation in women with polycystic ovary syndrome when compared with placebo (odds ratio [OR] 2.94; 95% confidence interval [CI] 1.43-6.02; number-needed-to-treat 4.0) and appears more effective for non-clomiphene-resistant women. Metformin and clomiphene increased the likelihood of ovulation (OR 4.39; 95% CI 1.94-9.96; number-needed-to-treat 3.7) and pregnancy (OR 2.67; 95% CI 1.45-4.94; number-needed-to-treat 4.6) when compared with clomiphene alone, especially in clomiphene-resistant and obese women with polycystic ovary syndrome. These treatment effects were greater for trials with shorter follow-up. CONCLUSION: Using all available evidence, this meta-analysis suggests that metformin increases the likelihood of ovulation and, in combination with clomiphene, increases the odds of both ovulation and pregnancy in women with polycystic ovary syndrome.
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Fármacos para a Fertilidade Feminina/uso terapêutico , Hipoglicemiantes/uso terapêutico , Metformina/uso terapêutico , Ovulação/efeitos dos fármacos , Síndrome do Ovário Policístico/tratamento farmacológico , Resultado da Gravidez , Clomifeno/uso terapêutico , Quimioterapia Combinada , Feminino , Fármacos para a Fertilidade Feminina/farmacologia , Humanos , Hipoglicemiantes/farmacologia , Nascido Vivo , Metformina/farmacologia , Razão de Chances , Gravidez , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
Recognition of an ovarian tumor as a metastasis from an undiagnosed primary gastrointestinal tract carcinoma can be difficult when specific symptoms referable to the primary tumor are lacking and the tumor simulates a primary ovarian neoplasm grossly and microscopically. Ovarian metastases of colorectal adenocarcinomas, in particular, continue to pose diagnostic challenges both clinically and pathologically. Clinicopathologic features of 20 cases of ovarian metastases from undiagnosed colorectal adenocarcinomas (U-CRAs) were compared with those of 22 cases having metastases from known colorectal adenocarcinomas (K-CRAs). Women with ovarian metastases from U-CRAs were significantly younger (mean age, 48 years; median, 47 years) than those with ovarian metastases from K-CRAs (mean, 61 years; median, 63 years) (P = 0.002), presented with clinical findings related to the ovarian metastases, often had elevated CA-125 levels, and lacked specific symptoms due to the colorectal carcinomas, which were diagnosed only at the time of intraoperative evaluation of the ovarian tumors. Mean/median ovarian tumor sizes (12.8/13.0 cm for U-CRAs; 14.1/15.8 cm for K-CRAs) and frequencies of bilaterality (45% for U-CRAs and 36% for K-CRAs) were not significantly different for the 2 groups; frequencies of clinically unilateral tumors of more than 10 cm were similar in both groups (30% for U-CRAs and 45% for KCRAs). Other features more commonly observed in ovarian metastases from U-CRAs included mucinous differentiation, extracellular mucin production, and some degree of cytokeratin 7 expression; endometrioid-like differentiation was more common in metastases from K-CRA, but a garland pattern of necrosis and the presence of a confluent glandular, rather than infiltrative, pattern of invasion were similarly common in both groups. In cases having ovarian metastases from U-CRA, the younger age of the women, uniform presentation as pelvic masses without symptoms referable to the bowel, elevated CA-125 levels, occasional presentation as a large clinically unilateral tumor, frequent mucinous differentiation, and frequent coexpression of cytokeratin 7 are features that can contribute to misclassification of these metastases as primary ovarian neoplasms.
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Adenocarcinoma/diagnóstico , Adenocarcinoma/secundário , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/patologia , Neoplasias Ovarianas/diagnóstico , Neoplasias Ovarianas/secundário , Adenocarcinoma/metabolismo , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/metabolismo , Antígeno Ca-125/metabolismo , Neoplasias Colorretais/metabolismo , Diagnóstico Diferencial , Feminino , Humanos , Queratina-7/metabolismo , Pessoa de Meia-Idade , Mucinas/metabolismo , Neoplasias Primárias Desconhecidas/diagnóstico , Neoplasias Primárias Desconhecidas/metabolismo , Neoplasias Primárias Desconhecidas/patologia , Neoplasias Ovarianas/metabolismo , Ovário/metabolismo , Ovário/patologia , Estudos RetrospectivosRESUMO
PURPOSE: Previous studies on team-based learning (TBL) in medical education demonstrated improved learner engagement, learner satisfaction, and academic performance; however, a paucity of information exists on modifications of the incentive structure of "traditional" TBL practices. The current study investigates the impact of modification to conventional Group Application exercises by examining student preference and student perceptions of TBL outcomes when Group Application exercises are excluded from TBL grades. METHODS: During the 2009-2010 and 2010-2011 academic years, 175 students (95.6% response rate) completed a 22-item multiple choice survey followed by 3 open response questions at the end of their second year of medical school. These students had participated in a TBL supplemented preclinical curriculum with graded Group Application exercises during year one and ungraded Group Application exercises during year two of medical school. RESULTS: Chi-square analyses showed significant differences between grading categories for general assessment of TBL, participation and communication, intra-team discussion, inter-team discussion, student perceptions of their own effort and development of teamwork skills. Furthermore, 83.8% of students polled prefer ungraded Group Application exercises with only 7.2% preferring graded and 9.0% indicating no preference. CONCLUSION: The use of ungraded Group Application exercises appears to be a successful modification of TBL, making it more "student-friendly" while maintaining the goals of active learning and development of teamwork skills.
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Global coverage with three doses of the diphtheria, tetanus and pertussis vaccine (DTP3) increased from less than 5% in 1974 to 82% in 2009 due to worldwide focus on universal vaccination. Nonetheless, pertussis remains the fifth-leading cause of vaccine-preventable deaths. This study examines DTP3 vaccination from 1980 through 2009 in three countries within Latin America, Bolivia, Brazil and Mexico, selected for their distinct health care systems and vaccination strategies. Similar to global trends, these nations have achieved dramatic improvements in pertussis immunization. In Bolivia, immunization rates increased from 11% to 85%; in Brazil, rates increased from 37% to 97%; and in Mexico, the immunization rates increased from 44% to 72%. Pertussis infections have concomitantly decreased from 1980 to 2009. In Bolivia, cases decreased from 44.4 per 100,000 people to zero reported cases. In Brazil, the incidence decreased from 37.6 to 0.5 cases per 100,000. The incidence in Mexico decreased from 8.2 to 0.5 cases per 100,000. In order to increase vaccination rates further, health systems must continue to raise awareness about disease prevention, expand health surveillance systems, and improve access to health services.
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Vacina contra Difteria, Tétano e Coqueluche/administração & dosagem , Coqueluche/epidemiologia , Bolívia/epidemiologia , Brasil/epidemiologia , Saúde Global , Humanos , Imunização , Incidência , México/epidemiologia , Saúde Pública , Estudos Retrospectivos , Coqueluche/prevenção & controleRESUMO
Clinical and healthcare decision makers have repeatedly endorsed patient-centered care as a goal of the health system. However, traditional methods of evaluation reinforce societal views, and research focusing on views of patients is often referred to as 'soft science.' Conjoint analysis presents a scientifically rigorous research tool that can be used to understand patient preferences and inform decision making. This paper documents applications of conjoint analysis in medicine and systematically reviews this literature in order to identify publication trends and the range of topics to which conjoint analysis has been applied. In addition, we document important methodological aspects such as sample size, experimental design, and method of analysis.Publications were identified through a MEDLINE search using multiple search terms for identification. We classified each article into one of three categories: clinical applications (n = 122); methodological contributions (n = 56); and health system applications (n = 47). Articles that did not use or adequately discuss conjoint analysis methods (n = 164) were discarded. We identified a near exponential increase in the application of conjoint analyses over the last 10 years of the study period (1997-2007). Over this period, the proportion of applications on clinical topics increased from 40% of articles published in MEDLINE from 1998 to 2002, to 64% of articles published from 2003 to 2007 (p = 0.002).The average sample size among articles focusing on health system applications (n = 556) was significantly higher than clinical applications (n = 277) [p = 0.001], although this 2-fold difference was primarily due to a number of outliers reporting sample sizes in the thousands. The vast majority of papers claimed to use orthogonal factorial designs, although over a quarter of papers did not report their design properties. In terms of types of analysis, logistic regression was favored among clinical applications (28%), while probit was most commonly used among health systems applications (38%). However, 25% of clinical applications and 33% of health systems articles failed to report what regression methods were used. We used the International Classification of Diseases - version 9 (ICD-9) coding system to categorize clinical applications, with approximately 26% of publications focusing on neoplasm. Program planning and evaluation applications accounted for 22% of the health system articles.While interest in conjoint analysis in health is likely to continue, better guidelines for conducting and reporting conjoint analyses are needed.
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OBJECTIVE: We sought to further elucidate the survival impact of cytoreductive surgery among patients with colon cancer metastatic to the ovary. METHODS: All women diagnosed with primary colon cancer metastatic to the ovary at a single institution from 1980 to 2005 were retrospectively identified. Survival analyses and comparisons were performed using Kaplan-Meier plots and the log rank test. RESULTS: A total of 39 patients with 40 cases of colon cancer metastatic to the ovary were identified. Patients with metastatic disease confined to the ovaries (n=11) had a median overall survival (OS) time of 61 months (range 15-120) compared to 17 months (range 0.5-73) for those with more extensive metastases (n=24) (p=0.0428). Patients undergoing optimal cytoreduction (residual < or =1 cm) had a median progression-free survival (PFS) of 11 months (range 0.5-120, n=26) compared to 2.5 months (range 0.5-12, n=9) for those receiving suboptimal cytoreduction (p=0.0001). Optimal cytoreduction was also associated with a significantly longer median OS (35 months, range 0.5-120) compared to suboptimal cytoreduction (median OS=7 months, range=0.5-17) (p<0.0001). The peri-operative mortality rate was 5%. Significant morbidity occurred in 10% of the cases. All major complications occurred in women with diffuse disease who underwent extensive cytoreductive surgery. CONCLUSIONS: The observation that optimal cytoreduction was associated with prolonged PFS and OS in both patients with localized ovarian and widespread metastases of colon cancer suggests a role for surgical management of metastatic colon cancer in women.
Assuntos
Neoplasias do Colo/patologia , Neoplasias do Colo/cirurgia , Neoplasias Ovarianas/secundário , Neoplasias Ovarianas/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Quimioterapia Adjuvante , Neoplasias do Colo/tratamento farmacológico , Intervalo Livre de Doença , Feminino , Humanos , Pessoa de Meia-Idade , Neoplasias Primárias Múltiplas/tratamento farmacológico , Neoplasias Primárias Múltiplas/patologia , Neoplasias Primárias Múltiplas/cirurgia , Segunda Neoplasia Primária/tratamento farmacológico , Segunda Neoplasia Primária/patologia , Segunda Neoplasia Primária/cirurgia , Neoplasias Ovarianas/tratamento farmacológico , Estudos Retrospectivos , Taxa de SobrevidaRESUMO
Uterine arteriovenous malformation (AVM) causes significant morbidity with vaginal bleeding. Traditional therapy is a hysterectomy with no potential for future pregnancy. We present a case of successful superselective embolization of uterine AVM using n-butyl cyanoacrylate with subsequent normal term pregnancy and uncomplicated vaginal delivery in 1 year.