Epidemiološki studij učinaka herbicida

A preliminary study of 324 Swedish railway workers exposed to herbicides between the years 1957-1971 showed 2 excess lung cancer cases, 1 adenocarcinoma and 1 oatcellcancer. Although the number of subjects was small, especially the number of cancers, the possibility that amitrole and combinations together with smoking might have caused the excess lung cancers cannot be ruled out.U ovom preliminarnom epidemiološkom istraživanju, autori su analizirali uzroke smrti među 324 radnika koji su u razdoblju od 1957. do 1971. godine bili izvrgnuti različitim herbicidima tijekom ukupno više od 46 dana. Autori su u račun uzimali incidenciju u općem i specifičnom mortalitetu švedske populacije pa su uspoređivali broj očekivanih i broj utvrđenih smrtnih slučajeva među eksponiranim radnicima. Premda su sveukupni brojevi maleni, ne može se isključiti mogućnost da je amitrol sam ili s pušenjem uvjetovao veći broj karcinoma pluća u eksponiranih radnika

Optimising the Diagnosis of Prostate Cancer in the Era of Multiparametric Magnetic Resonance Imaging : A Cost-effectiveness Analysis Based on the Prostate MR Imaging Study (PROMIS)

Background The current recommendation of using transrectal ultrasound-guided biopsy (TRUSB) to diagnose prostate cancer misses clinically significant (CS) cancers. More sensitive biopsies (eg, template prostate mapping biopsy [TPMB]) are too resource intensive for routine use, and there is little evidence on multiparametric magnetic resonance imaging (MPMRI). Objective To identify the most effective and cost-effective way of using these tests to detect CS prostate cancer. Design, setting, and participants Cost-effectiveness modelling of health outcomes and costs of men referred to secondary care with a suspicion of prostate cancer prior to any biopsy in the UK National Health Service using information from the diagnostic Prostate MR Imaging Study (PROMIS). Intervention Combinations of MPMRI, TRUSB, and TPMB, using different definitions and diagnostic cut-offs for CS cancer. Outcome measurements and statistical analysis Strategies that detect the most CS cancers given testing costs, and incremental cost-effectiveness ratios (ICERs) in quality-adjusted life years (QALYs) given long-term costs. Results and limitations The use of MPMRI first and then up to two MRI-targeted TRUSBs detects more CS cancers per pound spent than a strategy using TRUSB first (sensitivity = 0.95 [95% confidence interval {CI} 0.92–0.98] vs 0.91 [95% CI 0.86–0.94]) and is cost effective (ICER = £7,076 [€8350/QALY gained]). The limitations stem from the evidence base in the accuracy of MRI-targeted biopsy and the long-term outcomes of men with CS prostate cancer. Conclusions An MPMRI-first strategy is effective and cost effective for the diagnosis of CS prostate cancer. These findings are sensitive to the test costs, sensitivity of MRI-targeted TRUSB, and long-term outcomes of men with cancer, which warrant more empirical research. This analysis can inform the development of clinical guidelines. Patient summary We found that, under certain assumptions, the use of multiparametric magnetic resonance imaging first and then up to two transrectal ultrasound-guided biopsy is better than the current clinical standard and is good value for money. The use of multiparametric magnetic resonance imaging before transrectal ultrasound-guided biopsy can detect more clinically significant prostate cancer and be cost effective compared with the use of imaging post-biopsy

Clinical intervals and diagnostic characteristics in a cohort of prostate cancer patients in Spain: a multicentre observational study

Background: Little is known about the healthcare process for patients with prostate cancer, mainly because hospital-based data are not routinely published. The main objective of this study was to determine the clinical characteristics of prostate cancer patients, the diagnostic process and the factors that might influence intervals from consultation to diagnosis and from diagnosis to treatment. Methods: We conducted a multicentre, cohort study in seven hospitals in Spain. Patients' characteristics and diagnostic and therapeutic variables were obtained from hospital records and patients' structured interviews from October 2010 to September 2011. We used a multilevel logistic regression model to examine the association between patient care intervals and various variables influencing these intervals (age, BMI, educational level, ECOG, first specialist consultation, tumour stage, PSA, Gleason score, and presence of symptoms) and calculated the odds ratio (OR) and the interquartile range (IQR). To estimate the random inter-hospital variability, we used the median odds ratio (MOR). Results: 470 patients with prostate cancer were included. Mean age was 67.8 (SD: 7.6) years and 75.4 % were physically active. Tumour size was classified as T1 in 41.0 % and as T2 in 40 % of patients, their median Gleason score was 6.0 (IQR:1.0), and 36.1 % had low risk cancer according to the D'Amico classification. The median interval between first consultation and diagnosis was 89 days (IQR:123.5) with no statistically significant variability between centres. Presence of symptoms was associated with a significantly longer interval between first consultation and diagnosis than no symptoms (OR:1.93, 95%CI 1.29-2.89). The median time between diagnosis and first treatment (therapeutic interval) was 75.0 days (IQR:78.0) and significant variability between centres was found (MOR:2.16, 95%CI 1.45-4.87). This interval was shorter in patients with a high PSA value (p = 0.012) and a high Gleason score (p = 0.026). Conclusions: Most incident prostate cancer patients in Spain are diagnosed at an early stage of an adenocarcinoma. The period to complete the diagnostic process is approximately three months whereas the therapeutic intervals vary among centres and are shorter for patients with a worse prognosis. The presence of prostatic symptoms, PSA level, and Gleason score influence all the clinical intervals differently

Picropodophyllin causes mitotic arrest and catastrophe by depolymerizing microtubules via Insulin-like growth factor-1 receptor-independent mechanism

Picropodophyllin (PPP) is an anticancer drug undergoing clinical development in NSCLC. PPP has been shown to suppress IGF-1R signaling and to induce a G2/M cell cycle phase arrest but the exact mechanisms remain to be elucidated. The present study identified an IGF-1-independent mechanism of PPP leading to pro-metaphase arrest. The mitotic block was induced in human cancer cell lines and in an A549 xenograft mouse but did not occur in normal hepatocytes/mouse tissues. Cell cycle arrest by PPP occurred in vitro and in vivo accompanied by prominent CDK1 activation, and was IGF-1R-independent since it occurred also in IGF-1R-depleted and null cells. The tumor cells were not arrested in G2/M but in mitosis. Centrosome separation was prevented during mitotic entry, resulting in a monopolar mitotic spindle with subsequent prometaphase-arrest, independent of Plk1/Aurora A or Eg5, and leading to cell features of mitotic catastrophe. PPP also increased soluble tubulin and decreased spindle-associated tubulin within minutes, indicating that it interfered with microtubule dynamics. These results provide a novel IGF-1R-independent mechanism of antitumor effects of PPP

Is the decline of the increasing incidence of non-Hodgkin lymphoma in Sweden and other countries a result of cancer preventive measures?

Is the decline of the increasing incidence of non-Hodgkin lymphoma (NHL) in Sweden and other countries a result of cancer preventive measures? The yearly age-standardized incidence of NHL increased significantly in Sweden during 1971-1990, for men an average of 3.2% and for women 3.1%. The corresponding figures for 1991-2000 were -0.8% and -0.2%, respectively. A decline of the increasing incidence has also been seen in other countries, such as the United States, Finland, and Denmark. Immunosuppression is one established risk factor for NHL, possibly with interaction with Epstein-Barr virus. Phenoxyacetic acids and chlorophenols, both pesticides, have been associated with NHL. Use of these chemicals was banned in Sweden in 1977 and 1978, respectively. Also, persistent organic pollutants such as polychlorinated biphenyls, hexachlorobenzene, chlordanes, and dioxins have been shown to increase the risk. Exposure of the whole population occurs predominantly through the food chain. Exposure to such chemicals was highest in the 1960s and 1970s. Because of regulation in the 1970s, exposure has declined substantially in the population. The change in incidence of NHL in Sweden and other countries may serve as a good example of how prohibition and limitation of exposure may be reflected in cancer statistics some decades later

Pharmacotherapy and Family-Focused Treatment for Adolescents With Bipolar I and II Disorders: A 2-Year Randomized Trial

ObjectivePrevious studies have found that family-focused treatment is an effective adjunct to pharmacotherapy in stabilizing symptoms in adult bipolar disorder. The authors examined whether pharmacotherapy and family-focused treatment for adolescents with bipolar disorder was more effective than pharmacotherapy and brief psychoeducation (enhanced care) in decreasing time to recovery from a mood episode, increasing time to recurrence, and reducing symptom severity over 2 years.MethodA total of 145 adolescents (mean age, 15.6 years) with bipolar I or II disorder and a DSM-IV-TR manic, hypomanic, depressive, or mixed episode in the previous 3 months were randomly assigned, with family members, either to pharmacotherapy and family-focused treatment, consisting of psychoeducation (i.e., recognition and early intervention with prodromal symptoms), communication enhancement training, and problem-solving skills training, delivered in 21 sessions over 9 months; or to pharmacotherapy and three weekly sessions of enhanced care (family psychoeducation). Independent evaluators assessed participants at baseline, every 3 months during year 1, and every 6 months during year 2, using weekly ratings of mood.ResultsTwenty-two participants (15.2%) withdrew shortly after randomization. Time to recovery or recurrence and proportion of weeks ill did not differ between the two treatment groups. Secondary analyses revealed that participants in family-focused treatment had less severe manic symptoms during year 2 than did those in enhanced care.ConclusionsAfter an illness episode, intensive psychotherapy combined with best-practice pharmacotherapy does not appear to confer advantages over brief psychotherapy and pharmacotherapy in hastening recovery or delaying recurrence among adolescents with bipolar disorder

Measures and models for causal inference in cross-sectional studies: arguments for the appropriateness of the prevalence odds ratio and related logistic regression

<p>Abstract</p> <p>Background</p> <p>Several papers have discussed which effect measures are appropriate to capture the contrast between exposure groups in cross-sectional studies, and which related multivariate models are suitable. Although some have favored the Prevalence Ratio over the Prevalence Odds Ratio -- thus suggesting the use of log-binomial or robust Poisson instead of the logistic regression models -- this debate is still far from settled and requires close scrutiny.</p> <p>Discussion</p> <p>In order to evaluate how accurately true causal parameters such as Incidence Density Ratio (IDR) or the Cumulative Incidence Ratio (CIR) are effectively estimated, this paper presents a series of scenarios in which a researcher happens to find a preset ratio of prevalences in a given cross-sectional study. Results show that, provided essential and non-waivable conditions for causal inference are met, the CIR is most often inestimable whether through the Prevalence Ratio or the Prevalence Odds Ratio, and that the latter is the measure that consistently yields an appropriate measure of the Incidence Density Ratio.</p> <p>Summary</p> <p>Multivariate regression models should be avoided when assumptions for causal inference from cross-sectional data do not hold. Nevertheless, if these assumptions are met, it is the logistic regression model that is best suited for this task as it provides a suitable estimate of the Incidence Density Ratio.</p