Influence of public alcohol and tobacco use on general practitioners' advice: an international comparative study.

Background: Efficacy of advice for substance use is proven in general practice. Studies show high variability of perfomance. Especially intercountry variability has rarely been taken into account. Aim: To study the influence of public tobacco and alcohol use and health service characteristics on the general practitioners' involvement in counselling for tobacco and alcohol use. Methods: A multilevel analysis was performed distinguishing general practice level (workload, assistance, gender and age) and country level (health service characteristics and substance use). Data for practice level were used form 3 survey studies: the task profile study (32 European countries; 1992); a collaborative action in 5 European countries (1996) and a WHO trial (14 countries world wide; 1997). Health services' characteristics were obtained form literature. From WHO and OECD databases consumption (mean litres of pure alcohol / person / year used; mean grams of tobacco consumed / person / year) and percent change were derived for 4-year periods. Dependant variable was self-estimated extend of asking about use.Results: Variations in asking attributed to country level ranged up to 13% for tobacco and to 15% for alcohol. Only small effects (estimated coefficients 0,001-0,005) were encountered for practice level. Use and changes in use on tobacco consumption influenced practitioner's involvement significantly in one dataset, while use and change in alcohol use influenced asking on alcohol consumption in all surveys (-0,01 to -0,05). Moreover Scandinavian and English background influence practitioners positively and Eastern European country situation negatively. Conclusions: Practice variables (workload, gender, age) only influence prevention very little when country differences are accounted for. Use and changes in alcohol use influence involvement of general practitioners in health promotion more. (aut. ref.

Fasting mimicking diet as an adjunct toneoadjuvant chemotherapy for breast cancer in the multicentre randomized phase 2 DIRECT trial

Short-term fasting protects tumor-bearing mice against the toxic effects of chemotherapy while enhancing therapeutic efficacy. We randomized 131 patients with HER2-negative stage II/III breast cancer, without diabetes and a BMI over 18kgm(-2), to receive either a fasting mimicking diet (FMD) or their regular diet for 3 days prior to and during neoadjuvant chemotherapy. Here we show that there was no difference in toxicity between both groups, despite the fact that dexamethasone was omitted in the FMD group. A radiologically complete or partial response occurs more often in patients using the FMD (OR 3.168, P=0.039). Moreover, per-protocol analysis reveals that the Miller&Payne 4/5 pathological response, indicating 90-100% tumor-cell loss, is more likely to occur in patients using the FMD (OR 4.109, P=0.016). Also, the FMD significantly curtails chemotherapy-induced DNA damage in T-lymphocytes. These positive findings encourage further exploration of the benefits of fasting/FMD in cancer therapy. Trial number: NCT02126449. Preclinical evidence suggests that a fasting mimicking diet (FMD) can make cancer cells more vulnerable to chemotherapy, while protecting normal cells. In this randomized phase II clinical trial of 131 patients with HER2 negative early stage breast cancer, the authors demonstrate that FMD is safe and enhances the effects of neoadjuvant chemotherapy on radiological and pathological tumor response.Surgical oncolog

Survival of patients with deficient mismatch repair metastatic colorectal cancer in the pre-immunotherapy era

Contains fulltext : 230109.pdf (Publisher’s version ) (Closed access)BACKGROUND: Metastatic colorectal cancer patients with deficient mismatch repair (dMMR mCRC) benefit from immunotherapy. Interpretation of the single-arm immunotherapy trials is complicated by insignificant survival data during systemic non-immunotherapy. We present survival data on a large, comprehensive cohort of dMMR mCRC patients, treated with or without systemic non-immunotherapy. METHODS: Two hundred and eighty-one dMMR mCRC patients (n = 54 from three prospective Phase 3 CAIRO trials; n = 227 from the Netherlands Cancer Registry). Overall survival was analysed from diagnosis of mCRC (OS), from initiation of first-line (OS1) and second-line (OS2) systemic treatment. Cox regression analysis examined prognostic factors. As comparison for OS 2746 MMR proficient mCRC patients were identified. RESULTS: Of 281 dMMR patients, 62% received first-line and 26% second-line treatment. Median OS was 16.0 months (13.8-19.6) with antitumour therapy and 2.5 months (1.8-3.5) in untreated patients. OS1 was 12.8 months (10.7-15.2) and OS2 6.2 months (5.4-8.9) in treated dMMR patients. Treated dMMR patients had a 7.6-month shorter median OS than pMMR patients. CONCLUSION: Available data from immunotherapy trials lack a control arm with standard systemic treatment. Given the poor outcome compared to the immunotherapy results, our data strongly suggest a survival benefit of immunotherapy in dMMR mCRC patients