Quels professionnels travaillent dans les cabinets de médecine de famille ?. Panorama dans différents pays [Which professionals work in general practices ?. Overview in different countries]

The development of multi-professional teamwork in primary care is one solution adopted to meet the needs of care coordination and comprehensive patient management. This article describes the composition of primary care practices in terms of professionals other than general practitioners. It highlights the fact that Western countries are at quite different stages of development in this field

Papillomavirus humain : dépistage des cancers du col et de l’anus [Human Papillomavirus: screening of cervical and anal cancers]

Cervical cancer is preventable through primary and secondary prevention. Vaccination against the human papillomavirus (HPV), the virus necessary for the development of precancerous lesions, can prevent most of them. Screening by cytology for these precancerous (or cancerous) lesions can be replaced by screening for certain types of HPV, high risk (HR-HPV), causing cervical cancer. The presence of HR-HPV on the cervix should raise suspicion of concomitant infection in the anus, as both epithelia are highly susceptible. This attitude is dictated by the increase incidence in anal cancer in the population, which is also HPV-dependent and therefore also potentially preventable through vaccination and screening

Immunosurveillance encounters cancer metabolism.

Tumor cells reprogram nutrient acquisition and metabolic pathways to meet their energetic, biosynthetic, and redox demands. Similarly, metabolic processes in immune cells support host immunity against cancer and determine differentiation and fate of leukocytes. Thus, metabolic deregulation and imbalance in immune cells within the tumor microenvironment have been reported to drive immune evasion and to compromise therapeutic outcomes. Interestingly, emerging evidence indicates that anti-tumor immunity could modulate tumor heterogeneity, aggressiveness, and metabolic reprogramming, suggesting that immunosurveillance can instruct cancer progression in multiple dimensions. This review summarizes our current understanding of how metabolic crosstalk within tumors affects immunogenicity of tumor cells and promotes cancer progression. Furthermore, we explain how defects in the metabolic cascade can contribute to developing dysfunctional immune responses against cancers and discuss the contribution of immunosurveillance to these defects as a feedback mechanism. Finally, we highlight ongoing clinical trials and new therapeutic strategies targeting cellular metabolism in cancer

The use of whole body computed tomography does not lead to increased 24-h mortality in severely injured patients in circulatory shock.

The Advanced Trauma Life Support (ATLS) approach is generally accepted as the standard of care for the initial management of severely injured patients. While whole body computed tomography (WBCT) is still considered a contraindication in haemodynamically unstable trauma patients, there is a growing amount of data indicating the absence of harm from cross sectional imaging in this patient group. Our study aimed to compare the early mortality of unstable trauma patients undergoing a WBCT during the initial workup with those who did not. Single-center retrospective observational study based on the local trauma registry including 3525 patients with an ISS > 15 from January 2008 to June 2020. We compared the 24-h mortality of injured patients in circulatory shock undergoing WBCT with a control group undergoing standard workup only. Inclusion criteria were the simultaneous presence of a systolic blood pressure < 100 mmHg, lactate > 2.2 mmol/l and base excess < - 2 mmol/l as surrogate markers for circulatory shock. To control for confounding, a propensity score matched analysis with conditional logistic regression for adjustment of residual confounders and a sensitivity analysis using inverse probability weighting (IPW) with and without adjustment were performed. Of the 3525 patients, 161 (4.6%) fulfilled all inclusion criteria. Of these, 132 (82%) underwent WBCT and 29 (18%) standard work-up only. In crude and matched analyses, no difference in early (24 h) mortality was observed (WBCT, 23 (17.4%) and no-WBCT, 8 (27.6%); p = 0.21). After matching and adjustment for main confounders, the odds ratio for the event of death at 24 h in the WBCT group was 0.36 (95% CI 0.07-1.73); p = 0.20. In the present study, WBCT did not increase the risk of death at 24 h among injured patients in shock. This adds to the growing data indicating that WBCT may be offered to trauma patients in circulatory shock without jeopardizing early survival

SAKK57/16 Nab-paclitaxel and Gemcitabine in Soft Tissue Sarcoma (NAPAGE): a phase I/II trial.

To determine whether the combination of nab-paclitaxel with gemcitabine has activity in patients with pretreated soft tissue sarcoma (STS). NAPAGE is a phase Ib/II clinical trial investigating the combination of nab-paclitaxel (nab-pc) with gemcitabine employing two cohorts. One of a dose-de-escalation phase and one of expansion. In phase I, nab-pc was given at 150 mg/m <sup>2</sup> in combination with gemcitabine 1000 mg/m <sup>2</sup> every two weeks, until disease progression or unacceptable toxicity. This dose was recommended for phase II (RP2D), as there was no dose limiting toxicity (DLT) or discontinuations due to adverse events (AEs). The primary endpoint of the phase II was progression-free rate (PFR) at 3 months (H0: 20%, H1:40%). The secondary endpoints included progression free survival (PFS), overall survival (OS), AEs, objective response and patient-reported outcomes (PRO). Efficacy analysis was by intention to treat. The 3-month PFR was 56.4% (95% confidence interval CI: 39.6-72.2%). The 3-month and 6-month PFS were 58.4% (95% CI: 41.3-72.1%) and 44.6% (95% CI: 28.4-59.5%), respectively. Median PFS was 5.3 months (95% CI: 1.4-8.2) and median OS was 12.8 months (95% CI: 10.5-39.2). The most common treatment-related grade ≥ 3 AE were neutropenia (18%), followed by anemia (2.6%), hypertension (2.6%) and alanine aminotransferase increase (2.6%). Grade 1 and grade 2 peripheral sensory neuropathy (PNP) occurred in 15.4% and 20.5%, respectively. No grade 3-4 PNP was reported. Combining nab-pc and gemcitabine is safe. Promising activity is observed in pretreated STS patients with manageable toxicity. This regimen should be considered for further exploration

An updated model for predicting side-specific extraprostatic extension in the era of MRI-targeted biopsy.

Accurate prediction of extraprostatic extension (EPE) is pivotal for surgical planning. Herein, we aimed to provide an updated model for predicting EPE among patients diagnosed with MRI-targeted biopsy. We analyzed a multi-institutional dataset of men with clinically localized prostate cancer diagnosed by MRI-targeted biopsy and subsequently underwent prostatectomy. To develop a side-specific predictive model, we considered the prostatic lobes separately. A multivariable logistic regression analysis was fitted to predict side-specific EPE. The decision curve analysis was used to evaluate the net clinical benefit. Finally, a regression tree was employed to identify three risk categories to assist urologists in selecting candidates for nerve-sparing, incremental nerve sparing and non-nerve-sparing surgery. Overall, data from 3169 hemi-prostates were considered, after the exclusion of prostatic lobes with no biopsy-documented tumor. EPE was present on final pathology in 1,094 (34%) cases. Among these, MRI was able to predict EPE correctly in 568 (52%) cases. A model including PSA, maximum diameter of the index lesion, presence of EPE on MRI, highest ISUP grade in the ipsilateral hemi-prostate, and percentage of positive cores in the ipsilateral hemi-prostate achieved an AUC of 81% after internal validation. Overall, 566, 577, and 2,026 observations fell in the low-, intermediate- and high-risk groups for EPE, as identified by the regression tree. The EPE rate across the groups was: 5.1%, 14.9%, and 48% for the low-, intermediate- and high-risk group, respectively. In this study we present an update of the first side-specific MRI-based nomogram for the prediction of extraprostatic extension together with updated risk categories to help clinicians in deciding on the best approach to nerve-preservation

Mental health professionals' use of the ICD-11 classification of impulse control disorders and behavioral addictions: An international field study

Background and aims The ICD-11 chapter on mental, behavioral and neurodevelopmental disorders contains new controversial diagnoses including compulsive sexual behavior disorder (CSBD), intermittent explosive disorder (IED) and gaming disorder. Using a vignette-based methodology, this field study examined the ability of mental health professionals (MHPs) to apply the new ICD-11 diagnostic requirements for impulse control disorders, which include CSBD and IED, and disorders due to addictive behaviors, which include gaming disorder, compared to the previous ICD-10 guidelines. Methods Across eleven comparisons, members of the WHO's Global Clinical Practice Network (N = 1,090) evaluated standardized case descriptions that were designed to test key differences between the diagnostic guidelines of ICD-11 and ICD-10. Results The ICD-11 outperformed the ICD-10 in the accuracy of diagnosing impulse control disorders and behavioral addictions in most comparisons, while the ICD-10 was not superior in any. The superiority of the ICD-11 was particularly clear where new diagnoses had been added to the classification system or major revisions had been made. However, the ICD-11 outperformed the ICD-10 only in a minority of comparisons in which mental health professionals were asked to evaluate cases with non-pathological high involvement in rewarding behaviors. Discussion and Conclusions Overall, the present study indicates that the ICD-11 diagnostic requirements represent an improvement over the ICD-10 guidelines. However, additional efforts, such as training programs for MHPs and possible refinements of diagnostic guidance, are needed to avoid over-diagnosis of people who are highly engaged in a repetitive and rewarding behavior but below the threshold for a disorder

Drug Exposure of Long-Acting Cabotegravir and Rilpivirine in Older People With Human Immunodeficiency Virus: A Pharmacokinetic Modeling Study.

The life expectancy of people with human immunodeficiency virus (PWH) has significantly increased, thanks to combined antiretrovirals with improved potency and tolerability. One further step has been achieved with the development of long-acting (LA) injectable antiretrovirals, which allow for infrequent dosing. However, the pharmacokinetics of LA antiretrovirals has been poorly characterized in older PWH, as they are generally excluded from trials. We performed virtual studies using physiologically based pharmacokinetic (PBPK) modeling to determine the anticipated exposure of LA cabotegravir/rilpivirine in older individuals. Our PBPK model was verified against available observed data for LA cabotegravir and rilpivirine. Cohorts of virtual individuals aged 20-50, 50-65, or 65-85 years were generated to simulate the exposure of LA cabotegravir/rilpivirine for each age group. The fold changes in trough concentration (C <sub>min</sub> ) and in drug exposure (area under the time-concentration curve [AUC]) were determined for older relative to young individuals. The verified PBPK models predicted an increase in exposure within the 0.8-1.25 fold range for monthly LA cabotegravir/rilpivirine. The C <sub>min</sub> and AUC were predicted to be 29% and 26% higher in older compared with young adults for LA cabotegravir administered bimonthly (every 2 months) and 46% and 41% higher for LA rilpivirine bimonthly. The C <sub>min</sub> and AUC of LA cabotegravir and rilpivirine were predicted to be modestly increased in female compared with male individuals for all age groups. LA cabotegravir/rilpivirine exposure and trough concentrations are predicted to be higher in older than in young PWH; thus, older adults could have a lower risk to present suboptimal concentrations during the dosing interval