[Evolution of cancer treatment modalities]. / Évolution des modalités de traitement des cancers.

EVOLUTION OF CANCER TREATMENT MODALITIES. Innovation in oncology faces many challenges: increasing costs for the communities, constant changes in practices and organizations, and a desire to benefit as many patients as possible while respecting safety and effectiveness rules. It is essential to encourage innovation and support its development in order to reduce the loss of opportunities. Innovation is not restricted to the development stages of a molecule, or to clinical trials, but also concerns the organization of care paths. Mechanisms are in place to enable innovations to be implemented quickly and safely in France, and some recent examples of treatments have profoundly changed practices.

ÉVOLUTION DES MODALITÉS DE TRAITEMENT DES CANCERS. L'innovation en cancérologie fait face à de nombreux défis : accroissement des coûts pour la collectivité, modification constante des pratiques et des organisations, et volonté de faire bénéficier au plus grand nombre de patients possible des traitements les plus novateurs tout en respectant les règles de sécurité et d'efficacité. Il est essentiel de faire émerger l'innovation et d'accompagner son développement afin de diminuer les pertes de chance. L'innovation n'est pas limitée aux étapes du développement d'une molécule ou aux essais cliniques mais elle concerne également l'organisation des parcours de soins. Des dispositifs permettent la mise en oeuvre accélérée et sécurisée des innovations en France, et certains exemples récents de traitements ont profondément modifié les pratiques.

Verifying measurements on Siemens Atellica® instruments using clinically acceptable analytical performance specifications.

Measurements on clinical chemistry analysers must be verified to demonstrate applicability to their intended clinical use. We verified the performance of measurements on the Siemens Atellica® Solution chemistry analysers against the clinically acceptable analytical performance specifications, CAAPS, including the component of intra-individual biological variation, CVI. The relative standard uncertainty of measurement, i.e. analytical variation, CVA, was estimated for six example measurands, haemoglobin A1c in whole blood (B-HbA1c), albumin in urine (U-Alb), and the following measurands in plasma: sodium (P-Na), pancreatic amylase (P-AmylP), low-density lipoprotein cholesterol (P-LDL-C), and creatinine (P-Crea). Experimental CVA was calculated from single-instrument imprecision using control samples, variation between measurements on parallel instruments, and estimation of bias with pooled patient specimens. Each obtained CVA was compared with previously developed CAAPS. The calculated CVA was 1.4% for B-HbA1c (CAAPS 1.9% for single diagnostic testing, CAAPS 2.0% for monitoring after duplicate tests; IFCC units), 10.9% for U-Alb (CAAPS 44.9%), 1.2% for P-Na (CAAPS 0.6%, after triplicate testing 1.5%), 8.2% for P-AmylP (CAAPS 22.9%). The CVA was 4.9% for P-LDL-C (CAAPS for cardiovascular risk stratification 4.9% after four replicates), and 4.2% for P-Crea (CAAPS 8.0%). Three of the six measurands fulfilled the estimated clinical need. Results from P-Na measurements indicate a general need for improving the P-Na assays for emergency patients. It is necessary to consider CVI when creating diagnostic targets for laboratory tests, as emphasised by the CAAPS estimates of B-HbA1c and P-LDL-C.

Variability of Active Cervical Range of Motion Within and Between Days in Healthy Participants: A Prospective Observational Study.

OBJECTIVE: The purpose of this study was to determine the intraday and interday variability and systematic change over the day of active cervical range of motion (aCROM) measurements in asymptomatic persons using a clinically applicable measurement device. METHODS: A prospective observational study was performed. Sixteen adults (8 men and 8 women, median age 51 years) without neck pain in the last 3 months were recruited in 2 physiotherapy practices. Active cervical range of motion was estimated using the Apple iPhone application "3D Range of Motion." Measurements were performed 3 times a day for 7 days and spread over a period of 3 weeks. Mean values of aCROM were calculated. Intraday and interday variability was estimated by calculating limits of agreement. RESULTS: The limits of agreement for intraday variability ranged from ±12.1° for left rotation to ±15.5° for total rotation. For interday variability, the limits of agreement ranged from ±14.2° for right rotation to ±20.1° for total rotation. No systematic change over the day was found. CONCLUSION: This study showed substantial intraday and interday variability of aCROM measurements in asymptomatic people. No trend toward an increased or decreased aCROM was observed during the course of the day. When interpreting aCROM values, clinicians should consider the degree of variation in aCROM measurements over time.

Can a Single Measurement of Apixaban Levels Identify Patients at Risk of Overexposure? A Prospective Cohort Study.

Background Patients with atrial fibrillation (AF) are frequently treated with apixaban 2.5-mg twice daily (BID) off-label, presumably to reduce the bleeding risk. However, this approach has the potential to increase the risk of ischemic stroke. If a single measurement could reliably identify patients with high drug levels, the increased stroke risk may be mitigated by confining off-label dose reduction to such patients. Objectives This study aimed to determine whether a single high apixaban level is predictive of a similarly high level when the test is repeated in 2 months. Methods In this prospective cohort study of clinic patients receiving apixaban 5-mg BID for AF or venous thromboembolism, peak and trough apixaban levels were measured using the STA-Liquid anti-Xa assay at baseline and 2 months. We calculated the proportions of patients with levels that remained in the upper quintile. Results Of 100 enrolled patients, 82 came for a second visit, 55 of whom were treated with apixaban 5-mg BID. Seven (63.6%, 95% confidence interval [CI]: 35.4-84.8%) and nine (81.8%, 95% CI: 52.3-94.9%) of 11 patients with a baseline trough and peak level in the upper quintile, respectively, had a subsequent level that remained within this range. Only one (9.1%, 95% CI: 1.6-37.7%) patient had a subsequent level that fell just lower than the median. Conclusion The trough and peak levels of apixaban in patients who have a high level on a single occasion, usually remain high when the assay is repeated in 2 months. Accordingly, the finding of a high apixaban level in patients deemed to be at high risk of bleeding, allows physicians contemplating off-label use of the 2.5-mg BID dose to limit its use to selected patients who are less likely to be exposed to an increased risk of thrombosis.

Persistent median artery inside the carpal tunnel: description and surgical implications.

The median artery is usually a transient vessel during the embryonic period. However, this artery can persist in adult life as the persistent median artery. This paper aims to describe this relevant anatomical variation for surgeons, review the literature and discuss its clinical implications. A routine dissection was performed in the upper left limb of a male adult cadaver of approximately 50-60 years of age, embalmed in formalin 10%. The persistent median artery was identified emerging as a terminal branch of the common interosseous artery with a path along the ulnar side of the median nerve. In the wrist, the persistent median artery passed through the carpal tunnel, deep in the transverse carpal ligament. The dissection in the palmar region revealed no anastomosis with the ulnar artery forming the superficial palmar arch. The common digital arteries emerged from the ulnar artery and the persistent median artery. Such variation has clinical and surgical relevance in approaching carpal tunnel syndrome and other clinical disorders in the wrist.

Short term biological variation of common hematological parameters in healthy subjects in a South Asian population.

There is no rigorous publication on the biological variation of common hematological parameters in South Asians to date. Also, there are few publications worldwide dealing with a variation of Reticulocyte parameters. Therefore, an attempt was made to estimate the short term within-subject and between-subject biological variation of common hematological and reticulocyte parameters. Twenty-eight healthy individuals (fifteen males and thirteen females) were selected after clinical and laboratory examination. Blood was collected in K3-EDTA vials in the morning for six consecutive days and analysed in triplicate on the Sysmex XN-1000 analyzer. Outliers were excluded and the within-subject, between-subject and analytical coefficient of variation calculated after statistical analysis by nested repeated measures ANOVA. The Reference change values (RCV), and estimates for desirable imprecision, bias, total error and index of individuality calculated. The within-subject biological variation for the studied subset belonging to South Asia closely followed published European and American studies and were similar for males and females. The between-subject variation showed differences from the published studies for white blood cells, platelets, red blood cells, hemoglobin, platelet indices and reticulocyte hemoglobin as well as between males and females for hemoglobin, red blood cell count and hematocrit. All the indices of individuality were low. This study supports the contention that the conclusions from within-subject biological variation for common hematological parameters are important and transportable to a South Asian population for short-term serial measurements. For quality specifications dependent on between-subject variation, the lower estimates from European and American studies should be used.

Persistent median artery inside the carpal tunnel: description and surgical implications

The median artery is usually a transient vessel during the embryonic period. However, this artery can persist in adult life as the persistent median artery. This paper aims to describe this relevant anatomical variation for surgeons, review the literature and discuss its clinical implications. A routine dissection was performed in the upper left limb of a male adult cadaver of approximately 50-60 years of age, embalmed in formalin 10%. The persistent median artery was identified emerging as a terminal branch of the common interosseous artery with a path along the ulnar side of the median nerve. In the wrist, the persistent median artery passed through the carpal tunnel, deep in the transverse carpal ligament. The dissection in the palmar region revealed no anastomosis with the ulnar artery forming the superficial palmar arch. The common digital arteries emerged from the ulnar artery and the persistent median artery. Such variation has clinical and surgical relevance in approaching carpal tunnel syndrome and other clinical disorders in the wrist.

Cardiovascular Autonomic Neuropathy Predicts Higher HbA1c Variability in Subjects with Type 2 Diabetes Mellitus.

BACKGROUND: This study aimed to investigate the association between the presence and severity of cardiovascular autonomic neuropathy (CAN) and development of long-term glucose fluctuation in subjects with type 2 diabetes mellitus. METHODS: In this retrospective cohort study, subjects with type 2 diabetes mellitus who received cardiovascular autonomic reflex tests (CARTs) at baseline and at least 4-year of follow-up with ≥6 measures of glycosylated hemoglobin (HbA1c) were included. The severity of CAN was categorized as normal, early, or severe CAN according to the CARTs score. HbA1c variability was measured as the standard deviation (SD), coefficient of variation, and adjusted SD of serial HbA1c measurements. RESULTS: A total of 681 subjects were analyzed (294 normal, 318 early, and 69 severe CAN). The HbA1c variability index values showed a positive relationship with the severity of CAN. Multivariable logistic regression analysis showed that CAN was significantly associated with the risk of developing higher HbA1c variability (SD) after adjusting for age, sex, body mass index, diabetes duration, mean HbA1c, heart rate, glomerular filtration rate, diabetic retinopathy, coronary artery disease, insulin use, and anti-hypertensive medication (early CAN: odds ratio [OR], 1.65; 95% confidence interval [CI], 1.12 to 2.43) (severe CAN: OR, 2.86; 95% CI, 1.47 to 5.56). This association was more prominent in subjects who had a longer duration of diabetes (>10 years) and lower mean HbA1c (<7%). CONCLUSION: CAN is an independent risk factor for future higher HbA1c variability in subjects with type 2 diabetes mellitus. Tailored therapy for stabilizing glucose fluctuation should be emphasized in subjects with CAN.

Cardiovascular Autonomic Neuropathy Predicts Higher HbA1c Variability in Subjects with Type 2 Diabetes Mellitus

BACKGROUND: This study aimed to investigate the association between the presence and severity of cardiovascular autonomic neuropathy (CAN) and development of long-term glucose fluctuation in subjects with type 2 diabetes mellitus. METHODS: In this retrospective cohort study, subjects with type 2 diabetes mellitus who received cardiovascular autonomic reflex tests (CARTs) at baseline and at least 4-year of follow-up with ≥6 measures of glycosylated hemoglobin (HbA1c) were included. The severity of CAN was categorized as normal, early, or severe CAN according to the CARTs score. HbA1c variability was measured as the standard deviation (SD), coefficient of variation, and adjusted SD of serial HbA1c measurements. RESULTS: A total of 681 subjects were analyzed (294 normal, 318 early, and 69 severe CAN). The HbA1c variability index values showed a positive relationship with the severity of CAN. Multivariable logistic regression analysis showed that CAN was significantly associated with the risk of developing higher HbA1c variability (SD) after adjusting for age, sex, body mass index, diabetes duration, mean HbA1c, heart rate, glomerular filtration rate, diabetic retinopathy, coronary artery disease, insulin use, and anti-hypertensive medication (early CAN: odds ratio [OR], 1.65; 95% confidence interval [CI], 1.12 to 2.43) (severe CAN: OR, 2.86; 95% CI, 1.47 to 5.56). This association was more prominent in subjects who had a longer duration of diabetes (>10 years) and lower mean HbA1c ( < 7%). CONCLUSION: CAN is an independent risk factor for future higher HbA1c variability in subjects with type 2 diabetes mellitus. Tailored therapy for stabilizing glucose fluctuation should be emphasized in subjects with CAN.