Brolucizumab in Neovascular Age-Related Macular Degeneration and Diabetic Macular Edema: Ophthalmology and Diabetology Treatment Aspects.

Anti-vascular endothelial growth factor (anti-VEGF) therapies have become the standard of care in the treatment of neovascular age-related macular degeneration (nAMD) and diabetic macular edema (DME), resulting in a remarkable decrease in disease-related vision loss. However, the need for regular injections places a significant burden on patients, caregivers, and the healthcare system and improvements in vision may not be maintained long term. As a result of its drying potency and duration of action, brolucizumab, an intravitreal anti-VEGF therapy approved for the treatment of nAMD and DME, could decrease injection frequency for patients and provide an efficacious treatment; however, balancing its benefits and risks can be challenging. There have been reports of intraocular inflammation (IOI) in patients treated with brolucizumab, which, if left untreated, may result in severe vision loss. Recent evidence, however, indicates that early recognition of IOI and prompt and aggressive systemic corticosteroid treatment in response to posterior segment involvement can lead to favorable outcomes in these relatively rare but severe cases. A series of consensus meetings were conducted in 2022 between Swiss medical retina experts and diabetologists, discussing the current data for brolucizumab and exploring various challenges to its use, including the associated risk of IOI. The outcome is a collation of practical insights and guidance for ophthalmologists on the use of brolucizumab in patients with nAMD and DME, including patient selection and assessment, treatment regimen and monitoring, and the recognition and management of adverse events

An algorithm to identify patients with treated type 2 diabetes using medico-administrative data

<p>Abstract</p> <p>Background</p> <p>National authorities have to follow the evolution of diabetes to implement public health policies. An algorithm was developed to identify patients with treated type 2 diabetes and estimate its annual prevalence in Luxembourg using health insurance claims when no diagnosis code is available.</p> <p>Methods</p> <p>The DIABECOLUX algorithm was based on patients' age as well as type and number of hypoglycemic agents reimbursed between 1995 and 2006. Algorithm validation was performed using the results of a national study based on medical data. Sensitivity, specificity and predictive values were estimated.</p> <p>Results</p> <p>The sensitivity of the DIABECOLUX algorithm was found superior to 98.2%. Between 2000 and 2006, 22,178 patients were treated for diabetes in Luxembourg, among whom 21,068 for type 2 diabetes (95%). The prevalence was estimated at 3.79% in 2006 and followed an increasing linear trend during the period. In 2005, the prevalence was low for young age classes and increased rapidly from 40 to 70 for male and 80 for female, reaching a peak of, respectively 17.0% and 14.3% before decreasing.</p> <p>Conclusions</p> <p>The DIABECOLUX algorithm is relevant to identify treated type 2 diabetes patients. It is reproducible and should be transferable to every country using medico-administrative databases not including diagnosis codes. Although undiagnosed patients and others with lifestyle recommendations only were not considered in this study, this algorithm is a cheap and easy-to-use tool to inform health authorities. Further studies will use this tool with the aim of improving the quality of health care dedicated to diabetic patients in Luxembourg.</p

Genetic variation in insulin-like growth factor signaling genes and breast cancer risk among BRCA1 and BRCA2 carriers

Abstract Introduction Women who carry mutations in BRCA1 and BRCA2 have a substantially increased risk of developing breast cancer as compared with the general population. However, risk estimates range from 20 to 80%, suggesting the presence of genetic and/or environmental risk modifiers. Based on extensive in vivo and in vitro studies, one important pathway for breast cancer pathogenesis may be the insulin-like growth factor (IGF) signaling pathway, which regulates both cellular proliferation and apoptosis. BRCA1 has been shown to directly interact with IGF signaling such that variants in this pathway may modify risk of cancer in women carrying BRCA mutations. In this study, we investigate the association of variants in genes involved in IGF signaling and risk of breast cancer in women who carry deleterious BRCA1 and BRCA2 mutations. Methods A cohort of 1,665 adult, female mutation carriers, including 1,122 BRCA1 carriers (433 cases) and 543 BRCA2 carriers (238 cases) were genotyped for SNPs in IGF1, IGF1 receptor (IGF1R), IGF1 binding protein (IGFBP1, IGFBP2, IGFBP5), and IGF receptor substrate 1 (IRS1). Cox proportional hazards regression was used to model time from birth to diagnosis of breast cancer for BRCA1 and BRCA2 carriers separately. For linkage disequilibrium (LD) blocks with multiple SNPs, an additive genetic model was assumed; and for single SNP analyses, no additivity assumptions were made. Results Among BRCA1 carriers, significant associations were found between risk of breast cancer and LD blocks in IGF1R (global P = 0.011 for LD block 2 and global P = 0.012 for LD block 11). Among BRCA2 carriers, an LD block in IGFBP2 (global P = 0.0145) was found to be associated with the time to breast cancer diagnosis. No significant LD block associations were found for the other investigated genes among BRCA1 and BRCA2 carriers. Conclusions This is the first study to investigate the role of genetic variation in IGF signaling and breast cancer risk in women carrying deleterious mutations in BRCA1 and BRCA2. We identified significant associations in variants in IGF1R and IRS1 in BRCA1 carriers and in IGFBP2 in BRCA2 carriers. Although there is known to be interaction of BRCA1 and IGF signaling, further replication and identification of causal mechanisms are needed to better understand these associations

Copeptin for risk stratification in non-traumatic headache in the emergency setting: a prospective multicenter observational cohort study

In the emergency setting, non-traumatic headache is a benign symptom in 80% of cases, but serious underlying conditions need to be ruled out. Copeptin improves risk stratification in several acute diseases. Herein, we investigated the value of copeptin to discriminate between serious secondary headache and benign headache forms in the emergency setting.; Patients presenting with acute non-traumatic headache were prospectively enrolled into an observational cohort study. Copeptin was measured upon presentation to the emergency department. Primary endpoint was serious secondary headache defined by a neurologic cause requiring immediate treatment of the underlying disease. Secondary endpoint was the combination of mortality and hospitalization within 3 months. Two board-certified neurologist blinded to copeptin levels verified the endpoints after a structured 3-month-telephone interview.; Of the 391 patients included, 75 (19%) had a serious secondary headache. Copeptin was associated with serious secondary headache (OR 2.03, 95%CI 1.52-2.70, p &lt; 0.0001). Area under the curve (AUC) for copeptin to identify the primary endpoint was 0.70 (0.63-0.76). After adjusting for age &gt; 50, focal-neurological abnormalities, and thunderclap onset of symptoms, copeptin remained an independent predictive factor for serious secondary headache (OR 1.74, 95%CI 1.26-2.39, p = 0.001). Moreover, copeptin improved the AUC of the multivariate logistic clinical model (p-LR-test &lt; 0.001). Even though copeptin values were higher in patients reaching the secondary endpoint, this association was not significant in multivariate logistic regression.; Copeptin was independently associated with serious secondary headache as compared to benign headaches forms. Copeptin may be a promising novel blood biomarker that should be further validated to rule out serious secondary headache in the emergency department.; Study Registration on 08/02/2010 as NCT01174901 at clinicaltrials.gov

Measurement of the tau lepton lifetime with the three-dimensional impact parameter method.

A new method is presented for the measurement of the mean $\tau$ lepton lifetime using events in which $\tau$'s are pair-produced and both $\tau$'s decay to hadrons and $\nu_\tau$. Based on the correlation between the two $\tau$'s produced at a symmetric $e^+ e^-$ collider, the 3DIP method relies on the three-dimensional information from a double-sided vertex detector and on kinematic constraints for the precise measurement of the $\tau$ decay angles. Using the data collected from 1992 to 1994 with the ALEPH detector at LEP, a $\tau$ lifetime of $288.0 \pm 3.1 \pm 1.3$\fs is obtained from the sample in which both $\tau$'s decay to one charged track, and $292.8 \pm 5.6 \pm 3.0$\fs from the sample in which one $\tau$ decays to one prong and the other to three prongs. The results show small statistical correlations with those derived from other methods. When combined with the previously published ALEPH measurements, the resulting $\tau$ lifetime is $291.2 \pm 2.0 \pm 1.2$\fs

Measurement of the W-pair cross section in e+e−e^+ e^- collisions at 172 GeV

The e+e- --> W+W- cross section is measured in a data sample collected by ALEPH at a mean centre--of--mass energy of 172.09 GEV, corresponding to an integrated luminosity of 10.65 pb-1. Cross sections are given for the three topologies, fully leptonic, semi-leptonic and hadronic of a W-pair decay. Under the assumption that no other decay modes are present, the W-pair cross section is measured to be 11.7 +- 1.2 (stat.) +- 0.3 (syst.) pb. The existence of the triple gauge boson vertex of the Standard Model is clearly preferred by the data. The decay branching ratio of the W boson into hadrons is measured to be B(W --> hadrons) = 67.7 +- 3.1 (stat.) +- 0.7 (syst.)%, allowing a determination of the CKM matrix element |Vcs|= 0.98 +- 0.14 (stat.) +- 0.03 (syst.)

Measurement of the tau lepton lifetime with the three-dimensional impact parameter method.

A new method is presented for the measurement of the mean $\tau$ lepton lifetime using events in which $\tau$'s are pair-produced and both $\tau$'s decay to hadrons and $\nu_\tau$. Based on the correlation between the two $\tau$'s produced at a symmetric $e^+ e^-$ collider, the 3DIP method relies on the three-dimensional information from a double-sided vertex detector and on kinematic constraints for the precise measurement of the $\tau$ decay angles. Using the data collected from 1992 to 1994 with the ALEPH detector at LEP, a $\tau$ lifetime of $288.0 \pm 3.1 \pm 1.3$\fs is obtained from the sample in which both $\tau$'s decay to one charged track, and $292.8 \pm 5.6 \pm 3.0$\fs from the sample in which one $\tau$ decays to one prong and the other to three prongs. The results show small statistical correlations with those derived from other methods. When combined with the previously published ALEPH measurements, the resulting $\tau$ lifetime is $291.2 \pm 2.0 \pm 1.2$\fs

Measurement of the tau lepton lifetime with the three-dimensional impact parameter method.

A new method is presented for the measurement of the mean $\tau$ lepton lifetime using events in which $\tau$'s are pair-produced and both $\tau$'s decay to hadrons and $\nu_\tau$. Based on the correlation between the two $\tau$'s produced at a symmetric $e^+ e^-$ collider, the 3DIP method relies on the three-dimensional information from a double-sided vertex detector and on kinematic constraints for the precise measurement of the $\tau$ decay angles. Using the data collected from 1992 to 1994 with the ALEPH detector at LEP, a $\tau$ lifetime of $288.0 \pm 3.1 \pm 1.3$\fs is obtained from the sample in which both $\tau$'s decay to one charged track, and $292.8 \pm 5.6 \pm 3.0$\fs from the sample in which one $\tau$ decays to one prong and the other to three prongs. The results show small statistical correlations with those derived from other methods. When combined with the previously published ALEPH measurements, the resulting $\tau$ lifetime is $291.2 \pm 2.0 \pm 1.2$\fs

Measurement of the tau lepton lifetime with the three-dimensional impact parameter method.

A new method is presented for the measurement of the mean $\tau$ lepton lifetime using events in which $\tau$'s are pair-produced and both $\tau$'s decay to hadrons and $\nu_\tau$. Based on the correlation between the two $\tau$'s produced at a symmetric $e^+ e^-$ collider, the 3DIP method relies on the three-dimensional information from a double-sided vertex detector and on kinematic constraints for the precise measurement of the $\tau$ decay angles. Using the data collected from 1992 to 1994 with the ALEPH detector at LEP, a $\tau$ lifetime of $288.0 \pm 3.1 \pm 1.3$\fs is obtained from the sample in which both $\tau$'s decay to one charged track, and $292.8 \pm 5.6 \pm 3.0$\fs from the sample in which one $\tau$ decays to one prong and the other to three prongs. The results show small statistical correlations with those derived from other methods. When combined with the previously published ALEPH measurements, the resulting $\tau$ lifetime is $291.2 \pm 2.0 \pm 1.2$\fs