Statin-related adverse drug reactions in UK primary care consultations: A retrospective cohort study to evaluate the risk of cardiovascular events and all-cause mortality

AIMS: To investigate the risk of cardiovascular disease (CVD) events and all-cause mortality in patients with statin-related adverse drug reaction (ADR) consultation in primary care and examine whether different treatments following the ADR affect subsequent outcomes. METHODS: This was a retrospective cohort study of statin users between 2004 and 2019 using IQVIA Medical Research Data (formally known as the THIN database). Patients with statin-related ADR consultation were matched by propensity score (1:1) to statin users without ADR consultation based on demographics, comorbidities and concomitant medication. Cox proportional hazard regression was used to compare the risk of subsequent CVD event and all-cause mortality, stratified by history of CVD. In the secondary analysis among patients with statin-related ADR, treatment changes within a 1-year period following the ADR were examined and the outcomes were compared between different treatment groups. RESULTS: Among 1 564 687 statin users, 19 035 (1.22%) had a statin-related ADR consultation in primary care. The mean (standard deviation) follow-up time was 6.32 (3.74) years and 5.31 (3.83) years for CVD primary and secondary prevention cohorts, respectively. Statin-related ADR consultation was associated with subsequent CVD events in both cohorts (adjusted hazard ratio [HR] of 1.39 [95% CI 1.23, 1.57] and 1.34 [95% CI 1.25,1.42], respectively). In the secondary analysis among patients with statin-related ADR consultation, we found that (i) continued statin prescription or combination of any statin with additional lipid-lowering treatment (LLT) and (ii) other LLT only were associated with lower risks of CVD event (adjusted HR 0.71 [95% CI 0.64, 0.78] and 0.75 [95% CI 0.62, 0.92], respectively) and all-cause mortality (adjusted HR 0.46 [95% CI 0.42, 0.50] and 0.52 [95% CI, 0.43, 0.64], respectively), compared to discontinuation of all LLT. CONCLUSION: Statin-related ADR was associated with an increased risk of subsequent CVD event, indicating that these patients should be monitored more closely. Continued lipid-lowering medication is of importance to protect against CVD events and mortality

Nutritional Biomarkers, Gene-Diet Interaction, and Risk Factors for Type 2 Diabetes

10.1155/2016/8610501Journal of Diabetes Research2016861050

The Middle Stone Age in the Eastern Desert. EDAR 135 — a buried early MIS 5 horizon from Sudan

Middle Stone Age (MSA) lithic artefacts coming from dated layers preserved in their original stratigraphic position are still rare in Northeast Africa in general and in Sudan in particular. This paper aims to present the results of technological and functional analyses of an assemblage coming from a stratigraphic context, i.e. the upper level of the EDAR (Eastern Desert – Atbara River) 135 site, discovered in an abandoned gold mining pit in the Sudanese Eastern Desert, approximately 70 km east of the town of Atbara. The assemblage, which is based on locally available quartz and rhyolite, comes from a layer bracketed by OSL dates of 116 ± 13 and 125 ± 11 kya. Such dating places it within Marine Isotope Stage 5e–5d. Analysis of the assemblage revealed several characteristics that seem to set it apart from other MSA Northeast African inventories. Among these, the dominance of simple, non-predetermined core reduction strategies and expedient tool types, coupled with the lack of traces of Nubian Levallois technique, are the most conspicuous. Micro-traces of use on animal and plant matter were preserved on some of the tools. EDAR 135 is part of a newly discovered complex of sites that confirms the presence of Middle and Late Pleistocene hominins along one of the possible routes out of Africa towards Eurasia.publishedVersio

High-fidelity spin and optical control of single silicon-vacancy centres in silicon carbide

Scalable quantum networking requires quantum systems with quantum processing capabilities. Solid state spin systems with reliable spin–optical interfaces are a leading hardware in this regard. However, available systems suffer from large electron–phonon interaction or fast spin dephasing. Here, we demonstrate that the negatively charged silicon-vacancy centre in silicon carbide is immune to both drawbacks. Thanks to its 4A2 symmetry in ground and excited states, optical resonances are stable with near-Fourier-transform-limited linewidths, allowing exploitation of the spin selectivity of the optical transitions. In combination with millisecond-long spin coherence times originating from the high-purity crystal, we demonstrate high-fidelity optical initialization and coherent spin control, which we exploit to show coherent coupling to single nuclear spins with ∼1 kHz resolution. The summary of our findings makes this defect a prime candidate for realising memory-assisted quantum network applications using semiconductor-based spin-to-photon interfaces and coherently coupled nuclear spins

Obesity Early in Adulthood Increases Risk but Does Not Affect Outcomes of Hepatocellular Carcinoma

Despite the significant association between obesity and several cancers, it has been difficult to establish an association between obesity and hepatocellular carcinoma (HCC). Patients with HCC often have ascites, making it a challenge to accurately determine body mass index (BMI), and many factors contribute to the development of HCC. We performed a case–control study to investigate whether obesity early in adulthood affects risk, age of onset, or outcomes of patients with HCC

Physiological and pathophysiological homeostasis of astroglial channel proteins by Nedd4-2

Nedd4-2 is an E3 ubiquitin ligase, missense mutation of which is related to familial epilepsy, indicating its critical role in regulating neuronal network activity. However, Nedd4-2 substrates involved in neuronal network function have yet to be identified. Using mouse lines lacking Nedd4-1 and Nedd4-2, we identified astrocytic channel proteins inwardly rectifying K+ channel 4.1 (Kir4.1) and Connexin43 as Nedd4-2 substrates. We found that the expression of Kir4.1 and Connexin43 is increased upon conditional deletion of Nedd4-2 in astrocytes, leading to an elevation of astrocytic membrane ion permeability and gap junction activity, with a consequent reduction of γ-oscillatory neuronal network activity. Interestingly, our biochemical data demonstrate that missense mutations found in familial epileptic patients produce gain-of-function of Nedd4-2 gene product. Our data reveal a process of coordinated astrocytic ion channel proteostasis that controls astrocyte function and astrocyte-dependent neuronal network activity, and elucidate a potential mechanism by which aberrant Nedd4-2 function leads to epilepsy

Notable sequence homology of the ORF10 protein introspects the architecture of SARS-CoV-2

The current Coronavirus Disease 19 (COVID-19) pandemic, caused by Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) shows similar pathology to MERS and SARS-CoV, with a current estimated fatality rate of 1.4%. Open reading frame 10 (ORF10) is a unique SARS-CoV-2 accessory protein, which contains eleven cytotoxic T lymphocyte (CTL) epitopes each of nine amino acids in length. Twenty-two unique SARS-CoV-2 ORF10 variants have been identified based on missense mutations found in sequence databases. Some of these mutations are predicted to decrease the stability of ORF10 in silico physicochemical and structural comparative analyses were carried out on SARS-CoV-2 and Pangolin-CoV ORF10 proteins, which share 97.37% amino acid (aa) homology. Though there is a high degree of ORF10 protein similarity of SARS-CoV-2 and Pangolin-CoV, there are differences of these two ORF10 proteins related to their sub-structure (loop/coil region), solubility, antigenicity and shift from strand to coil at aa position 26 (tyrosine). SARS-CoV-2 ORF10, which is apparently expressed in vivo since reactive T cell clones are found in convalescent patients should be monitored for changes which could correlate with the pathogenesis of COVID-19

Effects of Resistance Training of Peripheral Muscles Versus Respiratory Muscles in Older Adults With Sarcopenia Who are Institutionalized: A Randomized Controlled Trial

[EN] This study compares the effects of two resistance training programs in peripheral and respiratory musculature on muscle mass and strength and physical performance and identifies the appropriate muscle mass parameter for assessing the intervention effects. Thirty-seven institutionalized older Spanish adults with sarcopenia were analyzed: control group (n = 17), respiratory muscle training group (n = 9), and peripheral muscle training group (n = 11). Measured outcomes were appendicular skeletal muscle mass (ASM/height(2), ASM/weight, and ASM/BMI), isometric knee extension, arm flexion and handgrip strength, maximal inspiratory and expiratory pressures, and gait speed pre- and postintervention. Trained groups participated in a 12-week program and improved in maximum static inspiratory pressure, maximum static expiratory pressure, knee extension, and arm flexion (p < .05), whereas nonsignificant changes were found in gait speed and ASM indexes pre-and postintervention in the three groups. In conclusion, resistance training improved skeletal muscle strength in the studied population, and any ASM index was found to be appropriate for detecting changes after physical interventions.This study was supported by Universitat de Valencia (UV-INV-AE14-269704) and has no conflict of interest to declare.Cebriá, M.; Balasch-Bernat, M.; Tortosa, M.; Balasch Parisi, S. (2018). Effects of Resistance Training of Peripheral Muscles Versus Respiratory Muscles in Older Adults With Sarcopenia Who are Institutionalized: A Randomized Controlled Trial. Journal of Aging and Physical Activity. 26(4):637-646. https://doi.org/10.1123/japa.2017-0268S63764626