Association between SGLT2 Inhibitors vs DPP-4 Inhibitors and Risk of Pneumonia Among Patients with Type 2 Diabetes

Context: Patients with diabetes are at a higher risk of pneumonia and pneumonia mortality. Sodium glucose co-transporter 2 inhibitors (SGLT2is), the latest class of glucose-lowering agents, were shown to reduce the risk of pneumonia in clinical trials. However, the real-world effectiveness of SGLT2is on the risk of pneumonia is largely unknown. Objective: To investigate the associations between SGLT2is use and the risk of pneumonia and pneumonia mortality compared with dipeptidyl peptidase-4 inhibitors (DPP4is) using an electronic medical database in Hong Kong. Design A retrospective cohort study. The “prevalent new-user” design was adopted to account for the previous exposure to the study drugs being compared. Propensity score (PS) matching (1:4) was used to balance the baseline characteristics of the 2 groups. Setting and participants Electronic health data of type 2 diabetes patients using SGLT2is and DPP4is between 2015 and 2018 was collected from the Clinical Data Analysis and Reporting System. Main Outcome Measures: Pneumonia incidence and mortality. Results: The PS-matched cohort consisted of 6664 users of SGLT2is and 26 656 users of DPP4is, with a mean follow-up of 3.8 years. Poisson regression showed that SGLT2is use was associated with lower risk of pneumonia compared with DPP4is with an absolute rate difference of 4.05 per 1000 person-years (95% CI, 2.61-5.51). The corresponding incidence rate ratio was 0.71 (95% CI, 0.62-0.81). Similar reduction in risk of pneumonia death was observed (hazard ratio 0.57; 95% CI, 0.42-0.77). Conclusion: Compared with DPP4is, SGLT2is use was associated with a reduced risk of pneumonia and pneumonia mortality in a real-world setting

Perception of Cantonese Parkinsonian speech

Abstract no. 1pSC18published_or_final_versio

Evidence for Shared Cognitive Processing of Pitch in Music and Language

Language and music epitomize the complex representational and computational capacities of the human mind. Strikingly similar in their structural and expressive features, a longstanding question is whether the perceptual and cognitive mechanisms underlying these abilities are shared or distinct – either from each other or from other mental processes. One prominent feature shared between language and music is signal encoding using pitch, conveying pragmatics and semantics in language and melody in music. We investigated how pitch processing is shared between language and music by measuring consistency in individual differences in pitch perception across language, music, and three control conditions intended to assess basic sensory and domain-general cognitive processes. Individuals’ pitch perception abilities in language and music were most strongly related, even after accounting for performance in all control conditions. These results provide behavioral evidence, based on patterns of individual differences, that is consistent with the hypothesis that cognitive mechanisms for pitch processing may be shared between language and music.National Science Foundation (U.S.). Graduate Research Fellowship ProgramEunice Kennedy Shriver National Institute of Child Health and Human Development (U.S.) (Grant 5K99HD057522

Sarcopenia and mortality in different clinical conditions: A meta-analysis

Objectives: Sarcopenia is recognized to be a health problem which is as serious as obesity, but its relevance to mortality is unclear. We conducted a meta-analysis of cohort studies on lean mass and mortality in populations with different health conditions. / Methods: In this study, a systematic search of PubMed, Cochrane Library and Embase was performed for cohort studies published before Dec 20, 2017 which examined the relationship between lean mass and mortality. We included studies reporting lean mass measurement by dual-energy X-ray absorptiometry, bioimpedance analysis or computed tomography, as continuous (per standard deviation [SD] decrease) or binary variables (using sarcopenia cutoffs). We excluded studies which used muscle mass surrogates, anthropometric measurement of muscle, rate of change in muscle mass, and sarcopenia defined by composite criteria. The primary study outcome was all-cause mortality. Pooled hazard ratio estimates were calculated using a random effects model. / Results: A total of 9602 articles were identified from the systematic search, and 188 studies with 98 468 participants from 34 countries were included in the meta-analysis. Of the 68 studies included in the present meta-analysis, the pooled HR was 1.36 and 1.74 for every SD decrease in lean mass and in people with low lean mass (cutoffs), respectively. Significant associations were also observed in elderly and all disease subgroups, irrespective of the measurement modalities. / Conclusions: Lower lean mass is robustly associated with increased mortality, regardless of health conditions and lean mass measurement modalities. This meta-analysis highlighted low lean mass as a key public health issue

The Derived Allele of ASPM Is Associated with Lexical Tone Perception

The ASPM and MCPH1 genes have been implicated in the adaptive evolution of the human brain [Mekel-Bobrov N. et al., 2005. Ongoing adaptive evolution of ASPM, a brain size determinant in homo sapiens. Science 309; Evans P.D. et al., 2005. Microcephalin, a gene regulating brain size, continues to evolve adaptively in humans. Science 309]. Curiously, experimental attempts have failed to connect the implicated SNPs in these genes with higher-level brain functions. These results stand in contrast with a population-level study linking the population frequency of their alleles with the tendency to use lexical tones in a language [Dediu D., Ladd D.R., 2007. Linguistic tone is related to the population frequency of the adaptive haplogroups of two brain size genes, ASPM and microcephalin. Proc. Natl. Acad. Sci. U.S.A. 104]. In the present study, we found a significant correlation between the load of the derived alleles of ASPM and tone perception in a group of European Americans who did not speak a tone language. Moreover, preliminary results showed a significant correlation between ASPM load and hemodynamic responses to lexical tones in the auditory cortex, and such correlation remained after phonemic awareness, auditory working memory, and non-verbal IQ were controlled. As in previous studies, no significant correlation between ASPM and cognitive measures were found. MCPH1 did not correlate with any measures. These results suggest that the association between the recently derived allele of ASPM is likely to be specific and is tied to higher level brain functions in the temporal cortex related to human communication

Sensitivity to musical emotion is influenced by tonal structure in congenital amusia

Emotional communication in music depends on multiple attributes including psychoacoustic features and tonal system information, the latter of which is unique to music. The present study investigated whether congenital amusia, a lifelong disorder of musical processing, impacts sensitivity to musical emotion elicited by timbre and tonal system information. Twenty-six amusics and 26 matched controls made tension judgments on Western (familiar) and Indian (unfamiliar) melodies played on piano and sitar. Like controls, amusics used timbre cues to judge musical tension in Western and Indian melodies. While controls assigned significantly lower tension ratings to Western melodies compared to Indian melodies, thus showing a tonal familiarity effect on tension ratings, amusics provided comparable tension ratings for Western and Indian melodies on both timbres. Furthermore, amusics rated Western melodies as more tense compared to controls, as they relied less on tonality cues than controls in rating tension for Western melodies. The implications of these findings in terms of emotional responses to music are discussed

Effect of alirocumab on mortality after acute coronary syndromes. An analysis of the ODYSSEY OUTCOMES randomized clinical trial

Background: Previous trials of PCSK9 (proprotein convertase subtilisin-kexin type 9) inhibitors demonstrated reductions in major adverse cardiovascular events, but not death. We assessed the effects of alirocumab on death after index acute coronary syndrome. Methods: ODYSSEY OUTCOMES (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab) was a double-blind, randomized comparison of alirocumab or placebo in 18 924 patients who had an ACS 1 to 12 months previously and elevated atherogenic lipoproteins despite intensive statin therapy. Alirocumab dose was blindly titrated to target achieved low-density lipoprotein cholesterol (LDL-C) between 25 and 50 mg/dL. We examined the effects of treatment on all-cause death and its components, cardiovascular and noncardiovascular death, with log-rank testing. Joint semiparametric models tested associations between nonfatal cardiovascular events and cardiovascular or noncardiovascular death. Results: Median follow-up was 2.8 years. Death occurred in 334 (3.5%) and 392 (4.1%) patients, respectively, in the alirocumab and placebo groups (hazard ratio [HR], 0.85; 95% CI, 0.73 to 0.98; P=0.03, nominal P value). This resulted from nonsignificantly fewer cardiovascular (240 [2.5%] vs 271 [2.9%]; HR, 0.88; 95% CI, 0.74 to 1.05; P=0.15) and noncardiovascular (94 [1.0%] vs 121 [1.3%]; HR, 0.77; 95% CI, 0.59 to 1.01; P=0.06) deaths with alirocumab. In a prespecified analysis of 8242 patients eligible for ≥3 years follow-up, alirocumab reduced death (HR, 0.78; 95% CI, 0.65 to 0.94; P=0.01). Patients with nonfatal cardiovascular events were at increased risk for cardiovascular and noncardiovascular deaths (P<0.0001 for the associations). Alirocumab reduced total nonfatal cardiovascular events (P<0.001) and thereby may have attenuated the number of cardiovascular and noncardiovascular deaths. A post hoc analysis found that, compared to patients with lower LDL-C, patients with baseline LDL-C ≥100 mg/dL (2.59 mmol/L) had a greater absolute risk of death and a larger mortality benefit from alirocumab (HR, 0.71; 95% CI, 0.56 to 0.90; Pinteraction=0.007). In the alirocumab group, all-cause death declined wit h achieved LDL-C at 4 months of treatment, to a level of approximately 30 mg/dL (adjusted P=0.017 for linear trend). Conclusions: Alirocumab added to intensive statin therapy has the potential to reduce death after acute coronary syndrome, particularly if treatment is maintained for ≥3 years, if baseline LDL-C is ≥100 mg/dL, or if achieved LDL-C is low. Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01663402

Psychosocial impact of Huntington's disease on Hong Kong Chinese families

Twenty-eight asymptomatic relatives from 7 Chinese families with Huntington's disease (HD) received psychosocial assessment. One third of these subjects (n = 9) had symptoms of anxiety and depression that warranted a Present State Examination (PSE) diagnosis. One quarter of these subjects (n = 8) would contemplate suicide if their predictive testing indicated a high risk of having the disease. This suicidal risk was associated with a PSE diagnosis of depression and a stress-coping repertoire with a high proportion of coping strategies of the avoidance type at the time of interview. Early and close liaison with these subjects for the detection of mental symptoms and provision of counselling on a balanced and positive coping style is essential.link_to_subscribed_fulltex

Positive effects of low LDL-C and statins on bone mineral density: an integrated epidemiological observation analysis and Mendelian Randomization study

Background: Low-density lipoprotein cholesterol (LDL-C) is suggested to play a role in osteoporosis but its association with bone metabolism remains unclear. Effects of LDL-C-lowering drugs on bone are also controversial. We aim to determine whether LDL-C is linked causally to bone mineral density (BMD) and assess the effects of LDL-C-lowering drugs on BMD. Methods: Association between blood lipid levels and BMD was examined by epidemiological observation analyses in a US representative cohort NHANES III (n = 3638) and the Hong Kong Osteoporosis Study (HKOS; n = 1128). Two-sample Mendelian randomization (MR), employing genetic data from a large-scale genome-wide association study (GWAS) of blood lipids (n = 188 577), total body BMD (TB-BMD) (n = 66 628) and estimated BMD (eBMD) (n= 142 487), was performed to infer causality between LDL-C and BMD. Genetic proxies for LDL-C-lowering drugs were used to examine the drugs’ effects on BMD. Results: In the NHANES III cohort, each standard deviation (SD) decrease in LDL-C was associated with a 0.045 SD increase in femoral neck BMD (95% CI: 0.009 − 0.081; P = 0.015). A similar increase in BMD was observed in the HKOS at femoral neck and lumbar spine. In MR analysis, a decrease in genetically predicted LDL-C was associated with an increase in TB-BMD {estimate per SD decrease, 0.038 [95% confidence interval (CI): 0.002 − 0.074]; P = 0.038} and eBMD [0.076 (0.042 − 0.111); P = 1.20x10−5]. Reduction in TB-BMD was causally associated with increased LDL-C [0.035 (0.033 − 0.066); P = 0.034]. Statins’ LDL-C-lowering proxies were associated with increased TB-BMD [0.18 (0.044 − 0.316); P = 9.600x10−3] and eBMD [0.143 (0.062 − 0.223); P = 5.165x10−4]. Conclusions: Negative causal association exists between LDL-C level and BMD. Statins’ LDL-C-lowering effect increases BMD, suggesting their protective effect on bone