Safety and Tolerability of Sacubitril/Valsartan Initiation in Inpatient Versus Outpatient Setting: A Retrospective Real World Study.

BACKGROUND: The Comparison of Pre- and Post-discharge Initiation of LCZ696 Therapy in HFrEF Patients After an Acute Decompensation Event (TRANSITION) and PIONEER-HF trialsa have shown that sacubitril/valsartan can be initiated early and safely in patients with heart failure with reduced ejection fraction (HFrEF) shortly after an acute heart failure episode during hospitalisation. However, it is unclear whether the results can be translated to Asian populations. Hence, this real-world study was designed with the aim of comparing the safety and tolerability of sacubitril/valsartan initiation in an inpatient versus outpatient setting. METHODS: A retrospective review for all patients initiated with sacubitril/valsartan from 1 November 2015 to 30 September 2018 was conducted in a tertiary health care institution in Singapore. Patients with HFrEF and aged ≥21 years were included. Incidence of adverse drug reactions (ADRs) and discontinuation rate of sacubitril/valsartan were compared between initiation of sacubitril/valsartan in inpatient and outpatient settings. Reasons for discontinuation were investigated. Subgroup analysis was performed. Cox regression was used to analyse the primary outcomes. RESULTS: Of the 1,022 patients who were screened, 840 (289 inpatient group; 551 outpatient group) were included. The inpatient group experienced significantly higher ADRs (34.6% vs 22.7%; adjusted hazard ratio [HR], 2.28; 95% confidence interval [CI], 1.68-3.10; p<0.01) and discontinuation rate (18.0% vs 10.3%; adjusted HR, 2.11; 95% CI, 1.37-3.26; p<0.01) than the outpatient group. The safety outcomes were consistent across all the subgroups. CONCLUSIONS: Initiation of sacubitril/valsartan in an inpatient group was associated with higher ADRs and discontinuation rate as compared with an outpatient group in an Asian population. However, given that the majority of patients in the inpatient cohort could tolerate sacubitril/valsartan, it would still be feasible to initiate this drug with close monitoring. Further randomised clinical trials in Asian populations are required to confirm this finding.

Study on the potential application of salivary inorganic anions in clinical diagnosis by capillary electrophoresis coupled with contactless conductivity detection.

A capillary electrophoresis approach with capacitively coupled contactless conductivity detection method has been developed for the determination of inorganic metabolites (thiocyanate, nitrite and nitrate) in human saliva. Field amplified sample injection, as a simple sample stacking technique, was used in conjunction for online preconcentration of above inorganic anions. A selective separation for the target anions from other coexisting constituents present in saliva could be obtained within 14min in a 10mmol/L His-90mmol/L HAc buffer (pH 3.70) at the separation voltage of -18kV. The limits of detection and limits of quantification of the three analytes were within the range of 3.1-4.9ng/mL (S/N=3) and 10-16ng/mL (S/N=10), respectively. The average recovery data were in the range of 81-108% at three different concentrations. This method provides a simple, rapid and direct approach for metabolite analyses of nitric oxide and cyanide based on noninvasive saliva sample, which presents a potential fast screening tool for clinical test.

Hollow-fiber liquid-phase microextraction coupled with miniature capillary electrophoresis for the trace analysis of four aliphatic aldehydes in water samples.

An environmentally friendly method for the trace analysis of four aliphatic aldehydes as water disinfection byproducts has been developed based on hollow-fiber liquid-phase microextraction followed by miniature capillary electrophoresis with amperometric detection. After derivatization with 2-thiobarbituric acid, four aliphatic aldehydes (formaldehyde, acetaldehyde, propylaldehyde, and butyraldehyde) became detectable by the amperometric detector. Under the optimum conditions, four aliphatic aldehydes can be well separated from the coexisting interferents as well as their homologs (pentanal, glyoxal, and methyl-glyoxal), and the limits of detection (S/N = 3) could reach sub-nanogram-per-milliliter level based on hollow-fiber liquid-phase microextraction. The proposed method has been applied for the analyses of above four aliphatic aldehydes in different water samples such as drinking water, tap water, and river water, and the average recoveries were in the range of 90-113%, providing an alternative to conventional and microchip capillary electrophoresis approaches.

Could low grade bacterial infection contribute to low back pain? A systematic review.

BACKGROUND: Recently, there has been both immense interest and controversy regarding a randomised, controlled trial which showed antibiotics to be effective in the treatment of chronic low back pain (disc herniation with Modic Type 1 change). While this research has the potential to result in a paradigm shift in the treatment of low back pain, several questions remain unanswered. This systematic review aims to address these questions by examining the role of bacteria in low back pain and the relationship between bacteria and Modic change. METHODS: We conducted electronic searches of MEDLINE and EMBASE and included studies that examined the relationship between bacteria and back pain or Modic change. Studies were rated based on their methodological quality, a best-evidence synthesis was used to summarise the results, and Bradford Hill's criteria were used to assess the evidence for causation. RESULTS: Eleven studies were identified. The median (range) age and percentage of female participants was 44.7 (41-46.4) years and 41.5% (27-59%), respectively, and in 7 of the 11 studies participants were diagnosed with disc herniation. Nine studies examined the presence of bacteria in spinal disc material and all identified bacteria, with the pooled estimate of the proportion with positive samples being 34%. Propionibacterium acnes was the most prevalent bacteria, being present in 7 of the 9 studies, with median (minimum, maximum) 45.0% (0-86.0) of samples positive. The best evidence synthesis found moderate evidence for a relationship between the presence of bacteria and both low back pain with disc herniation and Modic Type 1 change with disc herniation. There was modest evidence for a cause-effect relationship. CONCLUSIONS: We found that bacteria were common in the spinal disc material of people undergoing spinal surgery. There was moderate evidence for a relationship between the presence of bacteria and both low back pain with disc herniation and Modic Type 1 change associated with disc herniation and modest evidence for causation. However, further work is needed to determine whether these organisms are a result of contamination or represent low grade infection of the spine which contributes to chronic low back pain.

Quadrangular prism: a unique self-assembly from amphiphilic hyperbranched PMA-b-PAA.

The novel hyperbranched poly(methyl acrylate)-block-poly(acrylic acid)s (HBPMA-b-PAAs) are successfully synthesized via single-electron transfer-living radical polymerization (SET-LRP), followed with hydrolysis reaction. The copolymer solution could spontaneously form unimolecular micelles composed of the hydrophobic core (PMA) and the hydrophilic shell (PAA) in water. Results show that the size of spherical particles increases from 8.18 to 19.18 nm with increased pH from 3.0 to 12.0. Most interestingly, the unique regular quadrangular prisms with the large microstructure (5.70 µm in length, and 0.47 µm in width) are observed by the self-assembly of unimolecular micelles when pH value is below 2. Such self-assembly behavior of HBPMA-b-PAA in solution is significantly influenced by the pH cycle times and concentration, which show that increased polymer concentration favors aggregate growth.

Factors considered in end-of-life care decision making by health care professionals.

AIM: To explore the importance of factors influencing the end-of-life care decision making of health care professionals (HCPs) in Singapore. METHODS: This cross-sectional survey encompassed facets of patient, family, and HCP-related care considerations. In total, 187 questionnaires were distributed to physicians and nurses and had a response rate of 78.6%. RESULTS: The respondents rated patients' wishes (96.6%), their clinical symptoms (93.9%), and patients' beliefs (91.1%) very high. In all, 94.6% of the HCPs would respect a competent patient's wishes over the family's wishes when goals conflict. However, 59.9% of HCPs would abide by the family's wishes when the patient loses capacity even if the patient's previously expressed wishes are known. CONCLUSION: End-of-life care decision making by HCPs appears largely patient centered, although familial determination still wields significant influence with implications for advance care planning.