Use of antipsychotics and the risk of acute respiratory failure among adults: A disease risk score-matched nested case-control study.

AIMS: Evidence on acute respiratory failure (ARF) from antipsychotics is scant, and only 1 population-based study examined this drug safety issue in chronic obstructive pulmonary disease patients. Antipsychotics have been frequently prescribed off-label in adults, but whether antipsychotic use carries an increased ARF risk among adult patients is uncertain. METHODS: We adopted a nested case-control study analysing 716 493 adults aged ≥20 years, identified from the Taiwan nationwide healthcare claims records between January 2000 and December 2013. Among the study cohort, 7084 adults with ARF and 12,785 disease risk scored-matched randomly selected controls were analysed. Multivariable logistic regression models were employed to estimate odds ratios of ARF with antipsychotic usages. RESULTS: Current, recent, and recent past use of antipsychotics was associated with a 2.33-fold (95% confidence interval [CI] = 2.06-2.64), 1.79-fold (95% CI = 1.43-2.25) and 1.41-fold (95% CI = 1.20-1.66) increased risk of ARF, respectively, compared with nonuse, while antipsychotics discontinued >90 days carried no risk. A dose-dependent association was observed with current therapy of antipsychotics (test for trend, P < .001), in which antipsychotic use at >1 defined daily dose yielded the highest risk of 6.53-fold (95% CI = 3.33-12.79). The findings were robust to using carbamazepine as an active comparator. CONCLUSION: Antipsychotic use was associated with an increased risk of ARF in adult patients. The risk was dose-dependent and markedly higher with current use of antipsychotic agents at doses of 1 defined daily dose and above, <10% of this cohort. Physicians should be vigilant about any respiratory symptoms in patients currently receiving antipsychotics at such dose.

[New Treatment for Vascular Thrombosis Prevention in Patients With Atrial Fibrillation: Left Atrial Appendage Occlusion].

Atrial fibrillation (AF) is a common type of arrhythmia that increases significantly the risk of blood clots in the heart and of stroke. Therefore, stroke prevention is a key goal of AF treatment. In the past, patients were required to take anticoagulants for the remainder of their life, to regularly the monitor international normalized ratio (INR) of prothrombin time (PT), and to avoid possible negative interactions with various drugs and foods. Left atrial appendage occlusion (LAAO), a novel device and technique, was thus developed for AF patients with contraindications to anticoagulants and a high risk of bleeding. When using this technique, the occluder is placed on the left atrial appendage in order to effectively prevent blood stasis and thrombi accumulation. Transesophageal echocardiogram and computed tomography are conducted prior to the LAAO procedure, which is similar to the procedure used for cardiac catheterization. After the LAAO procedure, the patient remains in the intensive care unit (ICU), where vital signs, bleeding at the puncture site, and pericardial tamponade complications are monitored. Health education on daily activities, anticoagulant use, and regular follow-up should be given prior to hospital discharge. While LAAO may not reduce the incidence of stroke, the benefits of this procedure include a significant reduction in bleeding complications as compared to procedures that use oral anticoagulants. Further studies including long-term follow up and in-depth examinations of this procedure are necessary. The present article offers a reference for clinical staffs who are responsible for the care of patients treated using the LAAO procedure.

[Introduction of Hemodynamic Monitoring in Critical Care Units].

Hemodynamic monitoring is a very important treatment in intensive care units. Measurements taken during monitoring include pulmonary artery catheter (PAC), pulse-induced contour output (PiCCO), and non-invasive hemodynamic monitoring. PAC measures cardiopulmonary parameters using the thermodilution principle. PiCCO uses transpulmonary thermodilution and pulse contour analysis to measure cardiopulmonary parameters and extra-vascular lung water, to predict lung edema, and to differentiate between cardiogenic and non-cardiogenic respiratory failure. Non-invasive hemodynamic monitoring uses the thoracic electrical bioimpedance principle to measure electrical conductivity and then calculates stroke volume and cardiopulmonary parameters using the arrangement of red blood cells. The author is a nurse in an intensive care unit who is familiar with the various methods used in hemodynamic monitoring, with preparing the related devices, with briefing patients and family members prior to procedures, with related aseptic skills, with preventing complications during the insertion procedure, and with analyzing and interpreting those parameters accurately. The issues addressed in this paper are provided as a reference for nurses and other medical personnel to choose appropriate treatments when caring for critical patients.

ß-Selective C-Arylation of Diisobutylaluminum Hydride Modified 1,6-Anhydroglucose: Synthesis of Canagliflozin without Recourse to Conventional Protecting Groups.

The ß-selective phenylation of benzyl and boronate protected 1,6-anhydroglucose and the direct phenylation of unprotected 1,6-anhydroglucose (10), pretreated with i-Bu2AlH, i-Bu3Al, Et3Al, Me3Al, or n-octyl3Al, with triphenylalane or aryl(chloro)alanes is reported. The utility of the unprotected version of the method is demonstrated by the synthesis of the SGLT2 inhibitor, canagliflozin (1a), from commercially available 10 in one C-C bond-forming step. This approach circumvents the need for conventional protecting groups, and therefore no formal protection and deprotection steps are required.

ß-selective C-arylation of silyl protected 1,6-anhydroglucose with arylalanes: the synthesis of SGLT2 inhibitors.

The stereoselective arylation of hydroxy protected 1,6-anhydro-ß-d-glucose with arylalanes to provide ß-C-arylglucosides is reported. Modification of triarylalanes, Ar3Al, with strong Brønsted acids (HX) or AlCl3 produced more reactive arylating agents, Ar2AlX, while the incorporation of alkyl dummy ligands into the arylating agents was also viable. Me3Al and i-Bu2AlH were found useful in the in situ blocking of the C3-hydroxyl group of 2,4-di-O-TBDPS protected 1,6-anhydroglucose. The utility of the method was demonstrated by the synthesis of the SGLT2 inhibitor, canagliflozin.

Bilateral keratitis associated with afatinib therapy.

This case discussed a significant ocular side effect, bilateral keratitis, which could be induced by afatinib, an irreversible epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI). We explored the disease progression of a 52-year-old, stage IV nasopharyngeal carcinoma male patient, who was under afatinib treatment and had experienced progressive bilateral eye dryness and tenderness on increasing afatinib from 40 mg every other day to 40 mg daily. Clinical examination noted bilateral visual acuity reduction, diffuse superficial punctate keratopathy in the right eye, and a central epithelial defect in the left eye. Seidel test results were negative for both eyes, with no corneal infiltration, lagophthalmos, anterior chamber cell precipitation, or retinal lesion. Symptoms subsequently resolved after reducing the frequency of afatinib used, along with intensive ocular hydration. In summary, this case highlighted afatinib's potential link to bilateral keratitis, and early afatinib dose adjustment with supportive medication could significantly reverse the condition.

Formation of tetrahydrofurans via a 5-endo-tet cyclization of aziridines--synthesis of (-)-pachastrissamine.

The formation of tetrahydrofurans from 2-hydroxyalkyl-oxirane or aziridine is reported. The 5-endo-tet cyclization/ring opening of aziridine proceeded smoothly to give tetrahydrofurans (THFs) under mild conditions. In contrast, the corresponding process of oxirane was unsuccessful and a sequence of SN2 substitution/cyclization was required to form THFs. The application of the process to prepare ent-(-)-pachastrissamine is described.

Cucurbitacin E as inducer of cell death and apoptosis in human oral squamous cell carcinoma cell line SAS.

Human oral squamous cell carcinoma (OSCC) is a common form of malignant cancer, for which radiotherapy or chemotherapy are the main treatment methods. Cucurbitacin E (CuE) is a natural compound previously shown to be an antifeedant as well as a potent chemopreventive agent against several types of cancer. The present study investigates anti-proliferation (using MTT assay, CuE demonstrated cytotoxic activity against SAS cell with IC50 values at 3.69 µM) and induced apoptosis of human oral squamous cell carcinoma SAS cells after 24 h treatment with CuE. Mitochondrial membrane potential (MMP) and caspase activity were studied and our results indicate that CuE inhibits cell proliferation as well as the activation of apoptois in SAS cells. Both effects increased in proportion to the dosage of CuE and apoptosis was induced via mitochondria- and caspase-dependent pathways. CuE can induce cell death by a mechanism that is not dependent on apoptosis induction, and thus represents a promising anticancer agent for prevention and treatment of OSCC.

Assessing Agreement and Variability Among Alternative Devices for Intraocular Pressure Measurement: A Comparative Study.

Purpose: Intraocular pressure (IOP) measurement is critical in diagnosing and managing eye conditions. This study aims to assess the comparability of three alternative devices for measuring IOP: Noncontact tonometer, Icare rebound tonometer, and Tono-Pen. Patients and Methods: A cross-sectional study included 172 adult participants (87 males and 85 females) who underwent IOP and central corneal thickness (CCT) assessments. IOP was measured using Noncontact (Canon TX-20), Icare (Icare TA01i), and Tono-Pen (Tonopen XL). CCT was measured with the built-in pachymetry of the Noncontact tonometer. Correlation coefficients and Bland-Altman analyses were conducted to assess the relationships and agreements between these tonometers. Participants were grouped based on IOP and CCT levels. The mean of the standard deviation of the three tonometer results was calculated to evaluate measurement result variability. One-way analysis of variance was conducted for comparing between the groups. Results: IOP measurements among the three devices were not significantly different, indicating their comparability. Correlation analysis revealed strong correlations between the tonometers. Bland-Altman analysis showed good agreement, with the Icare rebound tonometer and Tono-Pen exhibiting narrower limits of agreement. Furthermore, IOP levels influenced measurement result variability, with higher IOP levels associated with greater variance. Conclusion: This study demonstrates that the alternative devices examined can provide reliable IOP measurements. It highlights the potential of these alternative devices for IOP measurement. These findings have implications for clinical practice, offering practitioners additional tools for accurate IOP assessment.

A Novel Salivary Sensor with Integrated Au Electrodes and Conductivity Meters for Screening of Diabetes.

The rise in diabetes cases is a growing concern due to the aging of populations. This not only places a strain on healthcare systems but also creates serious public health problems. Traditional blood tests are currently used to check blood sugar levels, but they are invasive and can discourage patients from regularly monitoring their levels. We recently developed nano-sensing probes that integrate Au microelectrodes and conductivity meters, requiring only 50 µL of saliva for measurement. The usage of the co-planar design of coating-free Au electrodes makes the measurement more stable, precise, and easier. This study found a positive correlation between the participant's fasting blood sugar levels and salivary conductivity. We observed a diabetes prevalence of 11.6% among 395 adults under 65 years in this study, using the glycated hemoglobin > 6.5% definition. This study found significantly higher salivary conductivity in the diabetes group, and also a clear trend of increasing diabetes as conductivity levels rose. The prediction model, using salivary conductivity, age, and body mass index, performed well in diagnosing diabetes, with a ROC curve area of 0.75. The study participants were further divided into low and high groups based on salivary conductivity using the Youden index with a cutoff value of 5.987 ms/cm. Individuals with higher salivary conductivity had a 3.82 times greater risk of diabetes than those with lower levels, as determined by the odds ratio calculation. In conclusion, this portable sensing device for salivary conductivity has the potential to be a screening tool for detecting diabetes.