Knowledge of Adverse Drug Reactions Reporting among Doctors and Nurses in a Tertiary Care Hospital: A Descriptive Cross-sectional Study.

INTRODUCTION: Doctors and nurses have a significant role in the detection of serious and unusual drug reactions. Effective implementation of an adverse drug reaction reporting system is required to ensure patient safety and quality care. This study's objective was to find the prevalence of good knowledge of adverse drug reaction reporting among the Doctors and nurses working in a tertiary care hospital. METHODS: A descriptive cross-sectional study was conducted among doctors and nurses from 15 February 2020 to 15 July 2020 at Birat Medical College and Teaching Hospital. The convenience sampling method was used to select 192 study participants. A semi-structured questionnaire was used to know the knowledge concept of adverse drug reaction reporting. Ethical clearance was taken from IRC (PA-047/2076-77) of Birat Medical College and Teaching Hospital. Written informed consent was taken from each study participant. Collected data were entered in Microsoft Excel 2010 and analyzed by Statistical Package for the Social Sciences v23. RESULTS: In total, 192 doctors and nurses, the questionnaires were distributed to 52 (27.1%) doctors and 140 (72.9%) nurses. The mean age of study participants was 28.14 years (SD±4.5). To know the prevalence of knowledge, 15 knowledge related questions of adverse drug reaction had asked. The majority of doctors and nurses had good knowledge about adverse drug reaction reporting, 75% and 64%, respectively. CONCLUSIONS: Overall, doctors and nurses have had good knowledge of adverse drug reaction reporting. Data shows there is still more gap in training and experience on adverse drug reaction reporting systems.

Utilization of Pre-Anesthetic Medications for Major Surgical Procedures at a Tertiary Care Center: A Descriptive Cross-sectional Study.

INTRODUCTION: Drug utilization research is an important tool to analyze the use of drugs with special emphasis on medical, social, and economic consequences in society. This study aims to find out the utilization of pre-anesthetic medications in a major surgical procedure. METHODS: A descriptive cross-sectional study was conducted from 15th April - 15th August 2019 in the postoperative ward at Birat Medical College and Teaching Hospital. The convenience sampling method was used after ethical clearance from the Institutional Review Committee (IRC) of Birat Medical College and Teaching Hospital, Biratnagar, Nepal. About 400 patients were studied. The collected data were entered into a statistical package for social science version 20 for further calculations at 95% Confidence Interval. RESULTS: Out of 400 patients, 215 (53.8%) of patients were underwent into different major surgeries. All patients received midazolam 2 mg except children (1 mg) and Pethidine 25 mg along with 0.2 mg glycopyrrolate 352 (88%), ondansetron 276 (69%) and others 58 (14.5%) as a preanesthetic agent. For general anesthesia propofol, 30 mg have been utilized followed by fentanyl 306 (76.5%) and others (halothane, isoflurane, etc) 115 (28.8%). In case of prophylactic drug were ceftriaxone 500 mg, 100 mg metoclopramide 387 (96.8%), dexamethasone 251 (62.8%), tramadol 237 (59.3%), 15 mg ketorolac 368 (92%), ranitidine 163 (40.8%), and pantoprazole 237 (59.3%). CONCLUSIONS: The most commonly administered pre-anesthetic drugs were midazolam, pethidine, glycopyrrolate, and ondansetron. The incidence of postoperative nausea and vomiting the patient within 24 hours after surgery was significantly very low.

Predictors of incomplete adherence, virologic failure, and antiviral drug resistance among HIV-infected adults receiving antiretroviral therapy in Tanzania.

BACKGROUND: Access to antiretroviral therapy is rapidly expanding in sub-Saharan Africa. Identifying the predictors of incomplete adherence, virologic failure, and antiviral drug resistance is essential to achieving long-term success. METHODS: A total of 150 subjects who had received antiretroviral therapy for at least 6 months completed a structured questionnaire and adherence assessment, and plasma human immunodeficiency virus (HIV) RNA levels were measured. Virologic failure was defined as an HIV RNA level >400 copies/mL; for patients with an HIV RNA level >1000 copies/mL, genotypic antiviral drug resistance testing was performed. Predictors were analyzed using bivariable and multivariable logistic regression models. RESULTS: A total of 23 (16%) of 150 subjects reported incomplete adherence. Sacrificing health care for other necessities (adjusted odds ratio [AOR], 19.8; P<.01) and the proportion of months receiving self-funded treatment (AOR, 23.5; P=.04) were associated with incomplete adherence. Virologic failure was identified in 48 (32%) of 150 subjects and was associated with incomplete adherence (AOR, 3.6; P=.03) and the proportion of months receiving self-funded antiretroviral therapy (AOR, 13.0; P=.02). Disclosure of HIV infection status to family members or others was protective against virologic failure (AOR, 0.10; P=.04). CONCLUSIONS: Self-funded treatment was associated with incomplete adherence and virologic failure, and disclosure of HIV infection status was protective against virologic failure. Efforts to provide free antiretroviral therapy and to promote social coping may enhance adherence and reduce rates of virologic failure.

Fourier transform near-infrared vibrational circular dichroism used for on-line monitoring the epimerization of 2,2-dimethyl-1,3-dioxolane-4-methanol: A pseudo racemization reaction.

Near-infrared (near-IR) Fourier transform vibrational circular dichroism (FT-VCD) spectroscopy has been used to monitor the epimerization of (S)-(+)-2,2-dimethyl-1,3-dioxolane-4-methanol (S-DDM). The near-IR-VCD spectra display clear isolated VCD bands at the range of 4700-5050 cm(-1) resulting from the OH stretch-bend combination bands of S-DDM, which were found to decrease in intensity with increasing reaction time. The near-IR-VCD spectra of 10 reference samples obtained were subjected to partial least-squares (PLS) regression analysis, and the results were used to build predictive models for enantiomeric excess (EE) determination. Multivariate regression was carried out on three different sets of spectra, corresponding to the epimerization of S-DDM in three different solvents: methylcyclohexane, carbon tetrachloride and tetrahydrofuran. The effects of solvent in DDM epimerization are discussed in terms of the relative stabilization of the reaction intermediate of the DDM epimerization reaction. The results of these near-IR-VCD studies for the determination of EE highlights the potential of VCD for in situ real-time process monitoring of the reaction kinetics of chiral molecules in solution.

Enantiomeric excess determination by fourier transform near-infrared vibrational circular dichroism spectroscopy: simulation of real-time process monitoring.

The first use of near-infrared (NIR) Fourier transform vibrational circular dichroism (FT-VCD) to follow changes in the enantiomeric excess (EE) of chiral sample molecules in time using a flow-cell sampling apparatus is reported. Simultaneous changes in the fractional composition and the EE of a mixture of two different chiral molecules were monitored as a function of time. This simulates the progress of the chemical reaction from a chiral reactant to a chiral product where the mole fractions and EE values of both species may change with time. For the molecules studied, alpha-pinene, camphor, and borneol, the accuracy of following EE changes for one species alone is approximately 2%, while for simultaneously following EE changes in two species it is approximately 3% for 30 min sampling periods at 16 cm(-1) spectral resolution. These findings demonstrate the potential for VCD to be used in the NIR region for real-time monitoring of the composition and %EE of chemical reactions involving the synthesis of chiral molecules.

Determination of enantiomeric excess in samples of chiral molecules using fourier transform vibrational circular dichroism spectroscopy: simulation of real-time reaction monitoring.

The first use of Fourier transform vibrational circular dichroism (FT-VCD) to follow changes in the percent enantiomeric excess (% EE) of chiral molecules in time using a flow cell sampling apparatus is reported. FT-VCD, as opposed to dispersive scanning VCD, eliminates the need to scan the VCD spectrum in time to monitor the % EE at more than one spectral location. The first use of partial least-squares chemometric analysis to determine % EE values from kinetic sets of VCD spectral data is also reported. These two advances have been used to monitor simultaneously changes in the fractional composition and the % EE of a mixture of two different chiral molecules. This simulates the progress of the chemical reaction from a chiral reactant to a chiral product where the % EE of both molecules can change with time. For the molecules studied, alpha-pinene, camphor, and borneol, the accuracy of following % EE changes for one species alone is approximately 1%, while for simultaneously following % EE changes in two species is approximately 2% for 10-20-min sampling periods at 4 cm(-)(1) spectral resolution. This accuracy can be increased for the same collection times or maintained for shorter periods of collection by lowering the spectral resolution. These findings demonstrate the potential for VCD to be used for real-time monitoring of the composition and % EE of chemical reactions involving the synthesis chiral molecules.

Extension of fourier transform vibrational circular dichroism into the near-infrared region: continuous spectral coverage from 800 to 10 000 cm(-1).

We report the first vibrational circular dichroism (VCD) spectra with continuous coverage from 800 cm(-1) in the mid-infrared (MIR) region to 10 000 cm(-1) in the near-infrared (NIR) region. This coverage is illustrated with MIR and NIR absorbance and VCD spectra of 2,2-dimethyl-dioxolane-4-methanol (DDM), alpha-pinene, and camphor that serve as calibration samples over this entire region. Commercially available, dual-source Fourier transform (FT) MIR and NIR VCD spectrometers were equipped with appropriate light sources, optics, and detectors, and were modified for dual-polarization-modulation (DPM) operation. The combination of liquid-nitrogen- and thermoelectric-cooled HgCdTe (MCT) detectors, as well as InGaAs and Germanium (Ge) detectors operating at room temperature, permitted collection of the desired absorbance and VCD spectra across the range of vibrational fundamental, combination band, and overtone frequencies. The spectra of DDM and alpha-pinene were measured as neat liquids and recorded for both enantiomers in the various spectral regions. Spectra for camphor were all measured in CCl(4) solution at a concentration of 0.6 M, except for the carbonyl-stretching region, where a more dilute concentration was used. The typical anisotropy ratios (g) of the three molecules were estimated with respect to their strongest VCD bands in each spectral region. It was found that for all three molecules in the spectral regions above 2000 cm(-1), anisotropy ratios are approximately the same order (10(-5)) of magnitude. However, in the MIR region, the typical anisotropy ratios are significantly different for the three molecules. This study demonstrates that with modern FT-VCD spectrometers modified for DPM operation, VCD spectra can be measured continuously across a wide spectral range from the MIR to nearly the visible region with an unsurpassed combination of signal-to-noise ratio and spectral resolution.

Enantioseparation of hydrochloride salts using carbon dioxide-based mobile phases with on-line polarimetric detection.

Most HPLC enantioseparations of amine analytes are performed using normal-phase systems containing mobile phases of heptane with ethanol (or 2-propanol) and an amine additive. Since salt-forms of amine analytes are usually insoluble in normal-phase eluents, free-base forms are synthesized for preparative chromatography. It would be highly desirable to directly chromatograph salt forms of amine analytes using mobile phases of carbon dioxide (CO(2)) and methanol (MeOH). Such separations would be readily suitable for preparative chromatography, since most amine salts are highly soluble in MeOH. In this article, advantages are shown for the use of supercritical fluid chromatography (SFC) instrumentation with tandem UV and polarimetric detection for confirming enantioseparation as well as for determining optimum preparative column injections. Examples are shown for racemic mixtures of propranolol HCl (I), thioridazine HCl (II), tramadol HCl (III), and flurbiprofen (IV), all of which resolved on Chiralpak AD-H chiral stationary phase using mobile-phase systems of CO(2) and MeOH without the use of basic or acidic additives.

Fast method development and rapid analysis using a screening approach for enantiomeric separations in capillary electrophoresis.

In order to speed up the trial-and-error process during enantioselective capillary electrophoresis methods development, a systemized approach is proposed to develop methods by applying several screening methods in the search for an initial separation. Screening methods combine high selectivity with broad applicability and are applied to find an initial enantiomeric separation during early pharmaceutical development (pre-Phase 1 to Phase 1). The goal is to achieve enantiomeric separation rapidly in order to characterize the chiral purity of pharmaceutical products. Dedicated, highly efficient screening methods are suggested for basic, neutral, and acidic compounds. In these screening methods, multiple chiral selectors are applied in mixtures at different buffer pH values. For the compounds studied, the technique allows fast method development. Furthermore, it is potentially applicable to a wide range of low-molecular-weight compounds and permits rapid analysis at low cost, since runs are performed in inexpensive, bare silica capillaries using ordinary buffer systems with only typical cyclodextrins as the selector. Along with simplicity and robustness, the approach results in sufficient efficacy (i.e., it is easy, straightforward, and reproducible, with a high success rate). Typical pharmaceutical applications are described. The major advantage of the screening approach to methods development is the decrease in development cycle time. The total screening time for one compound was about 5.3 hr on one CE instrument.

Quantitative analysis of incomplete HPLC resolution of enantiomers. Fit of polarimetric detection for D- and L-phenylalanine to a gaussian function.

This report compares laser-based polarimetric and UV data for quantitating incompletely resolved enantiomers by HPLC. Using L- and D-phenylalanine as a working model, response data is shown across the entire detection region while emphasizing the regions at or near 100% L, 100% D and 50:50 L:D at resolutions between 0.4 and 1.4. In general, the poorer the resolution, the greater the improvement in detectability with the polarimeter when compared to UV detection. This is due to the inherent bipolar nature of the polarimetric signal, which creates a well-defined crossing point for integration of an enantiomeric pair. In our previous work, we described the improvement in measurement precision when applying a bipolar gaussian peak model to the raw chromatographic peak data. This study will measure the model's effect on improving accuracy. This study should be applicable to other chiroptical detection strategies that produce a bipolar signal for enantiomers, such as circular dichroism and circularly polarized luminescence.

Determination of the absolute configuration of a key tricyclic component of a novel vasopressin receptor antagonist by use of vibrational circular dichroism.

We present the results of a study using vibrational circular dichroism (VCD) for (+)-1, which furnished an unambiguous determination of its absolute configuration as S. The most abundant conformation of (+)-1 in CDCl(3) solution was also established.

Reductive Amination of Aldehydes and Ketones with Sodium Triacetoxyborohydride. Studies on Direct and Indirect Reductive Amination Procedures(1).

Sodium triacetoxyborohydride is presented as a general reducing agent for the reductive amination of aldehydes and ketones. Procedures for using this mild and selective reagent have been developed for a wide variety of substrates. The scope of the reaction includes aliphatic acyclic and cyclic ketones, aliphatic and aromatic aldehydes, and primary and secondary amines including a variety of weakly basic and nonbasic amines. Limitations include reactions with aromatic and unsaturated ketones and some sterically hindered ketones and amines. 1,2-Dichloroethane (DCE) is the preferred reaction solvent, but reactions can also be carried out in tetrahydrofuran (THF) and occasionally in acetonitrile. Acetic acid may be used as catalyst with ketone reactions, but it is generally not needed with aldehydes. The procedure is carried out effectively in the presence of acid sensitive functional groups such as acetals and ketals; it can also be carried out in the presence of reducible functional groups such as C-C multiple bonds and cyano and nitro groups. Reactions are generally faster in DCE than in THF, and in both solvents, reactions are faster in the presence of AcOH. In comparison with other reductive amination procedures such as NaBH(3)CN/MeOH, borane-pyridine, and catalytic hydrogenation, NaBH(OAc)(3) gave consistently higher yields and fewer side products. In the reductive amination of some aldehydes with primary amines where dialkylation is a problem we adopted a stepwise procedure involving imine formation in MeOH followed by reduction with NaBH(4).