Appropriateness of empirical antibiotics: risk factors of adult patients with sepsis in the ICU.

Background The appropriateness of antibiotics is the basis for improving the survival of patients with sepsis. Objective This study aimed to determine the appropriateness of empirical antibiotics, reasons for non-appropriate empirical antibiotics, risk factors of mortality, length of stay in intensive care unit (ICU-LOS) and Acute Physiology And Chronic Health Evaluation II (APACHE II) score predictors in adult patients with sepsis. Setting An adult ICU of a tertiary hospital in  Malaysia. Methods A retrospective cohort study was conducted amongst patients with sepsis. Data were retrieved from the patients' files and computer system. Each case was reviewed for the appropriateness of empirical antibiotics based on ICU local guidelines, bacterial sensitivity, dose, frequency, creatinine clearance and time of administration of empirical antibiotics. Multivariable logistic and Cox regression modelling were performed to compute the adjusted association of receiving appropriate or inappropriate empirical antibiotics with ICU mortality. Multivariable linear regression modelling was performed using ICU-LOS and APACHE II scores. Main outcome measures were ICU mortality, severity score (APACHE II scores) and ICU-LOS. Results The total mortality rate amongst the 228 adult ICU patients was 84.6%. Males showed a higher mortality rate (119 [52.2%]) than females (74 [32.5%]). Inappropriate empirical antibiotics were significantly associated with mortality and ICU-LOS (P < 0.005). Results from multivariable logistic regression showed that the appropriateness of empirical antibiotics model was a potential predictor for survival (OR 0.395, 95% CI 0.184-0.850, P < 0.005). Results from simple linear regression indicated that the appropriateness of empirical antibiotics model was a remarkable predictor of decreasing ICU-LOS (R2 = 0.055, 95% CI - 7.184 to - 2.114, P < 0.001). Results from simple Cox regression suggested that the appropriateness of empirical antibiotics was a protective factor for ICU mortality (HR 0.610, 95% CI 0.433-0.858, P = 0.005). Multivariable Cox regression revealed that the administration of antibiotics exceeding the recommended dose based on creatinine clearance was a protective factor (HR 0.186, 95% CI 0.040-0.868, P = 0.032). Conclusion The appropriateness of empirical antibiotics is a good predictor for improving survival and decreasing ICU-LOS. Effective appropriateness of empirical antibiotics use and close adherence to the recommended dose can prevent the early mortality of patients with sepsis and acute renal failure.

Drug Utilization on Neonatal Wards: A Systematic Review of Observational Studies.

Despite limited evidence on safety and efficacy of drug use in neonates, drugs are extensively used in this age group. However, the availability of information on drug consumption in neonates, especially inpatient neonates, is limited. This paper systematically reviews published studies on drug utilization in hospitalized neonates. A systematic literature review was carried out to identify observational studies published from inception of databases used till August 2016. Four search engines, namely Medline, CINAHL, Embase, and PubMed, were used. Publications written in English that described drug utilization in neonatal wards were selected. Assessment of the data was based on the category of the study design, the objective of study and the method used in reporting drug consumption. A total of 20 drug utilization studies were identified, 12 of which focused on all drug classes, while the other eight evaluated antimicrobials. Studies were reported in Europe (n = 7), the United States (n = 6), India (n = 5), Brazil (n = 1), and Iran (n = 1). Substantial variance with regard to study types (study design and methods), data source, and sample size were found among the selected studies. Of the studies included, 45% were cross-sectional or retrospective, 40% were prospective studies, and the remaining 15% were point prevalence surveys. More than 70% of the studies were descriptive studies, describing drug consumption patterns. Fifteen per cent of the descriptive studies evaluated changes in drug utilization patterns in neonates. Volume of units was the most prevalent method used for reporting all drug categories. The ATC/DDD system for reporting drug use was only seen in studies evaluating antimicrobials. The most commonly reported drugs across all studies are anti-infectives for systemic use, followed by drugs for the cardiovascular system, the nervous system and the respiratory system. Ampicillin and gentamicin were the most prescribed antimicrobials in hospitalized neonates. The present review reveals that neonates are exposed to a high number of drugs and various methods are used to report drug consumption in this age group. The best measure of drug consumption to quantify prevalence of drug use in neonates remains to be identified and additional research in this area is warranted.

A rapid MCM-41 dispersive micro-solid phase extraction coupled with LC/MS/MS for quantification of ketoconazole and voriconazole in biological fluids.

A rapid dispersive micro-solid phase extraction (D-µ-SPE) combined with LC/MS/MS method was developed and validated for the determination of ketoconazole and voriconazole in human urine and plasma samples. Synthesized mesoporous silica MCM-41 was used as sorbent in d-µ-SPE of the azole compounds from biological fluids. Important D-µ-SPE parameters, namely type desorption solvent, extraction time, sample pH, salt addition, desorption time, amount of sorbent and sample volume were optimized. Liquid chromatographic separations were carried out on a Zorbax SB-C18 column (2.1 × 100 mm, 3.5 µm), using a mobile phase of acetonitrile-0.05% formic acid in 5 mm ammonium acetate buffer (70:30, v/v). A triple quadrupole mass spectrometer with positive ionization mode was used for the determination of target analytes. Under the optimized conditions, the calibration curves showed good linearity in the range of 0.1-10,000 µg/L with satisfactory limit of detection (≤0.06 µg/L) and limit of quantitation (≤0.3 µg/L). The proposed method also showed acceptable intra- and inter-day precisions for ketoconazole and voriconazole from urine and human plasma with RSD ≤16.5% and good relative recoveries in the range 84.3-114.8%. The MCM-41-D-µ-SPE method proved to be rapid and simple and requires a small volume of organic solvent (200 µL); thus it is advantageous for routine drug analysis.

A Retrospective Analysis of Spontaneous Adverse Drug Reactions Reports Relating to Paediatric Patients.

BACKGROUND: Spontaneous reporting on adverse drug reactions (ADR) has been established in Malaysia since 1987, and although these reports are monitored by the Malaysia drug monitoring authority, the National Pharmaceutical Control Bureau, information about ADRs in the paediatric patient population still remains unexplored. The aims of this study, therefore, were to characterize the ADRs reported in respect to the Malaysian paediatric population and to relate the data to specific paediatric age groups. METHODS: Data on all ADRs reported to the National Pharmaceutical Control Bureau between 2000 and 2013 for individuals aged from birth to 17 years old were analysed with respect to age and gender, type of reporter, suspected medicines (using the Anatomical Therapeutic Chemical classification), category of ADR (according to system organ class) as well as the severity of the ADR. RESULTS: In total, 11,523 ADR reports corresponding to 22,237 ADRs were analysed, with half of these reporting one ADR per report. Vaccines comprised 55.7% of the 11,523 ADR reports with the remaining being drug related ADRs. Overall, 63.9% of ADRs were reported for paediatric patients between 12 and 17 years of age, with the majority of ADRs reported in females (70.7%). The most common ADRs reported were from the following system organ classes: application site disorders (32.2%), skin and appendages disorders (20.6%), body as a whole general disorders (12.8%) and central and peripheral nervous system disorders (11.2%). Meanwhile, ADRs in respect to anti-infectives for systemic use (2194/5106; 43.0%) were the most frequently reported across all age groups, followed by drugs from the nervous system (1095/5106; 21.4%). Only 0.28% of the ADR cases were reported as fatal. A large proportion of the reports were received from healthcare providers in government health facilities. DISCUSSION: ADR reports concerning vaccines and anti-infectives were the most commonly reported in children, and are mainly seen in adolescents, with most of the ADRs manifesting in skin reactions. The majority of the ADR reports were received from nurses in the public sector, reporting ADRs associated with vaccine administration. The low fatality rate of ADR cases reported could potentially be caused by reporting bias due to the very low reporting percentage from the private healthcare institutions. This study indicates that ADR rates among Malaysian children are higher than in developed countries. Constant ADR reporting and monitoring, especially in respect to paediatric patients, should be undertaken to ensure their safety.

Determinants of functional status among survivors of severe sepsis and septic shock: One-year follow-up.

RATIONALE: Sepsis is a leading cause of intensive care unit (ICU) admissions worldwide and a major cause of morbidity and mortality. Limited data exist regarding the outcomes and functional status among survivors of severe sepsis and septic shock. OBJECTIVES: This study aimed to determine the functional status among survivors of severe sepsis and septic shock a year after hospital discharge. METHODS: Adult patients admitted between April 2007 and March 2010 to the medical-surgical ICU of a tertiary hospital in Saudi Arabia, were included in this study. The ICU database was investigated for patients with a diagnosis of severe sepsis or septic shock. Survival status was determined based on hospital discharge. Patients who required re-admission, stayed in ICU for less than 24 hours, had incomplete data were all excluded. Survivors were interviewed through phone calls to determine their functional status one-year post-hospital discharge using Karnofsky performance status scale. RESULTS: A total of 209 patients met the eligibility criteria. We found that 38 (18.1%) patients had severe disability before admission, whereas 109 (52.2%) patients were with severe disability or died one-year post-hospital discharge. Only one-third of the survivors had good functional status one-year post-discharge (no/mild disability). After adjustment of baseline variables, age [adjusted odds ratio (aOR) = 1.03, 95% confidence interval (CI) = 1.01-1.04] and pre-sepsis functional status of severe disability (aOR = 50.9, 95% CI = 6.82-379.3) were found to be independent predictors of functional status of severe disability one-year post-hospital discharge among survivors. CONCLUSIONS: We found that only one-third of the survivors of severe sepsis and septic shock had good functional status one-year post-discharge (no/mild disability). Age and pre-sepsis severe disability were the factors that highly predicted the level of functional status one-year post-hospital discharge.

Does the duration of smoking cessation have an impact on hospital admission and health-related quality of life amongst COPD patients?

BACKGROUND: Lack of awareness among ex-smokers on the benefits of sustaining smoking cessation may be the main cause of their smoking relapse. This study explored health-related quality of life (HRQoL) and hospital admission amongst chronic obstructive pulmonary disease (COPD) patients according to the duration of smoking cessation. MATERIALS AND METHODS: This study recruited COPD patients from a chest clinic who agreed to participate in a medication therapy-adherence program from January to June 2013. They were interviewed during their visits to obtain information regarding their smoking history and HRQoL. They were divided into three groups according to smoking status (sustained quitters, quit ≥5 years; quitters, quit <5 years; and smokers, smoking at least one cigarette/day). The effects of the duration of cessation on HRQoL and hospital admission were analyzed using a multinomial logistic model. RESULTS: A total of 117 participants with moderate COPD met the inclusion criteria, who were comprised of 41 sustained quitters, 40 quitters, and 36 smokers. Several features were similar across the groups. Most of them were married elderly men (aged >64 years) with low-to-middle level of education, who smoked more than 33 cigarettes per day and had high levels of adherence to the medication regimen. The results showed that sustained quitters were less likely to have respiratory symptoms (cough, phlegm and dyspnea) than smokers (odds ratio 0.02, confidence interval 0-0.12; P<0.001). The hospital admission rate per year was increased in quitters compared to smokers (odds ratio 4.5, confidence interval 1.91-10.59; P<0.005). CONCLUSION: A longer duration of quitting smoking will increase the benefits to COPD patients, even if they experience increased episodic respiratory symptoms in the early period of the cessation. Thus, the findings of this study show the benefits of early smoking cessation.

Patients' adherence to secondary prevention pharmacotherapy after acute coronary syndromes.

BACKGROUND: Secondary prevention pharmacotherapy improves outcomes after acute coronary syndrome (ACS). However, poor medication adherence is common, and various factors play a role in adherence. OBJECTIVES: The purpose of this study was to evaluate patients' level of adherence to evidence-based therapies at an average of 6 months after discharge for acs and to identify factors associated with self-reported non-adherence. SETTING: This prospective study was conducted in the outpatient cardiac clinics of Hospital Pulau Pinang, located in Penang Island, a northern state in Malaysia. METHOD: A random sample of ACS patients (n = 190) who had been discharged on a regimen of secondary preventive medications were included in this study. Six months after discharge and during their scheduled follow-up appointments to cardiac clinics, patients were interviewed using the translated eight-item Morisky Medication Adherence Scale. MAIN OUTCOME MEASURE: self-reported patients' adherence to medication. RESULTS: Six months following their hospital discharge, only 35 patients (18.4 %) reported high adherence. Medium adherence was reported in majority of patients (51.1 %). Low adherence was reported in 58 patients (30.5 %). Forgetfulness was the most frequently reported reason for patients' non-adherence to their medications (23.2 %). Furthermore, this study identified 5 factors-namely age, employment status, ACS subtypes, number of comorbidities, and number of prescription medications per day-that may influence Patients' level of adherence to the prescribed regimens. CONCLUSIONS: Our findings revealed a problem of non-adherence to secondary prevention medications among patients with ACS in Malaysia. Furthermore, this study demonstrates that older patients, unemployed patients, patients with more comorbid conditions, and those receiving multiple medications are less likely to adhere to their prescribed medications 6 months after hospital discharge.

Guidelines adherence and hypertension control at a tertiary hospital in Malaysia.

RATIONALE, AIMS AND OBJECTIVES: Existing literature suggests that doctors' poor adherence with guidelines is one of the major contributing factors to suboptimal control of hypertension. This study aims to evaluate doctors' adherence with Malaysian clinical practice guideline (CPG 2008) in a tertiary care hospital, and factors associated with guideline adherence and hypertension control. METHODS: This was a cross-sectional study conducted at Hospital Pulau Pinang, Penang, Malaysia. Prescriptions written by 26 enrolled doctors to 650 established hypertensive outpatients (25 prescriptions per enrolled doctor) were noted on visit 1 along with patients' demographic and clinical data. The noted prescriptions were classified either as compliant or non-compliant to CPG (2008). Five hundred twenty (80%) of the enrolled patients (20 patients per enrolled doctor) were followed for one more visit. Blood pressure (BP) noted on visit 2 was related to the prescription written on visit 1. SPSS 16 (SPSS Inc., Chicago, IL, USA) was used for data analysis. RESULTS: Three hundred forty-nine (67.1%) patients received guidelines compliant pharmacotherapy. In multivariate analysis, hypertension clinic had significant negative association with guidelines adherence. Two hundred sixty-five patients (51%) were at goal BP on visit 2. In multivariate analysis, angiotensin-converting enzyme inhibitors and guidelines adherence had significant positive, while renal disease, diabetes mellitus and diabetic clinic had significant negative association with hypertension control. CONCLUSIONS: An overall fair level of adherence with guidelines and better control of hypertension was observed. Guidelines compliant practices resulted in better control of hypertension. The gaps between what guidelines recommend and clinical practice were especially seen in the pharmacotherapy of uncomplicated hypertension and hypertension with diabetes mellitus and renal disease.

The SCIDOTS Project: evidence of benefits of an integrated tobacco cessation intervention in tuberculosis care on treatment outcomes.

BACKGROUND: There is substantial evidence to support the association between tuberculosis (TB) and tobacco smoking and that the smoking-related immunological abnormalities in TB are reversible within six weeks of cessation. Therefore, connecting TB and tobacco cessation interventions may produce significant benefits and positively impact TB treatment outcomes. However, no study has extensively documented the evidence of benefits of such integration. SCIDOTS Project is a study from the context of a developing nation aimed to determine this. METHODS: An integrated TB-tobacco intervention was provided by trained TB directly observed therapy short-course (DOTS) providers at five chest clinics in Malaysia. The study was a prospective non-randomized controlled intervention using quasi-experimental design. Using Transtheoretical Model approach, 120 eligible participants who were current smokers at the time of TB diagnosis were assigned to either of two treatment groups: conventional TB DOTS plus smoking cessation intervention (integrated intervention or SCIDOTS group) or conventional TB DOTS alone (comparison or DOTS group). At baseline, newly diagnosed TB patients considering quitting smoking within the next 30 days were placed in the integrated intervention group, while those who were contemplating quitting were assigned to the comparison group. Eleven sessions of individualized cognitive behavioral therapy with or without nicotine replacement therapy were provided to each participant in the integrated intervention group. The impacts of the novel approach on biochemically validated smoking cessation and TB treatment outcomes were measured periodically as appropriate. RESULTS: A linear effect on both 7-day point prevalence abstinence and continuous abstinence was observed over time in the intervention group. At the end of 6 months, patients who received the integrated intervention had significantly higher rate of success in quitting smoking when compared with those who received the conventional TB treatment alone (77.5% vs. 8.7%; p < 0.001). Furthermore, at the end of TB treatment (6 months or later), there were significantly higher rates of treatment default (15.2% vs. 2.5%; p = 0.019) and treatment failure (6.5% vs. 0%; p = 0.019) in the DOTS group than in the SCIDOTS group. CONCLUSION: This study provides evidence that connecting TB-tobacco treatment strategy is significant among TB patients who are smokers. The findings suggest that the integrated approach may be beneficial and confer advantages on short-term outcomes and possibly on future lung health of TB patients who quit smoking. This study may have important implications on health policy and clinical practice related to TB management among tobacco users.

Efficacy and safety of dexmedetomidine versus morphine in post-operative cardiac surgery patients.

OBJECTIVE: To compare the efficacy of dexmedetomidine versus morphine as a sedative/analgesic among post-operative cardiac surgery patients. METHOD: A randomized controlled open-label study was performed at the cardiothoracic intensive care unit of Penang Hospital, Malaysia. A total of 28 patients who underwent cardiac surgeries were randomly assigned to receive either dexmedetomidine or morphine. Both groups were similar in terms of preoperative baseline characteristics. Efficacy measures included sedation scores and pain intensity and requirements for additional sedative/analgesic. Mean heart rate and arterial blood pressure were used as safety measures. Other measures were additional inotropes, extubation time and other concurrent medications. RESULTS: The mean dose of dexmedetomidine infused was 0.12 [SD 0.03] µg kg⁻¹ h⁻¹, while that of morphine was 13.2 [SD 5.84] µg kg⁻¹ h⁻¹. Dexmedetomidine group showed more benefits in sedation and pain levels, additional sedative/analgesic requirements, and extubation time. No significant differences between the two groups for the outcome measures, except heart rate, which was significantly lower in the dexmedetomidine group. CONCLUSION: This preliminary study suggests that dexmedetomidine was at least comparable to morphine in terms of efficacy and safety among cardiac surgery patients. Further studies with larger samples are recommended in order to determine the significant effects of the outcome measures.

Tobacco use prevalence, knowledge, and attitudes among newly diagnosed tuberculosis patients in Penang State and Wilayah Persekutuan Kuala Lumpur, Malaysia.

BACKGROUND: There is sufficient evidence to conclude that tobacco smoking is strongly linked to tuberculosis (TB) and a large proportion of TB patients may be active smokers. In addition, a previous analysis has suggested that a considerable proportion of the global burden of TB may be attributable to smoking. However, there is paucity of information on the prevalence of tobacco smoking among TB patients in Malaysia. Moreover, the tobacco-related knowledge, attitudes, and behaviors of TB patients who are smokers have not been previously explored. This study aimed to document the prevalence of smoking among newly diagnosed TB patients and to learn about the tobacco use knowledge and attitudes of those who are smokers among this population. METHODS: Data were generated on prevalence rates of smoking among newly diagnosed TB patients in the State of Penang from January 2008 to December 2008. The data were obtained based on a review of routinely collated data from the quarterly report on TB case registration. The study setting comprised of five healthcare facilities (TB clinics) located within Penang and Wilayah Persekutuan, Kuala Lumpur health districts in Malaysia, which were involved in a larger project, known as SCIDOTS Project. A 58-item questionnaire was used to assess the tobacco use knowledge, attitudes and behaviors of those TB patients who were smokers. RESULTS: Smoking status was determinant in 817 of 943 new cases of TB from January to December 2008. Of this, it was estimated that the prevalence rates of current- and ex-smoking among the TB patients were 40.27% (329/817) and 13.95% (114/817), respectively. The prevalence of ever-smoking among patients with TB was estimated to be 54,220 per 100,000 population. Of 120 eligible participants for the SCIDOTS Project, 88 responded to the survey (73.3% response rate) and 80 surveys were analyzed (66.7% usable rate). The mean (+/- SD) total score of tobacco use knowledge items was 4.23 +/- 2.66 (maximum possible score=11). More than half of the participants (51.3%) were moderately dependent to nicotine. A moderately large proportion of the respondents (41.2%) reported that they have ever attempted to quit smoking, while more than half (56.3%) have not. Less than half (47.5%) of the study participants had knowledge about the body system on which cigarette smoking has the greatest negative effect. The majority wrongly believed that smokeless tobacco can increase athletic performance (60%) and that it is a safe and harmless product (46.2%). An overwhelming proportion (>80%) of the patients believed that: smoking is a waste of money, tobacco use is very dangerous to health, and that smokers are more likely to die from heart disease when compared with non-smokers. The use of smokeless tobacco was moderately prevalent among the participants with 28.8% reporting ever snuffed, but the use of cigar and pipe was uncommon. CONCLUSION: Smoking prevalence rate is high among patients with TB in Malaysia. These patients generally had deficiencies in knowledge of tobacco use and its health dangers, but had positive attitudes against tobacco use. Efforts should be geared towards reducing tobacco use among this population due to its negative impact on TB treatment outcomes.

Incidence of risk factors for developing hyperkalemia when using ACE inhibitors in cardiovascular diseases.

STUDY OBJECTIVE: To determine the incidence of and the risk factors associated with hyperkalemia, induced by ACEI-drug interactions among cardiac patients. SETTING: Five medical and cardiology wards of a tertiary care center in Malaysia. SUBJECTS: Five hundred cardiac inpatients, who received ACEIs concomitantly with other interacting drugs. METHOD: This was a prospective cohort study of 500 patients with cardiovascular diseases admitted to Penang Hospital between January to August 2006, who received ACEIs concomitantly with other interacting drugs. ACEI-drug interactions of clinical significance were identified using available drug information resources. Drug Interaction Probability Scale (DIPS) was used to assess the causality of association between ACEI-drug interactions and the adverse outcome (hyperkalemia). MAIN OUTCOME MEASURE: Hyperkalemia as an adverse clinical outcome of the interaction was identified from laboratory investigations. RESULTS: Of the 489 patients included in the analysis, 48 (9.8%) had hyperkalemia thought to be associated with ACEI-drug interactions. Univariate analysis using binary logistic regression revealed that advanced age (60 years or more), and taking more than 15 medications were independent risk factors significantly associated with hyperkalemia. However, current and previous smoking history appeared to be a protective factor. Risk factors identified as predictors of hyperkalemia secondary to ACEI-drug interactions by multi-logistic regression were: advanced age (adjusted OR 2.3, CI 1.07-5.01); renal disease (adjusted OR 4.7, CI 2.37-9.39); hepatic disease (adjusted OR 5.2, CI 1.08-25.03); taking 15-20 medications (adjusted OR 4.4, CI 2.08-9.19); and taking 21-26 medications (adjusted OR 9.0, CI 1.64-49.74). CONCLUSION: Cardiac patients receiving ACEIs concomitantly with potentially interacting drugs are at high risk of experiencing hyperkalemia. Old age, renal disease, hepatic disease, and receiving large number of medications are factors that may significantly increase their vulnerability towards this adverse outcome; thus, frequent monitoring is advocated.

Drug use and dosing in chronic kidney disease.

One of the most important drug-related problems in patients with chronic kidney disease (CKD) is medication dosing errors. Many medications and their metabolites are eliminated through the kidney. Thus, adequate renal function is important to avoid toxicity. Patients with renal impairment often have alterations in their pharmacokinetic and pharmacodynamic parameters. The clearance of drugs eliminated primarily by renal filtration is decreased by renal disease. Therefore, special consideration should be taken when these drugs are prescribed to patients with impaired renal function. Despite the importance of dosage adjustment in patients with CKD, such adjustments are sometimes ignored. Physicians and pharmacists can work together to accomplish safe drug prescribing. This task can be complex and require a stepwise approach to ensure effectiveness, minimise further damage and prevent drug nephrotoxicity.