Incidence, risk and risk factors for acute kidney injury associated with the use of intravenous indomethacin in neonatal patent ductus arteriosus: A 16-year retrospective cohort study

Background: Intravenous indomethacin has been used in infants for many years as the pharmacological closure of ductus arteriosus, but the incidence, risk, and risk factors of acute kidney injury (AKI) among infants treated with indomethacin, were still scarce. Objectives: To determine the incidence, risk, and risk factors of AKI among infants treated with indomethacin (exposed group) for patent ductus arteriosus (PDA) closure compared with the matched non-exposed infants. Methods: A matched retrospective cohort study of infants admitted to the neonatal intensive care unit of Songklanagarind Hospital from January 2003 to December 2018 was performed. All data were collected from computerized medical records. A non-exposed infant was matched (1:1) by gestational age and birth weight to each exposed infant. AKI, the outcome of interest, was diagnosed according to neonatal AKI definitions. The incidence (95% CI) of AKI was estimated for each group. Conditional logistic regression was used to estimate the odds ratio (OR) of developing AKI among those who received indomethacin compared with those who did not, adjusted for potential confounders (concomitantly used nephrotoxic potential medications including aminoglycosides, amphotericin B, vancomycin, furosemide, systemic corticosteroids, and systemic vasopressors and inotropes). Kaplan-Meier estimate was performed to examine probability of recovery from AKI after AKI events. Results: The matching resulted in 193 pairs of exposed and non-exposed infants. The incidences [95% CI] of AKI in the exposed and the non-exposed group, were 33.7% [27.0%:40.4%] and 15.5% [10.4%:20.7%], respectively. Indomethacin statistically increased the risk for developing (AU)

Efficacy and safety of combined isoniazid-rifampicin-pyrazinamide-levofloxacin dry powder inhaler in treatment of pulmonary tuberculosis: A randomized controlled trial.

OBJECTIVE: To determine the efficacy and safety of add-on dry powder for inhalation (DPI) of combined anti-TB agents prepared as a particulate system (study group) compared with placebo DPI (control group) in patients diagnosed with pulmonary TB. METHODS: This study was a randomized, placebo-controlled, double-blinded parallel design. Subjects were pulmonary TB patients, new or re-treatment, aged 18 years or older. The eligible patients were randomly allocated (1:1) to either the study group or the control group using stratified blocked randomization. The add-on DPI of combined anti-TB therapy (each capsule contained isoniazid 5 mg, rifampicin 2 mg, pyrazinamide 16 mg, and levofloxacin 2 mg) was used throughout the course of the standard oral anti-TB treatment. The primary outcome was Mycobacterium tuberculosis (MTB) sputum culture conversion measured after receiving treatment for eight weeks. Secondary outcomes were clinical signs and symptoms of pulmonary TB and adverse drug reactions (ADRs) related to anti-TB agents. The percentages of patients who achieved the primary outcome were compared (95% confidence interval). All analyses were performed using the modified intention-to-treat principle. RESULTS: 91 patients were randomly allocated: 44 to the study group and 47 to the control group. Important baseline data (%peak expiratory flow rate, chest X-ray findings, resistance to anti-TB agents, renal and liver function tests) were similar between the two groups. Although the percentages of patients who achieved the primary outcome were similar in both groups (34/44 [77.3%] in the study group and (34/47 [72.3%] in the control group; relative risk [RR] 1.07, 95% CI 0.84-1.36; p = 0.589), the study group patients seemed to achieve the primary outcome earlier than the control group (22/44 [50.0%] vs 15/47 [31.9%]; RR 1.57, 95% CI 0.94-2.61; p = 0.079) at the end of week 4. Cough was significantly lower in the study group than in the control group (23/44 [52.3%] vs 43/47 [91.5%]; RR 0.57, 95% CI 0.43-0.77; p < 0.001) at week 4 of treatment. Hemoptysis was found in approximately half of each group at baseline. The percentage of patients having hemoptysis was substantially reduced at week 2 of treatment (5 [11.4%] in the study group and 11 [23.0%] in the control group, p = 0.132). Regarding safety outcomes, no dyspnea or severe ADRs were reported. Adverse events (AEs) related to oral anti-TB agents, (e.g. liver function tests) were in normal ranges in most patients in both groups during the treatment. The incidences of common AEs reported (e.g. anorexia, dizziness, numbness, arthralgia, rash, and itching) were similar between the two groups, while the incidences of nausea and vomiting were significantly lower in the study group than the control group (38.6% vs 74.5%, p = 0.001, and 43.2% vs 66.0%, p = 0.029, respectively). CONCLUSIONS: Add-on combined anti-TB DPI therapy to the standard oral anti-TB treatment did not increase MTB sputum culture conversion at two months of treatment. However, the percentage of patients having cough in the study group was significantly lower than in the control group at two months after treatment. A reduction in cough might represent adequate response to treatment, and result in a decreased risk of spread of infection. Combined anti-TB DPI therapy was safe. Further study investigated in a larger sample using higher strengths of DPI therapy is required.

Incidence, risk and risk factors for acute kidney injury associated with the use of intravenous indomethacin in neonatal patent ductus arteriosus: A 16-year retrospective cohort study.

Background: Intravenous indomethacin has been used in infants for many years as the pharmacological closure of ductus arteriosus, but the incidence, risk, and risk factors of acute kidney injury (AKI) among infants treated with indomethacin, were still scarce. Objectives: To determine the incidence, risk, and risk factors of AKI among infants treated with indomethacin (exposed group) for patent ductus arteriosus (PDA) closure compared with the matched non-exposed infants. Methods: A matched retrospective cohort study of infants admitted to the neonatal intensive care unit of Songklanagarind Hospital from January 2003 to December 2018 was performed. All data were collected from computerized medical records. A non-exposed infant was matched (1:1) by gestational age and birth weight to each exposed infant. AKI, the outcome of interest, was diagnosed according to neonatal AKI definitions. The incidence (95% CI) of AKI was estimated for each group. Conditional logistic regression was used to estimate the odds ratio (OR) of developing AKI among those who received indomethacin compared with those who did not, adjusted for potential confounders (concomitantly used nephrotoxic potential medications including aminoglycosides, amphotericin B, vancomycin, furosemide, systemic corticosteroids, and systemic vasopressors and inotropes). Kaplan-Meier estimate was performed to examine probability of recovery from AKI after AKI events. Results: The matching resulted in 193 pairs of exposed and non-exposed infants. The incidences [95% CI] of AKI in the exposed and the non-exposed group, were 33.7% [27.0%:40.4%] and 15.5% [10.4%:20.7%], respectively. Indomethacin statistically increased the risk for developing AKI, crude OR 2.94[95%CI 1.77:4.90], McNemar's chi square p<0.001, and adjusted OR 2.73 [95%CI 1.55:4.80], p=0.001. The risk of AKI associated with potentially nephrotoxic medications were inconclusive. Time to recovery from AKI was relatively rapid, median recovery time was 3 days in both groups and all infants who developed AKI recovered within 6 days. Conclusions: The incidence of AKI among infants treated with indomethacin for PDA closure were doubled that in the indomethacin-nonexposed infants. Indomethacin significantly increased the risk of AKI, while the risk associated with other concomitant nephrotoxic medications were inconclusive. Transient nephrotoxicity associated with indomethacin should be balanced with the risk associated with delayed PDA closure. All infants receiving indomethacin should be routinely monitored for serum creatinine and/or urine output, throughout the treatment and one to two weeks after treatment cessation. Alternatives with better renal safety profiles should be considered in the population with higher risk of AKI.

Inpatient self-administered medication under the supervision of a multidisciplinary team: a randomized, controlled, blinded parallel trial

BACKGROUND: Self-administered medication (SAM) is encouraged in many hospitals worldwide as it increases patients' knowledge and understanding of their medication, but the effects on other outcomes, e.g. compliance or medication errors, were unclear. OBJECTIVES: To compare medication knowledge, adherence, medication errors, and hospital readmission among inpatients receiving SAM education under the supervision of a multidisciplinary team (study group) with those receiving routine nurse-administered medication (control group). METHODS: This study was a PROBE design. Inpatients with chronic diseases were randomly allocated (1:1) to either the study group or the control group using stratified-block randomization. Knowledge of medications was measured at hospital discharge and at the first two follow-up visits; adherence was measured at the first two follow-up visits, medication errors while in hospital, and hospital readmission within 60 days after discharge. For normally distributed continuous outcomes, mean difference and 95%CI were estimated; otherwise the median and the Mann-Whitney test p-value were reported. The percentage difference and 95%CI were reported for binary outcomes. RESULTS: 70 patients were randomized (35 in each group); all received complete follow-up. Both groups were similar at baseline. Mean (SD) age (years) were 59.2 (11.0) for the study group and 58.3 (12.0) for the control group. Percentages of females in the respective groups were 54.3 and 60.0. Mean time from discharge to the first follow-up visit was two weeks in both groups and time to the second follow-up visit were 68.8 days (study group) and 55.0 days (control group). The study group had significantly higher medication knowledge than the control group at hospital discharge (of the 10-point scale, medians, 8.56 and 6.18, respectively, p < 0.001). The corresponding figures were similar in both groups at the first follow-up visit (medians, 8.25 and 6.26, respectively, p < 0.001). Adherence to medication at the first visit in the study group (percentage mean 92.50% (SD=5.33%)) was significantly higher than that in the control group (79.60% (SD=5.96%)), percentage mean difference 12.90%, [95%CI 10.20%:15.60%], p < 0.001. Medication knowledge and adherence were sustained at the second follow-up visit. During hospitalization, no medication errors were found in the study group, and minimal errors occurred in the control group (1.48%, [95%CI 0.68%:2.28%] of doses administered, p = 0.001). Hospital readmission within 60 days after discharge was significantly lower in the study group (11.4%) than that in the control group (31.4%), percentage difference 20.0% (95%CI 1.4%:38.6%), 1-side Fisher exact p = 0.039. CONCLUSIONS: Among in-patients with chronic diseases, SAM program significantly increased knowledge of and adherence to prescribed medications. Medication errors regarding administration errors were infrequent but significantly higher in the control group. SAM reduced hospital readmission within 60 after discharge

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Inpatient self-administered medication under the supervision of a multidisciplinary team: a randomized, controlled, blinded parallel trial.

BACKGROUND: Self-administered medication (SAM) is encouraged in many hospitals worldwide as it increases patients' knowledge and understanding of their medication, but the effects on other outcomes, e.g. compliance or medication errors, were unclear. OBJECTIVES: To compare medication knowledge, adherence, medication errors, and hospital readmission among inpatients receiving SAM education under the supervision of a multidisciplinary team (study group) with those receiving routine nurse-administered medication (control group). METHODS: This study was a PROBE design. Inpatients with chronic diseases were randomly allocated (1:1) to either the study group or the control group using stratified-block randomization. Knowledge of medications was measured at hospital discharge and at the first two follow-up visits; adherence was measured at the first two follow-up visits, medication errors while in hospital, and hospital readmission within 60 days after discharge. For normally distributed continuous outcomes, mean difference and 95%CI were estimated; otherwise the median and the Mann-Whitney test p-value were reported. The percentage difference and 95%CI were reported for binary outcomes. RESULTS: 70 patients were randomized (35 in each group); all received complete follow-up. Both groups were similar at baseline. Mean (SD) age (years) were 59.2 (11.0) for the study group and 58.3 (12.0) for the control group. Percentages of females in the respective groups were 54.3 and 60.0. Mean time from discharge to the first follow-up visit was two weeks in both groups and time to the second follow-up visit were 68.8 days (study group) and 55.0 days (control group). The study group had significantly higher medication knowledge than the control group at hospital discharge (of the 10-point scale, medians, 8.56 and 6.18, respectively, p<0.001). The corresponding figures were similar in both groups at the first follow-up visit (medians, 8.25 and 6.26, respectively, p<0.001). Adherence to medication at the first visit in the study group (percentage mean 92.50% (SD=5.33%)) was significantly higher than that in the control group (79.60% (SD=5.96%)), percentage mean difference 12.90%, [95%CI 10.20%:15.60%], p<0.001. Medication knowledge and adherence were sustained at the second follow-up visit. During hospitalization, no medication errors were found in the study group, and minimal errors occurred in the control group (1.48%, [95%CI 0.68%:2.28%] of doses administered, p=0.001). Hospital readmission within 60 days after discharge was significantly lower in the study group (11.4%) than that in the control group (31.4%), percentage difference 20.0% (95%CI 1.4%:38.6%), 1-side Fisher exact p=0.039. CONCLUSIONS: Among in-patients with chronic diseases, SAM program significantly increased knowledge of and adherence to prescribed medications. Medication errors regarding administration errors were infrequent but significantly higher in the control group. SAM reduced hospital readmission within 60 after discharge.

Evaluation of Proinflammatory Cytokines and Adverse Events in Healthy Volunteers upon Inhalation of Antituberculosis Drugs.

Inhalation therapy is a promising drug delivery approach for tuberculosis treatment. However, there is always concern about the safety of the dosage form by inhalation as it may induce inflammation. Developing a new dosage form for inhalation must include tests for its safety especially for the tumor necrosis factor (TNF)-α and interleukine (IL)-1ß. The safety of four anti-tuberculosis (anti-TB) drugs administered via inhalation was assessed in healthy volunteers. Four anti-TB drugs; isoniazid, rifampicin, pyrazinamide and levofloxacin were prepared as dry powder and evaluated for uniformity of delivered dose and in vitro drug deposition. These four anti-TB dry powder formulations for inhalation met the criteria of uniformity of delivered dose and exhibited suitable size for lung delivery. Forty healthy volunteers were recruited and each was sequentially challenged with isoniazid, rifampicin, pyrazinamide and levofloxacin in different orders. Safety was monitored by measuring the pro-inflammatory cytokines in their sputum, lung function test, blood chemistry and adverse events. This study proves that all four anti-TB dry powders did not provoke inflammatory cytokines and are safe to healthy volunteers.

Physicians' practices regarding management of antituberculosis drug-induced hepatotoxicity.

To investigate the practices of physicians regarding the diagnosis and management of antituberculosis drug-induced hepatotoxicity (ATH), a cross sectional descriptive survey using a self-administered questionnaire with multiple choice questions was conducted among physicians who treated adult tuberculosis (TB) patients at 74 public hospitals in southern Thailand. Of the 272 questionnaires mailed, 204 (75%) were returned. Sixty-two physicians (31.0%) said they used alanine aminotransferase (ALT), aspartate aminotransferase (AST) and bilirubin concurrently to diagnose ATH. Only 9.0% of physicians adhered to the American Thoracic Society (ATS) guidelines of using either an ALT or AST level. Nearly all physicians (96.6%) withheld suspected antituberculosis (anti-TB) drugs in their management of ATH patients. While waiting for normalization of liver enzyme, the alternative combination regimen of ethambutol, ofloxacin, and streptomycin (EOS) was used by most physicians (99/197). Of the 197 physicians who withheld anti-TB drugs, 175 (88.8%) decided to reintroduce them. Among these, 169 (96.6%) used a sequential rechallenge method (16.6% prescribed a full dosage, 71.4% prescribed an increasing dosage) and 1 (0.6%) used a simultaneous rechallenge method. Isoniazid was prescribed as the first drug for rechallenge in 77.5% of physicians. Only 6.5% of physicians complied with the ATS guidelines by prescribing rifampicin as the first agent. The reported practices of physicians in the diagnosis and management of ATH noticeably diverged from ATS guidelines. However, alternative regimen selection and rechallenge method complied with ATS guidelines.

Incidence and risk for neutropenia/agranulocytosis among clozapine users: A retrospective cohort study.

Abstract Objective. To estimate the incidence and the risk of neutropenia or agranulocytosis (the outcome) associated with clozapine use (the exposure), and to identify risk factors. Methods. All data were derived from the computerized hospital database. Adult psychiatric patients were identified, and 95 incident clozapine users and 884 non-clozapine users were included. Cox proportional hazards regression was used to estimate the hazards ratio (HR) of developing the outcome after clozapine use adjusted for confounders. The interaction between clozapine and valproic acid was assessed a posteriori. Results. Throughout the 24-month follow-up, the incidence of neutropenia was 6.3% in the clozapine group and 5.8% in the non-clozapine group. One agranulocytosis was found in the non-clozapine group. The HR (95% CI) for neutropenia were: clozapine 1.33 (0.54-3.25) and age . 45 years 2.99 (1.63-5.48). Lithium, as an independent protective factor, reduced the risk for neutropenia by 85% compared with patients who did not receive lithium, HR 0.15 (95% CI 0.02-1.09). Valproic acid might potentiate the clozapine-associated neutropenia (HR 5.10, 95% CI 0.70-37.12). Conclusion. Clozapine might slightly increase the risk of neutropenia in psychiatric patients. Concerning clozapine-associated neutropenia, older patients are at increased risk and use of valproic acid concurrently with clozapine should be avoided.

Effect of pharmacist participation in the health care team on therapeutic drug monitoring utilization for antiepileptic drugs.

OBJECTIVE: To compare the proportions of appropriate TDM utilization regarding the indication, sampling time, and application of the measured drug levels of antiepileptic drugs (AEDs) between the pre-intervention period and pharmacist intervention period. MATERIAL AND METHOD: The baseline evaluation and pharmacist intervention study of TDM use for phenytoin, carbamazepine, or valproic acid were conducted at a medical teaching hospital in Southern Thailand. TDM requests, interpretation and dosage adjustment recommendations were mainly responsible by residents. In the intervention period, each of the three-step TDM process was assessed by the pharmacist for appropriateness and a suggestion provided if necessary prior to a final recommendation made by the resident. The criteria for appropriateness of TDM for AEDs were developed and validated by two neurologists. The present study included 44 TDM tests (22 patients) during the baseline period and 43 tests (27 patients) during the intervention period. The proportions of appropriate TDM utilization between the two periods were compared using Chi-square test. RESULTS: In the baseline period, proportions of appropriately performed TDM were: indication (63.6%), sampling time (47.7%), and application of drug levels (63.6%). Pharmacist intervention significantly increased the proportions of appropriate indication (97.7%, p = 0.001), sampling time (79.1, p = 0.0023), and applications (83.7%, p = 0.0293). There were 12 tests (27.3%) and 29 tests (67.4%) (p = 0.0001) during the baseline and the intervention period, respectively, that met all 3 criteria of appropriate TDM use. Sixteen requests without indication found in the baseline period was reduced to one in the intervention period, and thus reduced the unnecessary cost by 90%. Of 59 steady-state drug levels, 34 (57.6%, p = 0.0005) significantly correlated with clinical responses. CONCLUSION: Pharmacist intervention significantly improved appropriateness of TDM use, and substantially reduced unnecessary costs. Using a screening checklist including the indication, sampling time and data needed for proper interpretation of the results can help improve the appropriateness of TDM utilization.

Safety and efficacy of oral nifedipine versus terbutaline injection in preterm labor.

OBJECTIVE: To compare the safety and tocolytic efficacy of oral nifedipine with intravenous terbutaline for the management of threatened preterm labor. MATERIAL AND METHOD: Pregnant women between 24 and 36 completed weeks of single gestation with preterm labor were randomized to either oral nifedipine (n=20) or intravenous terbutaline (n=20) treatment. Nifedipine (immediate released capsule) 10 mg was crushed and swallowed, 10 mg every 20 minutes was allowed if necessary with a maximum 40 mg in the first hour. After that 20 mg nifedipine every 4 hours was given, up to 72 hours. Terbutaline was initially infused with the rate 10 g/min with an increment 5 microg/min every 10 minutes if required, until 25 microg/min was reached. Once the contractions had stopped for 2-6 hours, the patients were switched to subcutaneous injection with 0.25 mg terbutaline every 4 hours for 24 hours. The main safety outcome was the changes in maternal diastolic blood pressure from baseline and 1 hour after starting the treatment (deltaDBP(1hr)). Secondary outcomes were the efficacy to delay delivery > or =48 hours and 7 days, the adverse events and the birth outcomes. RESULTS: deltaDBP(1hr) was greater in the terbutaline group than that in the nifedipine group with no statistically significant difference. Hypotension (defined as BP < or = 90/60 mmHg) was found in one patient of the nifedipine group and two patients of the terbutaline group. Seventeen and 14 patients in the nifedipine group and 15 and 12 patients in the terbutaline group had delayed delivery > or =48 hours and 7 days, respectively. Mothers in the nifedipine group experienced fewer side effects than those in the terbutaline group. Maternal heart rate, at I hour after starting the treatment, increased significantly higher in the terbutaline group than in the nifedipine group. Birth outcomes were measured in all nifedipine group patients, but in only 16 of the terbutaline group patients. Six mothers in each group delivered after 37 weeks. Intraventricular hemorrhage (IVH) occurred in three babies (gestational aged 25, 29 and 37 weeks) born to mothers treated with terbutaline. In one baby, IVH related to trauma resulted from the delivery procedure. CONCLUSION: The safety and efficacy of nifedipine compares with that of terbutaline for treatment of preterm labor.

Clearance of vancomycin during high-efficiency hemodialysis.

BACKGROUND: Vancomycin is commonly used for the treatment of MRSA infections in critically ill patients with renal diseases. Vancomycin is mainly eliminated through the kidney. Its excretion is therefore substantially reduced in severe renal impaired patients. Although several studies have demonstrated that significant amounts of vancomycin are removed during High-Flux/High-Efficiency Hemo Dialysis (HF/HEHD), more data are required to optimize clinical applications. OBJECTIVE: Predict the appropriate vancomycin intradialytic dosage and dosing interval among patients receiving HEHD. MATERIAL AND METHOD: Twenty patients who were receiving HEHD with cellulose triacetate dialyzer were included to determine the vancomycin intradialytic clearance. Two patients were included twice and one patient was included three times due to reinfections. This gave rise to 24 patient-times. The study was carried out at Songklanagarind Hospital between January 2003 and March 2004. RESULTS: In a prospective opened label design, each patient received 1g vancomycin, 1 hour infusion, immediately after completion of HEHD. Six scheduled blood samples were drawn as follows: (1) 60 minutes following completion of vancomycin infusion (Cmax); (2) immediately before starting the second HEHD; (3) 2 hours after starting the second HEHD; (4) immediately after completion of the second HEHD; (5) immediately before starting the third HEHD; and (6) immediately after the third HEHD ended (Cmin). The authors measured vancomycin serum levels using HPLC technique. The serum concentrations were used to calculate all relevant pharmacokinetic parameters. The pharmacokinetic parameters (mean +/- SD) were: intradialytic clearance (CLHD) 93.4 +/- 37.1 mL/min; intradialytic elimination rate constant (k) 1.1 +/- 0.5 hr(-1); overall elimination half-life (t(1/2)) 77.1 +/- 37.8 hr; volume of distribution (Vd) 82.1 +/- 40.3 L; Cmax 25.8 +/- 8.12 mg/L (range 12.04-48.80); Cmin 6.2 +/- 3.1 mg/L; and % removal during the second HEHD 37.9 +/- 12.9. Subtherapeutic levels were found in 66.7% (16/24) and 91.6% (22/24) of patients after the second and the third HEHD, respectively. CONCLUSION: HEHD with cellulose triacetate dialyzer removes significant amount of vancomycin. Based on the authors' findings, a loading dose of 1 g, and 500 mg after every subsequent HEHD is recommended.

Valproic acid and risk of acute pancreatitis: a population-based case-control study.

To examine whether acute pancreatitis is associated with use of valproic acid. Through the population-based hospital discharge registries we identified all patients with an incident hospitalization of acute pancreatitis in the counties of North Jutland (data 1991 to 2003), Aarhus (data 1996 to 2003), and Viborg (data 1998 to 2003), Denmark. From the Danish Civil Registration System, we selected 10 sex-matched and age-matched population controls per case on the basis of risk set sampling. All prescriptions of valproic acid and other antiepileptic drugs within 90 days (present users) or 91 to 365 days (past users) before hospital admission with acute pancreatitis, or index date among controls, were collected from the prescription databases in the counties. We performed conditional logistic regression to estimate the relative risk of acute pancreatitis after exposure to valproic acid or other antiepileptic drugs, adjusting for gallstone diseases, alcohol-related diseases, hyperlipidemia, and hypercalcemia. We included 3083 cases of acute pancreatitis and 30,830 population controls. The adjusted odds ratio (OR) for acute pancreatitis in present users of valproic acid was 1.9 [95% confidence interval (CI), 1.1-3.3); for past users, the adjusted OR was 2.6 (95% CI, 0.8-8.7). For users of other antiepileptic drugs, the corresponding adjusted ORs were 1.6 (95% CI, 1.2-2.2) and 1.8 (95% CI, 1.1-3.0). Use of valproic acid is associated with an elevated relative risk estimate for acute pancreatitis, but it was not materially different from past use or use of other antiepileptic drugs. Therefore, our data challenge the hypothesis that valproic acid is an independent risk factor for acute pancreatitis.

Appropriateness of therapeutic drug monitoring for lithium.

OBJECTIVE: Evaluate the appropriateness of therapeutic drug monitoring (TDM) for lithium. MATERIAL AND METHOD: A retrospective chart review of all patients who received lithium for treatment of psychiatric disorders between January 2004 and October 2005 was done. The present study was investigated in a psychiatric hospital in Thailand Based on detailed chart review, the appropriateness of TDM utilization comprised of three aspects, i.e., the indication of TDM request, the time of blood sample taking in relation to the medication process, and the clinical applications of the reported serum lithium levels, were evaluated. The Morecambe Bay Shared Care Guideline 2003 was modified and used as criteria for evaluation. Altogether 91 serum lithium samples were measured among 60 patients. RESULT: In 66 (72.5%) of requests, clear indications for lithium TDM were recorded i.e., initiation therapy 41.8%, suspected toxicity 15.4%, patient compliance assessment 5.5%, after regimen changes 5.5%, and therapeutic failure 4.4%. Routine tests without specified indications were found in the remainder (27.5%), all were in-patients, which pointed to potentially redundant use. The time of sample taking was recorded in 37 (40.6%) of blood samples, all were taken from in-patients, after steady state had been reached. These data for out-patients were not recorded, except one noted that blood sample was drawn after the patient had not received lithium for four days. Serum lithium levels were reported in 83 (91.2%) samples. Of these, 37 (44.6%) were out of therapeutic range, and only 12 required dosage alterations. The evaluation demonstrated somewhat inappropriate use of reported lithium levels. Dose changes were done in some patients who required dosage adjustment. Among 14 toxicity-suspected patients, nine actually had serum lithium levels exceeding the therapeutic range. Of these, only one patient was subsequently switched to a reduced dose, three patients were discontinued while five patients were prescribed the pre-TDM doses. Similarly, in five toxicity-suspected patients whose serum lithium levels were below therapeutic range, lithium was discontinued in three patients and no dosage alteration, which was considerably acceptable, in two patients. The doses were increased in three out offour inadequately controlled patients whose serum lithium was lower than the therapeutic range. Overall, in only 33 (36.3%) requests was TDM performed appropriately according to the indication, sampling time and subsequent dose adjustment. CONCLUSION: The findings indicate the need to improve the utilization of TDM for lithium. Education for hospital personnel on appropriateness of serum sample collection, interpretation, and proper use of serum drug levels is encouraged. Development of a request form containing essential data, such as indication for TDM, current drug dosing regimen, time of last dose, patient compliance, test results and interpretations and clinical decision made, can help optimize TDM use and reduce unnecessary costs.

Adverse pregnancy outcome in users of sulfamethizole during pregnancy: a population-based observational study.

OBJECTIVE: To estimate the risk of adverse birth and neonatal outcome, and miscarriage in women who used sulfamethizole during pregnancy. METHODS: The association between use of sulfamethizole and adverse birth and neonatal outcome was investigated in a case-control and a cohort study in Denmark. We used data from the Prescription Database, the Birth Registry and the Hospital Discharge Registry in North Jutland County to study any association between sulfamethizole use and first recorded miscarriage. The cohort analysis included 3484 women who received a prescription for sulfamethizole from 30 days before conception to date of delivery, and 60175 women who did not use a sulphonamide-containing drug during pregnancy or 30 days before conception. The case-control analysis included 3347 women who had a miscarriage, of whom 90 had taken sulfamethizole, and 22599 primiparous controls who had a live birth. RESULTS: Among women who received prescriptions for sulfamethizole, adjusted odds ratios and 95% confidence intervals for adverse birth outcome were: malformation 1.17 (0.95-1.43); low birth weight 0.69 (0.49-0.98); pre-term birth 1.12 (0.97-1.30); stillbirth 1.02 (0.61-1.68); neonatal jaundice 1.14 (0.38-3.46); and for receiving a prescription for sulfamethizole within 1 week before miscarriage 1.66 (0.92-2.99). CONCLUSIONS: We found no increased risk of congenital malformation, stillbirth or pre-term birth, and no association between use of sulfamethizole late in pregnancy and risk of neonatal jaundice. There was an increased risk of miscarriage after exposure to sulfamethizole during the week before miscarriage, but further studies are needed to evaluate whether this increased risk is causal.

Adverse pregnancy outcome in women exposed to acyclovir during pregnancy: a population-based observational study.

This study aimed to examine the risk of adverse pregnancy outcomes in children born to mothers who redeemed a prescription for systemic or topical acyclovir during pregnancy. Data on prescriptions of acyclovir were obtained from the Danish North Jutland Prescription Database and data on pregnancy outcomes from the Danish Medical Birth Registry and the County Hospital Discharge Registry. The risk of malformations, low birth weight, preterm birth and stillbirth in users of acyclovir were compared with non-exposed women using a follow-up design, while the risk of spontaneous abortion was examined using a case-control design. 90 pregnant women had redeemed a prescription for systemic acyclovir, and 995 women for topical acyclovir, during 30 d before conception, or during their pregnancies from 1 January 1990 to 31 December 2001. The odds ratios (95% confidence intervals) of the exposed relative to the non-exposed for the systemic and topical acyclovir were: malformations, 0.69 (0.17-2.82) and 0.84 (0.51, 1.39); low birth weight, 2.03 (0.50-8.35) and 0.48 (0.21-1.07); preterm birth, 1.04 (0.38-2.85) and 0.95 (0.70-1.28); stillbirth (for topical acyclovir), 1.70 (0.80-3.60); and spontaneous abortion, 2.16 (0.60-7.80) and 1.29 (0.80-3.60). There is increasing evidence that the use of systemic acyclovir is not associated with an increased prevalence of malformations at birth and preterm delivery. The data for low birth weight and spontaneous abortion are still inconclusive, although the risk of spontaneous abortion is increased in women exposed to acyclovir during the first month of pregnancy. The use of topical acyclovir does not seem to be associated with any adverse pregnancy outcome, although data on stillbirth are inconclusive.

A randomized controlled educational intervention on emergency contraception among drugstore personnel in southern Thailand.

OBJECTIVE: to document the effectiveness of an educational intervention in improving knowledge of and practice in dispensing emergency contraception (EC) among drugstore personnel in Thailand. METHODS: Sixty of 120 drugstores in Hat Yai, a city in Southern Thailand, were randomly selected, and half of them were randomly assigned to participate in an educational program. Well-trained "secret" shoppers went into each store before the intervention and at 1 and 3 months after the program to assess the knowledge of and practice in dispensing EC among the drugstore personnel. RESULTS: Dispensing practices at baseline were poor to fair and knowledge was fair in both groups. Sellers in the intervention group improved significantly in choice of drug, advice provided, and knowledge of the time limit for initiating EC, but those in the control group did not. However, proper history taking on the time of intercourse and menstrual cycle was poor in both groups at all study periods. CONCLUSION: All drugstore personnel should be educated on the importance of history taking and on the time limit for initiating EC.