It is known that drug disposition is altered by concurrent administration of different drugs. Drug-drug interaction may also enhance a side effect that is linked to either drug. The purpose of this report is to demonstrate the usefulness of therapeutic drug monitoring (TDM) in the early detection of side effects induced by drug-drug interaction and its treatment.
The combined use of rifampicin and mexiletine may require an increase in the dose of mexdletin by about 50% due to increased clearance resulting from enzyme induction. In addition, three days after discontinuation of the rifampicin therapy, the serum mexiletine level increased from 0.83 mcg/ml to 2.44 mcg/ml. The patient has developed a tremor. After discontinuation of mexiletine medica-tion, the symptom disappeared in two days.
On the other hand, the patient who took theophylline and mexiletine together developed nausea, vomiting and tachycardia. Four days after initiation of the combination therapy, the serum theophyl-line level was in the toxic range of 27.3 mcg/ml. The patient's theophylline dose was decreased 25%, and side effects completely resolved. The serum theophylline concentration became normal (18.8 mcg/ml) seven days later.
Whatever the mechanism, these drug interactions may be sufficient to necessitate the adjustment of drug dosage, preferabily in accordance with serum drug concentration levels. These results suggest that TDM is useful for the suppression of incidence of side effects by drug interactions.

Objective: The purpose of the present study was to clarify the efficacy of alendronate and raloxifene for preventing bone loss in patients with hip fracture by monitoring bone mineral densities (BMDs) and biochemical markers during the 9-month period after fracture. Patients and Methods: Eighty-two female hip fracture patients from 50 to 99 years old (mean ± SD: 81.6 ± 9.5) were randomly divided into two groups; there were 46 patients in the alendronate-treated group (group ALN) and 36 patients in the raloxifene-treated group (group RLX). Drugs were administered to patients six weeks after their operations. Lumbar spine BMD and neck, trochanter, Ward's and total BMDs of the contralateral proximal femur, serum intact osteocalcin (intact OC), bone-specific alkaline phosphatase (BAP) and urinary N-terminal telopeptide of type I collagen (NTX) were measured just before the start of drug administration and at 9 months thereafter. Results: Twenty-two out of 46 patients in group ALN and 23 out of 36 patients in group RLX completed the study. The most common reason for dropping out was the patient's failure to visit the outpatient clinic. Trochanter BMD in group ALN tended to increase by 8.4% compared with the baseline, and total hip BMD in group RLX showed a significant increase (5.7%), although neck BMD in both groups decreased during the 9 months of treatment (–8.7% for group ALN and –4.2% for group RLX compared with the baseline). Spine BMD did not change significantly in eithr group. Serum BAP and urinary NTX decreased significantly in both groups. Serum intact OC did not change significantly. Conclusions: Both alendronate and raloxifene have a favorable effect on trochanter and total BMDs of the contralateral proximal femur in the short period after hip fracture. However, both drugs could not prevent bone loss in the femoral neck during the 9 months of treatment.

Background/Aims: The Heart Failure Association (HFA)-PEFF score is recognized as a simple method to diagnose heart failure (HF) with preserved ejection fraction (HFpEF). This study aimed to evaluate the relationship between HFA-PEFF scores and cardiovascular outcomes in HFpEF patients. Methods: A total of 502 consecutive HFpEF patients were prospectively observed for up to 1,500 days. Cardiovascular outcomes were compared between two groups of patients, defined by their HFA-PEFF scores: those who scored 2–4 (the intermediate-score group) and those who scored 5–6 group (the high-score group). Overall, 236 cardiovascular events were observed during the follow-up period (median, 1,159 days). Results: Kaplan-Meier analysis showed that there were significant differences in composite cardiovascular events and HF-related events between the intermediate-score group and the high-score group (p = 0.003 and p < 0.001, respectively). Multivariate Cox proportional hazards analysis showed that the HFA-PEFF scores significantly predicted future HF-related events (hazard ratio, 1.66; 95% confidence interval [CI], 1.11 to 2.50; p = 0.014); receiver operating characteristic analysis confirmed this relationship (area under the curve, 0.633; 95% CI, 0.574 to 0.692; p < 0.001). The cutoff HFA-PEFF score for the identification of HF-related events was 4.5. Decision curve analysis revealed that combining the HFA-PEFF score with conventional prognostic factors improved the prediction of HF-related events. Conclusions HFA-PEFF scores may be useful for predicting HF-related events in HFpEF patients.

Background/Aims: Nonalcoholic fatty liver disease (NAFLD) is associated with a multitude of adverse outcomes. We aimed to estimate the pooled incidence of NAFLD-related adverse events. Methods: We performed a systematic review and meta-analysis of cohort studies of adults with NAFLD to evaluate the pooled incidence of adverse events. Results: 19,406 articles were screened, 409 full-text articles reviewed, and 79 eligible studies (1,377,466 persons) were included. Mean age was 51.47 years and body mass index 28.90 kg/m2. Baseline comorbidities included metabolic syndrome (41.73%), cardiovascular disease (CVD) (16.83%), cirrhosis (21.97%), and nonalcoholic steatohepatitis (NASH) (58.85%). Incidence rate per 1,000 person-years for mortality included: all-cause (14.6), CVD-related (4.53), non-liver cancer-related (4.53), and liver-related (3.10). Incidence for liver-related events included overall (24.3), fibrosis progression (49.0), cirrhosis (10.9), liver transplant (12.0), and hepatocellular carcinoma (HCC) (3.39). Incidence for non-liver events included metabolic syndrome (25.4), hypertension (25.8), dyslipidemia (26.4), diabetes (19.0), CVD (24.77), renal impairment (30.3), depression/anxiety (29.1), and non-liver cancer (10.5). Biopsy-proven NASH had higher incidence of HCC (P=0.043) compared to non-NASH. Higher rates of CVD and mortality were observed in North America and Europe, hypertension and non-liver cancer in North America, and HCC in Western Pacific/Southeast Asia (P<0.05). No significant differences were observed by sex. Time-period analyses showed decreasing rates of cardiovascular and non-liver cancer mortality and increasing rates of decompensated cirrhosis (P<0.05). Conclusions People with NAFLD have high incidence of liver and non-liver adverse clinical events, varying by NASH, geographic region, and time-period, but not sex.