Clinical Characteristics and Outcomes of Drug-Induced Acute Kidney Injury Cases.

Introduction: Drug-induced acute kidney injury (DI-AKI) is a frequent adverse event. The identification of DI-AKI is challenged by competing etiologies, clinical heterogeneity among patients, and a lack of accurate diagnostic tools. Our research aims to describe the clinical characteristics and predictive variables of DI-AKI. Methods: We analyzed data from the Drug-Induced Renal Injury Consortium (DIRECT) study (NCT02159209), an international, multicenter, observational cohort study of enriched clinically adjudicated DI-AKI cases. Cases met the primary inclusion criteria if the patient was exposed to at least 1 nephrotoxic drug for a minimum of 24 hours prior to AKI onset. Cases were clinically adjudicated, and inter-rater reliability (IRR) was measured using Krippendorff's alpha. Variables associated with DI-AKI were identified using L1 regularized multivariable logistic regression. Model performance was assessed using the area under the receiver operating characteristic curve (ROC AUC). Results: A total of 314 AKI cases met the eligibility criteria for this analysis, and 271 (86%) cases were adjudicated as DI-AKI. The majority of the AKI cases were recruited from the United States (68%). The most frequent causal nephrotoxic drugs were vancomycin (48.7%), nonsteroidal antiinflammatory drugs (18.2%), and piperacillin/tazobactam (17.8%). The IRR for DI-AKI adjudication was 0.309. The multivariable model identified age, vascular capacity, hyperglycemia, infections, pyuria, serum creatinine (SCr) trends, and contrast media as significant predictors of DI-AKI with good performance (ROC AUC 0.86). Conclusion: The identification of DI-AKI is challenging even with comprehensive adjudication by experienced nephrologists. Our analysis identified key clinical characteristics and outcomes of DI-AKI compared to other AKI etiologies.

Inter-stimulus interval in audiometry for neonates.

The usual paradigm employed for both clinical and experimental evaluation of auditory responsiveness of newborns dictates that signal presentations be separated by a minimum of 15 s. Furthermore, this paradigm requires that there be 8 presentations of the signal and that two responses among the 8 trials should be taken as normal responsiveness. Many have been concerned about accepting 25% as normal, and would prefer a paradigm that could lead to increased responsiveness. A procedure with inter-stimulus intervals longer than 15 s might be that paradigm. Therefore, the following experiment employed inter-stimulus intervals of 15, 30 and 60 s to examine responsiveness of infants young enough to be in a newborn nursery. Each infant received 24 signal presentations (8 with each of the 3 inter-stimulus intervals), and these were counter-balanced across babies. Although there is evidence of response habituation across time, there is also evidence that longer inter-stimulus intervals do lead to increased responsiveness.

Antihypertensive drug therapy withdrawal in a general population.

To determine the fraction of all hypertensives who can be successfully withdrawn from antihypertensive medication, a study was conducted of a patient group originally drawn from a screened population of union members. Of 157 patients, 88 (56.1%) met preestablished blood pressure criteria for drug interruption, and 66 (75%) actually had medication withdrawn. Of these 66 patients, 69.8% and 54.5% followed up for one and two years, respectively, remained normotensive. Patients requiring reintroduction of antihypertensive therapy were distinguished from those remaining drug free by increased systolic blood pressure (141.4 +/- 13.2 vs 131.6 +/- 8.6 mm Hg) after one month. Extrapolation of the finding that 28% of the study population remained normotensive one year after drug therapy withdrawal suggests the possibility that as many as 5 million Americans currently taking antihypertensive drugs could have therapy interrupted for at least one year and thus avoid both the hazards and costs of drug therapy.

Initial antihypertensive therapy. Comparison of prazosin and hydrochlorothiazide.

Increasing awareness of the hazards of diuretic therapy has cast doubt on the appropriateness of its uniform use as initial treatment for hypertension. To establish the relative efficacy and acceptability of alternative forms of initial therapy, prazosin and hydrochlorothiazide were prospectively compared. In a one-year study, 62 patients with a diastolic blood pressure greater than or equal to 100 mm Hg were randomly allocated to receive one of the two agents. Twenty of 32 (63 percent) patients receiving prazosin and 17 of 30 (57 percent) receiving hydrochlorothiazide satisfied the year-long study requirements. For the most part, the dropout rate was not drug related. The percentages of subjects completing the study with the initial drug, without addition of a second drug, were identical in both groups (prazosin: 10 of 32 [31 percent] and hydrochlorothiazide: nine of 30 [30 percent]). In both treatment groups, blood pressure declined similarly and significantly (p less than 0.001) by the end of the study. The blood pressure of subjects receiving prazosin decreased from 150.3/105.8 mm Hg to 135.3/90.3 mm Hg, whereas the blood pressure of subjects receiving hydrochlorothiazide declined from 147.3/103.8 to 130.0/89.1 mm Hg. A reduction in diastolic blood pressure to less than 95 mm Hg was achieved in 80.0 percent of patients started with prazosin and in 78.6 percent of those started with hydrochlorothiazide. A further reduction to less than 90 mm Hg was achieved in 45.0 and 64.3 percent, respectively (not significant). Patients who completed the study with single-drug therapy in both treatment groups showed nonsignificant decreases in mean potassium levels from initial to final readings when compared with baseline readings (prazosin: 0.21 meq; hydrochlorothiazide: 0.41 meq). However, patients receiving prazosin had 11.5 percent of their readings less than or equal to 4.0 meq, whereas those receiving hydrochlorothiazide had 38.1 percent of their readings similarly distributed (p less than 0.05). Furthermore, four patients receiving hydrochlorothiazide had potassium levels less than or equal to 3.5 meq; none of those receiving prazosin had levels in that range. At baseline, no patient in the study had potassium levels of less than 4.0 meq. Prazosin-treated patients whose initial fasting blood glucose was less than 110 mg/dl had 3.7 percent (one of 27) of subsequent measurements greater than or equal to 110 mg/dl. These abnormal levels were found 18.2 percent (six of 33) (not significant) of the time in similar hydrochlorothiazide-treated subjects. Symptomatic side effects were primarily mild and transient in those receiving either drug alone.(ABSTRACT TRUNCATED AT 400 WORDS)

Step-down therapy for hypertension. Results in a community-based program.

The study reported here involved a systematic attempt to withdraw medication from participants in a community-based hypertension treatment program. Sixty-six of 88 patients with well-controlled mild or moderate disease had medication withdrawn after at least six months of treatment; nonpharmacologic intervention was not employed. After one year, 44 (66.6%) remained normotensive and drug free; after two years, 33 (50.0%). Of the 29 patients still available for three-year follow-up, 15 (51.7%) were still normotensive and drug free. Withdrawal of medication was associated with correction of hypokalemia and reversal of impaired glucose tolerance. Thus, nearly one fourth of these patients, who were believed to be reasonably representative of those with mild or moderate hypertension, could discontinue drug therapy and remain normotensive for at least one year. Substantial medical and economic benefits are to be realized from wide replication of this experience.

Blood pressure control programs on and off the worksite.

In order to assess the importance of physical accessibility in the efficacy of a union-sponsored, worksite-based hypertension detection and treatment program, the experience of patients offered identical systematic treatment in worksite and non-worksite settings was compared. Although attrition was greater in the offsite clinic in the first year, the difference disappeared by the second year. Successful blood pressure control was maintained over three years in both treatment sites. These results suggest that physical accessibility was not the sole or even the most important factor producing favorable results in this program. Other factors such as protocol-directed treatment by non-physicians, the categorical nature of the program, lack of cost, and a socially cohesive work community may singly or together be factors responsible for successful therapy.

Systolic hypertension: occurrence and treatment in a defined community.

Systolic hypertension, a disorder occurring predominantly in the elderly, is associated with an increased incidence of stroke and coronary artery disease. Based on the supposition that it is a risk factor, many authorities have urged that it be treated. This report concerns an experience in treating systolic hypertension in a defined ambulatory population of 898 hypertensive subjects in a work-site program. The systolic hypertension group (N = 39) was compared with a matched diastolic hypertension group and with a matched systolic/diastolic hypertension group (N = 39 each). The patients with systolic hypertension responded to standard treatment (chiefly with diuretics), but less satisfactorily than did the patients with diastolic hypertension. Side effects or toxicity were uncommon and did not interfere with the therapeutic regimen. However, the ultimate value of such therapy in the prevention of vascular complications remains to be determined.