Evidence for the association between hypomagnesemia and proton pump inhibitors (PPIs), highlighted by the 2011 FDA Drug Safety Communication, rests mainly on studies in hospitalized patients. Our ...objectives were to determine the prevalence of hypomagnesemia and its association with PPIs in the community setting. We performed a retrospective cross‐sectional analysis of a large health maintenance organization administrative database, including ambulatory patients with ≥1 serum magnesium concentrations between 2008 and 2011, the lowest referred to as “index magnesium.” In cases with any (index magnesium ≤0.7 mmol/L) or severe (≤0.55 mmol/L) hypomagnesemia, we analyzed (vs. controls, >0.7 mmol/L) the association with PPI or H2‐blocker use during the 4–12 months preceding the index magnesium by logistic regression analysis, adjusting for confounders. Among 95,205 subjects, 5,696 (6.0%) had any hypomagnesemia, which was severe in 454 (0.5%), with twofold higher prevalences in those with established risk factors. PPI use during the 4 months preceding the index magnesium was more common in cases of any hypomagnesemia (adjusted OR = 1.66; 95% CI, 1.55–1.78) and severe hypomagnesemia (adjusted OR = 3.79; 2.99–4.82) than in controls without acid suppression. Hypomagnesemia remained significantly associated with PPI use when using H2‐blocker‐users as reference (adjusted OR = 1.25 P = 0.003 and 2.65 P < 0.001 for any and severe hypomagnesemia, respectively). We conclude that hypomagnesemia is associated with PPI use in ambulatory patients.
Current guidelines recommend maintaining vancomycin trough concentrations between 15-20 mg/L for serious methicillin resistant staphylococcus aureus (MRSA) infections. This recommendation is based on ...limited evidence.
A retrospective study including patients with vancomycin susceptible MRSA infections (MIC< = 2 mg/L), treated with vancomycin. We compared outcomes among patients attaining high (> = 15mg/L) vs low (<15mg/L) trough vancomycin levels. We used a propensity score to matching patients achieving low and high levels and conducted an adjusted analysis in the propensity score (PS)-matched cohort using regression analysis. Primary outcome was 30-day all-cause mortality.
Among 285 patients included, there were no significant differences between patients achieving high and low vancomycin levels in mortality (46/131, 35.1% vs 41/154, 26.6%), clinical success, microbiological success, or nephrotoxicity. Similarly, in the PS-matched cohort (n = 162), there was no significant difference in mortality between patients with high and low vancomycin levels (24/53, 45.3% vs 57/109, 52.3%, respectively), adjusted odds ratio for mortality with high levels 0.63 (95% confidence interval 0.28-1.43). In both cohorts, patients with pneumonia achieving high levels had significantly higher clinical and microbiological success (PS-matched cohort: clinical success: 16/32, 50.0% vs 5/27, 18.5%, p = 0.012; microbiological success: 19/32, 59.4% vs 7/27, 25.9%, p = 0.010), without significant differences in mortality.
We found no association between vancomycin levels > = 15 mg/L and clinical outcomes in patients with MRSA infections. In patients with MRSA pneumonia, vancomycin levels > = 15 mg/L were associated with higher clinical success rates. Further larger cohort studies are needed to define optimal vancomycin levels according to the site of infection.
Warfarin and vitamin K intake in the era of pharmacogenetics Lurie, Yael; Loebstein, Ronen; Kurnik, Daniel ...
BJCP. British journal of clinical pharmacology/British journal of clinical pharmacology,
August 2010, Volume:
70, Issue:
2
Journal Article
Peer reviewed
Open access
The considerable variability in the warfarin dose–response relationship between individuals, is explained mainly by genetic variation in its major metabolic (CYP2C9) and target (VKORC1) enzymes. ...Despite the predominance of pharmacogenetics, environmental factors also affect the pharmacokinetics and pharmacodynamics of warfarin, and are often overlooked. Among these factors, dietary and supplemental vitamin K consumption is a controllable contributor to within‐, and between‐patient variability of warfarin sensitivity. In this commentary we review the current role of vitamin K in warfarin anticoagulation therapy, with emphasis on the following:
1 The effect of dietary and supplemental vitamin K on warfarin anticoagulation, beyond the impact of genetic variability in CYP2C9 and VKORC1. We deal separately with the effects of vitamin K on warfarin dose requirements during the induction of therapy, as opposed to its effect on stability of anticoagulation control during maintenance therapy.
2 The role of vitamin K supplementation in warfarin treated patients with vitamin K deficiency as well as in patients with unstable warfarin anticoagulation, and
3 The role of therapeutic vitamin K in cases of warfarin over‐anticoagulation.
Genetic variants in CYP2C9 and VKORC1 strongly affect steady-state warfarin dose. However, these variants also affect early international normalized ratio (INR) values during warfarin initiation. We ...examined whether CYP2C9/VKORC1 genotypes provide information about warfarin sensitivity additional to that provided by early INR responses. In 214 patients starting warfarin with INR-guided dose adjustments, we determined whether CYP2C9 and VKORC1 genotypes were associated with early measures of warfarin sensitivity (time to INR ≥ lower limit of therapeutic range; time to INR > 4; and first stable warfarin dose) after adjusting for early (days 4-6) and week 1 (days 7-9) INR values. Early INRs were associated with all outcomes (all P < .001) and were more informative than genotypes. For time to INR more than or equal to the lower limit of therapeutic range, adding either early INRs or genotypes to a baseline model (clinical variables only) increased the goodness-of-fit (R2) from 0.05 to 0.42 and 0.19, respectively (full model, R2 = 0.46). For first stable warfarin dose, adding either early INRs or genotypes to the baseline model increased the R2 from 0.08 to 0.32 and 0.27, respectively (full model, R2 = 0.40). After inclusion of week 1 INRs, CYP2C9 (P = .08) and VKORC1 (P = .30) were not associated with stable warfarin dose. Thus, much of the information provided by CYP2C9 and VKORC1 genotypes during warfarin initiation is captured by the early INR response.
Background Postoperative atrial fibrillation (PoAF) after cardiac surgery is common and associated with increased morbidity and mortality. Increased sympathetic activation after surgery contributes ...to PoAF, and β-blockers are the first-line recommendation for its prevention. We examined the hypothesis that common functional genetic variants in the β1 -adrenoreceptor, the mediator of cardiac sympathetic activation and drug target of β-blockers, are associated with the risk for PoAF and with the protective effect of β-blockers. Methods In a prospective cohort study, we studied 947 adult European Americans who underwent cardiac surgery at Vanderbilt University between 1999 and 2005. We genotyped 2 variants in the β1 -adrenoreceptor, rs1801253 (Arg389Gly) and rs1801252 (Ser49Gly), and used logistic regression to examine the association between genotypes and PoAF occurring within 14 days after surgery, before and after adjustment for demographic and clinical covariates. Results Postoperative atrial fibrillation occurred in 239 patients (25.2%) and was associated with rs1801253 genotype (adjusted P = .008), with Gly389Gly having an odds ratio of 2.63 (95% CI 1.42-4.89) for PoAF compared to the common Arg389Arg ( P = .002). In a predefined subgroup analysis, this association appeared to be stronger among patients without β-blocker prophylaxis (adjusted odds ratio 7.00, 95% CI 1.82-26.96, P = .005) compared to patients with β-blocker prophylaxis, among whom the association between rs1801253 genotype and PoAF was not statistically significant (adjusted P = .11). Conclusion The Gly389 variant in the β1 -adrenoreceptor is associated with PoAF, and this association appears to be modulated by β-blocker therapy. Future studies of the association of other adrenergic pathway genes with PoAF will be of interest.
Mushroom poisonings occur every year in Israel, mainly in the fall and winter seasons. During the fall/winter of 2020, we experienced an increase in calls to the Israel Poison Information Center ...(IPIC) concerning mushroom ingestions.
We conducted a retrospective review of mushroom poisonings reported to the IPIC during 2015-2020 using the electronic IPIC data base. For all calls about mushroom poisonings in 2020, we extracted data on patient demographics, geographic location of the picked mushroom, mycological identification (if available), IPIC recommendations, and clinical outcomes.
The IPIC received 105 calls concerning mushrooms ingestion in 2020, 65 (62%) during the last quarter. This corresponded to a 2.5-fold increase compared to the median annual rate between 2015 and 2019, and a 5-fold increase compared to the same fall/winter period in 2019. Most cases had no or only minor signs and symptoms, but 6% had moderate to severe poisoning. The severe poisonings, including one life-threatening were due to
and
ingestion.
Possible explanations for this outbreak include favorable climate conditions and increased outdoor activities of the public in response to restrictions on other leisure activities imposed during the COVID-19 pandemic.
Heart rate recovery (HRR) after exercise is an independent predictor of adverse cardiovascular outcomes. HRR is mediated by both parasympathetic reactivation and sympathetic withdrawal and is highly ...heritable. We examined whether common genetic variants in adrenergic and cholinergic receptors and transporters affect HRR. In our study 126 healthy subjects (66 Caucasians, 56 African Americans) performed an 8 min step-wise bicycle exercise test with continuous computerized ECG recordings. We fitted an exponential curve to the postexercise R-R intervals for each subject to calculate the recovery constant (kr) as primary outcome. Secondary outcome was the root mean square residuals averaged over 1 min (RMS1min), a marker of parasympathetic tone. We used multiple linear regressions to determine the effect of functional candidate genetic variants in autonomic pathways (6 ADRA2A, 1 ADRA2B, 4 ADRA2C, 2 ADRB1, 3 ADRB2, 2 NET, 2 CHT, and 1 GRK5) on the outcomes before and after adjustment for potential confounders. Recovery constant was lower (indicating slower HRR) in ADRA2B 301-303 deletion carriers (n = 54, P = 0.01), explaining 3.6% of the interindividual variability in HRR. ADRA2A Asn251Lys, ADRA2C rs13118771, and ADRB1 Ser49Gly genotypes were associated with RMS1min. Genetic variability in adrenergic receptors may be associated with HRR after exercise. However, most of the interindividual variability in HRR remained unexplained by the variants examined. Noncandidate gene-driven approaches to study genetic contributions to HRR in larger cohorts will be of interest.
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