1.
A Systematic Review and Meta-Analysis Comparing Heterogeneity in Body Mass Responses Between Low-Carbohydrate and Low-Fat Diets.
Smith, ES, Smith, HA, Betts, JA, Gonzalez, JT, Atkinson, G
Obesity (Silver Spring, Md.). 2020;(10):1833-1842
Abstract
OBJECTIVE An important notion in personalized medicine is that there is clinically relevant treatment response heterogeneity. Low-carbohydrate (CHO) and low-fat diets are widely adopted to reduce body mass. To compare individual differences in responses between two dietary interventions, a formal statistical comparison of response variances between study arms in a randomized controlled trial (RCT) is crucial. METHODS The change in variances in RCTs for the body mass responses to low-CHO dietary interventions versus change variances for the low-fat groups (typically considered as the comparator intervention) were compared. A literature search identified relevant RCTs (n = 25; 3,340 participants). The means and SDs of body mass change in low-CHO and low-fat study arms were extracted to calculate the variances of individual responses. These were meta-analyzed in a random-effects model and converted to the SD for individual responses. RESULTS The pooled SD for individual responses for body mass was 1.4 kg (95% CI: -1.1 to 2.3) with a wide 95% prediction interval of -6.3 to 10.4 kg. CONCLUSIONS Evidence is insufficient to suggest the response heterogeneity to low-CHO diets differs from that observed with low-fat diets.
2.
Genotype-guided warfarin dosing vs. conventional dosing strategies: a systematic review and meta-analysis of randomized controlled trials.
Tse, G, Gong, M, Li, G, Wong, SH, Wu, WKK, Wong, WT, Roever, L, Lee, APW, Lip, GYH, Wong, MCS, et al
British journal of clinical pharmacology. 2018;(9):1868-1882
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Abstract
AIMS: Previous trials on the effectiveness of genotype-guided warfarin dosing vs. conventional dosing have been inconclusive. We conducted a systematic review and meta-analysis of randomized trials comparing genotype-guided to conventional dosing strategies. METHODS PubMed and the Cochrane Library were searched up to 23 October 2017. RESULTS A total of 76 and 94 entries were retrieved were retrieved from PubMed and the Cochrane Library, respectively. A total of 2626 subjects in the genotype-guided dosing (mean age 63.3 ± 5.8 years; 46% male) and 2604 subjects in the conventional dosing (mean age 64.7 ± 6.1 years; 46% male) groups (mean follow-up duration 64 days) from 18 trials were included. Compared with conventional dosing, genotype-guided dosing significantly shortened the time to first therapeutic international normalized ratio (INR) (mean difference 2.6 days, standard error 0.3 days; P < 0.0001; I2 0%) and time to first stable INR (mean difference 5.9 days, standard error 2.0 days; P < 0.01; I2 94%). Genotype-guided dosing also increased the time in therapeutic range (mean difference 3.1%, standard error 1.2%; P < 0.01; I2 80%) and reduced the risks of both excessive anticoagulation, defined as INR ≥4 [risk ratio (RR) 0.87; 95% confidence interval (CI) 0.78, 0.98; P < 0.05; I2 : 0%), and bleeding (RR 0.82; 95% CI 0.69, 0.98; P < 0.05; I2 31%). No difference in thromboembolism (RR 0.84; 95% CI 0.56, 1.26; P = 0.40; I2 0%) or mortality (RR 1.16; 95% CI 0.46, 2.91; P = 0.76; I2 0%) was observed between the two groups. CONCLUSIONS Genotype-guided warfarin dosing offers better safety with less bleeding compared with conventional dosing strategies. No significant benefit on thromboembolism or mortality was evident.
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[How to individualize drug therapy based on pharmacogenetic information? A systematic review of published guidelines].
Hafner, S, Haubensak, S, Paul, T, Zolk, O
Deutsche medizinische Wochenschrift (1946). 2016;(21):e183-e202
Abstract
Background | Differences (polymorphisms) in genes encoding drug targets, drug transport proteins, or drug metabolizing enzymes may be responsible, among other factors, for the observed variation in patients' responses to medications. The field of pharmacogenetics aims to identify patients at higher genetically-determined risk of adverse effects or poor response to medication. This information would allow for modification of dosage or substitution with alternative therapy. However, there is a lack of awareness of pharmacogenetic clinical practise guidelines. Methods | A systematic literature review was conducted, using the Medline and PharmGKB databases, which focused on published guidelines for dosage modification or selection of drugs based on germline mutations in genes with pharmacokinetic or pharmacodynamic impact. Prescribing information from the European Medicines Agency, the German Federal Institute for Drugs and Medical Devices, and the US Food and Drug Administration was also screened for pharmacogenetic guidance. Results | The literature review revealed 20 guideline publications elucidating 43 drugs with recommendations for genotype-guided prescribing. Moreover, drug labels for 37 drugs also contained genotype-guided prescribing recommendations, some of which were linked to optional or obligatory pre-therapeutic pharmacogenetic testing. Conclusions | Existing guidelines for genotype-based drug prescribing are rarely derived from prospective, controlled trials; thus, their level of evidence is usually low. Even with low-quality evidence, strong recommendations can be made in favour of pharmacogenetic modification of prescription, such as for abacavir and the HLA-B genotype, if there is a large and certain difference between the benefits and harms. For other drug-gene pairs, such as vitamin K antagonists and CYP2C9/VKORC1, the net benefit from the pharmacogenetic-based dosing strategy is small and matter of debate. Because pharmacogenetics is playing a growing role in drug development and pre-prescription genotyping will become more widespread, specific pharmacogenetic guidance for treating physicians will become increasingly important.