Summary
The association between serum 25-hydroxyvitamin D level and post-fracture mortality indicates beneficial relatively high serum 25-hydroxyvitamin D concentrations. A 1-year cohort study on 245 ...hip fracture patients in Finland indicated the lowest 3-year mortality and highest survival among patients with serum 25-hydroxyvitamin D level of 50–74 nmol/L.
Purpose
To explore pre-fracture serum 25-hydroxyvitamin D level as a factor associated with post-fracture survival among a cohort of hip fracture patients in Finland.
Methods
A prospectively collected cohort of hip fracture patients (
n
= 245, 70% women) from two hospitals was followed for 3.2 post-hip fracture years. Serum 25-hydroxyvitamin D was measured in admission to the hospital and classified: < 50, 50–74, 75–99, and ≥ 100 nmol/L. Survival was analyzed with a Bayesian multivariate model. Relative survival was explored with the life table method according to serum 25-hydroxyvitamin D. Mortality according to serum 25-hydroxyvitamin D level and to the hospital was calculated.
Results
Mortality in the patients with serum 25-hydroxyvitamin D level of 50–74 nmol/L was significantly lower than in all other patients together at every post-fracture year. The most important factors for survival were age under 85 years; living in an actual/private home; serum 25-hydroxyvitamin D level of 50–74 nmol/L, followed by 75–99 nmol/L; ASA classes 1–2 and 3; and female sex. The mean age of patients with serum 25-hydroxyvitamin D level of 50–99 nmol/L was significantly higher than in other levels. Relative survival was highest in men, women, and patients in hospital B with serum 25-hydroxyvitamin D level of 50–74 nmol.
Conclusion
The highest 3-year survival and the lowest mortality in this cohort appeared in patients with pre-fracture serum 25-hydroxyvitamin D level of 50–74 nmol/L. This result differs from similar studies and is lower than the recommended level of 25-hydroxyvitamin D among hip fracture patients. The results should be examined in future research with larger data.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Up to 30% of patients with obsessive-compulsive disorder (OCD) exhibit an inadequate response to serotonin reuptake inhibitors (SRIs). To date, genetic predictors of OCD treatment response have not ...been systematically investigated using genome-wide association study (GWAS). To identify specific genetic variations potentially influencing SRI response, we conducted a GWAS study in 804 OCD patients with information on SRI response. SRI response was classified as 'response' (n=514) or 'non-response' (n=290), based on self-report. We used the more powerful Quasi-Likelihood Score Test (the MQLS test) to conduct a genome-wide association test correcting for relatedness, and then used an adjusted logistic model to evaluate the effect size of the variants in probands. The top single-nucleotide polymorphism (SNP) was rs17162912 (P=1.76 × 10(-8)), which is near the DISP1 gene on 1q41-q42, a microdeletion region implicated in neurological development. The other six SNPs showing suggestive evidence of association (P<10(-5)) were rs9303380, rs12437601, rs16988159, rs7676822, rs1911877 and rs723815. Among them, two SNPs in strong linkage disequilibrium, rs7676822 and rs1911877, located near the PCDH10 gene, gave P-values of 2.86 × 10(-6) and 8.41 × 10(-6), respectively. The other 35 variations with signals of potential significance (P<10(-4)) involve multiple genes expressed in the brain, including GRIN2B, PCDH10 and GPC6. Our enrichment analysis indicated suggestive roles of genes in the glutamatergic neurotransmission system (false discovery rate (FDR)=0.0097) and the serotonergic system (FDR=0.0213). Although the results presented may provide new insights into genetic mechanisms underlying treatment response in OCD, studies with larger sample sizes and detailed information on drug dosage and treatment duration are needed.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Risky decision-making is a common, heritable endophenotype seen across many psychiatric disorders. Its underlying genetic architecture is incompletely explored. We examined behavior in the Balloon ...Analogue Risk Task (BART), which tests risky decision-making, in two independent samples of European ancestry. One sample (n = 1138) comprised healthy participants and some psychiatric patients (53 schizophrenia, 42 bipolar disorder, 47 ADHD); the other (n = 911) excluded for recent treatment of various psychiatric disorders but not ADHD. Participants provided DNA and performed the BART, indexed by mean adjusted pumps. We constructed a polygenic risk score (PRS) for discovery in each dataset and tested it in the other as replication. Subsequently, a genome-wide MEGA-analysis, combining both samples, tested genetic correlation with risk-taking self-report in the UK Biobank sample and psychiatric phenotypes characterized by risk-taking (ADHD, Bipolar Disorder, Alcohol Use Disorder, prior cannabis use) in the Psychiatric Genomics Consortium. The PRS for BART performance in one dataset predicted task performance in the replication sample (r = 0.13, p = 0.000012, pFDR = 0.000052), as did the reciprocal analysis (r = 0.09, p = 0.0083, pFDR=0.04). Excluding participants with psychiatric diagnoses produced similar results. The MEGA-GWAS identified a single SNP (rs12023073; p = 3.24 × 10
) near IGSF21, a protein involved in inhibitory brain synapses; replication samples are needed to validate this result. A PRS for self-reported cannabis use (p = 0.00047, pFDR = 0.0053), but not self-reported risk-taking or psychiatric disorder status, predicted behavior on the BART in our MEGA-GWAS sample. The findings reveal polygenic architecture of risky decision-making as measured by the BART and highlight its overlap with cannabis use.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Summary
Hypovitaminosis D is a problem among hip fracture patients. In a 1-year cohort study comprising 245 hip fracture patients (mean age of females 81 years and males 78 years) from south-eastern ...Finland, the mean 25-hydroxyvitamin D S-25(OH)D concentration was 73(SD 31) nmol/L. Vitamin D supplementation has been integrated into our current practice.
Introduction
The objectives of this study are to verify vitamin D levels among hip fracture patients and to compare the results with a similar study conducted in the same two hospitals covering the same geographic area 12 years ago.
Methods
A prospective cohort comprising 245 Caucasian hip fracture patients was enrolled in the study in two acute hospitals in south-eastern Finland (61° N) over a 12-month period in 2015–2016. The S-25(OH)D was measured using 25-hydroxyvitamin D electrochemiluminescence binding assay. The S-25(OH)D concentrations were compared with the corresponding concentrations of a similar cohort analyzed in the same two hospitals 12 years ago.
Results
Of the 245 patients, 70% were women with a mean age of 81 (SD 10) years, while the men had a mean age of 78 (SD 12) years (
p
< 0.01). The total mean S-25(OH)D concentration was 73 (SD 31.3) nmol/L. Regional differences were found: 15% in hospital A and 36% in hospital B had a S-25(OH(D level < 50 nmol/L, and the mean S-25(OH)D level was 79.2 (SD 31.7) nmol/L in hospital A and 62.4 (SD 27.5) nmol/L in hospital B (
p
< 0.001). No differences were found in S-25(OH)D concentrations by either the place of residence or the time of year. Overall, the percentage of patients with a sufficient vitamin D level (> 50 nmol/L) was remarkably higher in 2015–2016 (77%) than in 2003–2004 (22%).
Conclusion
Our results indicate that vitamin D supplementation has been widely integrated into our current practice. However, regional differences were found in the S-25(OH)D concentrations for which the reasons are unknown.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Antipsychotic-induced weight gain (AIWG) is a common side effect with a high genetic contribution. We reanalyzed genome-wide association study (GWAS) data from the Clinical Antipsychotic Trials of ...Intervention Effectiveness (CATIE) selecting a refined subset of patients most suitable for AIWG studies. The final GWAS was conducted in N=189 individuals. The top polymorphisms were analyzed in a second cohort of N=86 patients. None of the single-nucleotide polymorphisms was significant at the genome-wide threshold of 5x10(-8). We observed interesting trends for rs9346455 (P=6.49x10(-6)) upstream of OGFRL1, the intergenic variants rs7336345 (P=1.31 × 10(-5)) and rs1012650 (P=1.47 × 10(-5)), and rs1059778 (P=1.49x10(-5)) in IBA57. In the second cohort, rs9346455 showed significant association with AIWG (P=0.005). The combined meta-analysis P-value for rs9346455 was 1.09 × 10(-7). Our reanalysis of the CATIE GWAS data revealed interesting new variants associated with AIWG. As the functional relevance of these polymorphisms is yet to be determined, further studies are needed.The Pharmacogenomics Journal advance online publication, 1 September 2015; doi:10.1038/tpj.2015.59.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Methylphenidate (MPH) reduces hyperactive-impulsive symptoms common in children with autism spectrum disorders (ASDs), however, response and tolerability varies widely. We hypothesized monoaminergic ...gene variants may moderate MPH effects in ASD, as in typically developing children with attention-deficit/hyperactivity disorder. Genotype data were available for 64 children with ASD and hyperactivity who were exposed to MPH during a 1-week safety/tolerability lead-in phase and 58 who went on to be randomized to placebo and three doses of MPH during a 4-week blinded, crossover study. Outcome measures included the Clinical Global Impression-Improvement (CGI-I) scale and the Aberrant Behavior Checklist (ABC-hyperactivity index). A total of 14 subjects discontinued the study because of MPH side effects. Subjects were genotyped for variants in DRD1-DRD5, ADRA2A, SLC6A3, SLC6A4, MAOA and MAOB, and COMT. Forty-nine percent of the sample met positive responder criteria. In this modest but relatively homogeneous sample, significant differences by DRD1 (P=0.006), ADRA2A (P<0.02), COMT (P<0.04), DRD3 (P<0.05), DRD4 (P<0.05), SLC6A3 (P<0.05) and SLC6A4 (P<0.05) genotypes were found for responders versus non-responders. Variants in DRD2 (P<0.001) and DRD3 (P<0.04) were associated with tolerability in the 14 subjects who discontinued the trial. For this first MPH pharmacogenetic study in children with ASD, multiple monoaminergic gene variants may help explain individual differences in MPH's efficacy and tolerability.
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DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UILJ, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
•All studied drugs and their co-use increase the risk of falls and fractures.•No change in use of BZDs and z-hypnotics in hip fracture patients in 12 years.•No difference in the consistency of ...prescribed and detected and BZDs either.•Point prevalence and appropriateness of medication should be regularly assessed.•Instructions for medication safety assessment are available.
We described the use of benzodiazepines (BZDs), z-hypnotics, and antidepressants; analyzed the consistency between recorded and detected BZDs among hip fracture patients admitted to two Finnish hospitals during one year; and compared the results with corresponding results from 12 years earlier.
Current use of medication was obtained from the National Prescription Register. Urine and blood samples used to detect BZD were taken during admission. The following Anatomical Therapeutic Chemical (ATC) classes were included: BZDs: N05BA, N05CD; z-hypnotics: N05CF; and antidepressants: N06A.The presence of BZDs in urine was analyzed using immunoassay. Positive BZDs were confirmed by gas chromatography mass spectrometry. BZDs in serum were analyzed using liquid chromatography. Concordance between recorded and detected BZDs was calculated with kappa (κ) and described using a Venn diagram.
A total of 245 patients were enrolled in the study. BZD was detected in 18 %. Kappa was 0.39 (95 % CI 0.25−0.53). Overlap of detected and recorded BZDs was 59 %. According to the prescription register, 18 % used z-hypnotics, and according to both the detection of BZDs and register, 49 % used BZDs and/or z-hypnotics. 22 % used antidepressants and 15 % used combinations of the studied drugs concomitantly.
Use rate of BZDs and/or z-hypnotics was similar to that 12 years ago. No difference in the consistency between our previous and present study was found either. All studied drugs and their concomitant use increase the risk for fractures. In the elderly, point prevalence of medication and appropriateness should be regularly assessed.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Second-generation antipsychotic exposure, in both children and adults, carries significant risk for excessive weight gain that varies widely across individuals. We queried common variation in key ...energy balance genes (FTO, MC4R, LEP, CNR1, FAAH) for their association with weight gain during the initial 8 weeks in the two NIMH Research Units on Pediatric Psychopharmacology Autism Network trials (N=225) of risperidone for treatment of irritability in children/adolescents aged 4-17 years with autism spectrum disorders. Variants in the cannabinoid receptor (CNR)-1 promoter (P=1.0 × 10(-6)), CNR1 (P=9.6 × 10(-5)) and the leptin (LEP) promoter (P=1.4 × 10(-4)) conferred robust-independent risks for weight gain. A model combining these three variants was highly significant (P=1.3 × 10(-9)) with a 0.85 effect size between lowest and highest risk groups. All results survived correction for multiple testing and were not dependent on dose, plasma level or ethnicity. We found no evidence for association with a reported functional variant in the endocannabinoid metabolic enzyme, fatty acid amide hydrolase, whereas body mass index-associated single-nucleotide polymorphisms in FTO and MC4R showed only trend associations. These data suggest a substantial genetic contribution of common variants in energy balance regulatory genes to individual antipsychotic-associated weight gain in children and adolescents, which supersedes findings from prior adult studies. The effects are robust enough to be detected after only 8 weeks and are more prominent in this largely treatment naive population. This study highlights compelling directions for further exploration of the pharmacogenetic basis of this concerning multifactorial adverse event.
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