PTPN22 polymorphisms,but not R620W,were associated with the genetic susceptibility of systemic lupus erythematosus and rheumatoid arthritis in a Chinese Han population

ObjectivesThe present study aimed to detect a possible association between PTPN22 gene polymorphisms and rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) in a Chinese Han population.Methods7 PTPN22 SNPs were genotyped in 358 patients with RA and 713 patients with SLE, as well as 564 RA controls and 672 SLE controls by Restriction Fragment Length Polymorphism (RFLP). Association analyses were conducted on the whole data set. Significant relationships were also examined between clinical features and SNPs for both RA and SLE.ResultsRs2476601 was lack of polymorphism with a ⩽0.1% frequency in both SLE and RA patients and healthy controls in our study. The two SNPs rs1217414 and rs3811021 of PTPN22 shown strong association with both SLE (rs1217414T: p_adj = 6.07e−004, OR = 0.57; rs3811021C: p_adj = 4.68e−005, OR = 0.65) and RA (rs1217414T: p_adj = 2.01e−008, OR = 0.26; rs3811021C: p_adj = 0.028, OR = 0.70). And the rs3765598 revealed a strong risk factor for SLE (p = 9.38e−009, p_adj = 6.57e−008, OR = 1.93), but not for RA (p = 0.48, OR = 1.12). Moreover, protective haplotype ACTTC in RA (p = 7.73e−016, p_adj = 5.51−015, OR[95%CI] = 0.02[0.002–0.10]) and SLE (p = 8.29e−018, p_adj = 5.80e−017, OR[95%CI] = 0.11[0.06–0.21]) were observed. In addition, the distribution of risk haplotypes ACGTC and GCTTT in RA (ACGTC: p = 0.0006, p_adj = 0.004, OR[95%CI] = 1.85[1.29–2.63]; GCTTT: p = 2.62e−005, p_adj = 1.85e−004, OR[95%CI] = 2.40[1.57–3.65]) and SLE (ACGTC: p = 0.0006, p_adj = 0.004, OR[95%CI] = 1.85[1.29–2.63]; ACGTC: p = 7.74e−011, p_adj = 6.81e−010, OR[95%CI] = 2.21[1.12–3.34]; GCTTT: p = 2.40[1.57–3.65], p_adj = 2.26e−006, OR[95%CI] = 2.64[1.79–3.87]) were significant different from that in controls. Furthermore, significant association was observed between the PTPN22 rs3765598 and antinuclear antibodies 1 (ANA1) in SLE.ConclusionsOur data provide strong evidence that the rs1217414 and rs3811021 in PTPN22 gene might be common protective factors contributed to SLE and RA susceptibility in the Chinese Han population. While, the rs3765598 might increase the genetic susceptibility of SLE, but not RA.     

Genetic associations of killer immunoglobulin like receptors and class I human leukocyte antigens on childhood acute lymphoblastic leukemia among north Indians

BackgroundMolecular interactions between KIRs and their cognate HLA class-I ligands, play a central role in the regulation of natural killer (NK) cell responses in malignancies. We aimed to determine the role of KIR genes and their HLA ligands in genetic predisposition of childhood acute lymphoblastic leukemia (ALL).MethodsGenotyping of 16 KIR genes, along with HLA class-I groups C1/C2 and Bw4 super-type ligands, was carried-out in 137 childhood ALL cases and 274 healthy controls.ResultsWe observed an increased incidence of activating KIRs namely; 2DS2 (OR = 2.23, p = <0.001), 2DS3 (OR = 1.74, p = 0.011), 3DS1 (OR = 2.22, p = <0.001), 2DS5 (OR = 2.10, p = 0.001), 2DS1 (OR = 4.42, p = <0.001) and 2DS4 (OR = 2.88, p = <0.001) genes in childhood ALL cases compared to controls. Frequency of BB genotype that possess 2–6 activating KIR genes was predominant in cases compared to controls (OR = 2.55, p = <0.001). KIR-receptor/HLA-ligand combinations analysis revealed a moderate risk of almost 2-fold for activating KIR-ligand combinations namely; KIR2DS1-HLAC2, KIR2DS2-HLAC1 and KIR3DS1-HLABw4 in childhood ALL cases.ConclusionOur data suggests the role for KIR genes and their HLA ligands in aetiology of childhood ALL.     

L’âge des culots globulaires transfusés influence-t-il toujours le pronostic des patients en réanimation ?

ObjectiveFew studies have shown that aged packed red blood cells (RBC) transfusion negatively influenced the outcome of ICU patients, probably related to storage lesions which could be decreased by leukodepletion of RBC. The purpose of this study was to evaluate the impact of aged leukodepleted-RBC pack, on the outcome of ICU patients.DesignRetrospective, observational, cohort study in a Medical Intensive Care Unit.PatientsConsecutive patients admitted during the years 2005 and 2006, and requiring a transfusion. We recorded patient's demographic data, number of RBC unit and age of each RBC, length of ICU, mortality during ICU stay.ResultsFive hundred and thirty-four patients were included with global mortality was 26.6%, length of stay in ICU six days (3–14) and SAPS II 48 (35–62). RBC equaling to 5.9 were transfused per patients (22.7% < 14 days and 57.3% < 21 days). The number of RBC was significantly higher in the dead patients group, but the rate of RBC stored less than 21 days was not different (54% versus 60%; p = 0.21). In a multivariate logistic model, independent predictors of ICU death were SAPS II (OR = 1.02 per point, p < 0.001), number of RBC (OR = 1.08 per RBC, p < 0.001), length of stay in ICU (p < 0.001). Similar results were obtained while introducing the age of RBC as time dependent covariates in a multivariate Cox's model.ConclusionsRBC transfused in our ICU are old. The ICU outcome is independently associated with the number of leucodepleted RBC transfused, but not with their age.     

Does intraoperative transfusion during total knee arthroplasty reduce the need for transfusion after surgery?: A preliminary retrospective cohort study

ObjectivesAfter total knee arthroplasty (TKA), many patients experience anemia due to blood loss. To prevent postoperative anemia and allogeneic blood transfusion after TKA, we used prophylactic allogeneic or autologous blood transfusion intraoperatively. This study evaluated the effects of prophylactic transfusion during TKA.Materials and methodsThis retrospective cohort study included 579 patients receiving scheduled unilateral TKA. We allocated the patients into three groups, the prophylactic allogeneic transfusion (Group AL), prophylactic autologous transfusion (Group AT), and no prophylactic transfusion with intra-articular tranexamic acid administration (Group C) groups. After propensity score matching, we compared the rate of postoperative allogeneic blood transfusions until three days after TKA, postoperative hemoglobin and hematocrit levels until four days after TKA, and the side effects in each groups.ResultsThe postoperative allogeneic blood transfusion rates were statistically higher in group AL and AT than in group C (18.2% and, 18.9% vs 2.3%, respectively; P < 0.000). The postoperative hemoglobin and hematocrit levels were statistically lower in group Auto than in group C (P < 0.0001), but the levels in group AL were not different from those of group C (P = 0.493 vs. P = 0.384 respectively). In addition, the side effects were statistically higher in group AL and AT than in group C.ConclusionProphylactic intra-operative transfusions did not reduce the rates of allogeneic transfusions and produced more side effects and hypotension after surgery than intra-articular tranexamic acid administration with no prophylactic transfusion in patients undergoing TKAs.     

Association between IFNL4 rs368234815 polymorphism and sustained virological response in chronic hepatitis C patients undergoing PEGylated interferon/ribavirin therapy: A meta-analysis

Background and aimsMany studies have been published on the association between IFNL4 rs368234815 single-nucleotide polymorphism (SNP) and sustained virological response (SVR) in chronic hepatitis C (CHC) patients undergoing treatment with PEGylated interferon (PEG-IFN) plus ribavirin (RBV). Because of the variable and sometimes inconsistent results, we performed a meta-analysis to estimate the association between these factors.MethodsWe conducted a search of the literature published prior to July 1, 2014. The pooled results were analyzed as the odds ratios (ORs) and corresponding 95% confidence intervals (CIs) using random-effect model.ResultsThe pooled results revealed that the rs368234815 TT/TT genotype was significantly correlated with SVR in HCV-1/4-infected Caucasian patients (OR = 4.65, 95% CI = 3.36–6.42, P < 0.00001) but not in HCV-2/3-infected Caucasian patients (OR = 1.44, 95% CI: 0.89–2.33, P = 0.13). Conversely, the rs368234815 ΔG/ΔG genotype was significantly linked to treatment failure in Caucasian patients (OR = 0.49, 95% CI: 0.38–0.64, P < 0.00001), regardless of the HCV genotype.ConclusionThe results of the meta-analysis suggest that IFNL4 rs368234815 polymorphism may be a predictor of SVR in Caucasian HCV-1/4-infected patients.     

Alpha tryptase allele of Tryptase 1 (TPSAB1) gene associated with Dengue Hemorrhagic Fever (DHF) and Dengue Shock Syndrome (DSS) in Vietnam and Philippines

We previously reported, significantly higher levels of Chymase and Tryptase in early stage plasma of DSS patients prior to the occurrence of shock suggesting a possible role of mast cells in dengue pathogenesis. To further investigate, we analyzed CMA1 promoter SNP (rs1800875) and TPSAB1 gene alleles, which encode the Human Chymase and α- and β- tryptase 1 enzymes respectively, for susceptibility to Dengue Hemorrhagic Fever (DHF) and Dengue Shock Syndrome (DSS) in patients from hospitals in Vietnam (Ho Chi Minh City and Vinh Long) and the Philippines. While the CMA1 promoter SNP (rs1800875) was not associated with DHF/DSS, the homozygous form of α-tryptase allele was associated with DSS patients in Vinh Long and the Philippines (OR = 3.52, p < 0.0001; OR = 3.37, p < 0.0001, respectively) and with DHF in Ho Chi Minh City (OR = 2.54, p = 0.0084). Also, a statistically significant association was observed when DHF and DSS were combined in Vinh Long (OR = 1.5, p = 0.034) and the Philippines (OR = 2.36, p = 0.0004); in Ho Chi Minh City when DHF and DSS were combine an association was observed, but it was not statistically significant (OR = 1.5, p = 0.0505). Therefore, the α-tryptase might have a possible effect on the susceptibility to severe form of Dengue infection.     

A meta-analysis of P2X7 gene-1513A/C polymorphism and pulmonary tuberculosis susceptibility

ObjectiveA meta-analysis was performed to determine the association between P2X7-1513A/C polymorphism and pulmonary tuberculosis susceptibility.MethodsBased on comprehensive searches of the MEDLINE, EMBASE and ISI Web of knowledge, China National Knowledge Infrastructure (CNKI) and Wanfang Database, we identified eligible studies about the association between P2X7-1513A/C polymorphism and pulmonary tuberculosis susceptibility.ResultsA total of 1916 cases and 2194 controls in 10 studies were pooled together for evaluation of the overall association between P2X7-1513A/C polymorphism and susceptibility of pulmonary tuberculosis. Allele model (A vs. C: p = 0.15; OR = 0.86, 95% CI = 0.69–1.06), homozygous model (AA vs. CC: p = 0.22; OR = 0.78, 95% CI = 0.53–1.16), and heterozygous model (AC vs. CC: p = 0.23; OR = 0.80, 95% CI = 0.56–1.15) did not show decreased risk of developing pulmonary tuberculosis. Similarly, dominant model (AA + AC vs. CC: p = 0.19; OR = 0.80, 95% CI = 0.56–1.12) and recessive model (AA vs. AC + CC: p = 0.21; OR = 0.85, 95% CI = 0.66–1.10) failed to show decreased risk of developing pulmonary tuberculosis. In Indians, allele model (A vs. C: p = 0.0006; OR = 0.69, 95% CI = 0.55–0.85), and recessive model (AA vs. AC + CC: p = 0.0003; OR = 0.62, 95% CI = 0.48–0.80) indicated significant association between P2X7-1513A/C polymorphism and susceptibility to pulmonary tuberculosis.ConclusionsOur pooled data suggest a association between P2X7-1513A/C polymorphism and the prevalence of pulmonary tuberculosis among Indian populations.     

Relationship between depression and frailty in older adults: A systematic review and meta-analysis

AimDepression and frailty are prevalent and burdensome in older age. However, the relationships between these entities are unclear and no quantitative meta- analysis exists. We conducted a systematic review and meta-analysis to investigate the associations between depression and frailty.MethodsTwo authors searched major electronic databases from inception until November-2016 for cross-sectional/longitudinal studies investigating depression and frailty. The strength of the reciprocal associations between frailty and depression was assessed through odds ratios (ORs) adjusted for potential confounders.ResultsFrom 2306 non duplicated hits, 24 studies were included. The overall prevalence of depression in 8023 people with frailty was 38.60% (95% CI 30.07–47.10, I² = 94%). Those with frailty were at increased odds of having depression (OR adjusted for publication bias 4.42, 95%CI 2.66–7.35, k = 11), also after adjusting for potential confounders (OR = 2.64; 95%CI: 1.59–4.37, I² = 55%, k = 4). The prevalence of frailty in 2167 people with depression was 40.40% (95%CI 27.00–55.30, I² = 97%). People with depression were at increased odds of having frailty (OR = 4.07, 95%CI 1.93–8.55, k = 8). The pooled OR for incident frailty, adjusted for a median of 7 confounders, was 3.72 (95%CI 1.95–7.08, I² = 98%, k = 4), whilst in two studies frailty increased the risk of incident depression with an OR = 1.90 (95%CI 1.55–2.32, I² = 0%).ConclusionThis meta-analysis points to a reciprocal interaction between depression and frailty in older adults. Specifically, each condition is associated with an increased prevalence and incidence of the other, and may be a risk factor for the development of the other. However, further prospective investigations are warranted.     

Circulating osteoprotegerin and asymptomatic carotid atherosclerosis in postmenopausal non diabetic women

PurposeOsteoprotegerin (OPG) is a bone metabolism regulator but it is also involved in vascular calcification. Its role in the development of atherosclerosis is still a subject of debate. Postmenopausal women seem to have an increased risk for cardiovascular disease. The aim of the study is to evaluate the relationship between serum OPG and asymptomatic carotid atherosclerosis in postmenopausal non-diabetic women.Material/methodsCarotid artery examination was performed in 100 postmenopausal women without diabetes mellitus and overt cardiovascular disease, using B-mode ultrasonography to determine the carotid intima-media thickness (CIMT) and the presence of plaques. Serum OPG was measured in all study participants and its relationship with clinical, biochemical and vascular parameters was evaluated.ResultsCIMT correlated with age (r = 0.45, p < 0.001), years since menopause (r = 0.30, p = 0.003), abdominal circumference (r = 0.25, p = 0.01) and OPG (r = 0.23, p = 0.02). Carotid plaques correlated with age (p < 0.001), obesity (p = 0.03), abdominal circumference (p = 0.03) and CIMT (p < 0.001), but not with serum OPG (p = 0.86). In regression analyses the independent predictors for CIMT were age (β = 0.717, p < 0.001), OPG (β = 0.214, p = 0.02), and years since menopause (β = −0.334, p = 0.04) and for the presence of carotid plaques were obesity (p = 0.04, OR = 3.90), CIMT (p < 0.001, OR = 6408.86) and smoking (p = 0.02, OR = 687.93).ConclusionOPG is associated with cardiovascular risk factors, CIMT, but not with the presence of asymptomatic carotid plaques in non diabetic postmenopausal women. OPG may be a marker of cardiovascular risk.     

Juvenile rheumatoid arthritis and asthma,but not childhood-onset systemic lupus erythematosus are associated with FCRL3 polymorphisms in Mexicans

A regulatory single nucleotide polymorphism located in the 5′ region (?169T/C) of the Fc receptor-like 3 (FCRL3_3) gene has been associated with both susceptibility and protection in immune diseases. This case–control study aimed to evaluate the association between FCRL3 polymorphisms and juvenile rheumatoid arthritis (JRA), asthma, and childhood-onset systemic lupus erythematosus (SLE) in a Mexican population. We performed PCR-based genotyping to identify four FCRL3 single nucleotide polymorphisms (FCRL3_3 to FCRL3_6) in patients with JRA (n = 202), asthma (n = 239), or childhood-onset SLE (n = 377), and healthy controls (n = 400). The case–control analysis showed a male-gender dependent association between the FCRL3_3C, FCRL3_5C, and FCRL3_6A alleles and either JRA (OR = 0.57, p = 0.003; OR = 0.55, p = 0.002; OR = 0.53, p = 0.0007, respectively) or asthma (OR = 0.72, p = 0.04; OR = 0.74, p = 0.05; OR = 0.70, p = 0.02, respectively). As expected, minor alleles of these SNPs with the CGCA haplotype were also significantly associated with JRA (OR = 0.35, p = 0.00005) and asthma (OR = 0.61, p = 0.007). We found no association between FCRL3 SNPs or haplotypes and childhood-onset SLE. These results supported the notion that FCRL3 is involved in the etiology of several immune diseases. Our results also suggested that SNPs located in the FCRL3 gene were protective against JRA and asthma in male Mexican patients.     

Genetic polymorphisms in TNFSF13 and FDX1 are associated with IgA nephropathy in the Han Chinese population

IgA nephropathy (IgAN) is the most common primary glomerulonephritis worldwide, and its pathogenesis is influenced by both genetic and environmental factors. In this study, we evaluated 23 tag single-nucleotide polymorphisms (tSNPs) in 21 IgAN-associated genes, in 200 subjects with IgAN and 310 healthy gender- and age-matched unrelated control subjects with no history of renal disease or hypertension. Using the co-dominant model, we found that two genotypes of rs3803800 in TNFSF13 were associated with an increased risk of IgAN: “GA” (OR = 1.03, 95% CI = 0.71–1.51, p = 0.018) and “AA” (OR = 2.45, 95% CI = 1.29–4.65, p = 0.018). The “AA” genotype was also associated with an increased risk of IgAN in the recessive model (OR = 2.41, 95% CI = 1.30–4.46, p = 0.018), as was the genotype “AA” rs10488764 in FDX1 (OR = 1.88, 95% CI = 1.01–3.53, p = 0.048). Interestingly, we found that the allele “A” of rs3803800 in TNFSF13 is associated with a decreased risk of IgAN in females (OR = 0.43, 95% CI = 0.20–0.95, p = 0.009), but with an increased risk in males (OR = 1.78, 95% CI = 0.86–3.66, p = 0.009). Our findings, combined with previously reported results, suggest that TNFSF13 and FDX1 have potential roles in IgAN in the Han Chinese population. This information may be useful in the development of early prognostics for IgAN.     

HPV and lung cancer risk: A meta-analysis

The potential causal association between human papillomavirus (HPV) and lung cancer (LC) remains controversial. We performed this meta-analysis to evaluate whether HPV infection in lung tissue is associated with LC compared with non-cancer controls. We also quantified this association in different LC subtypes. MEDLINE, EMBASE and Web of Science were searched through March 2014, using the search terms “lung cancer”, “human papillomavirus”, “HPV” and their combinations. Association was tested using odds ratio (OR) with 95% confidence intervals (95% CI). Heterogeneity was assessed using Q and I² statistic. Finally, nine studies, for a total of 1094 LCs and 484 non-cancer controls, were identified as eligible publications. The pooled results showed that HPV infection was associated with LC (OR = 5.67, 95% CI: 3.09–10.40, P < 0.001). Similar results were also observed in HPV16 and/or HPV18 (HPV16/18) infection analyses (OR = 6.02, 95% CI: 3.22–11.28, P < 0.001). HPV16/18 was significantly associated with lung squamous cell carcinoma (SCC) (OR = 9.78, 95% CI: 6.28–15.22, P < 0.001), while the pooled OR was 3.69 in lung adenocarcinoma (95% CI: 0.99–13.71, P = 0.052). Our results suggest that lung tissue with HPV infection has a strong association with LC, and especially, HPV16/18 infection significantly increases SCC risk, which indicates a potential pathogenesis link between HPV and LC.     

Genetic variation in Micro-RNA genes of host genome affects clinical manifestation of symptomatic Human Cytomegalovirus infection

BackgroundMicro-RNAs are implicated in various physiological and pathologic processes. In this study, we tested whether Micro-RNA gene variants of host-genome affect clinical manifestation of symptomatic HCMV infection.MethodologyHCMV infection was detected by fluorescent PCR and immuno-histochemistry. The detection of genetic variants of four studied Micro-RNA tag-SNPs was done through PCR-RFLP assay and validated with DNA sequencing.ResultsWe observed an increased risk ranged from 3-folds to 5-folds among symptomatic HCMV cases for mutant genotype of rs2910164 (crude OR = 3.11, p = 0.009 and adjusted OR = 3.25, p = 0.007), rs11614913 (crude OR = 3.20, p = 0.006 and adjusted OR = 3.48, p = 0.004) and rs3746444 (crude OR = 4.91, p = 0.002 and adjusted OR = 5.28, p = 0.002) tag-SNPs. Interestingly, all the tag-SNPs that were significant after multiple comparisons at a FDR of 5% in symptomatic HCMV cases remained significant even after bootstrap analysis, providing internal validation to these results. Multifactor Dimensionality Reduction (MDR) analysis revealed 5-folds increased risk for symptomatic HCMV cases under the four-factor model (rs2910164, rs2292832, rs11614913 and rs3746444).ConclusionsThese results suggest that Micro-RNA gene variants of host-genome may affect clinical manifestation of symptomatic HCMV infection.     

Efficacy and safety of paliperidone extended-release in schizophrenia patients with prominent affective symptoms

BackgroundThis post-hoc analysis evaluated the effects of paliperidone extended-release (ER) in patients with schizophrenia and prominent affective symptoms.MethodsPooled data from three 6-week, randomized, double-blind, placebo-controlled studies were analyzed. Subjects received fixed doses of paliperidone ER 3–12 mg/day or placebo. Prominent affective symptoms were defined as depressive (Positive and Negative Syndrome Scale [PANSS] depression item score of ≥ 5 [moderately severe]) and/or manic (PANSS grandiosity score of ≥ 4 [moderate], plus a score of ≥ 4 [moderate] on at least 1 PANSS item for excitement, hostility, uncooperativeness, or poor impulse control). Assessments included PANSS, Clinical Global Impressions-Severity (CGI-S), Personal and Social Performance (PSP) scale, and adverse events (AEs).ResultsAmong 193 patients with prominent affective symptoms, 140 received paliperidone ER and 53 received placebo. Paliperidone ER showed significant mean (SD) improvements vs. placebo in PANSS total (? 20.5 [23.8] vs. ? 6.3 [27.2]; p < 0.001, respectively) and all factor scores (p < 0.01). Significant mean (SD) improvements were observed in PSP (7.2 [15.8] vs. 0.4 [14.6]; p = 0.004) and CGI-S (? 0.9 [1.2] vs. ? 0.3 [1.2]; p < 0.001) scores. Most common AEs with paliperidone ER vs. placebo: headache (16.4% vs. 13.2%), insomnia (7.9% vs. 9.4%), akathisia (7.1% vs. 1.9%), sedation (7.1% vs. 3.8%).LimitationsThese studies were not designed to examine patients with prominent affective symptoms. Authors' clinical judgment was used to define prominent affective symptoms, using relevant PANSS items.ConclusionsPaliperidone ER was well tolerated and associated with significantly greater improvements in symptomatology, functioning, and overall clinical status vs. placebo in patients with schizophrenia and prominent affective symptoms.     

The impact of a closed-loop electronic blood transfusion system on transfusion errors and staff time in a children's hospital

ObjectivesTo assess the impact of a closed-loop electronic blood transfusion system on transfusion errors and staff time.Materials and methodsBefore and after study in all wards of a children's hospital, involving patients and staff of all the wards. The changes were closed-loop electronic blood transfusion, barcode patient identification, electronic blood transfusion administration records and error pop-up warning. The main outcome measures were percentage of blood transfusion errors, time spent on transfusion tasks.ResultsTransfusion errors were identified in 3.87% of 2556 blood transfusion orders pre-intervention and 0.78% of 2577 orders afterwards (P < 0.01). Phlebotomists, nurses, and physicians may make mistakes, including wrong blood type when apply for blood, wrong patient when blood draw or transfusion, wrong dose when apply for blood and the wrong tube label when blood draw or cross-matching, which are significantly reduced after change (1.09% vs 0.31%, 1.13% vs 0%, 0.31% vs 0%, 1.33% vs.0.78%, P < 0.01). Time spent on blood apply was 5.3 ± 1.2 min, hand over blood bag at the transfusion department was 14.9 ± 1.4 min and blood transfusion was 15.8 ± 2.4 min. Time per transfusion round decreased to 2.6 ± 1.0 min, 6.3 ± 1.6 min and 9.3 ± 2.2 min respectively (P < 0.01).ConclusionsA closed-loop electronic blood transfusion, barcode patient identification and error pop-up warning reduced transfusion errors, and increased confirmation of patient and blood types identity before transfusion. Time spent on blood transfusion tasks reduced.     

Association of vitamin D deficiency and frailty: A systematic review and meta-analysis

There is a biologically plausible association between low vitamin D, specifically serum 25-hydroxyvitamin D [25(OH)D] level, and frailty. We conducted a systematic review and meta-analysis to describe the association between low 25(OH)D level and frailty. We searched literature in OVID (Medline), EMBASE, Web of Knowledge and Cochrane CENTRAL Library Issue in May 2016, for cohort studies evaluating association of low 25(OH)D level with the risk of frailty. Studies were reviewed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses(PRISMA) guidelines. A total of seven studies(17,815 participants)were eligible in our study. The prevalence of frailty ranged from 3.9% to 31.9%. The pooled OR of frailty for the lowest versus the highest level of vitamin D was 1.27 (95% CI = 1.17–1.38, I² = 59%), suggesting that low level of vitamin D was significantly associated with the risk of frailty. In addition, results of subgroups analysis indicated that low level of vitamin D was significantly associated with the risk of frailty in female (pooled OR = 1.27, 95% CI = 1.15–1.40). Similar result was also found when frailty was defined by the Fried criteria or the modified Fried criteria (pooled OR = 1.25, 95% CI = 1.14–1.37), and FRAIL scale (pooled OR = 1.55, 95% CI = 1.07–2.25). Compared to the highest level of 25(OH)D, the association between frailty and the lowest level of 25(OH)D was significant in our study.     

Exercise training for managing behavioral and psychological symptoms in people with dementia: A systematic review and meta-analysis

This systematic review and meta-analysis of randomized controlled trials assessed the effects of exercise on behavioral and psychological symptoms of dementia (BPSD, including depression) in people with dementia (PWD). Secondary outcomes for the effects of exercise were mortality and antipsychotic use. Twenty studies were included in this review (n = 18 in the meta-analysis). Most studies used a multicomponent exercise training (n = 13) as intervention; the control group was often a usual care (n = 10) or a socially-active (n = 8) group. Exercise did not reduce global levels of BPSD (n = 4. Weighted mean difference −3.884; 95% CI −8.969–1.201; I² = 69.4%). Exercise significantly reduced depression levels in PWD (n = 7). Standardized mean difference −0.306; 95% CI −0.571 to −0.041; I² = 46.8%); similar patterns were obtained in sensitivity analysis performed among studies with: institutionalized people (p = 0.038), multicomponent training (p = 0.056), social control group (p = 0.08), and low risk of attrition bias (p = 0.11). Exploratory analysis showed that the principal BPSD (other than depression) positively affected by exercise was aberrant motor behavior. Exercise had no effect on mortality. Data on antipsychotics were scarce. In conclusion, exercise reduces depression levels in PWD. Future studies should examine whether exercise reduces the use (and doses) of antipsychotics and other drugs often used to manage BPSD.     

The adsorption of preferential binding peptides to apatite-based materials

The objective of this work was to identify peptide sequences with high affinity to bone-like mineral (BLM) to provide alternative design methods for functional bone regeneration peptides. Adsorption of preferential binding peptide sequences on four apatite-based substrates [BLM and three sintered apatite disks pressed from powders containing 0% CO₃^2? (HA), 5.6% CO₃^2? (CA5), 10.5% CO₃^2? (CA10)] with varied compositions and morphologies was investigated. A combination of phage display, ELISA, and computational modeling was used to elucidate three 12-mer peptide sequences APWHLSSQYSRT (A), STLPIPHEFSRE (S), and VTKHLNQISQSY (V), from 243 candidates with preferential adsorption on BLM and HA. Overall, peptides S and V have a significantly higher adsorption to the apatite-based materials in comparison to peptide A (for S vs. A, BLM p = 0.001, CA5 p < 0.001, CA10 p < 0.001, HA p = 0.038; for V vs. A, BLM p = 0.006, CA5 p = 0.033, CA10 p = 0.029). FT-IR analysis displayed carbonate levels in CA5 and CA10 dropped to approximately 1.1–2.2% after sintering, whereas SEM imaging displayed CA5 and CA10 possess distinct morphologies. Adsorption results normalized to surface area indicate that small changes in carbonate percentage at a similar morphological scale did not provide enough carbonate incorporation to show statistical differences in peptide adsorption. Because the identified peptides (S and V) have preferential binding to apatite, their use can now be investigated in bone and dentin tissue engineering, tendon and ligament repair, and enamel formation.     

Role of ITPA and SLC28A2 genes in the prediction of anaemia associated with protease inhibitor plus ribavirin and peginterferon in hepatitis C treatment

BackgroundAnaemia is a common side-effect of ribavirin (RBV) use that overwhelms management of hepatitis C when protease inhibitors are added.AimTo assess the pharmacogenomic impact of candidate genes SLC28A2, SLC28A3 and ITPA on anaemia in patients receiving triple therapy.MethodsPatients (n = 161) with chronic hepatitis C genotype 1 treated with telaprevir (n = 95) or boceprevir (n = 66) were included. Using RT-PCR we genotyped ITPA (rs1127354, rs7270101) and SLC28A3 (rs56350726, rs10868138) and SLC28A2 (rs11854484). Clinically significant anaemia (CSA) was diagnosed when at least one of the following criteria was observed: (a) haemoglobin <8.5 g/dL during treatment; (b) blood transfusion required; (c) erythropoietin administered.ResultsCSA occurred in 44% (69/157) of patients and was associated with SLC28A2 rs11854484 [CC/CT genotypes: 33% (26/78) vs. TT genotype: 56% (36/64); p = 0.006]. Further, the needed for blood transfusion was related to genotype [CC: 0% (0/18) vs. CT: 13% (8/61) vs. TT: 27% (17/64); p = 0.016]. Similarly, ITPA rs1127354 genotypes [AA/AC: 19% (3/16) vs. CC: 45% (61/135; p = 0.060] were linked to CSA. In multivariate analysis, SLC28A2 rs11854484 TT genotype (OR:2.33;95%CI:1.10–4.95; p = 0.027), female sex (OR:2.54;95% CI:1.13–5.71;p = 0.024) and Hb drop at week 4) OR: 1.36; 95CI%: 1.11–1.67; p = 0.003) were independently associated with CSA. Similarly, ITPA rs1127354 genotypes [AA/AC: 16% (3/19) vs. CC: 63% (85/134); p = 0.0001] and ITPA rs6051702 genotypes [CC/CA: 46% (26/57) vs. CC: 65% (60/93); p = 0.023] were related to Hb drop of >3g/dL at week 4.ConclusionsIn patients receiving first generation protease inhibitors, genotype SLC28A2 rs11854484 predicts CSA, and helps to identify a subgroup of patients with better tolerance of triple therapy.     

Using mobile health technology to deliver decision support for self-monitoring after lung transplantation

BackgroundLung transplant recipients (LTR) experience problems recognizing and reporting critical condition changes during their daily health self-monitoring. Pocket PATH^®, a mobile health application, was designed to provide automatic feedback messages to LTR to guide decisions for detecting and reporting critical values of health indicators.ObjectivesTo examine the degree to which LTR followed decision support messages to report recorded critical values, and to explore predictors of appropriately following technology decision support by reporting critical values during the first year after transplantation.MethodsA cross-sectional correlational study was conducted to analyze existing data from 96 LTR who used the Pocket PATH for daily health self-monitoring. When a critical value is entered, the device automatically generated a feedback message to guide LTR about when and what to report to their transplant coordinators. Their socio-demographics and clinical characteristics were obtained before discharge. Their use of Pocket PATH for health self-monitoring during 12 months was categorized as low (≤25% of days), moderate (>25% to ≤75% of days), and high (>75% of days) use. Following technology decision support was defined by the total number of critical feedback messages appropriately handled divided by the total number of critical feedback messages generated. This variable was dichotomized by whether or not all (100%) feedback messages were appropriately followed. Binary logistic regression was used to explore predictors of appropriately following decision support.ResultsOf the 96 participants, 53 had at least 1 critical feedback message generated during 12 months. Of these 53 participants, the average message response rate was 90% and 33 (62%) followed 100% decision support. LTR who moderately used Pocket PATH (n = 23) were less likely to follow technology decision support than the high (odds ratio [OR] = 0.11, p = 0.02) and low (OR = 0.04, p = 0.02) use groups. The odds of following decision support were reduced in LTR whose income met basic needs (OR = 0.01, p = 0.01) or who had longer hospital stays (OR = 0.94, p = 0.004). A significant interaction was found between gender and past technology experience (OR = 0.21, p = 0.03), suggesting that with increased past technology experience, the odds of following decision support to report all critical values decreased in men but increased in women.ConclusionsThe majority of LTR responded appropriately to mobile technology-based decision support for reporting recorded critical values. Appropriately following technology decision support was associated with gender, income, experience with technology, length of hospital stay, and frequency of use of technology for self-monitoring. Clinicians should monitor LTR, who are at risk for poor reporting of recorded critical values, more vigilantly even when LTR are provided with mobile technology decision support.