Antiretroviral Medication Adherence and Amplified HIV Transmission Risk Among Sexually Active HIV-Infected Individuals in Three Diverse International Settings

Successful biomedical prevention/treatment-as-prevention (TasP) requires identifying individuals at greatest risk for transmitting HIV, including those with antiretroviral therapy (ART) nonadherence and/or ‘amplified HIV transmission risk,’ defined as condomless sex with HIV-uninfected/unknown-status partners when infectious (i.e., with detectable viremia or STI diagnosis according to Swiss criteria for infectiousness). This study recruited sexually-active, HIV-infected patients in Brazil, Thailand, and Zambia to examine correlates of ART nonadherence and ‘amplified HIV transmission risk’. Lower alcohol use (OR = .71, p < .01) and higher health-related quality of life (OR = 1.10, p < .01) were associated with greater odds of ART adherence over and above region. Of those with viral load data available (in Brazil and Thailand only), 40 % met Swiss criteria for infectiousness, and 29 % had ‘amplified HIV transmission risk.’ MSM had almost three-fold (OR = 2.89, p < .001) increased odds of ‘amplified HIV transmission risk’ (vs. heterosexual men) over and above region. TasP efforts should consider psychosocial and contextual needs, particularly among MSM with detectable viremia.     

What Prevents Central Asian Migrant Workers from Accessing HIV Testing? Implications for Increasing HIV Testing Uptake in Kazakhstan

Several barriers prevent key populations, such as migrant workers, from accessing HIV testing. Using data from a cross-sectional study among Central Asian migrant workers (n = 623) in Kazakhstan, we examined factors associated with HIV testing. Overall, 48% of participants had ever received an HIV test. Having temporary registration (AOR 1.69; (95% CI [1.12–2.56]), having an employment contract (AOR 2.59; (95% CI [1.58–4.23]), being able to afford health care services (AOR 3.61; (95% CI [1.86–7.03]) having a medical check-up in the past 12 months (AOR 1.85; 95% CI [1.18–2.89]), and having a regular doctor (AOR 2.37; 95% CI [1.20–4.70]) were associated with having an HIV test. HIV testing uptake among migrants in Kazakhstan falls far short of UNAIDS 90-90-90 goals. Intervention strategies to increase HIV testing among this population may include initiatives that focus on improving outreach to undocumented migrants, making health care services more affordable, and linking migrants to health care.     

Relationship Power and Sexual Violence Among HIV-Positive Women in Rural Uganda

Gender-based power imbalances place women at significant risk for sexual violence, however, little research has examined this association among women living with HIV/AIDS. We performed a cross-sectional analysis of relationship power and sexual violence among HIV-positive women on anti-retroviral therapy in rural Uganda. Relationship power was measured using the Sexual Relationship Power Scale (SRPS), a validated measure consisting of two subscales: relationship control (RC) and decision-making dominance. We used multivariable logistic regression to test for associations between the SRPS and two dependent variables: recent forced sex and transactional sex. Higher relationship power (full SRPS) was associated with reduced odds of forced sex (AOR = 0.24; 95 % CI 0.07–0.80; p = 0.020). The association between higher relationship power and transactional sex was strong and in the expected direction, but not statistically significant (AOR = 0.47; 95 % CI 0.18–1.22; p = 0.119). Higher RC was associated with reduced odds of both forced sex (AOR = 0.18; 95 % CI 0.06–0.59; p < 0.01) and transactional sex (AOR = 0.38; 95 % CI 0.15–0.99; p = 0.048). Violence prevention interventions with HIV-positive women should consider approaches that increase women’s power in their relationships.     

Prevalence of HIV Infection and Risk Behaviors Among Younger and Older Injecting Drug Users in the United States, 2009

This study compared HIV sero-prevalence and risk behaviors between younger and older injecting drug users (IDUs). IDUs aged ≥18 years were interviewed for the 2009 National HIV Behavioral Surveillance System. Using GEE regression, we assessed characteristics of younger (18–29 years) and older (≥30 years) IDUs, and factors associated with past 12-month receptive syringe sharing and unprotected sex (vaginal/anal). Of 10,090 participants, 10 % were younger. HIV sero-prevalence was lower among younger than older IDUs (4 vs. 10 %, p = 0.001). Younger IDUs were more likely (p ≤ 0.002) to be non-black race/ethnicity, report higher household income, homelessness, being arrested and to engage in receptive syringe sharing and unprotected sex. In multivariable models, age remained associated (p < 0.001) with receptive syringe sharing (aPR = 1.14, 95 % CI1.07–1.22) and unprotected sex (aPR = 1.10, 95 % CI1.06–1.14). Although younger IDUs had lower HIV prevalence, their behaviors place them at increased risk of HIV infection and could lead to a rapid spread in this susceptible population.     

Disease severity and treatment requirements in familial inflammatory bowel disease

Purpose

Several studies demonstrate an increased prevalence and concordance of inflammatory bowel disease among the relatives of patients. Other studies suggest that genetic influence is over-estimated. The aims of this study are to evaluate the phenotypic expression and the treatment requirements in familial inflammatory bowel disease, to study the relationship between number of relatives and degree of kinship with disease severity and to quantify the impact of family aggregation compared to other environmental factors.

Methods

Observational analytical study of 1211 patients followed in our unit. We analyzed, according to the existence of familial association, number and degree of consanguinity, the phenotypic expression, complications, extraintestinal manifestations, treatment requirements, and mortality. A multivariable analysis considering smoking habits and non-steroidal-anti-inflammatory drugs was performed.

Results

14.2% of patients had relatives affected. Median age at diagnosis tended to be lower in the familial group, 32 vs 29, p = 0.07. In familial ulcerative colitis, there was a higher proportion of extraintestinal manifestations: peripheral arthropathy (OR = 2.3, p = 0.015) and erythema nodosum (OR = 7.6, p = 0.001). In familial Crohn’s disease, there were higher treatment requirements: immunomodulators (OR = 1.8, p = 0.029); biologics (OR = 1.9, p = 0.011); and surgery (OR = 1.7, p = 0.044). The abdominal abscess increased with the number of relatives affected: 5.1% (sporadic), 7.0% (one), and 14.3% (two or more), p=0.039. These associations were maintained in the multivariate analysis.

Conclusions

Familial aggregation is considered a risk factor for more aggressive disease and higher treatment requirements, a tendency for earlier onset, more abdominal abscess, and extraintestinal manifestations, remaining a risk factor analyzing the influence of some environmental factors.

     

Association of the ATIC 347 C/G polymorphism with responsiveness to and toxicity of methotrexate in rheumatoid arthritis: a meta-analysis

This study investigated whether the 5-aminoimidazole-4-carboxamide ribonucleotide transformylase gene (ATIC) 347 C/G polymorphism can predict the response to or toxicity of methotrexate (MTX) in patients with rheumatoid arthritis (RA). We conducted a meta-analysis of studies on the association between ATIC 347 C/G polymorphism and non-responsiveness to or toxicity of MTX in RA patients, using PUBMED, EMBASE, and COCHRANE. Nine comparative studies from 6 articles including 1056 RA patients met our inclusion criteria. This final group of studies comprised 5 studies on response to MTX and 4 on toxicity of MTX in RA patients in relation to the ATIC 347 C/G polymorphism status. Meta-analysis showed association between the ATIC 347 GG + GC genotype and non-response to MTX therapy (OR = 1.572, 95 % CI 1.146–2.156, p = 0.005). Stratification by ethnicity indicated significant association between the ATIC 347 GG + GC genotype and non-response to MTX in Caucasians (OR = 1.884, 95 % CI 1.236–2.873, p = 0.003), but not in Asian patients. Similarly, associations were noted for the ATIC 347 C/G polymorphism through analysis using recessive and overdominant models. Meta-analysis revealed association between the ATIC 347 GG + GC genotype and MTX toxicity (OR = 1.454 95 % CI 1.034–2.044, p = 0.032). Stratification by ethnicity indicated significant association between the ATIC 347 GG + GC genotype and MTX toxicity in Caucasians (OR = 1.741, 95 % CI 1.080–2.806, p = 0.023), but not in Asian patients. The ATIC 347 C/G polymorphism may be associated with non-responsiveness to and or toxicity of MTX in Caucasian RA patients.     

Genetic variant of <Emphasis Type="BoldItalic">IL-10RA</Emphasis> and susceptibility to rheumatoid arthritis in a Chinese population

The aim of this study was to investigate the relationship between the single-nucleotide polymorphisms (SNPs) of interleukin 10 alpha receptor (IL10RA) gene and rheumatoid arthritis (RA) in a Chinese population. We examined 533 RA patients and 958 subjects as a control group. Three IL-10RA SNPs (rs9610, rs2229113 and rs3135932) were genotyped using TaqMan genotyping assays on Fluidigm 192.24 system. The IL-10RA rs9610 A allele was increased in patient group compared with control subjects (OR = 1.232, 95 % CI = 1.052–1.442, p = 0.030). Significant difference in genotype distribution was found in RA patients and controls (χ2 = 15.32, p < 0.001). We also discovered a statistical significance under the dominant model (GG + AG versus AA: OR = 0.676, 95 % CI = 0.546–0.837, p < 0.001). However, no significant difference was discovered in the recessive model (GG versus AG + AA: OR = 1.013, 95 % CI = 0.754–1.361, p = 0.932). Interestingly, significant differences were detected both in the allele and genotype frequencies of rs9610 between anti-CCP positive patients and anti-CCP negative patients (χ2 = 7.209, p = 0.007; χ2 = 9.061, p = 0.011; respectively). We also found a significant difference in genotype frequency at rs9610 in females compared with males (χ2 = 7.658, p = 0.022). Unfortunately, we failed to find any significant results between two IL-10RA SNPs (rs2229113 and rs3135932) and RA susceptibility. The findings suggest that IL-10RA rs9610 polymorphism might contribute to RA susceptibility.     

Which Psychological Factors are Related to HIV Testing? A Quantitative Systematic Review of Global Studies

Deciding to test for HIV is necessary for receiving HIV treatment and care among those who are HIV-positive. This article presents a systematic review of quantitative studies on relationships between psychological (cognitive and affective) variables and HIV testing. Sixty two studies were included (fifty six cross sectional). Most measured lifetime testing. HIV knowledge, risk perception and stigma were the most commonly measured psychological variables. Meta-analysis was carried out on the relationships between HIV knowledge and testing, and HIV risk perception and testing. Both relationships were positive and significant, representing small effects (HIV knowledge, d = 0.22, 95 % CI 0.14–0.31, p < 0.001; HIV risk perception, OR 1.47, 95 % CI 1.26–1.67, p < 0.001). Other variables with a majority of studies showing a relationship with HIV testing included: perceived testing benefits, testing fear, perceived behavioural control/self-efficacy, knowledge of testing sites, prejudiced attitudes towards people living with HIV, and knowing someone with HIV. Research and practice implications are outlined.     

Polymorphisms within the neuronal cadherin (<Emphasis Type="Italic">CDH2</Emphasis>) gene are associated with obsessive-compulsive disorder (OCD) in a South African cohort

OCD is characterised by recurrent obsessions and compulsions that result in severe distress and increased risk for comorbidity. Recently published findings have indicated that the neuronal cadherin gene (CDH2) plays a role in the development of canine OCD, and led us to investigate the human ortholog, CDH2, in a human OCD cohort. Seven CDH2 polymorphisms were selected and genotyped in a South African Caucasian cohort of 234 OCD patients and 180 healthy controls using TaqMan assays. Polymorphisms were analysed in a single-locus and haplotypic context. Of the seven polymorphisms, two reached statistical significance for OCD under additive and codominant models of inheritance (rs1120154 and rs12605662). CDH2 SNP, rs1120154, C-allele carriers were found to be significantly associated with lower risk to develop OCD compared to TT-homozygotes (OR = 0.49; 95 % CI: 0.32–0.75; p < 0.001), and rs12605662 G-allele carriers were significantly associated with reduced risk OCD compared to TT-homozygotes (OR = 0.46; 95 % CI: 0.30–0.71; p < 0.001), Furthermore, a single haplotype was found to infer an increased risk for OCD diagnosis (*rs8087457-rs1148374: A-T). Polymorphisms within the CDH2 gene are associated with susceptibility to OCD in a South African cohort.     

Polymorphisms of the <Emphasis Type="Italic">TGF-β1</Emphasis> gene and the risk of acquired aplastic anemia in a Chinese population

Acquired aplastic anemia (AA) is a hematological disease characterized by failure of bone marrow hematopoiesis resulting in pancytopenia. While immune-mediated destruction of hematopoietic stem/progenitor cells (HSPCs) plays a central role in the pathophysiology of acquired AA, the transforming growth factor-β1 (TGF-β1) is crucial in adjusting the immune system. The aim of our study was to investigate the role of TGF-β1 gene polymorphisms rs1800469 and rs2317130 in susceptibility to acquired AA. Via the approach of SNaPshot, we genotyped rs1800469 and rs2317130 in 101 patients with acquired AA and 165 controls. It derived us to the conclusion that the genotype TT of rs1800469 (C/T) was significantly associated with decreased risk of acquired AA (adjusted OR = 0.39, 95% CI = 0.18–0.83, P = 0.014). Furthermore, this decreased risk was more pronounced among male patients (adjusted OR = 0.35, 95% CI = 0.13–0.95, P = 0.038) and SAA/vSAA (severe AA/very severe AA) patients (adjusted OR = 0.31, 95% CI = 0.12–0.77, P = 0.02) compared with controls in subgroup analysis. However, a significant increased risk was observed in the genotype distributions of rs2317130 for TT genotype (adjusted OR = 2.52, 95% CI = 1.03–6.19, P = 0.04) compared with the CC genotype among the SAA/vSAA patients and controls in the severity stratification analysis. Our results indicated that TGF-β1 gene polymorphisms might be involved in the munity of acquired AA in a Chinese population. This initial analysis provides valuable clues for further study of TGF-β1 pathway genes in acquired AA.     

Alcohol and Sexual Risk Behaviors Among Male Central Asian Labor Migrants and Non-migrants in Kazakhstan: Implications for HIV Prevention

This paper examines the association between alcohol consumption and sexual risk behaviors (unprotected sex, multiple sex partners, sex under influence of drugs or alcohol and commercial sex) in a sample of Central Asian migrant and non-migrant laborers in the largest marketplace in Kazakhstan. We used data from The Silk Road Health Project, conducted from 2010 to 2013 with 1342 male migrant and non-migrant market workers. Participants were selected through respondent driven sampling at the Baraholka Market in Almaty, Kazakhstan. We used regression analyses adjusting for potential confounders to examine the relationship between alcohol consumption and sexual risk behavior. We found that hazardous drinking was associated with an increase in the odds of sex under the influence of drugs (aOR = 6.09, 95% CI 3.48, 10.65; p < .001) and purchasing commercial sex (aOR = 2.02, 95% CI 1.02, 4.02; p < .05). We identified potential targets for HIV interventions to reduce sexual risk behaviors among this key population.     

RABBIT risk score and ICU admission due to infection in patients with rheumatoid arthritis

Rheumatoid arthritis (RA) patients are at increased risk of infection. Aim of the present study was to investigate whether RA patients admitted to an intensive care unit (ICU) due to infection have higher Rheumatoid Arthritis Observation of Biologic Therapy (RABBIT) risk scores compared to control RA patients. Seventy-four RA patients (32.4% male) admitted to an ICU due to infection (from January 2002 to December 2013) and 74 frequency-matched control RA patients (16.2% male) were included in this cross-sectional study. There was strong evidence for a higher RABBIT risk score in ICU patients (median 2.0; IQR 1.3–3.2) as compared to controls (1.3; IQR 0.8–2.0; p < 0.0001). Traditional disease-modifying anti-rheumatic drugs (DMARDs) (82.4 vs 64.9%; p = 0.015) and biological DMARDs (28.4 vs 14.9%; p = 0.012) were more frequently given to RA patients without ICU admission. Glucocorticoid users were more frequently found in the ICU group (51.4 vs 31.1%; p = 0.012). In a multivariable analysis tDMARD use was associated with lower (OR 0.38; 95% CI 0.15–0.93; p = 0.034) and glucocorticoid use with borderline higher odds of ICU admission (OR 2.05; 95% CI 0.92–4.58; p = 0.078). Chronic obstructive pulmonary disease (OR 2.89; 95% CI 1.10–7.54; p = 0.03), chronic kidney disease (OR 16.08; 95% CI 2.00–129.48; p = 0.009), and age category (OR 2.67; 95% CI 1.46–4.87; p = 0.001) were strongly associated with ICU admission. There was a strong trend towards higher odds of ICU admission with increasing RABBIT risk score. Use of tDMARDs was associated with lower odds of ICU admission. In an adjusted analysis, bDMARDs were not associated with ICU admission. COPD, CKD, and age were strong risk factors for ICU admission.     

A Functional Aryl Hydrocarbon Receptor Genetic Variant,Alone and in Combination with Parental Exposure,is a Risk Factor for Congenital Heart Disease

Recent experimental studies showed that ablation of the aryl hydrocarbon receptor (AhR) as well as its activation by exogenous ligands disrupt the molecular networks involved in heart formation and function, leading to congenital heart disease (CHD). However, no evidence is available about the role of AhR in humans. We assessed the prevalence of a functional AhR genetic variant (p.Arg554Lys) in CHD patients as well as its joint effects with parental exposure. A total of 128 CHD patients (76 males; age 6.2 ± 6.7 years) and 274 controls (160 males; age at birth) were genotyped for the AhR polymorphism by using the TaqMan^® Drug Metabolism Genotyping assay. Both case and control parents completed a structured questionnaire on demographic, lifestyle and preconception exposures. Genotype (p = 0.001) and allele (p < 0.0001) distributions of AhR p.Arg554Lys differed significantly between patients and controls. A significant elevated CHD risk was found under dominant (OR = 2.9, 95% CI 1.9–4.6, p < 0.0001) and additive genetic models (OR = 6.2, 95% CI 2–19, p = 0.001). There was a significant interaction between 554-Lys allele and paternal smoking exposure (OR_smoking = 1.6, 95% CI = 0.9–2.9; OR_allele = 2.6, 95% CI = 1.3–5; OR_interaction = 4.9, 95% CI = 2.4–9.9, p _interaction < 0.0001). Additionally, 554-Lys allele exacerbated the effect of maternal periconceptional exposure (OR_exposure = 1.6, 95% CI = 0.8–3; OR_allele = 2.6, 95% CI = 1.5–4.5; OR_interaction = 5.7; 95% CI = 2.6–12, p _interaction < 0.0001). Our findings showed that the AhR p.Arg554Lys polymorphism, alone and in combination with parental exposures, is associated with the CHD risk, highlighting the significant role of AhR in the cardiovascular development.     

Associations of <Emphasis Type="Italic">methylenetetrahydrofolate reductase</Emphasis> (<Emphasis Type="Italic">MTHFR</Emphasis>) C677T and A1298C polymorphisms with genetic susceptibility to rheumatoid arthritis: a meta-analysis

The aim of our study was to conduct a meta-analysis to assess whether combined evidence shows associations between C677T and A1298C polymorphisms of methylenetetrahydrofolate reductase (MTHFR) and genetic susceptibility to rheumatoid arthritis (RA). A total of 11 articles involving 20 comparisons were included, containing 12 comparisons for the MTHFR C677T polymorphism and 8 comparisons for the MTHFR A1298C polymorphism. Significant evidence was detected for the association of RA susceptibility with the MTHFR C677T polymorphism T allele under allelic contrast and dominant model in Asians (T versus C, OR = 1.300, 95 % CI = 1.104–1.531, p = 0.002; TT + CT versus CC, OR = 1.495, 95 % CI = 1.187–1.882, p = 0.001). Significant association between RA susceptibility and the MTHFR A1298C polymorphism A allele under recessive model was found in the overall meta-analysis (AA versus AC + CC, OR = 1.281, 95 % CI = 1.048–1.565, p = 0.016). Our meta-analysis results demonstrate that the MTHFR C677T polymorphism is involved in the genetic susceptibility of RA in Asians, and the MTHFR A1298C polymorphism is associated with genetic susceptibility to RA in the overall population. Given the paucity of studies, especially in non-Asian populations, further studies with larger sample sizes are required to elucidate the role of MTHFR polymorphisms in the genetic basis of RA in different ethnic populations.     

Role of out of hours primary care service in limiting inappropriate access to emergency department

Out of hours (OOH) doctors can have an important gate-keeping role over the access to the emergency department (ED), but the outcome and the quality of their ED referrals have been poorly studied. We aimed to investigate the outcome of patients referred to ED from OOH service and the determinants of admission or short-stay dispositions. We collected retrospectively data about referrals to ED from a local OOH service in the north-east of Italy using the OOH paper register and the ED electronic database, over the period of 01/10/2012 to 31/03/2013. Out of 5217 patients accessing the OOH service, 408 referrals were included in our analysis. 45.3% (185) of the referrals were admitted to hospital or the short-stay unit, 26 patients (=6.4%) were discharged as non-urgent outgoing codes after no specialist consultation or test, suggesting inappropriate referrals, and, of the remaining 197 (=48%), only 10 did not undergo any investigation or consultation. Significant determinants of admission were: age ≥65 years (OR = 2.619; 95% CI 1.528–4.491, p < 0.0001), domiciliary examination (OR = 2.168; 95% CI 1.353–3.476, p = 0.001), nursing home/palliative care setting (OR = 2.563; 95% CI 1.228–5.351, p = 0.012) and OOH triage code, ranging from an OR of 7.47 (95% CI 3.028–18.433) for minor urgencies to an OR of 26.835 (95% CI 6.761–106.508, p < 0.0001) for emergencies, in comparison to no urgent codes. OOH service seems to play an effective gate-keeping role limiting ED access. Determinants of admission to hospital suggest some simple interventions that could improve the adequacy of ED referral from OOH service.     

Polymorphic variants of antioxidative defense enzymes and their gene-gene epistatic interactions in systemic lupus erythematode patients

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease in which pathogenesis oxidative stress has an important role. Single nucleotide polymorphisms (SNPs) in the genes that code enzymes involved in the antioxidative defense are possible factors that are responsible for their decreased activity of antioxidative defense enzymes. Thus, the aim of the study was to examine association of SNPs in these genes with SLE. A total of176 subjects were involved in this study. CAT A-21T (rs7943316), CAT C-262T (rs1001139) and manganese SOD (MnSOD) Ala16Val (rs4880) SNPs were determined using PCR-RFLP method, while GSTT1 and GSTM1 were determined using multiplex PCR. The obtained results showed significant differences in the distribution of genotypes (df = 2; p = 0.001) and alleles (p < 0.001; OR = 2.227; 95% CI = 1.429–3.741) of rs4880 between patients and controls. MnSODValVal genotype showed association with neurologic manifestations (p = 0.016; OR = 6.7; 95% CI = 1.18–37.89), while homozygous GSTT1 showed association with musculoskeletal manifestations of SLE (p = 0.008; OR = 4.168; 95% CI = 1.364–12.737). AlaVal/T+M+ genotype combination is a high-risk genotype for SLE. SNP–SNP interaction model showed positive correlation between CAT A-21T and CAT C-262T SNPs in SLE patients which was not influenced by the linkage disequilibrium (r ² = 0.005; D′ = 0.071). MnSODVal allele is a risk factor for SLE, as well as for SLE with neurologic manifestations, while homozygous GSTT1 genotype is a risk factor for SLE with musculoskeletal manifestations. Catalase SNPs (C-262T and A-21T) show positive correlation in the model of SNP–SNP interaction.     

Incidence and risk factors of fractures in patients with rheumatoid arthritis: an Asian prospective cohort study

Rheumatoid arthritis (RA) patients have high risk for osteoporosis and fracture. We aimed to identify the incidence rate and risk factors of fractures in Asian RA patients. A total of 3557 RA patients in the KORean Observational study Network for Arthritis (KORONA) were included and observed over a mean follow-up of 18 months. A fracture was assessed as total, major, or minor fractures; major fracture was defined as a vertebral or hip fracture, and the other fractures were classified as minor fractures. The standardized incidence ratio (SIR) of fracture in RA patients was calculated compared with general population, and possible risk factors for fractures were explored using multivariable logistic regression analyses. A total of 194 patients with 215 fractures were observed, and the SIR of the total fracture in RA patients was 2.2 [95 % confidence interval (CI) 1.9–2.6]. The SIRs of major and minor fractures were 1.5 (CI 1.1–2.0) and 3.0 (CI 2.5–3.7), respectively. Advanced age [odds ratio (OR) 1.03, CI 1.02–1.05, p < 0.01] and having history of prior fracture (OR 2.17, CI 1.54–3.08, p < 0.01) were risk factors for total fractures. In addition, higher HAQ increased fracture risk (OR 2.02, CI 1.05–3.89, p = 0.04), whereas the use of bisphosphonate showed protective effect for future fractures (OR 0.34, CI 0.14–0.87, p = 0.02) in patients with osteoporosis. RA patients had a 2.2-fold increased risk of fractures as compared with general population. In Asian RA patients, advanced age and history of prior fracture were the most important risk factors for new fractures.     

Pudendal nerve testing does not contribute to surgical decision making following anorectal testing in patients with faecal incontinence

Purpose

Faecal incontinence (FI) is a debilitating condition, which affects approximately 2–17 % of the population. Clinical assessment, physiological testing and imaging are usually used to evaluate the pathophysiology and guide management of FI. By analysing patient characteristics, symptoms and investigative findings, the aim of this study was to identify which patient characteristics and investigations influence patient management.

Methods

Data was prospectively collected for all patients with FI presenting to a single surgeon at the Royal Prince Alfred Hospital, Sydney, between March 2002 and September 2013. Continuous data was analysed using the independent T-test. Categorical data was analysed using chi-square tests and logistic regression.

Results

Three hundred ninety-eight patients were reviewed; 96 % were female and the mean age was 57 years. Surgical intervention was recommended for 185 patients (47 %) should biofeedback fail. Independent predictors for surgical recommendation were prolapse (p < 0.001, adjusted OR = 4.9 [CI 2.9–8.2]), a functional sphincter length <1 cm (p = 0.032, OR = 1.7 [CI 1.1–2.8]), an external anal sphincter defect (p = 0.028, OR = 1.8 [CI 1.1–3.1]) and a Cleveland Clinic Incontinence Score ≥10 (p = 0.029, OR = 1.7 [CI 1.1–2.6]).

Conclusion

Independent predictors of surgical recommendation included the presence of prolapse, a functional sphincter length <1 cm, an external anal sphincter defect and a Cleveland Clinic Incontinence Score ≥ 10. Pudendal neuropathy was not a predictor of surgical intervention, leading us to question the utility of this investigation.

     

Association Study Between Coronary Artery Disease and rs1333049 Polymorphism at 9p21.3 Locus in Italian Population

In this study, we verify the association between the rs1333049 single nucleotide polymorphism (9p21.3) within CDKN2A-CDKN2B and coronary artery disease (CAD) in an Italian population. We replicated rs1333049_G allele association with a significantly reduced risk of CAD (OR = 0.816; 95% confidence interval [0.705–0.945]; p = 0.0065) in 711 CAD patients and 755 normal healthy individuals. This effect is maintained even stratifying patients by gender and by risk factors. A significant association was found with age of CAD onset. Interestingly, we found a protective trend of association between the rs1333049_G allele and peripheral artery disease, a progressive atherosclerotic condition in which plaque builds up in the arteries that carry blood to the head, organs, and limbs (OR = 0.724; 95% CI [0.520–1.007]; p = 0.054). No genotype-phenotype association was found with more severe CAD clinical parameters. If certain genetic factors predispose individuals to adverse outcomes, the knowledge of a patient’s genotype may influence clinical management.     

IRAK2 is associated with susceptibility to rheumatoid arthritis

This study was performed to investigate the association of the single nucleotide polymorphisms of interleukin-1 receptor-associated kinase 2 (IRAK2) rs3844283 and rs708035 with rheumatoid arthritis (RA). IRAK2 rs3844283 and rs708035genotyping was determined by mutagenically separated PCR with specifically designed primers in a cohort of 222 (30 men, 192 women, mean age 49 years) adult RA patients and 224 matched controls. IRAK2 rs3844283 C allele was detected in 66% of RA patients and 74% of controls. The CC genotype was the most frequent genotype in both RA patients (45.5%) and the controls (56.3%). The G allele was found to be associated with RA susceptibility (OR = 1.47, 95% CI = 1.10–1.96, p = 0.008). The GG genotype was found to be associated with RA in the co-dominant and the dominant models (OR = 2.03, 95% CI = 1.08–3.81, p = 0.042 and OR = 1.54, 95% CI = 1.06–2.23, p = 0.023, respectively). IRAK2 rs708035 was found not to be in the Hardy-Weinberg equilibrium. The hyperfunctional IRAK2 rs708035 A allele was more frequent in RA patients than in controls (69.9 versus 62.2%, respectively, p = 0.015). Moreover, IRAK2 rs708035 and IRAK2 rs3844283 were in linkage disequilibrium and the GA haplotype was significantly more frequent in RA patients than in controls (p = 0.034). This study for the first time ever reports the association of IRAK2 rs3844283, IRAK2 rs708035, and the corresponding haplotypes with RA. Functional studies are recommended to elucidate the risk posed by the GA haplotype for the development of RA.