Comparison of Fecal Calprotectin and Myeloperoxidase in Predicting Outcomes in Inflammatory Bowel Disease.

BACKGROUND: Biomarkers have been proposed as surrogate treatment targets for the management of inflammatory bowel disease (IBD); however, their relationship with IBD-related complications remains unclear. This study investigated the utility of neutrophil biomarkers fecal calprotectin (fCal) and fecal myeloperoxidase (fMPO) in predicting a complicated IBD course. METHODS: Participants with IBD were followed for 24 months to assess for a complicated IBD course (incident corticosteroid use, medication escalation for clinical disease relapse, IBD-related hospitalizations/surgeries). Clinically active IBD was defined as Harvey-Bradshaw index >4 for Crohn's disease (CD) and simple clinical colitis activity index >5 for ulcerative colitis (UC). Area under the receiver-operating-characteristics curves (AUROC) and multivariable logistic regression assessed the performance of baseline symptom indices, fCal, and fMPO in predicting a complicated disease IBD course at 24 months. RESULTS: One hundred and seventy-one participants were included (CD, n = 99; female, n = 90; median disease duration 13 years [interquartile range, 5-22]). Baseline fCal (250 µg/g; AUROC = 0.77; 95% confidence interval [CI], 0.69-0.84) and fMPO (12 µg/g; AUROC = 0.77; 95% CI, 0.70-0.84) predicted a complicated IBD course. Fecal calprotectin (adjusted OR = 7.85; 95% CI, 3.38-18.26) and fMPO (adjusted OR = 4.43; 95% CI, 2.03-9.64) were associated with this end point after adjustment for other baseline variables including clinical disease activity. C-reactive protein (CRP) was inferior to fecal biomarkers and clinical symptoms (pdifference < .05) at predicting a complicated IBD course. A combination of baseline CRP, fCal/fMPO, and clinical symptoms provided the greatest precision at identifying a complicated IBD course. CONCLUSIONS: Fecal biomarkers are independent predictors of IBD-related outcomes and are useful adjuncts to routine clinical care.

Ease and comfort of pre-oxygenation with high-flow nasal oxygen cannulae vs. facemask: a randomised controlled trial.

The Difficult Airway Society recommends that all patients should be pre-oxygenated before the induction of general anaesthesia, but this may not always be easy or comfortable and anaesthesia may often be induced without full pre-oxygenation. We tested the hypothesis that high-flow nasal oxygen cannulae would be easier and more comfortable than facemasks for pre-oxygenation. We randomly allocated 199 patients undergoing elective surgery aged ≥ 10 years to pre-oxygenation using either high-flow nasal oxygen or facemask. Ease and comfort were assessed by anaesthetists and patients on 10-cm visual analogue scale and six-point smiley face scale, respectively. Secondary endpoints included end-tidal oxygen fraction after securing a definitive airway and time to secure an airway. A mean difference (95%CI) between groups in ratings of -0.76 (-1.25 to -0.27) cm for ease of use (p = 0.003) and -0.45 (-0.75 to -0.13) points for comfort (p = 0.006), both favoured high-flow nasal oxygen. A mean difference (95%CI) between groups in end-tidal oxygen fraction of 3.89% (2.41-5.37%) after securing a definitive airway also favoured high-flow nasal oxygen (p < 0.001). There was no significant difference between groups in the number of patients with hypoxaemia (Sp O2 < 90%) or severe hypoxaemia (Sp O2 < 85%) lasting ≥ 1 min or ≥ 2 min; in the proportion of patients with an end-tidal oxygen fraction < 87% in the first 5 min after tracheal intubation (52.2% vs. 58.9% in facemask and high-flow nasal oxygen groups, respectively; p = 0.31); or in time taken to secure an airway (11.6 vs. 12.2 min in facemask and high-flow nasal oxygen groups, respectively; p = 0.65). In conclusion, we found pre-oxygenation with high-flow nasal oxygen to be easier for anaesthetists and more comfortable for patients than pre-oxygenation with a facemask, with no clinically relevant differences in end-tidal oxygen fraction after securing a definitive airway or time to secure an airway. The differences in ease and comfort were modest.

Ovine FABP4 Variation and Its Association With Flystrike Susceptibility.

Flystrike is a major cost and a welfare issue for the New Zealand sheep industry. There are several factors that can predispose sheep to flystrike, such as having fleecerot, a urine-stained breech, and "dags" (an accumulation of fecal matter in the wool of the breech). The FABP4 gene (FABP4) has been associated with variation in ovine fleecerot resistance, with a strong genetic correlation existing between fleecerot and flystrike occurrence. In this study, blood samples were collected from sheep with and without flystrike for DNA typing. PCR-SSCP analyses were used to genotype two regions of ovine FABP4. Sheep with the A 1 variant of FABP4 were found to be less likely (odds ratio 0.689, P = 0.014) to have flystrike than those without A 1. The likelihood of flystrike occurrence decreased as copy number of A 1 increased (odds ratio 0.695, P = 0.006). This suggests that FABP4 might be a candidate gene for flystrike resilience in sheep, although further research is required to verify this association.

The effect of antibiotic timing on culture yield in paediatric osteoarticular infection.

PURPOSE: To assess the influence of antibiotic timing on surgical culture yield in paediatric patients with haematogenous osteoarticular infection. METHODS: All patients aged 0 to 15 years admitted to a National Children's Hospital with the diagnosis of acute, haematogenous, osteoarticular infection (osteomyelitis and/or septic arthritis) between June 1997 and December 2016 were retrospectively analyzed. Only patients with positive blood cultures undergoing surgery for culture and debridement were included. Patients were allocated into pre-treatment and post-treatment groups, according to whether they received antibiotics before or after surgical cultures were obtained. Outcomes measured included baseline variables, treatment characteristics and surgical culture yield. RESULTS: A total of 131 patients were included; 107 patients in the pre-treatment group and 24 patients in the post-treatment group. There was no significant difference with respect to patient age (p = 0.870), white blood cell count (p = 0.197), ethnicity (p = 0.203) or infection multi-focality (p = 0.883) between the two groups.The administration of systemic antibiotics prior to obtaining surgical cultures had no clinically significant effect on surgical culture yield (rate of positive surgical cultures, 85% (pre-treatment) versus 54.2% (post-treatment); p = 0.002). Within the pre-treatment group, there was no significant difference in duration of pre-surgical antibiotic treatment between patients who had positive or negative surgical cultures (mean duration, 45.9 hours (positive cultures) versus 47.9 hours (negative cultures); p = 0.743). CONCLUSION: In paediatric patients with acute, haematogenous, osteoarticular infection, antibiotic administration before surgery does not decrease surgical culture yield. Our results suggest that paediatric patients presenting with suspected osteoarticular infection should receive appropriate systemic antibiotics promptly after blood cultures are obtained. LEVEL OF EVIDENCE: Level III - retrospective case-control study.

MR Imaging Characteristics Associate with Tumor-Associated Macrophages in Glioblastoma and Provide an Improved Signature for Survival Prognostication.

BACKGROUND AND PURPOSE: In glioblastoma, tumor-associated macrophages have tumor-promoting properties. This study determined whether routine MR imaging features could predict molecular subtypes of glioblastoma that differ in the content of tumor-associated macrophages. MATERIALS AND METHODS: Seven internally derived MR imaging features were assessed in 180 patients, and 25 features from the Visually AcceSAble Rembrandt Images feature set were assessed in 164 patients. Glioblastomas were divided into subtypes based on the telomere maintenance mechanism: alternative lengthening of telomeres positive (ALT+) and negative (ALT-) and the content of tumor-associated macrophages (with [M+] or without [M-] a high content of macrophages). The 3 most frequent subtypes (ALT+/M-, ALT-/M+, and ALT-/M-) were correlated with MR imaging features and clinical parameters. The fourth group (ALT+/M+) did not have enough cases for correlation with MR imaging features. RESULTS: Tumors with a regular margin and those lacking a fungating margin, an expansive T1/FLAIR ratio, and reduced ependymal extension were more frequent in the subgroup of ALT+/M- (P < .05). Radiologic necrosis, lack of cystic component (by both criteria), and extensive peritumoral edema were more frequent in ALT-/M+ tumors (P < .05). Multivariate testing with a Cox regression analysis found the cystic imaging feature was additive to tumor subtype, and O6-methylguanine methyltransferase (MGMT) status to predict improved patient survival (P < .05). CONCLUSIONS: Glioblastomas with tumor-associated macrophages are associated with routine MR imaging features consistent with these tumors being more aggressive. Inclusion of cystic change with molecular subtypes and MGMT status provided a better estimate of survival.

Five-year follow-up of a prospective randomised trial comparing ceramic-on-metal and metal-on-metal bearing surfaces in total hip arthroplasty.

AIMS: The primary aim of this independent prospective randomised trial was to compare serum metal ion levels for ceramic-on-metal (CoM) and metal-on-metal (MoM) bearing surfaces in total hip arthroplasty (THA). Our one-year results demonstrated elevation in metal ion levels above baseline with no significant difference between the CoM and MoM groups. This paper reviews the five-year data. PATIENTS AND METHODS: The implants used in each patient differed only in respect to the type of femoral head (ceramic or metal). At five-year follow-up of the 83 enrolled patients, data from 67 (36 CoM, 31 MoM) was available for comparison. RESULTS: The mean serum cobalt (Co) and chromium (Cr) ion levels remained above baseline in both groups (CoM: Co 1.16 µg/l (0.41 to 14.67), Cr 1.05 µg/l (0.16 to 12.58); MoM: Co 2.93 µg/l (0.35 to 30.29), Cr 1.85 µg/l (0.36 to 17.00)) but the increase was significantly less in the CoM cohort (Co difference p = 0.001, Cr difference p = 0.002). These medium-term results, coupled with lower revision rates from national joint registries, suggest that the performance of CoM THA may be superior to that of MoM. CONCLUSION: While both bearing combinations have since been withdrawn these results provide useful information for planning clinical surveillance of CoM THAs and warrants continued monitoring. Cite this article: Bone Joint J 2017;99-B:1298-1303.

Association between variation in faecal egg count for a natural mixed field-challenge of nematode parasites and TLR4 variation.

Research has shown that Toll-like receptor 4 (TLR4) is important in immune responses to some helminth parasites. In sheep, variation in the PAMP region of TLR4 may result in structurally and thus functionally different TLR4 molecules, and this may consequently lead to variation in the TLR4 response to parasite infections. This study involved three separate, but related sheep breeds (Merino, Polwarth and Corriedale sheep) and a total of 885 lambs from five New Zealand farms that underwent a mixed field-challenge from gastro-intestinal parasites. Faecal samples were collected at approximately 4 and 9 months of age and faecal egg counts (FECs) for Nematodirus spp. and Strongyle species determined, along with the total number of eggs per gram (EPG). Analysis of the five farms collectively revealed an association (P=0.023) between the presence of TLR4 variant *02 (mean 24 EPG) and the absence of the variant (mean 32 EPG) at 9 months of age. Conversely the presence of *03 had a significantly (P=0.047) higher mean Nematodirus spp. FEC (mean 42 EPG) compared to the absence (mean 28 EPG) at 9 months of age. More associations were revealed when the data were split according to the dominant faecal parasite species. With a predominantly Trichostrongylus spp. FEC group of lambs at 9 months of age, the presence of TLR4 variant *02 was found to have significantly (P=0.003) lower Nematodirus spp. FEC (mean 4 EPG), and also significantly (P=0.033) lower total FEC (mean 312 EPG) when compared to sheep without the variant (mean 15 EPG and 449 EPG, respectively). The presence of TLR4 variant *03 and *04 were associated or tended to be associated (P=0.010 and P=0.088, respectively) with higher Nematodirus spp. FEC (mean 25 EPG and 22 EPG, respectively) when compared to lambs without the variant (mean 10 EPG and 11 EPG, respectively). These results suggest that TLR4 variation may be affecting the immune response to gastro-intestinal parasites in sheep, although principally to Nematodirus spp. infections and not Strongyle species infections.

No change in neuropsychological dysfunction or emotional processing during treatment of major depression with cognitive-behaviour therapy or schema therapy.

BACKGROUND: Impaired neuropsychological functioning is a feature of major depression. Previous studies have suggested that at least some aspects of neuropsychological functioning improve with successful treatment of major depression. The extent to which medications may affect the degree of normalization of these functions is unclear. The aim of the current study was to examine the course of neuropsychological functioning during treatment of major depression with cognitive-behaviour therapy (CBT) or schema therapy (ST). METHOD: A total of 69 out-patients with a primary diagnosis of major depression and 58 healthy controls completed mood ratings, neuropsychological measures, and measures of emotional processing at baseline and after 16 weeks. Participants were randomized after baseline assessment to a year-long course of CBT or ST. Patients reassessed at 16 weeks were medication-free throughout the study. RESULTS: Significant neuropsychological impairment was evident at baseline in depressed participants compared with healthy controls. After 16 weeks of psychotherapy, mean depression rating scores fell more than 50%. However, no neuropsychological measures showed convincing evidence of significant improvement and emotional processing did not change. CONCLUSIONS: Persisting impairment in neuropsychological functioning after the first 16 weeks of CBT or ST suggests a need to modify psychological treatments to include components targeting cognitive functioning.

Postprandial capillary-venous glucose gradient in Type 1 diabetes: magnitude and clinical associations in a real world setting.

AIMS: To determine the magnitude of the peripheral glucose gradient in patients with Type 1 diabetes in a real world setting and to explore its relationship with insulin dose and macronutrient intake. METHODS: All patients used mealtime analogue insulin. The glucose gradient was assessed using antecubital fossa venous and finger-stick capillary samples, collected concurrently at room temperature. Baseline sampling occurred before the administration of an insulin dose and breakfast of the patient's choosing. Breakfast was consumed an average of 15 min after baseline. The macronutrient content of breakfast was documented. Sampling was repeated 1 and 2 h after baseline. RESULTS: The mean (95% CI) plasma capillary-venous glucose gradient values for 43 patients were: pre-breakfast, 0.21 (0.08-0.34) mmol/l; 1 h after baseline, 0.87 (0.66-1.07) mmol/l; and 2 h after baseline, 0.52 (0.33-0.71) mmol/l. Glucose gradient and dietary carbohydrate intake (g/kg body weight) were positively correlated at both 1 h (P < 0.01) and 2 h after baseline (P < 0.01). No relationship was observed between this gradient and mealtime insulin dose, or the glucose concentration at either time point. CONCLUSIONS: In patients with Type 1 diabetes, a clinically significant glucose gradient is present after the ingestion of a carbohydrate-rich meal. As postprandial capillary and venous plasma glucose concentrations are not equivalent, defining the site of sample collection is important.

A novel troponin T peptide in humans: Assay, biochemistry and preliminary findings in acute coronary syndromes.

INTRODUCTION: High sensitivity assays for cardiac troponin (cTn) have reduced time to diagnosis of myocardial infarction (MI) but at costs to diagnostic specificity. We hypothesised that measurement of an upstream open reading frame peptide (uORF) from the human cTnT gene (TnTuORF) might improve cTn specificity in MI patients. METHODS: A novel immunoassay to TnTuORF was developed and used to document circulating concentrations in normal healthy volunteers (n=150); assess potential trans-organ secretion in patients undergoing cardiac catheterisation (n=16); characterise temporal TnTuORF concentrations during ST-elevation MI (STEMI, n=4) and assess the potential of TnTuORF to assist the diagnosis and prognosis of MI in patients presenting with chest pain suspicious of ACS (n=502). Plasma immunoreactive TnTuORF was characterised on reverse phase and size exclusion HPLC. RESULTS: In normal volunteers and suspected acute coronary syndrome (ACS) patients, TnTuORF had no relationship with TnI or TnT. Trans-organ venous sampling suggested TnTuORF secretion is not exclusively cardiac based. In STEMI patients, TnTuORF concentrations decreased for up to 12h after onset. In suspected ACS patients, TnTuORF could not diagnose MI (ROC AUC=0.446, P=0.117) but could diagnose cardiac disorders other than MI (AUC=0.79, P<0.001). CONCLUSION: This is the first evidence for a circulating uORF peptide. TnTuORF does not appear to aid the diagnosis of MI but further studies to assess its potential in cardiovascular disease are required.

Removal of the syndesmotic screw after the surgical treatment of a fracture of the ankle in adult patients does not affect one-year outcomes: a randomised controlled trial.

Our aim was to compare the one-year post-operative outcomes following retention or removal of syndesmotic screws in adult patients with a fracture of the ankle that was treated surgically. A total of 51 patients (35 males, 16 females), with a mean age of 33.5 years (16 to 62), undergoing fibular osteosynthesis and syndesmotic screw fixation, were randomly allocated to retention of the syndesmotic screw or removal at three months post-operatively. The two groups were comparable at baseline. One year post-operatively, there was no significant difference in the mean Olerud-Molander ankle score (82.4 retention vs 86.7 removal, p = 0.367), the mean American Orthopedic Foot and Ankle Society ankle-hindfoot score (88.6 vs 90.1, p = 0.688), the mean American Academy of Orthopedic Surgeons foot and ankle score (96.3 vs 94.0, p = 0.250), the mean visual analogue pain score (1.0 vs 0.7, p = 0.237), the mean active dorsiflexion (10.2° vs 13.0°, p = 0.194) and plantar flexion (33.6° vs 31.3°, p = 0.503) of the ankle, or the mean radiological tibiofibular clear space (5.0 mm vs 5.3 mm, p = 0.276) between the two groups. A total of 19 patients (76%) in the retention group had a loose and/or broken screw one year post-operatively. We conclude that removal of a syndesmotic screw produces no significant functional, clinical or radiological benefit in adult patients who are treated surgically for a fracture of the ankle.

The use of a lipped acetabular liner decreases the rate of revision for instability after total hip replacement: a study using data from the New Zealand Joint Registry.

We compared the rate of revision for instability after total hip replacement (THR) when lipped and non-lipped acetabular liners were used. We hypothesised that the use of a lipped liner in a modular uncemented acetabular component reduces the risk of revision for instability after primary THR. Using data from the New Zealand Joint Registry, we found that the use of a lipped liner was associated with a significantly decreased rate of revision for instability and for all other indications. Adjusting for the size of the femoral head, the surgical approach and the age and gender of the patient, this difference remained strongly significant (p < 0.001). We conclude that evidence from the New Zealand registry suggests that the use of lipped liners with modular uncemented acetabular components is associated with a decreased rate of revision for instability after primary THR.

Variation in exon 10 of the ovine calpain 3 gene (CAPN3) and its association with meat yield in New Zealand Romney sheep.

Variation in the ovine CAPN3 gene was analysed using PCR-single strand conformational polymorphism, and its effect on growth and carcass traits was assessed in 513 New Zealand Romney lambs produced by 17 unrelated rams. Among the four allelic variants detected, the presence of variant *02 was found to be associated with an increased proportion of shoulder yield (absent: 32.6±0.01%; present: 33.4±0.03%; P=0.016), and tended to be associated with increased shoulder yield (lean meat yield of the shoulder expressed as a percentage of the hot carcass weight) (absent: 16.6±0.06%; present: 17.02±0.20%; P=0.067). No association was detected with growth traits or other carcass traits.

Genetic variation in the renin-angiotensin-aldosterone system is associated with cardiovascular risk factors and early mortality in established coronary heart disease.

This study examined renin-angiotensin-aldosterone (RAAS) system gene variants for associations with cardiovascular risk factors and outcomes in coronary heart disease. Coronary disease patients (n=1186) were genotyped for 21 single-nucleotide polymorphisms (SNPs) within angiotensinogen (AGT), angiotensin-converting enzyme (ACE), angiotensin-II type-1 receptor (AGTR1) and aldosterone synthase (CYP11B2). Associations with all-cause mortality and cardiovascular readmissions were assessed over a median of 3.0 years. The AGT M235T 'T' allele was associated with a younger age of clinical coronary disease onset (P=0.006), and the AGT rs2478545 minor allele was associated with lower circulating natriuretic peptides (P=0.0001-P=0.001) and E/E(1) (P=0.018). Minor alleles of AGT SNPs rs1926723 and rs11122576 were associated with more frequent history of renal disease (P0.04) and type-2 diabetes (P0.02), higher body mass index (P0.02) and greater mortality (P0.007). AGT rs11568054 minor allele carriers had more frequent history of renal disease (P=0.04) and higher plasma creatinine (P=0.033). AGT rs6687360 minor allele carriers exhibited worse survival (P=0.02). ACE rs4267385 was associated with older clinical coronary disease onset (P=0.008) and hypertension (P=0.013) onset, increased plasma creatinine (P=0.01), yet greater mortality (P=0.044). Less history of hypertension was observed with the AGTR1 rs12685977 minor allele (P=0.039). Genetic variation within the RAAS was associated with cardiovascular risk factors and accordingly poorer survival.

A prospective, randomised controlled trial comparing ceramic-on-metal and metal-on-metal bearing surfaces in total hip replacement.

In a double-blinded randomised controlled trial, 83 patients with primary osteoarthritis of the hip received either a ceramic-on-metal (CoM) or metal-on-metal (MoM) total hip replacement (THR). The implants differed only in the bearing surfaces used. The serum levels of cobalt and chromium and functional outcome scores were compared pre-operatively and at six and 12 months post-operatively. Data were available for 41 CoM and 36 MoM THRs (four patients were lost to follow-up, two received incorrect implants). The baseline characteristics of both cohorts were similar. Femoral head size measured 36 mm in all but two patients who had 28 mm heads. The mean serum cobalt and chromium levels increased in both groups, with no difference noted between groups at six months (cobalt p = 0.67, chromium p = 0.87) and 12 months (cobalt p = 0.76, chromium p = 0.76) post-operatively. Similarly, the mean Oxford hip scores, Western Ontario and McMaster Universities Osteoarthritis index and University of California, Los Angeles activity scores showed comparable improvement at 12 months. Our findings indicate that CoM and MoM couplings are associated with an equivalent increase in serum cobalt and chromium levels, and comparable functional outcome scores at six and 12-months follow-up.

An association between lifespan and variation in insulin-like growth factor I receptor in sheep.

Longevity in livestock is a valuable trait. When productive animals live longer, fewer replacement animals need to be raised. However, selection for longevity is not commonly the focus of breeding programs as direct selection for long-lived breeding stock is virtually impossible until late in the reproductive life of the animal. Additionally the underlying genetic factors or genes associated with longevity are either not known, or not well understood. In humans, there is evidence that IGF 1 receptor (IGF1R) is involved in longevity. Polymorphism in the IGF1R gene has been associated with longevity in a number of species. Recently, 3 alleles of ovine IGF1R were identified, but no analysis of the effect of IGF1R variation on sheep longevity has been reported. In this study, associations between ovine IGF1R variation, longevity and fertility were investigated. Polymerase chain reaction-single strand conformational polymorphism (PCR-SSCP) was used to type IGF1R variation in 1,716 New Zealand sheep belonging to 6 breeds and 36 flocks. Ovine IGF1R C was associated with age when adjusting for flock (present 5.5 ± 0.2 yr, absent 5.0 ± 0.1 yr, P = 0.02). A general linear mixed effects model suggested an association (P = 0.06) between age and genotype, when correcting for flock. Pairwise comparison (least significant difference) of specific genotypes revealed the difference to be between AA (5.0 ± 0.1 yr) and AC (5.6 ± 0.2 yr, P = 0.02). A weak negative Pearson correlation between fertility and longevity traits was observed (r = -0.25, P < 0.01). The finding of an association between variation in IGF1R and lifespan in sheep may be useful in prolonging the lifespan of sheep.

Gene expression confirms a potentially receptive endometrium identified by histology in fertile women.

BACKGROUND: To use contemporary biochemical markers to characterize mRNA/gene expression in the potentially fertile secretory endometrium to confirm its identification based on histological characteristics in order to develop a clinically applicable test. METHODS: Nine, fertile, cycling Caucasian women were sampled from one IVF clinic. Endometrial samples were collected from them in two to four menstrual cycles at 2 and 7 days post first significant rise in blood LH. Separate endometrial glands and stroma populations were obtained by laser microdissection. Linear polymerase chain reaction amplified mRNAs which were hybridized to both Affymetrix U133 Plus2 and Agilent 4 × 44K microarrays followed by gene set analysis. Four histopathologists reviewed the sample set using the same histological criteria to date and characterize the non-receptive and potentially receptive samples. RESULTS: mRNA expression of microdissected glands and stroma provided molecular signatures that characterized the two specific phases of the cycle with distinct clustering patterns. Cell proliferation and five other associated biological pathways were significantly down-regulated when the endometrium is considered potentially receptive accompanied by an increase in secreted glycoproteins mRNAs in the potentially receptive glands. Reported histological findings identified the presence of one histological feature characteristic of each phase: glandular mitoses indicated a non-receptive endometrium, whereas a potentially receptive endometrium was distinguished by supranuclear vacuolation. CONCLUSIONS: This study defined a transcriptome characteristic of active cell proliferation in the non-receptive samples with a marked overall down-regulation of this pathway in potentially receptive samples-suggesting a transitional state associated with receptivity but not implantation. However, microarrays involve expensive, specialized testing and require significant post-data analysis. Sampling according to endocrinological and molecular prediction improved the consistency of histological assessment and allowed reliable histological markers of glandular mitosis in the non-receptive phase and supranuclear vacuolation of the potentially receptive endometrium to be identified. Thus, histology can provide an affordable, clinically applicable test in the context of reproduction.

Polypharmacy--we make it worse! A cross-sectional study from an acute admissions unit.

Although polypharmacy is a major problem in the elderly, very few data have been published from Australasia. We retrospectively audited 68% of elderly patients admitted acutely to our medical unit (n= 424, mean age 80.3 ± 8 years) during a 30-day period (September, 2008). We found that long-term medications increased during hospital stay from 6.6 ± 4 to 7.7 ± 4 (P < 0.001). Adverse drug reactions were responsible for 24 admissions (5.7%). Polypharmacy is made worse by acute admission to hospital.

KCNE5 polymorphism rs697829 is associated with QT interval and survival in acute coronary syndromes patients.

INTRODUCTION: The KCNE family is a group of small transmembrane channel proteins involved in potassium ion (K(+)) conductance. The X-linked KCNE5 gene encodes a regulator of the K(+) current mediated by the potassium channel KCNQ1. Polymorphisms in KCNE5 have been associated with altered cardiac electrophysiological properties in human studies. We investigated associations of the common rs697829 polymorphism from KCNE5 with baseline characteristics, baseline electrocardiographic (ECG) measurements, and patient survival in a cohort of post-acute coronary syndromes (ACS) patients (the Coronary Disease Cohort Study cohort). METHODS AND RESULTS: DNA samples (n = 1,740) were genotyped for rs697829 using a TaqMan assay. Baseline ECG data revealed corrected QT (QTc) interval was associated with rs697829 in male, but not female, patients, being extended in the G genotype group (A 416 ± 1.71; G 431 ± 4.25 ms, P = 0.002). Covariate-adjusted survival was poorest in G genotype patients in Cox proportional hazard modeling of mortality data of males (P(overall) = 0.020). Male patients with G genotype had a hazard ratio of 1.44 (1.11-2.33) for death when compared to the A genotype male patients (P = 0.048) after adjustment for age, baseline log-transformed N-terminal pro-B-type natriuretic peptide (NTproBNP), ß-blocker and insulin treatment, QTc interval, history of myocardial infarction, and physical activity score. CONCLUSION: This study suggests an association between rs697829, a common single nucleotide polymorphism (SNP) from KCNE5, and ECG measurements and survival in postacute ACS patients. Prolonged subclinical QT interval may be a marker of adverse outcome in this group of patients.

Anaemia is highly prevalent among unselected internal medicine inpatients and is associated with increased mortality, earlier readmission and more prolonged hospital stay: an observational retrospective cohort study.

BACKGROUND: Anaemia is associated with adverse outcomes in elderly community-dwelling individuals, but this problem is less well characterised in the inpatient setting. AIMS: To determine the prevalence of anaemia and its associations in a well-defined cohort of internal medicine inpatients. METHODS: A retrospective cohort study of non-elective admissions under internal medicine at Palmerston North Hospital, New Zealand, was conducted for 4 months of 2008 with outcome analysis on 1 March 2010. RESULTS: At admission, 497 of 1491 (33.3%) patients were anaemic by World Health Organization criteria (haemoglobin <130 g/L for males; <120 g/L for females). Anaemia was more prevalent in males (38.1%) than females (28.2%), P < 0.001, in patients aged 65 years or older (41%) than in those under 65 (21.3%), P < 0.001, in New Zealand Europeans (34.3%) than in Maori and people from the Pacific Islands (26.4%), P= 0.04, and in patients admitted primarily because of malignancy, endocrine/metabolic disease, infection, and acute coronary syndrome/congestive heart failure (P < 0.001). Anaemia was independently associated with increased length of hospital stay (7.3 days vs 5.1 days in non-anaemic patients; P < 0.001), with mortality (P < 0.001) and unplanned hospital readmission (P < 0.001) during the follow-up period. Anaemia was infrequently acknowledged or investigated. Secondary analysis using a haemoglobin threshold of 110 g/L showed similar results. CONCLUSIONS: Anaemia is highly prevalent among medical inpatients with variation because of gender, age, race and reason for admission. Anaemia independently predicts for prolonged hospital stay, increased mortality and shorter time to readmission, but is usually not documented or investigated in this setting.