Reverse total shoulder arthroplasty for acute proximal humeral fracture has comparable 10-year outcomes to elective indications: results from the New Zealand Joint Registry.

HYPOTHESIS AND BACKGROUND: Recently, the indication of reverse total shoulder arthroplasty (RTSA) has expanded beyond rotator cuff arthropathy to include treatment of complex acute proximal humeral fracture (PHF). Limited previous studies have compared the long-term clinical and functional outcomes of patients undergoing RTSA for PHF vs. elective indications for degenerative conditions. The purpose of this study was to compare implant survivorship, reasons for revision and functional outcomes in patients undergoing RTSA for acute PHF with those undergoing elective RTSA in a population-based cohort study. METHODS: Prospectively collected data from the New Zealand Joint Registry from 1999 to 2021 and identified 6862 patients who underwent RTSA. Patients were categorized by preoperative indication, including PHF (10.8%), rotator cuff arthropathy (RCA) (44.5%), osteoarthritis (OA) (34.1%), rheumatoid arthritis (RA) (5.5%), and old traumatic sequelae (5.1%). Revision-free implant survival and functional outcomes (Oxford Shoulder Scores [OSSs] at the 6-month, 5-year, and 10-year follow-ups) were adjusted by age, sex, American Society of Anesthesiologists class, and surgeon experience and compared. RESULTS: Revision-free implant survival at 10 years for RTSA for PHF was 97.3%, compared with 96.1%, 93.7%, 92.8%, and 91.3% for OA, RCA, RA and traumatic sequelae, respectively. When compared with RTSA for PHF, the adjusted risk of revision was significantly higher for traumatic sequelae (hazard ratio = 2.3, P = .023) but not for other elective indications. The most common reason for revision in the PHF group was dislocation or instability (42.9%), which was similar to the OA (47.6%) and traumatic sequelae (33.3%) groups. At 6 months post-surgery, OSSs were significantly lower for the PHF group compared with the RCA, OA, and RA groups (31.1 vs. 35.6, 37.7, and 36.5, respectively, P < .001), and similar to traumatic sequelae (31.7, P = .431). At 5 years, OSSs were only significantly lower for PHF compared with OA (37.4 vs. 41.0, P < .001) and there was no difference between the PHF and other groups. At 10 years, there were no significant differences between groups. CONCLUSIONS: RTSA for PHF demonstrated reliable long-term survivorship and functional outcomes compared with elective indications. Despite lower functional outcomes in the early postoperative period for the PHF group, implant survivorship was similar in patients undergoing RTSA for the primary indication of acute PHF compared with RCA, OA, and RA and superior compared to the primary indication of traumatic sequelae.

Clinical and functional outcomes of TKA after HTO or UKA: a New Zealand Joint Registry Study.

INTRODUCTION: Surgical options for patients with unicompartmental knee osteoarthritis include high tibial osteotomy (HTO) or unicompartmental knee arthroplasty (UKA). When managing younger patients with a higher chance of further surgery, the outcome of any subsequent conversion to total knee arthroplasty (TKA) also needs to be considered. The aim of this study was to compare implant survivorship and patient-reported outcomes for patients undergoing TKA after previous HTO or UKA, with comparisons for age, gender and comorbidities. METHODS: Revision risk and 6-month Oxford Knee Scores (OKS) from the New Zealand Joint Registry were compared for patients who underwent TKA after HTO (HTO-TKA; n = 1556) or UKA (UKA-TKA; n = 965) between 1999 and 2019, with a comparison group of primary TKA (n = 110,948). Mean follow-up was 8.2 years. RESULTS: Adjusted revision risk was similar for HTO-TKA and UKA-TKA groups (hazard ratio (HR) 1.04, p = 0.84); and risk for both groups were higher than primary TKA (HTO-TKA HR 1.45, p = 0.002; UKA-TKA HR 1.51, p = 0.01). Overall adjusted mean OKS at 6 months for HTO-TKA (36.2) was similar to primary TKA (36.8, p = 0.23); and both were higher than UKA-TKA (34.2, p < 0.001). For the youngest patient group (< 55 years), revision rates of UKA-TKA were two-fold higher than HTO-TKA (2.8 vs. 1.3 per 100 component yrs, p < 0.03). HTO-TKA had better OKS (37.5 vs. 34.1, p < 0.0001) for males. Mean OKS for UKA-TKA was lower than HTO-TKA for patients with ASA 1-2 (35.6 vs. 37.5, p < 0.01). CONCLUSION: The findings from this study suggest that revision rate following TKA after HTO and UKA are similar. However, TKA after HTO have superior functional outcomes compared with TKA after UKA and are comparable to functional outcomes post primary TKA. The results support the use of HTO for young, male and less co-morbid patients.

Predictors of Intensive Care Admission in Hypoxemic Bronchiolitis Infants, Secondary Analysis of a Randomized Trial.

OBJECTIVES: To evaluate in a preplanned secondary analysis of our parent randomized controlled trial predictors of intensive care unit (ICU) admission in infants with bronchiolitis and analyze if these predictors are equally robust for children receiving high-flow or standard-oxygen. STUDY DESIGN: A secondary analysis of a multicenter, randomized trial of infants aged <12 months with bronchiolitis and an oxygen requirement was performed using admission and outcome data of all 1472 enrolled infants. The primary outcome was ICU admission. The predictors evaluated were baseline characteristics including physiological data and medical history. RESULTS: Of the 1472 enrolled infants, 146 were admitted to intensive care. Multivariate predictors of ICU admission were age (weeks) (OR: 0.98 [95% CI: 0.96-0.99]), pre-enrolment heart rate >160/min (OR: 1.80 [95% CI: 1.23-2.63]), pre-enrolment SpO2 (transcutaneous oxygen saturation) (%) (OR: 0.91 [95% CI: 0.86-0.95]), previous ICU admission (OR: 2.16 [95% CI: 1.07-4.40]), and time of onset of illness to hospital presentation (OR: 0.78 [95% CI: 0.65-0.94]). The predictors were equally robust for infants on high-flow nasal cannula therapy or standard-oxygen therapy. CONCLUSION: Age <2 months, pre-enrolment heart rate >160/min, pre-enrolment SpO2 of <87%, previous ICU admission and time of onset of ≤2 days to presentation are predictive of an ICU admission during the current hospital admission of infants with bronchiolitis independent of oxygenation method used. TRIAL REGISTRATION: ACTRN12613000388718.

Descriptive Epidemiology of Pediatric Inflammatory Bowel Disease in Oceania: A Systematic Review and Meta-Analysis.

OBJECTIVES: Pediatric inflammatory bowel diseases (IBDs) are chronic, idiopathic illnesses of the digestive tract, which can impact adversely on children's quality of life and burden health systems. International studies have shown these diseases are increasing. The aim was to describe pediatric IBD epidemiology across Oceania by conducting a systematic review and meta-analysis of incidence and prevalence. METHODS: Medline, EMBASE and Web of Science databases were searched in October 2022 for studies reporting rates of IBD, Crohn disease (CD), or ulcerative colitis (UC) in children (≤19 years). Several data collection methodologies were included and pooled estimates of incidence and prevalence were calculated using a random effects model with I2 measures of heterogeneity. RESULTS: Nineteen articles provided 15 incidence and 7 prevalence studies. Fourteen studies were from Australia, 8 studies from New Zealand, and no studies were found from the Pacific Islands. Study dates ranged from 1950 to 2020 with 11 studies using population-based designs. Pooled estimates for annual incidence were IBD 4.1 (3.4-4.8, I2 = 98.7), CD 2.3 (1.9-2.7, I2 = 98.6), and UC 0.9 (0.6-1.1, I2 = 96.8) per 100,000 person-years. Prevalence rates were IBD 36.0 (23.5-48.5, I2 = 98.4), CD 23.2 (6.6-39.8, I2 = 97.8), and UC 7.6 (2.7-12.5, I2 = 99.6) per 100,000 persons. CONCLUSIONS: Pediatric IBD is prevalent in Oceania with high incidence rates, particularly for CD. Low rates of IBD were observed in indigenous Australian, Maori, and New Zealand Pacific children and there were no studies from the Pacific Islands highlighting this as an area in need of further research.

Short-term outcomes following 159 stemmed pyrolytic carbon shoulder hemiarthroplasties and how they compare with conventional hemiarthroplasties and total shoulder arthroplasties in patients younger than 60 years with osteoarthritis: results from the New Zealand National Joint Registry.

BACKGROUND: Despite the increasing use of pyrolytic carbon (pyrocarbon) hemiarthroplasty (PyCHA), clinical data reporting on its outcomes remain scarce. To date, no studies have compared the outcomes of stemmed PyCHA vs. conventional hemiarthroplasty (HA) and anatomic total shoulder arthroplasty (aTSA) in young patients. The primary aim of this study was to report on the outcomes of the first 159 stemmed PyCHAs performed in New Zealand. The secondary aim was to compare the outcomes of stemmed PyCHA vs. HA and aTSA in patients aged <60 years with osteoarthritis. We hypothesized that stemmed PyCHA would be associated with a low revision rate. We further hypothesized that in young patients, PyCHA would be associated with a lower revision rate and superior functional outcomes compared with HA and aTSA. METHODS: Data from the New Zealand National Joint Registry were used to identify patients who underwent PyCHA, HA, and aTSA between January 2000 and July 2022. The total number of revisions in the PyCHA group was determined, and the indications for surgery, reasons for revision, and types of revision were recorded. In patients aged <60 years, a matched-cohort analysis was performed comparing functional outcomes using the Oxford Shoulder Score (OSS). The revision rate of PyCHA was compared with that of HA and aTSA, calculated as revisions per 100 component-years. RESULTS: In total, 159 cases of stemmed PyCHA were performed and 5 cases underwent revision, resulting in an implant retention rate of 97%. Among patients aged <60 years with shoulder osteoarthritis, 48 underwent PyCHA compared with 150 who underwent HA and 550 who underwent aTSA. Patients treated with aTSA had a superior OSS compared with PyCHA and HA patients. The difference in the OSS between the aTSA and PyCHA groups exceeded the minimal clinically important difference of 4.3. There was no difference in revision rates between the groups. CONCLUSIONS: This study represents the largest cohort of patients treated with PyCHA and is the first to compare stemmed PyCHA with HA and aTSA in young patients. In the short term, PyCHA appear to be a promising implant with an excellent implant retention rate. In patients aged <60 years, the revision rate is comparable between PyCHA and aTSA. However, aTSA remains the implant of choice to optimize early postoperative function. Further studies are required to elucidate the long-term outcomes of PyCHA, particularly how they compare with those of HA and aTSA in young patients.

The Strongest Oxford Knee Score Predictors of Subsequent Revision are "Overall Pain," "Limping When Walking," and "Knee Giving Way".

BACKGROUND: The Oxford Knee Score (OKS) is used to measure knee arthroplasty outcomes; however, it is unclear which questions are more relevant. Our aims were to (1) identify which OKS question(s) were the strongest predictors of subsequent revision and (2) compare the predictive ability of the "pain" and "function" domains. METHODS: All primary total knee arthroplasties (TKAs) and unicompartmental knee arthroplasties (UKAs) in the New Zealand Joint Registry between 1999 and 2019 with an OKS at 6 months (TKA n = 27,708; UKA n = 8,415), 5 years (TKA n = 11,519; UKA n = 3,365) or 10 years (TKA n = 6,311; UKA n = 1,744) were included. Prediction models were assessed using logistic regressions and receiver operating characteristic analyses. RESULTS: A reduced model with 3 questions ("overall pain," "limping when walking," "knee giving way") showed better diagnostic ability than full OKS for predicting UKA revision at 6 months (area under the curve [AUC]: 0.80 versus 0.78; P < .01) and 5 years (0.81 versus 0.77; P = .02), and comparable diagnostic ability for predicting TKA revision at all time points (6 months, 0.77 versus 0.76; 5 years, 0.78 versus 0.75; 10 years, 0.76 versus 0.73; all not significant), and UKA revision at 10 years (0.80 versus 0.77; not significant). The pain domain had better diagnostic ability for predicting subsequent revision for both procedures at 5 and 10 years. CONCLUSION: Questions on "overall pain", "limping when walking", and "knee giving way" were the strongest predictors of subsequent revision. Attention to low scores from these questions during follow-up may allow for prompt identification of patients most at risk of revision.

Are Lipped Polyethylene Liners Associated with Increased Revision Rates in Patients with Uncemented Acetabular Components? An Observational Cohort Study.

BACKGROUND: Recurrent dislocation after THA remains a serious complication that carries with it a high risk of revision surgery. Previous studies have shown reduced dislocation rates with the use of lipped polyethylene (PE) liners in modular uncemented acetabular components, but there may be increased wear because of impingement, which may lead to aseptic loosening in the longer term; whether the aggregate benefit of lipped PE liners outweighs the risks associated with their use remains controversial. QUESTIONS/PURPOSES: We used data from the New Zealand Joint Registry to (1) compare Kaplan-Meier survival rates, (2) rates of revisions for dislocation between neutral and lipped PE liners, and (3) revision rates for aseptic loosening for the four most commonly used modular uncemented cups. METHODS: We used data from the New Zealand Joint Registry (NZJR) to identify 31,247 primary THAs using the four most commonly used uncemented modular acetabular implants from January 1, 1999 to December 31, 2018. The lipped liner group comprised 49% males (9924 of 20,240) compared with 42% (4669 of 11,007) in the neutral group (p < 0.001); 96% (19,382 of 20,240) of patients in the liner group had OA versus 95% (10,450 of 11,007) in the neutral group (p < 0.001). There was no difference in other patient characteristics such as age (mean 66.9 years), BMI (mean 29 ± 6 kg/m) and American Society of Anesthesiologists grade. The mean follow-up was 5.1 years (SD 3.9) and longest follow-up 19.3 years. The NZJR has more than 96% capture rate and data entry is a mandatory requirement of members of the New Zealand Orthopaedic Association. Kaplan-Meier survival rates were compared between 20,240 lipped and 11,007 neutral PE liners. Highly cross-linked polyethylene was used in 99% of lipped liner cups and 85% of neutral liner cups. Associated hazard ratios were calculated using a Cox regression analysis with a Kaplan-Meier revision-free estimates plot. RESULTS: The Kaplan-Meier survival at 10 years for lipped PE liners was 96% (95% confidence interval 95.4 to 96.2) and for neutral liners 95% (95% CI 94.7 to 95.9). After controlling for age, gender approach, femoral head size, and the use of image guidance, the all-cause revision risk was greater for neutral PE liners than that for lipped PE liners (HR 1.17 [95% CI 1.06 to 1.36]; p = 0.032). There was a higher risk of revision for dislocation in those with neutral PE liners than in those with lipped liners (HR 1.84 [95% CI 1.41 to 2.41]; p < 0.001) but no difference in the revision rate for aseptic acetabular component loosening (HR 0.85 [95% CI 0.52 to 1.38]; p = 0.511). CONCLUSIONS: The use of a lipped PE liner is not associated with a higher rate of aseptic loosening in patients who undergo primary THA compared with a neutral PE liner. Lipped PE liners are associated with lower rates of dislocation and lower all-cause revision rates without any increased association with revision rates for wear and aseptic loosening. LEVEL OF EVIDENCE: Level III, therapeutic study.

Cemented vs. uncemented glenoid fixation in total shoulder arthroplasty for osteoarthritis: a New Zealand Joint Registry study.

BACKGROUND: Total shoulder arthroplasty (TSA) is commonly performed for shoulder osteoarthritis (OA). Uncemented metal-backed (MB) glenoid components were introduced in an attempt to avoid glenoid loosening. New Zealand and Australian Joint Registry studies have shown significantly higher revision rates when uncemented MB glenoids are used. We used the New Zealand Joint Registry (NZJR) to compare all-cause revision rates and functional scores for TSA and investigated the trends of glenoid fixation used in New Zealand. METHODS: The NZJR was accessed for all primary TSA undertaken for OA from January 2000 to December 2017. Patient demographics were collated. All-cause revision rates were reported as rate per 100 component-years. Analysis was repeated excluding the uncemented SMR L2 glenoid (LimaCorporate), as it was a potential confounder. Kaplan-Meier survival analysis was performed. Oxford Shoulder Scores at both 6 months and 5 years were analyzed. RESULTS: A total of 2613 TSAs were performed for OA during the study period, representing 85.0% of all TSAs in New Zealand. Overall, 62.1% of the patients were female. In addition, 69.6% of glenoids were cemented and 30.4% uncemented. The most common uncemented MB glenoid was SMR 86.6% (LimaCorporate), and cemented was Global (DePuy) 49.8%. The revision rate for TSA with uncemented glenoids was significantly higher at 2.03 compared with cemented at 0.41 per 100 component-years (P < .001). Hazard ratio 5.0 for revision of uncemented glenoids. No significant difference was found in Oxford Scores at 6 months (39.7 vs. 40.3, P = .13) or 5 years (42.1 vs. 42.8, P = .22). The most common mode of failure was glenoid loosening in cemented glenoids (44.4%), and component failure in uncemented (34.8%). Revision for rotator cuff, deep infection, and instability were comparable between groups. When excluding SMR L2, uncemented MB glenoid all-cause revision rates remained significantly higher than cemented (1.42 vs. 0.41 per 100 component-years, P < .001). SMR L1 uncemented MB glenoids had a higher revision rate than the non-SMR uncemented glenoids (1.61 vs. 0.18 per 100 component-years, P = .009). Uncemented glenoid use peaked in New Zealand in 2011 at 46.7% of TSAs but declined to 20.1% in 2017. CONCLUSIONS: In the NZJR, primary TSAs undertaken for OA have a significantly higher all-cause revision rate when the glenoid component is uncemented. Uncemented glenoids have a 5.0 times higher revision rate. Excluding SMR L2 glenoids from the analysis, the significantly higher revision rate remained for uncemented glenoids. These data reaffirm that uncemented MB glenoids are associated with higher revision rates.

Earthquake brain: Impairment of spatial memory following long-term earthquake-related stress.

OBJECTIVES: The primary aim of this study was to investigate neuropsychological function in patients with earthquake-related posttraumatic stress disorder, compared with earthquake-exposed but resilient controls. We hypothesised that individuals with posttraumatic stress disorder would have poorer neuropsychological performance on tests of verbal and visuospatial learning and memory compared with the earthquake-exposed control group. The availability of groups of healthy patients from previous studies who had been tested on similar neuropsychological tasks prior to the earthquakes allowed a further non-exposed comparison. METHOD: In all, 28 individuals with posttraumatic stress disorder and 89 earthquake-exposed controls completed tests of verbal and visuospatial learning and memory and psychomotor speed. Further comparisons were made with non-exposed controls who had been tested before the earthquakes. RESULTS: No significant difference in performance on tests of verbal or visuospatial memory was found between the earthquake-exposed groups (with and without posttraumatic stress disorder), but the posttraumatic stress disorder group was significantly slowed on tests of psychomotor speed. Supplementary comparison with historical, non-exposed control groups showed that both earthquake-exposed groups had poorer performance on a test of visuospatial learning. CONCLUSION: The key finding from this study is that there were no differences in verbal or visuospatial learning and memory in individuals with posttraumatic stress disorder compared with similarly earthquake-exposed controls. Compared with non-exposed controls, both earthquake-exposed groups had poorer performance on a test of visuospatial (but not verbal) learning and memory. This offers preliminary evidence suggesting that it is earthquake (trauma) exposure itself, rather than the presence of posttraumatic stress disorder that affects aspects of neuropsychological functioning. If replicated, this may have important implications for how information is communicated in a post-disaster context.

Psychological distress and psychiatric disorder after natural disasters: systematic review and meta-analysis.

BACKGROUND: Natural disasters are increasing in frequency and severity. They cause widespread hardship and are associated with detrimental effects on mental health.AimsOur aim is to provide the best estimate of the effects of natural disasters on mental health through a systematic review and meta-analysis of the rates of psychological distress and psychiatric disorder after natural disasters. METHOD: This systematic review and meta-analysis is limited to studies that met predetermined quality criteria. We required included studies to make comparisons with pre-disaster or non-disaster exposed controls, and sample representative populations. Key studies were identified through a comprehensive search of PubMed, EMBASE and PsycINFO from 1980 to 3 March 2017. Random effects meta-analyses were performed for studies that reported key outcomes with appropriate statistics. RESULTS: Forty-one studies were identified by the literature search, of which 27 contributed to the meta-analyses. Continuous measures of psychological distress were increased after natural disasters (combined standardised mean difference 0.63, 95% CI 0.27-0.98, P = 0.005). Psychiatric disorders were also increased (combined odds ratio 1.84, 95% CI 1.43-2.38, P < 0.001). Rates of post-traumatic stress disorder and depression were significantly increased after disasters. Findings for anxiety and alcohol misuse/dependence were not significant. High rates of heterogeneity suggest that disaster-specific factors and, to a lesser degree, methodological factors contribute to the variance between studies. CONCLUSIONS: Increased rates of psychological distress and psychiatric disorders follow natural disasters. High levels of heterogeneity between studies suggest that disaster variables and post-disaster response have the potential to mitigate adverse effects.Declaration of interestNone.

Vitamin-mineral treatment improves aggression and emotional regulation in children with ADHD: a fully blinded, randomized, placebo-controlled trial.

BACKGROUND: Evaluation of broad-spectrum micronutrient (vitamins and minerals) treatment for childhood ADHD has been limited to open-label studies that highlight beneficial effects across many aspects of psychological functioning. METHOD: This is the first fully blinded randomized controlled trial of medication-free children (n = 93) with ADHD (7-12 years) assigned to either micronutrients (n = 47) or placebo (n = 46) in a 1:1 ratio, for 10 weeks. All children received standardized ADHD assessments. Data were collected from clinicians, parents, participants and teachers across a range of measures assessing ADHD symptoms, general functioning and impairment, mood, aggression and emotional regulation. RESULTS: Intent-to-treat analyses showed significant between-group differences favouring micronutrient treatment on the Clinical Global Impression-Improvement (ES = 0.46), with 47% of those on micronutrients identified as 'much' to 'very much' improved versus 28% on placebo. No group differences were identified on clinician, parent and teacher ratings of overall ADHD symptoms (ES ranged 0.03-0.17). However, according to clinicians, 32% of those on micronutrients versus 9% of those on placebo showed a clinically meaningful improvement on inattentive (OR = 4.9; 95% CI: 1.5-16.3), but no group differences on improvement in hyperactive-impulsive symptoms (OR = 1.0; 95% CI: 0.4-2.5). Based on clinician, parent and teacher report, those on micronutrients showed greater improvements in emotional regulation, aggression and general functioning compared to placebo (ES ranged 0.35-0.66). There were two dropouts per group, no group differences in adverse events and no serious adverse events identified. Blinding was successful with guessing no better than chance. CONCLUSIONS: Micronutrients improved overall function, reduced impairment and improved inattention, emotional regulation and aggression, but not hyperactive/impulsive symptoms, in this sample of children with ADHD. Although direct benefit for core ADHD symptoms was modest, with mixed findings across raters, the low rate of adverse effects and the benefits reported across multiple areas of functioning indicate micronutrients may be a favourable option for some children, particularly those with both ADHD and emotional dysregulation. Trial registered with the Australian New Zealand Clinical Trials Registry ACTRN12613000896774.

The ALCCaS Trial: A Randomized Controlled Trial Comparing Quality of Life Following Laparoscopic Versus Open Colectomy for Colon Cancer.

BACKGROUND: This study reports the quality-of-life assessment of the ALCCaS trial. The ALCCaS trial compared laparoscopic and open resection for colon cancer. It reported equivalence of survival at 5 years. Quality of life was measured as a secondary outcome. OBJECTIVE: This study aimed to report on the quality of life data of the ALCCaS Trial. DESIGN: This study reports a randomized controlled trial comparing laparoscopic with open colonic resection. SETTINGS: The study was conducted in Australasia. PATIENTS: Patients with a single adenocarcinoma of the right, left, or sigmoid colon, presenting for elective treatment, were eligible for randomization. INTERVENTIONS: Open and laparoscopic colonic resections were performed. MAIN OUTCOME MEASURES: Patient symptoms and quality of life were measured using the Symptoms Distress Scale, the Quality of Life Index, and the Global Quality of Life Score preoperatively, and at 2 days, 2 weeks, and 2 months postoperatively. RESULTS: Of the 592 patients enrolled in ALCCaS, 425 completed at least 1 quality-of-life measure at 4 time points (71.8% of cohort). Those who received the laparoscopic intervention had better quality of life postoperatively in terms of the Symptoms Distress Scale (p < 0.01), Quality of Life Index (p < 0.01), and Global Quality of Life (p < 0.01). In intention-to-treat analyses, those assigned to laparoscopic surgery had a better quality of life postoperatively in terms of the Symptoms Distress Scale (p < 0.01) and Quality of Life Index (p < 0.01), whereas Global Quality of Life was not significant (p = 0.056). The subscales better for laparoscopic resection at all 3 postoperative time points were appetite, insomnia, pain, fatigue, bowel, daily living, and health (p < 0.05). LIMITATIONS: The primary limitation was the different response rates for the 3 quality-of-life measures. CONCLUSIONS: There was a short-term gain in quality of life maintained at 2 months postsurgery for those who received laparoscopic relative to open colonic resection. See Video Abstract at http://links.lww.com/DCR/A691.

Plasma levels of soluble VEGF receptor isoforms, circulating pterins and VEGF system SNPs as prognostic biomarkers in patients with acute coronary syndromes.

BACKGROUND: Development of collateral circulation in coronary artery disease is cardio-protective. A key process in forming new blood vessels is attraction to occluded arteries of monocytes with their subsequent activation as macrophages. In patients from a prospectively recruited post-acute coronary syndromes cohort we investigated the prognostic performance of three products of activated macrophages, soluble vascular endothelial growth factor (VEGF) receptors (sFlt-1 and sKDR) and pterins, alongside genetic variants in VEGF receptor genes, VEGFR-1 and VEGFR-2. METHODS: Baseline levels of sFlt-1 (VEGFR1), sKDR (VEGFR2) and pterins were measured in plasma samples from subgroups (n = 513; 211; 144, respectively) of the Coronary Disease Cohort Study (CDCS, n = 2067). DNA samples from the cohort were genotyped for polymorphisms from the VEGFR-1 gene SNPs (rs748252 n = 2027, rs9513070 n = 2048) and VEGFR-2 gene SNPs (rs2071559 n = 2050, rs2305948 n = 2066, rs1870377 n = 2042). RESULTS: At baseline, levels of sFlt-1 were significantly correlated with age, alcohol consumption, NTproBNP, BNP and other covariates relevant to cardiovascular pathophysiology. Total neopterin levels were associated with alcohol consumption at baseline. 7,8 dihydroneopterin was associated with BMI. The A allele of VEGFR-2 variant rs1870377 was associated with higher plasma sFlt-1 and lower levels of sKDR at baseline. Baseline plasma sFlt-1 was univariately associated with all cause mortality with (p < 0.001) and in a Cox's proportional hazards regression model sFlt-1 and pterins were both associated with mortality independent of established predictors (p < 0.027). CONCLUSIONS: sFlt-1 and pterins may have potential as prognostic biomarkers in acute coronary syndromes patients. Genetic markers from VEGF system genes warrant further investigation as markers of levels of VEGF system components in these patients. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry. ACTRN12605000431628 . 16 September 2005, Retrospectively registered.

Clinical response to treatment in inpatients with depression correlates with changes in activity levels and psychomotor speed.

BACKGROUND: Monitoring clinical response to treatment in depressed inpatients, particularly identifying early improvement, may be sub-optimal. This may impact adversely on patients through longer admissions and sub-optimal pharmacotherapy. Psychomotor speed is a prominent neuropsychological function which changes as recovery occurs. This study examines simple techniques used to quantify psychomotor change and their potential to contribute to monitoring recovery. METHODS: Activity levels were continuously monitored in patients diagnosed with a major depressive episode from four acute psychiatric wards using two actigraphs (commercial and scientific) for 3 weeks and linear regression used to calculate a gradient to express rate of change. Psychomotor speed was assessed using the simple Coin Rotation Task. Mood and functioning were rated using the Quick Inventory of Depressive Symptoms, Clinical Global Impression Scale and Functioning Assessment Short Test. The assessments were completed at baseline and follow-up (3 weeks), and correlations were calculated for all change measures. RESULTS: In all, 24 inpatients were recruited but not all completed baseline and follow-up measures. Change in activity count ( N = 16) and psychomotor speed ( N = 13) correlated significantly with improvement in clinical measures of depressive symptoms. Actigraphs were acceptable to hospital inpatients. LIMITATIONS: The limited size of this pilot study precludes the analysis of predictive power or the influence of other variables such as depression subtypes, age, gender or variations related to medications. CONCLUSION: Early change in simple activity and psychomotor speed warrant further investigation for utility in measuring treatment response in depressed inpatients.

Ibogaine treatment outcomes for opioid dependence from a twelve-month follow-up observational study.

BACKGROUND: The psychoactive indole alkaloid ibogaine has been associated with encouraging treatment outcomes for opioid dependence. The legal status of ibogaine in New Zealand provides a unique opportunity to evaluate durability of treatment outcomes. OBJECTIVE: To examine longitudinal treatment effects over a 12-month period among individuals receiving legal ibogaine treatment for opioid dependence. METHOD: This observational study measured addiction severity as the primary outcome in 14 participants (50% female) over 12 months post-treatment using the Addiction Severity Index-Lite (ASI-Lite) following a single ibogaine treatment by either of two treatment providers. Secondary effects on depression were assessed via the Beck Depression Inventory-II (BDI-II). The Subjective Opioid Withdrawal Scale (SOWS) was collected before and immediately after treatment to measure opioid withdrawal symptoms. RESULTS: Nonparametric comparisons via Friedman Test between baseline and 12-month follow-up for participants completing all interviews (n = 8) showed a significant reduction for the ASI-Lite drug use (p = 0.002) composite score. Reductions in BDI-II scores from baseline to 12-month follow-up were also significant (p < 0.001). Significant reductions in SOWS scores for all participants (n = 14) were also observed acutely after treatment (p = 0.015). Patients with partial data (n = 4) also showed reductions in ASI-Lite drug use scores and family/social status problems. One patient enrolled in the study died during treatment. CONCLUSION: A single ibogaine treatment reduced opioid withdrawal symptoms and achieved opioid cessation or sustained reduced use in dependent individuals as measured over 12 months. Ibogaine's legal availability in New Zealand may offer improved outcomes where legislation supports treatment providers to work closely with other health professionals.

C-Type Natriuretic Peptides in Coronary Disease.

AIMS: C-type natriuretic peptide (CNP) is a paracrine growth factor expressed in the vascular endothelium. Although upregulated in atheromatous arteries, the predictive value of plasma CNP products for outcome in coronary disease is unknown. This study aimed to compare the prognostic value of plasma CNP products with those of other natriuretic peptides in individuals with coronary artery disease, and investigate their associations with cardiac and renal function. METHODS AND RESULTS: Plasma concentrations of CNP and amino-terminal proCNP (NT-proCNP) were measured at baseline in 2129 individuals after an index acute coronary syndrome admission and related to cardiac and renal function, other natriuretic peptides [atrial NP (ANP) and B-type NP (BNP)] and prognosis (primary end point, mortality; secondary end point, cardiac readmission). Median follow-up was 4 years. At baseline, and in contrast to CNP, ANP, and BNP, plasma NT-proCNP was higher in males and weakly related to cardiac function but strongly correlated to plasma creatinine. All NPs were univariately associated with mortality. Resampling at 4 and 12 months in survivors showed stable concentrations of NT-proCNP whereas all other peptides declined. When studied by diagnosis (myocardial infarction, unstable angina) at index admission using a multivariate model, NT-proBNP predicted mortality and readmission in myocardial infarction. In unstable angina, only NT-proCNP predicted both mortality and cardiac readmission. CONCLUSIONS: In contrast to the close association of NT-proBNP with cardiac function, and predictive value for outcome after myocardial infarction, plasma NT-proCNP is highly correlated with renal function and is an independent predictor of mortality and cardiac readmission in individuals with unstable angina.

An evaluation of Health of the Nation Outcome Scales data to inform psychiatric morbidity following the Canterbury earthquakes.

OBJECTIVE: Following the onset of the Canterbury, New Zealand earthquakes, there were widespread concerns that mental health services were under severe strain as a result of adverse consequences on mental health. We therefore examined Health of the Nation Outcome Scales data to see whether this could inform our understanding of the impact of the Canterbury earthquakes on patients attending local specialist mental health services. METHOD: Health of the Nation Outcome Scales admission data were analysed for Canterbury mental health services prior to and following the Canterbury earthquakes. These findings were compared to Health of the Nation Outcome Scales admission data from seven other large District Health Boards to delineate local from national trends. Percentage changes in admission numbers were also calculated before and after the earthquakes for Canterbury and the seven other large district health boards. RESULTS: Admission Health of the Nation Outcome Scales scores in Canterbury increased after the earthquakes for adult inpatient and community services, old age inpatient and community services, and Child and Adolescent inpatient services compared to the seven other large district health boards. Admission Health of the Nation Outcome Scales scores for Child and Adolescent community services did not change significantly, while admission Health of the Nation Outcome Scales scores for Alcohol and Drug services in Canterbury fell compared to other large district health boards. Subscale analysis showed that the majority of Health of the Nation Outcome Scales subscales contributed to the overall increases found. Percentage changes in admission numbers for the Canterbury District Health Board and the seven other large district health boards before and after the earthquakes were largely comparable with the exception of admissions to inpatient services for the group aged 4-17 years which showed a large increase. CONCLUSION: The Canterbury earthquakes were followed by an increase in Health of the Nation Outcome Scales scores for attendees of local mental health services compared to other large district health boards. This suggests that patients presented with greater degrees of psychiatric distress, social disruption, behavioural change and impairment as a result of the earthquakes.

The Outcomes and Patterns of Treatment Failure After Surgery for Locally Recurrent Rectal Cancer.

OBJECTIVE: To assess the outcomes and patterns of treatment failure of patients who underwent pelvic exenteration surgery for recurrent rectal cancer. BACKGROUND: Despite advances in the management of rectal cancer, local recurrence still occurs. For appropriately selected patients, pelvic exenteration surgery can achieve long-term disease control. METHODS: Prospectively maintained databases of 5 high volume institutions for pelvic exenteration surgery were reviewed and data combined. We assessed the combined endpoints of overall 5-year survival, cancer-specific 5-year mortality, local recurrence, and the development of metastatic disease. RESULTS: Five hundred thirty-three patients who had undergone surgery for locally recurrent rectal cancer were identified. Five-year cancer-specific survival for patients with a complete (R0) resection is 44%, which was achieved in 59% of patients. For those with R1 and R2 resections, the 5-year survival was 26% and 10%, respectively. Radical resection required sacrectomy in 170 patients (32%), and total cystectomy in 105 patients (20%). Treatment failure included local recurrence alone in 75 patients (14%) and systemic metastases with or without local recurrence in 226 patients (42%). Chemoradiotherapy before exenteration was associated with a significant (P < 0.05) improvement in overall 5-year cancer-specific survival for those patients with an R0 resection. Postoperative chemotherapy did not alter outcomes. CONCLUSIONS: R0 resection of the pelvic recurrence is the most significant factor affecting overall and disease-free survival. The surgery is complex and often highly morbid, and where possible patients should be given perioperative chemoradiotherapy. Further investigations are required to determine the role of adjuvant chemotherapy.

Telomere profiles and tumor-associated macrophages with different immune signatures affect prognosis in glioblastoma.

Telomere maintenance is a hallmark of cancer and likely to be targeted in future treatments. In glioblastoma established methods of identifying telomerase and alternative lengthening of telomeres leave a significant proportion of tumors with no defined telomere maintenance mechanism. This study investigated the composition of these tumors using RNA-Seq. Glioblastomas with an indeterminate telomere maintenance mechanism had an increased immune signature compared with alternative lengthening of telomeres and telomerase-positive tumors. Immunohistochemistry for CD163 confirmed that the majority (80%) of tumors with an indeterminate telomere maintenance mechanism had a high presence of tumor-associated macrophages. The RNA-Seq and immunostaining data separated tumors with no defined telomere maintenance mechanism into three subgroups: alternative lengthening of telomeres like tumors with a high presence of tumor-associated macrophages and telomerase like tumors with a high presence of tumor-associated macrophages. The third subgroup had no increase in tumor-associated macrophages and may represent a distinct category. The presence of tumor-associated macrophages conferred a worse prognosis with reduced patient survival times (alternative lengthening of telomeres with and without macrophages P=0.0004, and telomerase with and without macrophages P=0.013). The immune signatures obtained from RNA-Seq were significantly different between telomere maintenance mechanisms. Alternative lengthening of telomeres like tumors with macrophages had increased expression of interferon-induced proteins with tetratricopeptide repeats (IFIT1-3). Telomerase-positive tumors with macrophages had increased expression of macrophage receptor with collagenous structure (MARCO), CXCL12 and sushi-repeat containing protein x-linked 2 (SRPX2). Telomerase-positive tumors with macrophages were also associated with a reduced frequency of total/near total resections (44% vs >76% for all other subtypes, P=0.014). In summary, different immune signatures are found among telomere maintenance mechanism-based subgroups in glioblastoma. The reduced extent of surgical resection of telomerase-positive tumors with macrophages suggests that some tumor-associated macrophages are more unfavorable.

Heart Fatty Acid Binding Protein and cardiac troponin: development of an optimal rule-out strategy for acute myocardial infarction.

BACKGROUND: Improved ability to rapidly rule-out Acute Myocardial Infarction (AMI) in patients presenting with chest pain will promote decongestion of the Emergency Department (ED) and reduce unnecessary hospital admissions. We assessed a new commercial Heart Fatty Acid Binding Protein (H-FABP) assay for additional diagnostic value when combined with cardiac troponin (using a high sensitivity assay). METHODS: H-FABP and high-sensitivity troponins I (hs-cTnI) and T (hs-cTnT) were measured in samples taken on-presentation from patients, attending the ED, with symptoms triggering investigation for possible acute coronary syndrome. The optimal combination of H-FABP with each hs-cTn was defined as that which maximized the proportion of patients with a negative test (low-risk) whilst maintaining at least 99 % sensitivity for AMI. A negative test comprised both H-FABP and hs-cTn below the chosen threshold in the absence of ischemic changes on the ECG. RESULTS: One thousand seventy-nine patients were recruited including 248 with AMI. H-FABP < 4.3 ng/mL plus hs-cTnI < 10.0 ng/L together with a negative ECG maintained >99 % sensitivity for AMI whilst classifying 40.9 % of patients as low-risk. The combination of H-FABP < 3.9 ng/mL and hs-cTnT < 7.6 ng/L with a negative ECG maintained the same sensitivity whilst classifying 32.1 % of patients as low risk. CONCLUSIONS: In patients requiring rule-out of AMI, the addition of H-FABP to hs-cTn at presentation (in the absence of new ischaemic ECG findings) may accelerate clinical diagnostic decision making by identifying up to 40 % of such patients as low-risk for AMI on the basis of blood tests performed on presentation. If implemented this has the potential to significantly accelerate triaging of patients for early discharge from the ED.