University Hospital Waterford

BACKGROUND: Severe, refractory obsessive-compulsive disorder (OCD) is a disabling condition. Stimulation of the subthalamic nucleus, a procedure that is already validated for the treatment of movement disorders, has been proposed as a therapeutic option. METHODS: In this 10-month, crossover, double-blind, multicenter study assessing the efficacy and safety of stimulation of the subthalamic nucleus, we randomly assigned eight patients with highly refractory OCD to undergo active stimulation of the subthalamic nucleus followed by sham stimulation and eight to undergo sham stimulation followed by active stimulation. The primary outcome measure was the severity of OCD, as assessed by the Yale-Brown Obsessive Compulsive Scale (Y-BOCS), at the end of two 3-month periods. General psychopathologic findings, functioning, and tolerance were assessed with the use of standardized psychiatric scales, the Global Assessment of Functioning (GAF) scale, and neuropsychological tests. RESULTS: After active stimulation of the subthalamic nucleus, the Y-BOCS score (on a scale from 0 to 40, with lower scores indicating less severe symptoms) was significantly lower than the score after sham stimulation (mean [+/-SD], 19+/-8 vs. 28+/-7; P=0.01), and the GAF score (on a scale from 1 to 90, with higher scores indicating higher levels of functioning) was significantly higher (56+/-14 vs. 43+/-8, P=0.005). The ratings of neuropsychological measures, depression, and anxiety were not modified by stimulation. There were 15 serious adverse events overall, including 1 intracerebral hemorrhage and 2 infections; there were also 23 nonserious adverse events. CONCLUSIONS: These preliminary findings suggest that stimulation of the subthalamic nucleus may reduce the symptoms of severe forms of OCD but is associated with a substantial risk of serious adverse events. (ClinicalTrials.gov number, NCT00169377.)

PURPOSE: The benefit of adjuvant therapy (AT) for biliary tract cancer (BTC) is unclear, with conflicting results from nonrandomized studies. We report a systematic review and meta-analysis to determine the impact of AT on survival. METHODS: Studies published between 1960 and November 2010, which evaluated adjuvant chemotherapy (CT), radiotherapy (RT), or both (CRT) compared with curative-intent surgery alone for resected BTC were included. Only tumors of the gallbladder and bile ducts were assessed. Published data were extracted and computed into odds ratios (ORs) for death at 5 years. Subgroup analyses of benefit based on lymph node (LN) or resection margin positivity (R1) were prespecified. Data were weighted by generic inverse variance and pooled using random-effect modeling. RESULTS: Twenty studies involving 6,712 patients were analyzed. There was a nonsignificant improvement in overall survival with any AT compared with surgery alone (pooled OR, 0.74; P = .06). There was no difference between gallbladder and bile duct tumors (P = .68). The association was significant when the two registry analyses were excluded. Those receiving CT or CRT derived statistically greater benefit than RT alone (OR, 0.39, 0.61, and 0.98, respectively; P = .02). The greatest benefit for AT was in those with LN-positive disease (OR, 0.49; P = .004) and R1 disease (OR, 0.36; P = .002). CONCLUSION: This analysis supports AT for BTC. Prospective randomized trials are needed to provide better rationale for this commonly used strategy. On the basis of our data, such trials could involve two active comparators rather than a no-treatment arm among patients with LN-positive or R1 disease.

INTRODUCTION: We analyzed the prevalence of cardiovascular (CV) disease in patients with rheumatoid arthritis (RA) and its association with traditional CV risk factors, clinical features of RA, and the use of disease-modifying antirheumatic drugs (DMARDs) in a multinational cross-sectional cohort of nonselected consecutive outpatients with RA (The Questionnaires in Standard Monitoring of Patients with Rheumatoid Arthritis Program, or QUEST-RA) who were receiving regular clinical care. METHODS: The study involved a clinical assessment by a rheumatologist and a self-report questionnaire by patients. The clinical assessment included a review of clinical features of RA and exposure to DMARDs over the course of RA. Comorbidities were recorded; CV morbidity included myocardial infarction, angina, coronary disease, coronary bypass surgery, and stroke. Traditional risk factors recorded were hypertension, hyperlipidemia, diabetes mellitus, smoking, physical inactivity, and body mass index. Unadjusted and adjusted hazard ratios (HRs) (95% confidence interval [CI]) for CV morbidity were calculated using Cox proportional hazard regression models. RESULTS: Between January 2005 and October 2006, the QUEST-RA project included 4,363 patients from 48 sites in 15 countries; 78% were female, more than 90% were Caucasian, and the mean age was 57 years. The prevalence for lifetime CV events in the entire sample was 3.2% for myocardial infarction, 1.9% for stroke, and 9.3% for any CV event. The prevalence for CV risk factors was 32% for hypertension, 14% for hyperlipidemia, 8% for diabetes, 43% for ever-smoking, 73% for physical inactivity, and 18% for obesity. Traditional risk factors except obesity and physical inactivity were significantly associated with CV morbidity. There was an association between any CV event and age and male gender and between extra-articular disease and myocardial infarction. Prolonged exposure to methotrexate (HR 0.85; 95% CI 0.81 to 0.89), leflunomide (HR 0.59; 95% CI 0.43 to 0.79), sulfasalazine (HR 0.92; 95% CI 0.87 to 0.98), glucocorticoids (HR 0.95; 95% CI 0.92 to 0.98), and biologic agents (HR 0.42; 95% CI 0.21 to 0.81; P < 0.05) was associated with a reduction of the risk of CV morbidity; analyses were adjusted for traditional risk factors and countries. CONCLUSION: In conclusion, prolonged use of treatments such as methotrexate, sulfasalazine, leflunomide, glucocorticoids, and tumor necrosis factor-alpha blockers appears to be associated with a reduced risk of CV disease. In addition to traditional risk factors, extra-articular disease was associated with the occurrence of myocardial infarction in patients with RA.

BACKGROUND: To date, delirium prevalence and incidence in acute hospitals has been estimated from pooled findings of studies performed in distinct patient populations. OBJECTIVE: To determine delirium prevalence across an acute care facility. DESIGN: A point prevalence study. SETTING: A large tertiary care, teaching hospital. PATIENTS: 311 general hospital adult inpatients were assessed over a single day. Of those, 280 had full data collected within the study's time frame (90%). MEASUREMENTS: Initial screening for inattention was performed using the spatial span forwards and months backwards tests by junior medical staff, followed by two independent formal delirium assessments: first the Confusion Assessment Method (CAM) by trained geriatric medicine consultants and registrars, and, subsequently, the Delirium Rating Scale-Revised-98 (DRS-R98) by experienced psychiatrists. The diagnosis of delirium was ultimately made using DSM-IV (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition) criteria. RESULTS: Using DSM-IV criteria, 55 of 280 patients (19.6%) had delirium versus 17.6% using the CAM. Using the DRS-R98 total score for independent diagnosis, 20.7% had full delirium, and 8.6% had subsyndromal delirium. Prevalence was higher in older patients (4.7% if <50 years and 34.8% if >80 years) and particularly in those with prior dementia (OR=15.33, p<0.001), even when adjusted for potential confounders. Although 50.9% of delirious patients had pre-existing dementia, it was poorly documented in the medical notes. Delirium symptoms detected by medical notes, nurse interview and patient reports did not overlap much, with inattention noted by professional staff, and acute change and sleep-wake disturbance noted by patients. CONCLUSIONS: Our point prevalence study confirms that delirium occurs in about 1/5 of general hospital inpatients and particularly in those with prior cognitive impairment. Recognition strategies may need to be tailored to the symptoms most noticed by the detector (patient, nurse or primary physician) if formal assessments are not available.

BACKGROUND: Multimorbidity affects up to one quarter of primary care populations. It is associated with reduced quality of life, an increased risk of mental health difficulties and increased healthcare utilisation. Functional decline is defined as developing difficulties with activities of daily living and is independently associated with poorer health outcomes. The aim of this systematic review was to examine the association between multimorbidity and functional decline and to what extent multimorbidity predicts future functional decline. METHODS: A systematic literature search (1990-2014) and narrative analysis was conducted. INCLUSION CRITERIA: Population; Community-dwelling adults (≥18 years), Risk; Multimorbidity defined as the presence of ≥2 chronic medical conditions in an individual, Primary outcome; Physical functional decline measured using a validated instrument, Study design; cross-sectional or cohort studies. The following databases were included: PubMed, EMBASE, CINAHL, the Cochrane Library and the International Research Community on Multimorbidity (IRCMo) publication list. Methodological quality assessment of included studies was conducted with a suitable risk of bias tool. RESULTS: A total of 37 studies were eligible for inclusion (28 cross-sectional studies and 9 cohort studies). The majority of cross-sectional studies (n = 24/28) demonstrated a consistent association between multimorbidity and functional decline. Twelve of these studies reported that increasing numbers of chronic condition counts were associated with worsening functional decline. Nine cohort studies included 14,133 study participants with follow-up periods ranging from one to six years. The majority (n = 5) found that multimorbidity predicted functional decline. Of the five studies that reported the impact of increasing numbers of conditions, all reported greater functional decline with increasing numbers of conditions. One study examined disease severity and found that this also predicted greater functional decline. Overall, cohort studies were of good methodological quality but were mixed in terms of participants, multimorbidity definitions, follow-up duration, and outcome measures. CONCLUSIONS: The available evidence indicates that multimorbidity predicts future functional decline, with greater decline in patients with higher numbers of conditions and greater disease severity. This review highlights the importance of considering physical functioning when designing interventions and systems of care for patients with multimorbidity, particularly for patients with higher numbers of conditions and greater disease severity.

BACKGROUND: Eculizumab, a humanized monoclonal antibody against complement protein C5 that inhibits terminal complement activation, has been shown to prevent complications of paroxysmal nocturnal hemoglobinuria (PNH) and improve quality of life and overall survival, but data on the use of eculizumab in women during pregnancy are scarce. METHODS: We designed a questionnaire to solicit data on pregnancies in women with PNH and sent it to the members of the International PNH Interest Group and to the physicians participating in the International PNH Registry. We assessed the safety and efficacy of eculizumab in pregnant patients with PNH by examining the birth and developmental records of the children born and adverse events in the mothers. RESULTS: Of the 94 questionnaires that were sent out, 75 were returned, representing a response rate of 80%. Data on 75 pregnancies in 61 women with PNH were evaluated. There were no maternal deaths and three fetal deaths (4%). Six miscarriages (8%) occurred during the first trimester. Requirements for transfusion of red cells increased during pregnancy, from a mean of 0.14 units per month in the 6 months before pregnancy to 0.92 units per month during pregnancy. Platelet transfusions were given in 16 pregnancies. In 54% of pregnancies that progressed past the first trimester, the dose or the frequency of use of eculizumab had to be increased. Low-molecular-weight heparin was used in 88% of the pregnancies. Ten hemorrhagic events and 2 thrombotic events were documented; both thrombotic events occurred during the postpartum period. A total of 22 births (29%) were premature. Twenty cord-blood samples were examined for the presence of eculizumab; the drug was detected in 7 of the samples. A total of 25 babies were breast-fed, and in 10 of these cases, breast milk was examined for the presence of eculizumab; the drug was not detected in any of the 10 breast-milk samples. CONCLUSIONS: Eculizumab provided benefit for women with PNH during pregnancy, as evidenced by a high rate of fetal survival and a low rate of maternal complications. (ClinicalTrials.gov number, NCT01374360.).

We present the radiographic results after flexor digitorum longus tendon transfer combined with a medial displacement calcaneal osteotomy for the treatment of posterior tibial tendon insufficiency. Eighteen patients with posterior tibial tendon insufficiency were reviewed from 12 to 26 months after surgery. The 15 women and 3 men had a mean age of 54 years (range, 38-72 years). The talar-first metatarsal and talonavicular coverage angles were measured before and after surgery on the anteroposterior weightbearing radiographs. The mean preoperative talar-first metatarsal and talonavicular coverage angles were 21 degrees (range, 3-45 degrees) and 34 degrees (range, 0-55 degrees), respectively. The mean postoperative values for these angles were 8.5 degrees (range, 0-35 degrees) and 21 degrees (range, -30-45 degrees), respectively. The mean talar-first metatarsal angle decreased from 21 degrees to 8.5 degrees, a mean improvement of 12.5 degrees, and the mean talonavicular coverage angle decreased from 34 degrees to 21 degrees, a mean improvement of 13 degrees. On the lateral weightbearing radiographs, the talar-first metatarsal angle and the distance from the medial cuneiform to the floor were measured before and after surgery. The mean preoperative values were -22 degrees (range, -10 to -40 degrees) and 9 mm (range, 1-19 mm), respectively. The mean postoperative values were -9 degrees (range, +5 to -25 degrees) and 16 mm (range, 10-28 mm), respectively. The mean talar-first metatarsal angle decreased from -22 to -9 degrees (a mean improvement of 13 degrees), and the distance from the medial cuneiform to the floor increased from 9 to 16 mm (a mean improvement of 7 mm). We conclude that the use of a combined medial displacement osteotomy of the calcaneus with a tendon transfer for treatment of posterior tibial tendon insufficiency may offset the inherent weakness of the flexor digitorum longus transfer by reducing the antagonistic deforming force of heel valgus.

Objectives: To evaluate the accuracy and reproducibility of a three-dimensional (3D) optical laser-scanning device to record the surface detail of plaster study models. To determine the accuracy of physical model replicas constructed from the 3D digital files.Design and setting: A method comparison study using 30 dental study models held in the Orthodontic Department, School of Dentistry, Cardiff University.Materials and methods: Each model was captured three-dimensionally, using a commercially available Minolta VIVID 900 non-contact 3D surface laser scanner (Konica Minolta Inc., Tokyo, Japan), a rotary stage and Easy3DScan integrating software (TowerGraphics, Lucca, Italy). Linear measurements were recorded between landmarks, directly on each of the plaster models and indirectly on the 3D digital surface models, on two separate occasions by a single examiner. Physical replicas of two digital models were also reconstructed from their scanned data files, using a rapid prototyping (RP) manufacturing process, and directly evaluated for dimensional accuracy.Results: The mean difference between measurements made directly on the plaster models and those made on the 3D digital surface models was 0.14 mm, and was not statistically significant (P = 0.237). The mean difference between measurements made on both the plaster and virtual models and those on the RP models, in the z plane was highly statistically significant (P <0.001).Conclusions: The Minolta VIVID 900 digitizer is a reliable device for capturing the surface detail of plaster study models three-dimensionally in a digital format but physical models of appropriate detail and accuracy cannot be reproduced from scanned data using the RP technique described.

BACKGROUND: Evidence suggests that schizophrenia may be a disorder with origins in early intrauterine mal-development. We have constructed a comprehensive anthropometric scale for the evaluation of dysmorphic features as an index of the nature and timing of developmental disturbance. METHOD: A detailed set of craniofacial and bodily measures was compiled and applied to 174 patients with schizophrenia and 80 matched control subjects. RESULTS: Patients had significantly higher scores on this scale and displayed multiple anomalies of the craniofacial region with an overall narrowing and elongation of the mid-face and lower face. Twelve craniofacial anomalies independently distinguished patients from controls and these variables correctly classified 95% of patients and 80% of control subjects. CONCLUSIONS: This new scale, while procedurally more exacting than the Waldrop scale, more clearly defines the topography of anomalies previously suspected in individuals with schizophrenia. These findings constitute direct evidence for disturbed craniofacial development in schizophrenia and indicate origins in the foetal period during which the characteristic human facial pattern evolves in close association with brain differentiation.

OBJECTIVE: To compare the performance of different definitions of remission in a large multinational cross-sectional cohort of patients with rheumatoid arthritis (RA). METHODS: The Questionnaires in Standard Monitoring of Patients with RA (QUEST-RA) database, which (as of January 2008) included 5,848 patients receiving usual care at 67 sites in 24 countries, was used for this study. Patients were clinically assessed by rheumatologists and completed a 4-page self-report questionnaire. The database was analyzed according to the following definitions of remission: American College of Rheumatology (ACR) definition, Disease Activity Score in 28 joints (DAS28), Clinical Disease Activity Index (CDAI), clinical remission assessed using 42 and 28 joints (Clin42 and Clin28), patient self-report Routine Assessment of Patient Index Data 3 (RAPID3), and physician report of no disease activity (MD remission). RESULTS: The overall remission rate was lowest using the ACR definition of remission (8.6%), followed by the Clin42 (10.6%), Clin28 (12.6%), CDAI (13.8%), MD remission (14.2%), and RAPID3 (14.3%); the rate of remission was highest when remission was defined using the DAS28 (19.6%). The difference between the highest and lowest remission rates was >or=15% in 10 countries, 5-14% in 7 countries, and <5% in 7 countries (the latter of which had generally low remission rates [<5.5%]). Regardless of the definition of remission, male sex, higher education, shorter disease duration, smaller number of comorbidities, and regular exercise were statistically significantly associated with remission. CONCLUSION: The use of different definitions of RA remission leads to different results with regard to remission rates, with considerable variation among countries and between sexes. Reported remission rates in clinical trials and clinical studies have to be interpreted in light of the definition of remission that has been used.

BACKGROUND: Hidradenitis suppurativa (HS) is a chronic suppurative condition which is poorly responsive to treatment and is characterized by significant morbidity. Successful treatment of HS in patients treated with infliximab for concomitant Crohn's disease has been reported. More recent reports of positive responses to infliximab [an antitumour necrosis factor (TNF)-alpha agent] in patients who have HS but not Crohn's disease are encouraging. OBJECTIVES: TNF-alpha is implicated in many inflammatory disorders and we wished to determine the efficacy of subcutaneous etanercept, a competitive inhibitor of TNF-alpha in the control of HS symptoms. METHODS: We commenced six patients with severe, recalcitrant HS on etanercept (25 mg subcutaneously twice weekly in all cases). All patients had a normal chest X-ray and negative purified protein derivative test prior to treatment and were closely monitored throughout the treatment period for signs of infection. Patients self-assessed their disease activity and completed Dermatology Life Quality Index (DLQI) questionnaires immediately before the introduction of therapy and 24 weeks later in the case of four patients, and 12 weeks later in the case of two others. All patients were asked to estimate the time lapse between commencement of treatment and initial response. RESULTS: Treatment was well tolerated by all patients with no reported adverse reactions. A marked reduction in self-reported disease activity (mean reduction of 61% at 24 weeks), in DLQI scores (mean reduction of 64% at 24 weeks) and in relapse rates occurred. All patients rated etanercept as their most effective treatment to date. CONCLUSIONS: Our results show the effectiveness of etanercept in this group of patients with particularly challenging disease. Etanercept, unlike infliximab, may be administered subcutaneously, rendering costly day-case admissions unnecessary.

PURPOSE: YouTube is a global medium used predominantly by young adults (aged 18-49 years). This study examined the quality of YouTube information regarding ACL injury and reconstruction. METHODS: YouTube was searched on the 13th of June 2015 for "ACL" and "anterior cruciate ligament" with/without associated terms of "injury", "reconstruction", and "surgery". Videos were evaluated by two independent reviewers [EF (Reviewer 1), (Reviewer 2)] using two recognized information scoring systems (Modified DISCERN (MD) 0-5 and JAMA Benchmark 0-4) and an adaptation of a score designed for written ACL information [ACL Specific Score (ASS) 0-25]. The ASS categorized scores as very good (21-25), good (16-20), moderate (11-15), poor (6-10), and very poor (0-5). Number of views/likes/dislikes, animation, and continent of origin and source (e.g., corporate/educational) were recorded. Correlation of video characteristics with number of views was examined using the analysis of variance (ANOVA) model. Agreement between reviewers was assessed by Interclass Correlation Co-efficient (ICC). RESULTS: Following a filtering process of the 964,770 identified videos, 39 videos were retained. The mean MD score was 2.3 (standard deviation (SD) ±0.9) for Reviewer 1 and 2.2 (SD ±0.9) for Reviewer 2 (ICC = 0.7). The mean JAMA score was 2.5(SD ±0.7) for Reviewer 1 and 2.3 (SD ±0.7) for Reviewer 2 (ICC = 0.8). The mean ASS was 6.3 (SD ±3.5) for Reviewer 1 and 4.6 (SD ±2.9) for Reviewer 2 (ICC = 0.9). Five videos achieved moderate score (13%), while 15 (38%) and 19 (49%) scored as poor and very poor, respectively. There was no correlation between number of views and video quality/video source for any scoring system. CONCLUSION: The majority of videos viewed on YouTube regarding ACL injury and treatment are of low quality.

Historical influences still permeate contemporary nursing practise. These are mirrored in organizational philosophies, transactional and autocratic leadership styles and disempowered staff. Whilst there is disparity amongst the theorists' definitions of leadership, there is consensus pertaining to the attributes necessary to realize effective leadership. Transformational leadership is heralded as new criterion for nurse managers, and can be achieved through training, education and professional development in key leadership competencies. To achieve a chain reaction, charismatic transformational leaders espouse intellectual stimulation and individual consideration to empower staff and enhance patient care. Nurse managers that develop and foster transformational leadership can surmount oppressive traditions and confidently navigate a complex and rapidly changing health care environment.

PURPOSE: High-dose aldesleukin (HD IL2) received FDA approval for the treatment of metastatic renal cell carcinoma (MRCC) in 1992, producing a 14% objective response rate (ORR) and durable remissions. Retrospective studies suggested that clinical and pathologic features could predict for benefit. The Cytokine Working Group conducted this prospective trial to validate proposed predictive markers of response to HD IL2. EXPERIMENTAL DESIGN: Standard HD IL2 was administered to prospectively evaluate whether the ORR of patients with mRCC with "good" predictive pathologic features based on an "integrated selection" model [ISM (e.g., clear-cell histology subclassification and carbonic anhydrase-9 (CA-9) IHC staining] was significantly higher than the ORR of a historical, unselected population. Archived tumor was collected for pathologic analysis including tumor programmed death-ligand 1 (PD-L1) expression. RESULTS: One hundred and twenty eligible patients were enrolled between June 11 and September 7; 70% were Memorial Sloan Kettering Cancer Center (New York, NY) intermediate risk, 96% had clear cell RCC, and 99% had prior nephrectomy. The independently assessed ORR was 25% (30/120, 95% CI, 17.5%-33.7%, P = 0.0014; 3 complete responses, 27 partial responses) and was higher than a historical ORR. Thirteen patients (11%) remained progression free at 3 years and the median overall survival was 42.8 months. ORR was not statistically different by ISM classification ("good-risk" 23% vs. "poor-risk" 30%; P = 0.39). ORR was positively associated with tumor PD-L1 expression (P = 0.01) by IHC. CONCLUSIONS: In this prospective, biomarker validation study, HD IL2 produced durable remissions and prolonged survival in both "good" and "poor-risk" patients. The proposed ISM was unable to improve the selection criteria. Novel markers (e.g., tumor PD L1 expression) appeared useful, but require independent validation.

AIM: The results of a study designed to investigate the predictive value of preoperative anterior chamber depth (ACD) and intraocular pressure (IOP) are reported. The relation between these factors and their effect on the reduction in IOP following phacoemulsification cataract surgery was also studied. METHODS: The ACD and IOP were prospectively measured in 103 non-glaucomatous eyes of 103 patients who underwent uneventful phacoemulsification and posterior chamber intraocular lens (PCIOL) implantation. Other data which were recorded included best corrected visual acuity, axial length, lens thickness, and severity of lens opacity. RESULTS: The ACD increased by a mean (SD) of 1.10 (0.44) mm (p<0.00001) and this increase was significantly and inversely related to preoperative ACD (r(2) = 68%; p<0.01). IOP dropped by a mean of 2.55 (1.78) mm Hg following cataract surgery (p<0.0001), and this reduction was significantly and positively related to preoperative IOP (r(2) = 56%; p<0.01), and significantly and inversely related to preoperative ACD (r(2) = 21%; p<0.01). A novel ratio, the pressure to depth (PD) ratio (preoperative IOP/preoperative ACD), was found to be significantly and positively related to the surgically induced reduction in IOP (r(2) = 73%; p<0.01), and IOP was reduced by > or =4 mm Hg in all patients with a PD ratio >7. CONCLUSION: The reduction in IOP following cataract surgery was found to be positively related to preoperative IOP, and inversely related to preoperative ACD. Furthermore, these results indicate that a novel index, the PD ratio, is strongly predictive for IOP reduction following cataract extraction, and may prove useful in surgical decision making.

DNA repair gene polymorphisms and mutations are known to influence cancer risk. We studied whether polymorphisms in DNA double strand break (DSB) repair genes are associated with epithelial ovarian cancer (EOC) risk. Up to 1,600 cases and 4,241 controls from 4 separate genetic association studies from 3 countries were genotyped for 13 single nucleotide polymorphisms (SNP) in 6 genes (BRCA1, NBS1, RAD51, RAD52, XRCC2 and XRCC3) involved in homologous recombination of DNA double strand breaks. Genotype specific risks were estimated as odds ratios (OR) by unconditional logistic regression. No association was detected between EOC risk and BRCA1 Q356R, BRCA1 P871L, RAD51 g135c, RAD51 g172t, RAD52 c2259t, NBS1 L34L, NBS1 E185Q, NBS1 A399A, NBS1 P672P, XRCC2 g4324c, XRCC2 c41657t and XRCC3 T241M. The XRCC2 R188H polymorphism was associated with a modest reduction in EOC risk: OR for heterozygotes was 0.8 (95% confidence interval [CI] = 0.7-1.0) and for rare homozygotes 0.3 (0.1-0.9). The XRCC3 a4541g polymorphism, situated in the 5'UTR, and the intronic XRCC3 a17893g polymorphism were not associated with EOC risk in general, but when the serous EOC subset only was analysed, the OR for heterozygotes for a4541g was 1.0 (0.9-1.2) and for the rare homozygotes 0.5 (0.3-0.9). For the XRCC3 a17893g polymorphism, the OR for the heterozygotes and the rare homozygotes were 0.8 (0.7-0.9) and 0.9 (0.7-1.2), respectively. In our study, some polymorphisms in XRCC2 and XRCC3 genes were associated with EOC risk. Further research on the role of these genes on epithelial ovarian cancer is warranted.

PURPOSE: To assess the risk factors for endothelial cell loss after phacoemulsification cataract surgery performed by a junior resident. SETTING: Ophthalmic teaching hospital, Dublin, Ireland. METHODS: This prospective study included 40 eyes having divide-and-conquer phacoemulsification cataract surgery by a junior resident under the supervision of an experienced surgeon. Nine variables were examined to assess the risk for corneal endothelial cell loss postoperatively. RESULTS: The mean overall endothelial cell loss was 11.6%. Longer surgery time, longer absolute and effective phaco time, higher mean ultrasound power, and higher cataract density were significantly associated with endothelial cell loss on univariate analysis. Multivariate analysis identified a grade 3 nucleus (severely dense) and long absolute phaco time as independent predictors for endothelial cell loss, with longer absolute phaco time the stronger predictor. CONCLUSIONS: Divide-and-conquer phacoemulsification cataract surgery was a safe technique in the hands of an ophthalmic trainee. This study supports advice to junior surgeons to choose cases with less dense cataracts as this will help reduce the absolute phaco time and thus minimize endothelial cell loss.

BACKGROUND: As a result of the decline in Haemophilus influenzae type b (Hib) disease caused by the widespread use of conjugate vaccines, non-type b H. influenzae will become a more important cause of H. influenzae (Hi) disease. Characterization of the clinical and epidemiologic features of non-b Hi disease is needed in the Hib vaccine era. METHODS: A prospective active surveillance study of invasive Hi disease involving pediatricians in the United Kingdom and Republic of Ireland. For the first phase of the study (October 1, 1992, to October 31, 1995) pediatricians were asked to report any child who had invasive Hi disease and who had received Hib conjugate vaccine. For the second phase of the study (November 1, 1995. To December 31, 1998) pediatricians were asked to report any child with invasive Hi disease regardless of vaccination status. RESULTS: During the study period 102 cases of invasive non-type b Hi disease and 106 cases of invasive Hib disease were reported in children who had been fully vaccinated against Hib. Children with non-type b disease were younger (16 vs. 22 months of age, P = 0.08), less likely to have meningitis and epiglottitis (P < or = 0.001) and more likely to have pneumonia and bacteremia (P < or = 0.001) than children with type b disease. For the last 2 years of the study invasive Hi disease occurring in a fully vaccinated child was more likely to be caused by a non-b strain than by a type b strain (58 vs. 38). In 1998 the incidence of non type-b Hi disease in all children <5 years of age in the UK was 1.3/100,000 as compared with an incidence of Hib disease of 0.6/100,000. The majority (88%) of non-b strains isolated in children were nontypable strains. CONCLUSIONS: Non-b Hi is a rare cause of disease in children, but in the Hib vaccine era it has become more common than type b as a cause of Hi disease in fully vaccinated children.

BACKGROUND: Patients presenting with suspected appendicitis pose a diagnostic challenge. The appendicitis inflammatory response (AIR) score has outperformed the Alvarado score in two retrospective studies. The aim of this study was to evaluate the AIR Score and compare its performance in predicting risk of appendicitis to both the Alvarado score and the clinical impression of a senior surgeon. METHODS: All parameters included in the AIR and Alvarado scores as well as the initial clinical impression of a senior surgeon were prospectively recorded on patients referred to the surgical on call team with acute right iliac fossa pain over a 6-month period. Predictions were correlated with the final diagnosis of appendicitis. RESULTS: Appendicitis was the final diagnosis in 67 of 182 patients (37 %). The three methods of assessment stratified similar proportions (~40 %) of patients to a low probability of appendicitis (p = 0.233) with a false negative rate of <8 % that did not differ between the AIR score, Alvarado score or clinical assessment. The AIR score assigned a smaller proportion of patients to the high probability zone than the Alvarado score (14 vs. 45 %) but it did so with a substantially higher specificity (97 %) and positive predictive value (88 %) than the Alvarado score (76 and 65 %, respectively). CONCLUSIONS: The AIR score is accurate at excluding appendicitis in those deemed low risk and more accurate at predicting appendicitis than the Alvarado score in those deemed high risk. Its use as the basis for selective CT imaging in those deemed medium risk should be considered.

Haemophilus influenzae type b (Hib) conjugate vaccines have proved extremely efficacious in healthy children. True Hib vaccine failures are rare. Hib conjugate vaccines were introduced for routine immunization in the United Kingdom and the Republic of Ireland in 1992. Coincident with this, active prospective and national surveillance via pediatricians, microbiologists, and public health physicians was commenced to assess the clinical and immunological factors associated with vaccine failure. During the 6 years of the study, 115 children with true vaccine failure were reported. Of the children who were vaccinated before 12 months of age, a clinical risk factor was detected in 20%, an immunological deficiency was detected in 30%, and one or both were detected in 44%. Children who were vaccinated after 12 months of age were more likely to have one or both factors (67%). Thirty percent (33 of 105) of children with true vaccine failure had a low Hib antibody response (concentration, <1.0 microg/mL) after disease, but the majority then responded to a further dose of Hib vaccine. Children who develop Hib disease despite vaccination deserve further clinical and immunological evaluation.