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Background Patients with human papillomavirus–related oropharyngeal cancers have excellent outcomes but experience clinically significant toxicities when treated with standard chemoradiotherapy (70 Gy). We hypothesized that functional imaging could identify patients who could be safely deescalated to 30 Gy of radiotherapy. Methods In 19 patients, pre- and intratreatment dynamic fluorine-18-labeled fluoromisonidazole positron emission tomography (PET) was used to assess tumor hypoxia. Patients without hypoxia at baseline or intratreatment received 30 Gy; patients with persistent hypoxia received 70 Gy. Neck dissection was performed at 4 months in deescalated patients to assess pathologic response. Magnetic resonance imaging (weekly), circulating plasma cell-free DNA, RNA-sequencing, and whole-genome sequencing (WGS) were performed to identify potential molecular determinants of response. Samples from an independent prospective study were obtained to reproduce molecular findings. All statistical tests were 2-sided. Results Fifteen of 19 patients had no hypoxia on baseline PET or resolution on intratreatment PET and were deescalated to 30 Gy. Of these 15 patients, 11 had a pathologic complete response. Two-year locoregional control and overall survival were 94.4% (95% confidence interval = 84.4% to 100%) and 94.7% (95% confidence interval = 85.2% to 100%), respectively. No acute grade 3 radiation–related toxicities were observed. Microenvironmental features on serial imaging correlated better with pathologic response than tumor burden metrics or circulating plasma cell-free DNA. A WGS-based DNA repair defect was associated with response (P = .02) and was reproduced in an independent cohort (P = .03). Conclusions Deescalation of radiotherapy to 30 Gy on the basis of intratreatment hypoxia imaging was feasible, safe, and associated with minimal toxicity. A DNA repair defect identified by WGS was predictive of response. Intratherapy personalization of chemoradiotherapy may facilitate marked deescalation of radiotherapy.

ObjectiveDespite good prognosis for patients with low-risk endometrial cancer, a small subset of women with low-grade/low-stage endometrial cancer experience disease recurrence and death. The aim of this study was to characterize clinical features and mutational profiles of recurrent, low-grade, non-myoinvasive, ‘ultra-low risk’ endometrioid endometrial adenocarcinomas.MethodsWe retrospectively identified patients with International Federation of Gynecology and Obstetrics (FIGO) stage IA endometrioid endometrial cancers who underwent primary surgery at our institution, between January 2009 and February 2017, with follow-up of ≥12 months. ‘Ultra-low risk’ was defined as FIGO tumor grade 1, non-myoinvasive, and lacking lymphovascular space invasion. Tumor-normal profiling using massively parallel sequencing targeting 468 genes was performed. Microsatellite instability was assessed using MSIsensor. DNA mismatch repair (MMR) protein proficiency was determined by immunohistochemistry.ResultsA total of 486 patients with ultra-low risk endometrioid endometrial cancers were identified: 14 (2.9%) of 486 patients developed a recurrence. Median follow-up for non-recurrent endometrioid endometrial cancers: 34 (range 12–116) months; for recurrent endometrioid endometrial cancers: 50.5 (range 20–116) months. Patients with recurrent disease were older, had lower body mass index, and were most commonly non-White (p=0.025, pPTEN and PIK3CA mutations were present in both groups. Exon 3 CTNNB1 hotspot mutations were found in 4/9 (44%) recurrent and 8/27 (30%) non-recurrent (p=0.44).ConclusionsPatients diagnosed with ultra-low risk endometrioid endometrial cancers have an overall excellent prognosis. However, in our study, 2.9% of patients with no identifiable clinical or pathologic risk factors developed recurrence. Further work is warranted to elucidate the mechanism for recurrence in this population.

Objective To determine whether COVID‐19 may adversely affect outcome of myocardial infarction (MI) patients in Hong Kong, China. Background The COVID‐19 pandemic has infected thousands of people and placed enormous stress on healthcare system. Apart from being an infectious disease, it may affect human behavior and healthcare resource allocation which potentially cause treatment delay in MI. Methods This was a single center cross‐sectional observational study. From November 1, 2019 to March 31, 2020, we compared outcome of patients admitted for acute ST‐elevation MI (STEMI) and non‐ST elevation MI (NSTEMI) before (group 1) and after (group 2) January 25, 2020 which was the date when Hong Kong hospitals launched emergency response measures to combat COVID‐19. Results There was a reduction in daily emergency room attendance since January 25, 2020 (group 1,327/day vs. group 2,231/day) and 149 patients with diagnosis of MI were included into analysis (group 1 N = 85 vs. group 2 N = 64). For STEMI, patients in group 2 tended to have longer symptom‐to‐first medical contact time and more presented out of revascularization window (group 1 27.8 vs. group 2 33%). The primary composite outcome of in‐hospital death, cardiogenic shock, sustained ventricular tachycardia or fibrillation (VT/VF) and use of mechanical circulatory support (MCS) was significantly worse in group 2 (14.1 vs. 29.7%, p = .02). Conclusions More MI patients during COVID‐19 outbreak had complicated in‐hospital course and worse outcomes. Besides direct infectious complications, cardiology community has to acknowledge the indirect effect of communicable disease on our patients and system of care.

Equid herpesvirus type 1 (EHV-1) is a common viral infection associated with varied clinical outcomes including respiratory disease, abortion and neurological disease. We have characterized EHV-1 sequences (n = 38) obtained from cases of equine abortion in Poland between 1999 and 2016, based on sequencing of PCR products from open reading frames (ORF) 30 and 68 of the EHV-1 genome. The majority (81.6%) of sequences were not classified into any of the previously described groups based on the ORF68 sequence. The remaining sequences belonged to ORF68 group III (7.9%) or IV (10.5%). A haplotype network analysis did not show any obvious structure within networks of local Polish sequences, nor within a global network of 215 EHV-1 sequences when these networks were coloured based on the geographical origin of viruses or date of detection. Our data suggest that ORF68 does not provide a reliable molecular marker for epidemiological studies of EHV-1, at least in a global sense. Its usefulness to aid local investigations of individual outbreaks remains to be established. All but two Polish EHV-1 sequences belonged to the ORF30 N752 genotype. The two ORF30 D752 viruses were obtained from abortion cases in 2009 and 2010. Hence, abortion cases that occurred in Poland between 1999 and 2016 were caused predominantly by EHV-1 with the ORF30 N752 genotype, with no indication of an increase in the prevalence of the ORF30 D752 variant. Electronic supplementary material The online version of this article (doi:10.1007/s00705-017-3376-3) contains supplementary material, which is available to authorized users.

Corneal collagen cross-linking therapy is a relatively new treatment for progressing corneal ectasias such as keratoconus. Here the authors discuss the case of a 22-year-old male who underwent collagen cross-linking for treatment of progressive keratoconus, who then developed a serious post operative complication of a sterile keratitis.

Objectives To describe the feasibility and safety of transcatheter aortic valve implantation (TAVI) with a visiting on-site cardiac surgery program for surgical back-up. Background Both European and American guidelines recommend institutional cardiac surgery back-up for TAVI. However, the conversion to cardiac surgery is very rare, many complications of TAVI can be managed by catheter techniques and a visiting team can also provide surgical stand-by. Therefore, the need for institutional cardiac surgery (by a surgeon who routinely performs conventional surgical valve replacement at the institution performing TAVI) has been questioned. Methods A retrospective review of consecutive TAVI cases with visiting on-site cardiac surgery was performed. Key demographic, echocardiographic, and procedural data were collected prospectively. Results A total of 97 patients (81.9 ± 6.3 years) with high-risk criteria (log Euroscore 21.6 ± 14.4, chronic renal failure 39.2%, severe systolic dysfunction 24.7%) underwent TAVI with visiting on-site cardiac surgery at our institution. Local anesthesia with or without conscious sedation was used in 94.8% of patients. Procedural technical success was 100%, with 2 episodes of tamponade (both treated with pericardiocentesis) and a 16.5% vascular complication rate (all treated conservatively or percutaneously). Thirty-day mortality was 3.1%, with 5.2% rate of stroke and 8.2% rate of major bleeding. There were no conversions to surgery. Conclusions TAVI can be done safely in the setting of a hospital with visiting on-site cardiac surgery. This requires careful patient selection, experienced operators and surgeons in experienced centers with well-established criteria and processes of care. In this setting, it may be an option for hospitals without institutional cardiac surgery. (J Interven Cardiol 2015;28:76–81)

Objective To evaluate the 1-year clinical outcomes of patients who received the Resolute Onyx™ stent. Methods This was a single-centre, retrospective registry analysis that reviewed the clinical data from all patients who were implanted with a Resolute Onyx™ stent between March 2015 and February 2016. Clinical follow-up was performed at 1 year post-implantation. Results A total of 252 patients received a Resolute Onyx™ stent and two patients were lost to follow-up. The mean age of the cohort was 66.9 years and 113 (45.2%) had diabetes mellitus. Thirty-eight patients (15.2%) had left main disease and 73 (29.2%) had three-vessel disease. A total of 175 patients (70.0%) had small vessel disease (20 mm). The 1-year target lesion failure was 4.4% (11 of 250), cardiovascular death occurred in eight patients (3.2%), ischaemia-driven target lesion revascularization was undertaken in five patients (2.0%) and stent thrombosis occurred in one patient (0.4%). Conclusion The Resolute Onyx™ stent showed a favourable 1-year clinical performance in a real-world population.

Heart failure is a growing epidemic, with more patients living longer and suffering from this disease. There is a growing segment of patients who have persistent symptoms despite pharmacologic therapy. In an era when transplants are rare, the need for devices and interventions that can assist ventricular function is paramount. This review goes through the devices used in heart failure, including left ventricular reconstruction, aortic counterpulsation, short-term mechanical circulatory support, long-term mechanical circulatory support, and right heart interventions.

The objective of this study was to determine the effects of prescription omega-3 (n-3) fatty acid ethyl esters (Omacor®) on blood pressure, plasma lipids, and inflammatory marker concentrations in patients awaiting carotid endarterectomy. Patients awaiting carotid endarterectomy (n = 121) were randomised to Omacor® or olive oil as placebo (2 g/day) until surgery (median 21 days). Blood pressure, plasma lipids, and plasma inflammatory markers were determined. There were significant decreases in systolic and diastolic blood pressure and in plasma triglyceride, total cholesterol, low density lipoprotein-cholesterol, soluble vascular cellular adhesion molecule 1, and matrix metalloproteinase 2 concentrations, in both groups. The extent of triglyceride lowering was greater with Omacor® (25%) compared with placebo (9%). Soluble E-selectin concentration was significantly decreased in the Omacor® group but increased in the placebo group. At the end of the supplementation period there were no differences in blood pressure or in plasma lipid and inflammatory marker concentrations between the two groups. It is concluded that Omacor® given at 2 g/day for an average of 21 days to patients with advanced carotid atherosclerosis lowers triglycerides and soluble E-selectin concentrations, but has limited broad impact on the plasma lipid profile or on inflammatory markers. This may be because the duration of intervention was too short or the dose of n-3 fatty acids was too low.

We present the prenatal detection of a 1p32.1p31.3 microdeletion (3.46 Mb) by array comparative genomic hybridization (CGH) associated with fetal agenesis of the corpus callosum (ACC) and cerebellar vermian hypoplasia. Analysis of cultured amniocytes showed a normal karyotype. Our observations strengthen the association between this locus and central nervous system development. In addition, the fetus reported herein underscores the importance of array CGH analysis when ACC is detected prenatally, especially when there are additional central nervous system anomalies, to search for submicroscopic imbalances which can facilitate further management and parental counselling. Moreover, the presence of urinary tract anomalies should alert the clinician to the possibility of a 1p interstitial deletion, although the absence of such does not exclude it. Further reports will help to provide more information on the long-term outcomes of individuals with such microdeletion as there are only limited data.

Giant hiatus hernia (GHH) are difficult to manage effectively. This study reports a laparoscopic, prosthesis-free technique to repair of GHH. Retrospective analysis of a prospectively populated database of a single surgeon’s experience of GHH (>30 % intrathoracic stomach) repair using a novel, uniform technique was performed. Routine postoperative endoscopy, quality of life (QOL), and Visick scoring was conducted. Surgery was conducted in 100 patients (70F, 30 M). Mean (standard deviation [SD]) age was 69.1 (±11.4), median (interquartile range) ASA was 2 (range, 2–3), and mean (SD) body mass index (BMI) was 29.1 (±4.5). Mean follow-up was 574.1 (±240.5) days. One (1 %) patient was converted to an open procedure due to technical issues. Median stay was 2.5 days (range, 2–4). One postoperative death occurred secondary to respiratory sepsis. Eight (8 %) patients had perioperative complications: 4 major (PE, non-ST elevation MI, postoperative bleed managed conservatively, infected mediastinal fluid collection); and 4 minor (pneumothorax, asymptomatic troponin leak, subacute small bowel obstruction, and urinary retention). Ninety-nine (99 %) patients had objective screening for recurrence at 3–6 months. Two (2 %) patients have had symptomatic recurrence of their hiatus hernia; both involved a recurrent fundal herniation. Another seven (7 %) had small (

Objective We sought to determine lifetime costs, morbidity, and mortality associated with varying adherence to antihypertensive and 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors (statin) therapy in a hypertensive population. Methods A model was constructed to compare costs and outcomes under three adherence scenarios: no treatment, ideal adherence, and real-world adherence. Simulated patients' characteristics matched those of participants in the Anglo-Scandinavian Cardiac Outcomes Trial–Lipid-Lowering Arm and event probabilities were calculated with Framingham Heart Study risk equations. The real-world adherence scenario employed adherence data from an observational study of a US population; risk reductions at each level of adherence were based on linear extrapolations from clinical trials. Outputs included life expectancy, frequencies of primary and secondary coronary heart disease and stroke, and direct medical costs in 2006 US$. The incremental cost per life-year gained and incremental cost per event avoided were calculated comparing the three adherence scenarios. Results Mean life expectancy was 14.73 years (no-treatment scenario), 15.07 (real-world adherence), and 15.49 (ideal adherence). The average number of cardiovascular events per patients was 0.738 (no treatment), 0.610 (real-world adherence), and 0.441 (ideal adherence). The incremental cost of real-world adherence versus no treatment is $30,585 per life-year gained, and ideal adherence versus real-world adherence is $22,121 per life-year gained. Conclusions Hypertensive patients taking antihypertensive and statin therapy at real-world adherence levels can be expected to receive approximately 50% of the potential benefit seen in clinical trials. Depending on its cost, the incremental benefits of an effective adherence intervention program could make it an attractive value.

Background: Many older individuals have concomitant hypertension and dyslipidaemia — two conditions that, together with age, increase the risk of adverse cardiovascular events. Adherence to antihypertensive (AH) and lipid-lowering (LL) therapy is therefore particularly important in older patients with concomitant hypertension and dyslipidaemia. Objective: To determine patterns and predictors of adherence to concomitant AH and LL therapy among an older Medicare-eligible population. Methods: Enrolees (n = 4052) aged ≥65 years who initiated treatment with both AH and LL therapy within a 90-day period were studied in this retrospective cohort study conducted in a US managed care organization. Adherence to AH and LL medications was measured as the proportion of days covered by any AH and/or LL medication in each 3-month interval, from the start of concomitant therapy for up to 36 months (mean follow-up 19.5 months). In each interval, patients were considered ‘adherent’ to AH and LL therapy if they had filled prescriptions sufficient to cover ≥80% of days with both medication classes. A multivariable regression model evaluated potential predictors of adherence to concomitant therapy, including patient demographics, clinical characteristics and health services use patterns at baseline. Results: The percentage of patients adherent to both AH and LL therapy declined rapidly, before stabilizing, with 40.5%, 32.7% and 32.9% adherent at 3, 6 and 12 months, respectively. At each timepoint, an additional 27.8–35.0% of patients were adherent to either AH or LL therapy, but not both. Adherence was on average greater to AH than LL therapy. After adjusting for age, sex and other potential predictors, patients were more likely to be adherent if AH/LL therapies were initiated closer together in time (adjusted odds ratio [AOR] 1.13 for 0–30 days vs 61–90 days, p = 0.0563), had a history of cardiovascular disease (AOR 1.27, p = 0.0004), took fewer additional medications (AOR 0.43 for six or more medications vs zero or one medication, p < 0.0001) or had more outpatient physician visits in the prior year (AOR 1.26 for four to six visits vs zero to one visit, p < 0.0027). Conclusion: Adherence to concomitant AH and LL therapy among older adults is poor. Modifiable factors that may improve adherence in Medicare-eligible patients include initiating therapy concurrently and reducing patients’ overall pill burden.

To analyse 2-year hospitalization and cost data collected during a prospective, double-blind, randomized, controlled trial comparing amlodi-pine, enalapril and placebo in normotensive patients with coronary artery disease (CAD). All patients who were enrolled in the CAMELOT study were included in this economic substudy. Patients with CAD and normal blood pressure were randomized to amlodipine, enalapril or placebo, and followed up for 24 months (between 1999 and 2004). Data on hospitalizations and medication use were obtained from the clinical trial. Costs were assigned from secondary sources. Total costs ($US, year 2004 values) were estimated as the sum of costs associated with cardiovascular hospitalizations, study medications and concomitant cardiovascular medications. Costs and resource use were analysed by treatment arm overall and for selected patient subgroups. Cost differences were evaluated using nonparametric bootstrap techniques. Of 1991 patients enrolled, 663 were treated with amlodipine, 673 were treated with enalapril and 655 were treated with placebo. Significantly fewer patients were hospitalized for cardiovascular reasons in the amlodipine group (16.4%) than in the placebo group (22.7%;p < 0.01), but not compared with the enalapril group (20.1%;p = 0.09). The amlodipine group also had numerically fewer days in hospital per patient (1.1) than the enalapril (1.3) and placebo (1.5) groups. Mean 2-year per-patient costs in the amlodipine group were estimated to be $US609 and $US717 lower than for the placebo and enalapril groups, respectively. These results suggest that use of amlodipine may reduce costs of care among CAD patients with normal blood pressure.

The authors examined treatment rates in managed‐care patients with hypertension (HTN) only or dyslipidemia (DYS) only compared with patients who had both (HTN+DYS). A retrospective, cross‐sectional claims analysis was performed in a 2002 US national managed‐care database of 1.23 million continuously eligible members aged 18 years or older. Median age was 44.0 years, 8.8% were aged 65 years or older, and 53.2% were women. Study criteria identified 354,324 patients, 32.9% with HTN only, 34.7% with DYS only, and 32.4% with HTN+DYS. Overall, 49.7% of HTN patients had DYS and 48.3% of DYS patients had HTN. Patients with HTN+DYS were significantly older, more likely to have cardiovascular comorbidities, and more likely to use medications and hospital facilities than were patients with HTN only or DYS only (P

NCEP ATP III (National Cholesterol Education Program Adult Treatment Panel III) guidelines recommend that for patients at high risk for cardiovascular disease (CVD), lipid-lowering therapy should be considered even at relatively low cholesterol levels (low-density lipoprotein-cholesterolor=100 mg/dL). Furthermore, the ASCOT-LLA (Anglo-Scandinavian Cardiac Outcomes Trial-Lipid-Lowering Arm) has demonstrated the importance of statin therapy in the primary prevention of major cardiovascular events in people with hypertension andor=3 cardiovascular risk factors with total cholesterol levels ofor=250 mg/dL (or=6.5 mmol/L).To analyze the utilization of antihypertensive and lipid-lowering medications, and associated rates of BP and cholesterol goal attainment, in the primary prevention of CVD among patients with hypertension.Retrospective cross-sectional analysis of data from outpatient medical records (including BP, co-morbidities, and medications) abstracted for visits between 1 October 2001 and 30 September 2003 to the Atlanta Veterans Affairs Medical Center (VAMC). Patients were tracked for at least 1 year.Veterans newly diagnosed with hypertension, with lipid levelsor=240 mg/dL (or=6.2 mmol/L) and no prior coronary heart disease, and who were seeking care at the VAMC were included in the analysis. Patients were grouped by the presence of3 oror=3 cardiovascular risk factors in addition to hypertension.The frequency of utilizing antihypertensive and lipid-lowering medications, and attainment of BP targets were assessed based on the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7) guidelines (140/90 mm Hg, or130/80 mm Hg for patients with diabetes mellitus or chronic kidney disease) and a ratio of total cholesterol/high-density lipoprotein-cholesterol (HDL-C)6.A total of 7839 veterans were included. Mean age was 58.7+/-13.2 years, and 93.8% were men. Among patients withor=3 cardiovascular risk factors, 81.9% received any antihypertensive medication and 60.4% were prescribed multiple antihypertensive agents compared with 69.7% and 44.3% of patients, respectively, in the group with3 cardiovascular risk factors. Lipid-lowering medications were prescribed to 55.3% of patients withor=3 cardiovascular risk factors, and to 33.8% of those with3 cardiovascular risk factors. Overall, 14.3% of patients met both BP and lipid targets (8.1% and 17.4% of patients withor=3 and3 cardiovascular risk factors, respectively [p0.0001]). JNC 7 goals were attained in 27.9% of patients withor=3 cardiovascular risk factors and 41.7% of those with3 cardiovascular risk factors (p0.001). Total cholesterol/HDL-C ratio6 was achieved by 32.3% of patients withor=3 cardiovascular risk factors and 52.1% of those with3 cardiovascular risk factors (p0.001).Veterans withor=3 risk factors for CVD were treated more intensively, but levels of goal attainment were lower compared with patients with3 cardiovascular risk factors. Our results suggest that the therapeutic strategies used by physicians in the Atlanta VAMC need to be adapted in order to improve lipid goal attainment among patients with hypertension, and thereby further reduce the risk of cardiovascular events.

Hypertension and hypercholesterolemia are important modifiable risk factors for cardiovascular disease (CVD). We examined the prevalence, treatment, and control of combined hypertension and hypercholesterolemia in United States adults agedor=20 years (n=2,864, projected to 118 million, 52% women) from the National Health and Nutrition Examination Survey 2001 to 2002 by gender, age group, ethnicity, and co-morbidities (metabolic syndrome, diabetes mellitus [DM], and preexisting CVD). Hypertension was defined as blood pressure ofor=140/90 mm Hg (or=130/80 mm Hg if DM was present) or on treatment. Hypercholesterolemia was defined as a low-density lipoprotein cholesterol level ofor=130 mg/dl (or=100 mg/dl if DM or CVD was present) or on treatment. The overall prevalence of hypertension, hypercholesterolemia, and hypertension and hypercholesterolemia combined was 30%, 47%, and 18%, respectively. The incidence of the 2 combined was 20% in women versus 16% in men (p0.05), ranging from 1.9% in those aged 20 to 29 years to 56% in those agedor=80 years (p0.001). Combined hypertension and hypercholesterolemia was least prevalent in Hispanics (9.8% compared with 19% in whites and 22% in African-Americans, p0.01) and highest in those with CVD plus DM or metabolic syndrome (69%), CVD only (44%), DM only (41%), and metabolic syndrome only (37%). Of those with combined hypertension and hypercholesterolemia, 29% were being treated (8.3% in those aged 20 to 29 years to 38% in those aged 70 to 79 years, p0.01). Treatment was least prevalent in Hispanics (12% vs 24% in African-Americans and 30.4% in whites, p0.01). Overall control of hypertension and hypercholesterolemia was only 9% and was low in all disease groups (5.5% to 16%). In conclusion, treatment and control of combined hypertension and hypercholesterolemia are suboptimal. Increased efforts to improve treatment of these conditions are needed.

The relative efficacy of long-acting calcium channel antagonists and angiotensin II receptor blocking agents has been described in clinical trials; however, their effectiveness in an actual practice setting has not been well studied. This study assessed the effectiveness of 2 commonly prescribed antihypertensives, amlodipine and losartan, either as monotherapy or as add-on for patients insufficiently controlled on beta-blocker or diuretic therapy. This was a retrospective, observational study that utilized electronic medical records. Hypertensive patients more than 40 years old who were new users of amlodipine or losartan were included in the study. Patients with congestive heart failure or those using antihypertensives other than diuretics or beta-blockers were excluded. Blood pressure (BP) readings were followed up to 6 months after enrollment. Univariate and multivariate regression models were used to assess the impact of amlodipine or losartan therapy on hemodynamic end points and on JNC-VI BP stage. A total of 346 patients met the entry criteria. Of these, 275 (79.5%) amlodipine and 71 (20.5%) were prescribed losartan. Mean changes in systolic and diastolic blood pressure were greater for patients receiving amlodipine in univariate and multivariate analyses (reduction of 20/8 and 11/4 mm Hg, respectively; P

Background The objective of this retrospective observational analysis is to examine the clinical effectiveness of amlodipine besylate as monotherapy or in combination with other antihypertensive drugs (AHDs) in systolic blood pressure (BP) control and BP goal attainment, according to the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC) 6, JNC 7, and American Diabetes Association (ADA)recommendations, within a multicenter ambulatory care setting. Methods Hypertensive adults (n = 1175) were identified during a 4-year period (1998 to 2001) from a large commercially available electronic medical record (EMR) database. Patients were required to have initiated therapy with amlodipine and have at least one BP measurement within 6 months before, and 12 months after, the medication start date. Patients were divided into cohorts based on the number of AHDs used before, and continued through, the initiation of amlodipine. Mean change in systolic BP was compared from pre- to post-amlodipine, and adjusted change in systolic BP was calculated using multivariate regression. The percentage of patients attaining BP goal was also calculated. Results In the order of increasing number of AHDs before initiation of amlodipine (0, 1, 2, ≥3 previous AHDs): adjusted systolic BP change in mm Hg was −16.1 (95% confidence interval [CI]: −17.9, −14.3), −17.6 (95% CI: −19.6, −15.5), −16.7 (95% CI: −19.0, −14.5), and −15.7 (95% CI: −18.7, −12.8), respectively; BP goal attainment was 39%, 45%, 41%, and 45%, respectively. Amlodipine initiation in all regimens showed statistically significant incremental systolic BP reduction and BP goal attainment from baseline (P Conclusions This study suggests that amlodipine besylate is effective alone or as an add-on therapy to diverse classes of agents.

5-Fluorouracil (5-FU) and its pro-drug Capecitabine have been widely used in treating colorectal cancer. However, not all patients will respond to the drug, hence there is a need to develop reliable early predictive biomarkers for 5-FU response. Here, we report a novel potentially functional Single Nucleotide Polymorphism (pfSNP) approach to identify SNPs that may serve as predictive biomarkers of response to 5-FU in Chinese metastatic colorectal cancer (CRC) patients. 1547 pfSNPs and one variable number tandem repeat (VNTR) in 139 genes in 5-FU drug (both PK and PD pathway) and colorectal cancer disease pathways were examined in 2 groups of CRC patients. Shrinkage of liver metastasis measured by RECIST criteria was used as the clinical end point. Four non-responder-specific pfSNPs were found to account for 37.5% of all non-responders (P

Objective: To identify methylated genes in serum with diagnostic potentials for early colorectal cancer (CRC).Methods: Serum methylation levels of up to 12 genes were measured in two sets of serum samples with the second set from 26 stage I CRC patients and 26 age/gender-matched controls.Results: Serum methylation levels of TAC1, SEPT9, and EYA4 were significant discriminants between stage I CRC and healthy controls. Combination of TAC1 and SEPT9 rendered 73.1% sensitivity with 92.3% specificity.Conclusion: Serum methylation levels of TAC1. SEPT9 and EYA4 may be useful biomarkers for early detection of CRC though a validation study is necessary.

Introduction Paravalvular leak (PVL) after percutaneous transcatheter aortic valve replacement (TAVR) is associated with significant morbidity and mortality. Percutaneous PVL closure has been reported for balloon-expandable valves but not self-expandable valves. Methods We conducted a review of cases at our center where patients who received TAVR with self-expandable valves and went on to develop severe PVL underwent percutaneous closure. Baseline demographic, TAVR procedural, PVL procedural, and follow-up data were collected. Results A total of five patients with severe PVL after TAVR with a self-expanding valve underwent percutaneous PVL closure. Four of five patients had a trial of balloon postdilatation after valve deployment and had significant persistent PVL. In all five patients, PVL went from moderate-severe to mild-moderate PVL. There were no adverse events. Conclusion Percutaneous PVL closure for severe PVL self-expanding valve for TAVR is a safe and efficacious procedure. Procedural technique involves transesophageal guidance, a high approach through the valve struts, deployment of an appropriate size device, and careful monitoring. This method may be part of the algorithm for severe PVL after TAVR. © 2013 Wiley Periodicals, Inc.

Objectives To determine the procedural safety, safety, and efficacy of left atrial appendage (LAA) occlusion in octogenarians. Background Elderly patients with atrial fibrillation (AF) often do not receive appropriate anticoagulation. LAA occlusion is an option for patients with AF and contraindications to anticoagulation. Not much is known about the procedural safety and clinical efficacy of LAA occlusion in the very elderly. Methods A retrospective review of LAA cases at our institution between 2002 and 2013 in patients 80 years of age or older was performed. Demographic, echocardiographic, procedural, and clinical follow-up data were collected. Results Seventy-five cases were attempted in patients 80 years of age or older (average age 83.4 ± 2.8 years, 53.3% males). Hypertension, coronary artery disease, and heart failure were present in 96, 41.3, and 36%, respectively. Mean CHADS2 and CHA2DS-VASc scores were 3.3 and 5.2. Devices used included the WATCHMAN, ACP, PLAATO, Lariat, and Coherex devices, which were attempted in 34.7, 36, 17.3, 5.3, and 5.3%, respectively. Overall procedural success, safety endpoint, and 1-year device efficacy was 90.1, 3.9, and 97.4%, respectively. Conclusion LAA closure is a safe and efficacious method of stroke prevention in the very elderly with AF. © 2013 Wiley Periodicals, Inc.

Background Reasons for race and gender differences in controlling elevated low density lipoprotein (LDL) cholesterol may be related to variations in prescribed lipid-lowering therapy. We examined the effect of lipid-lowering drug treatment and potency on time until LDL control for black and white women and men with a baseline elevated LDL. Methods We studied 3,484 older hypertensive patients with dyslipidemia in 6 primary care practices over a 4-year timeframe. Potency of lipid-lowering drugs calculated for each treated day and summed to assess total potency for at least 6 and up to 24 months. Cox models of time to LDL control within two years and logistic regression models of control within 6 months by race-gender adjust for: demographics, clinical, health care delivery, primary/specialty care, LDL measurement, and drug potency. Results Time to LDL control decreased as lipid-lowering drug potency increased (P < 0.001). Black women (N = 1,440) received the highest potency therapy (P < 0.001) yet were less likely to achieve LDL control than white men (N = 717) (fully adjusted hazard ratio [HR] 0.66 [95% CI 0.56-0.78]). Black men (N = 666) and white women (N = 661) also had lower adjusted HRs of LDL control (0.82 [95% CI 0.69, 0.98] and 0.75 [95% CI 0.64-0.88], respectively) than white men. Logistic regression models of LDL control by 6 months and other sensitivity models affirmed these results. Conclusions Black women and, to a lesser extent, black men and white women were less likely to achieve LDL control than white men after accounting for lipid-lowering drug potency as well as diverse patient and provider factors. Future work should focus on the contributions of medication adherence and response to treatment to these clinically important differences.

A previous study in 4703 patients suggested that a single-pill combination of amlodipine and atorvastatin is associated with greater adherence to therapy than a two-pill calcium channel antagonist (calcium channel blocker [CCB]) and HMG-CoA reductase inhibitor (statin) regimen. However, the impact of prior medication use on the potential adherence benefits of single-pill amlodipine/atorvastatin has not been studied.To compare adherence to single-pill amlodipine/atorvastatin versus two-pill CCB + statin regimens in a large managed care population, stratified according to prior CCB and statin use.This retrospective study was conducted among managed care enrolees in the US. Patients included in the analysis had to have a pharmacy claim for single-pill amlodipine/atorvastatin or claims for both a CCB and a statin within any 30-day window between April 2004 and April 2005. Adherence was measured over 6 months following the index date (the date of the first single-pill amlodipine/atorvastatin claim or of the claim for the second medication class for any two-pill CCB + statin regimen) as the proportion of days covered (PDC) by both CCB and statin therapy; patients were considered 'adherent' if PDC wasor =80%. Patients were divided into four cohorts based on pre-index CCB and statin use: (i) naive (CCB)/naive (statin); (ii) experienced (CCB)/naive (statin); (iii) naive (CCB)/experienced (statin); and (iv) experienced (CCB)/experienced (statin). Within each cohort, adherence was compared for patients receiving single-pill amlodipine/atorvastatin versus two-pill amlodipine + atorvastatin or other two-pill CCB + statin regimens (including amlodipine or atorvastatin but not both) at index. Multivariable logistic regression with propensity score weighting was used to adjust for covariates, including age, sex and co-morbidities.In total, 35,430 patients were included in the analysis. At month 6 (after adjusting for covariates), patients in the experienced (CCB)/naive (statin) cohort receiving single-pill amlodipine/atorvastatin were more than twice as likely to be adherent as those receiving two-pill amlodipine + atorvastatin (odds ratio [OR] 2.20; p0.0001) or other two-pill CCB + statin regimens (OR 2.75; p0.0001). Similarly, patients in the naive (CCB)/experienced (statin) cohort receiving single-pill amlodipine/atorvastatin were more likely to be adherent than those receiving two-pill amlodipine + atorvastatin (OR 1.72; p0.0001) or other two-pill CCB + statin regimens (OR 2.81; p0.0001). In contrast, in the naive (CCB)/naive (statin) cohort there was no significant difference in adherence between patients receiving single-pill amlodipine/atorvastatin versus two-pill amlodipine + atorvastatin (OR 1.00), although patients receiving single-pill amlodipine/atorvastatin were slightly more likely to be adherent than those receiving other two-pill CCB + statin regimens (OR 1.29; p0.01). In the experienced (CCB)/experienced (statin) cohort there was also no significant difference between patients receiving single-pill amlodipine/atorvastatin versus two-pill amlodipine + atorvastatin (OR 1.08), and only a slightly greater likelihood of achieving adherence to single-pill amlodipine/atorvastatin versus other two-pill CCB + statin regimens (OR 1.19; p0.01).This large retrospective study confirms previous observations that single-pill amlodipine/atorvastatin can help improve adherence versus two-pill CCB + statin regimens. However, greater improvements in adherence are likely to be observed in patients with prior experience of either CCB or statin therapy than in those either naive to, or experienced with, both therapies.

Objective To examine n −3 polyunsaturated fatty acid (PUFA) incorporation into atherosclerotic plaques and the association with plaque inflammation and stability. Methods and results Patients awaiting carotid endarterectomy ( n =121) were randomised to consume control capsules or n −3 PUFA ethyl ester capsules until surgery (median 21 days). The fatty acid compositions of plasma and carotid plaque phospholipids, plaque features, and expression of inflammatory genes were determined. The proportion of eicosapentaenoic acid (EPA) was higher ( P n −3 PUFA group. Plaques from patients in the n −3 PUFA group had fewer foam cells ( P =0.0390). There were no other differences between plaques in the two groups with regard to histological characteristics or morphology. Plaque stability was not different between the two groups. However, the EPA content of plaque phospholipids was inversely associated with plaque instability ( P =0.0209), plaque inflammation ( P =0.0108), the number of T cells in the plaque ( P =0.0097) and a summary score considering a range of plaque features ( P =0.0425). Plaques from patients who received n −3 PUFAs had significantly lower levels of mRNA for matrix metalloproteinases (MMP)-7 ( P =0.0055), -9 ( P =0.0048) and -12 ( P =0.0044) and for interleukin-6 ( P =0.0395) and intercellular adhesion molecule 1 ( P =0.0142). Conclusions Atherosclerotic plaques readily incorporate EPA. A higher plaque EPA content is associated with a reduced number of foam cells and T cells, less inflammation and increased stability.

BACKGROUND Racial disparities in hypertension control are well documented, yet the contribution of providers to these disparities remains unclear. The objective of this study was to examine whether provider management of uncontrolled hypertension differed by patient race. METHODS In a retrospective cohort of 16,881 hypertensive adults in six academic primary care practices from 1/2004 to 12/2006, we evaluated hypertension control in black vs. white patients according to expert guidelines and, among those with uncontrolled hypertension, whether antihypertensive drugs were intensified by providers. Generalized estimating equations accounted for clustering and adjusted sequentially and additively for patient, provider, and practice characteristics, as well as health-care utilization and antihypertensive medication potency. RESULTS Black patients' visits (55.5% of 132,730 visits) had a higher unadjusted odds (1.63, 95% confidence interval (CI) 1.57-1.69) of uncontrolled hypertension than white patients' visits; the fully adjusted odds ratio remained significant (1.40, CI 1.33-1.48, P < 0.001). Among 66,327 visits with uncontrolled hypertension, no intensification of antihypertensive drugs was less likely for blacks' visits before adjustment (0.80, CI 0.76-0.83, P < 0.001) but moderated in the fully adjusted model (adjusted odds ratio 0.93, CI 0.87-0.99, P < 0.05) compared with whites' visits. Accounting for provider race, intensification was more likely at black patients' visits compared with white patients' visits. CONCLUSIONS In our study, black patients had poorer hypertension control, and providers were more likely to intensify antihypertensive drugs at visits of black compared with white patients as appropriate. These data suggest that more research is needed to understand racial disparities in hypertension control.

Treatment guidelines for dyslipidemic patients have focused on lipid levels and risk assessments. However, normolipidemic patients who have multiple risk factors for cardiovascular disease may also benefit from HMG-CoA reductase inhibitor (statin) therapy.We examined the frequency of statin prescriptions in patients initiating antihypertensive drug treatment in a US managed-care setting. STUDY DESIGN AND PATIENT: This retrospective cohort study used the PharMetrics' Patient-Centric Database to identify enrollees initiating antihypertensive treatment (September 2001 to February 2004). Patients newly treated with antihypertensives and with various levels of coronary heart disease (CHD) risk (including dyslipidemia, established CHD, type 2 diabetes mellitus, and no CHD but three or more cardiovascular risk factors) were included in the study.Cumulative probability of receiving statin therapy each month after antihypertensive initiation. Multivariable logistic regression was used to identify factors associated with receiving concomitant statin therapy.Of 142 389 patients (mean age 51.7 years) newly treated with antihypertensives, 32 056 (22.5%) were prescribed statins within 1 year. The cumulative probability of being prescribed a statin increased with increasing numbers of CHD risk factors, irrespective of dyslipidemia status. After adjusting for age, sex, and other potential predictors, patients were more likely to receive statin therapy if they had a history of dyslipidemia (adjusted odds ratio [AOR] 5.68 [95% CI 5.52, 5.85]), established CHD/congestive heart failure (AOR 3.39 [95% CI 3.16, 3.63]), or three or more additional cardiovascular risk factors but no CHD (AOR 3.01 [95% CI 2.74, 3.30]).Among patients beginning antihypertensive treatment, those with established CHD or CHD risk factors were more likely to receive statins, but a substantial fraction did not fill any statin prescription. The increased use of statin therapy could benefit many hypertensive patients with additional CHD risk factors.

Purpose. The association between prescription burden and medication adherence in patients initiating antihypertensive and lipid-lowering therapy was studied. Methods. Patients enrolled in managed care organizations who initiated antihypertensive therapy coincident with lipid-lowering therapy (no more than 90 days apart) between January 1, 1997, and April 30, 2000, were eligible for inclusion. Analysis was limited to new users of antihypertensive and lipid-lowering therapy. The proportion of days covered (PDC) by antihypertensive and lipid-lowering therapy was calculated for the first year after therapy initiation; patients with a PDC of ≥80% for both drug classes were considered adherent. Prescription burden was defined as the number of prescription medications taken in the year prior to starting antihypertensive and lipid-lowering therapy. Demographic, clinical, and health-service-use variables associated with both prescription burden and medication adherence were measured using medical and pharmacy claims data from the year before initiation of antihypertensive and lipid-lowering therapy. Results. Among 5759 patients, the mean ± S.D. prescription burden was 3.6 ± 3.7 (median, 3) medications, and the mean ± S.D. PDC with antihypertensive and lipid-lowering therapy was 53.9% ± 31.9% (median, 58.5%). Among patients with 0, 1, and 2 prior medications, 41%, 35%, and 30% of patients were adherent, respectively, to antihypertensive and lipid-lowering therapy. Among patients with 10 or more prior medications, 20% were adherent. Conclusion. Among patients in a managed care database taking antihypertensive and lipid-lowering medications, adherence to those regimens became less likely as the number of prescription medications increased. The reduction in adherence with additional prescription medications was greatest in patients with the fewest preexisting prescriptions.

Although efficacious medications are available to treat hypertension and dyslipidemia, treatment adherence is often poor. This retrospective study evaluated adherence in patients newly initiating antihypertensive (AH) and lipid-lowering (LL) therapies simultaneously versus within 180 days of one another. Data were analyzed for US managed care plan enrollees initiating AH before LL (cohort 1;n = 7099), LL before AH (cohort 2; n = 3229), or AH/LL simultaneously (cohort 3; n = 5072). A multivariate model evaluated potential predictors of adherence (medication possession ratio >or= 0.80 over a bimonthly period). Percentages of patients adherent to AH/LL at 2, 6, and 12 months were as follows: 59.4%, 32.7%, and 31.3% in cohort 1; 45.0%, 30.8%, and 31.0% in cohort 2; and 75.2%, 34.4%, and 34.0% in cohort 3, respectively. After adjustment for potential confounders, patients initiating AH before LL therapy, or LL before AH therapy, were less likely to be adherent than patients prescribed both agents simultaneously (odds ratios = 0.838 and 0.691, respectively; P , 0.0001). Synchronous initiation of AH and LL therapies is an important predictor of adherence.

Hypertension (HTN) and dyslipidemia are major risk factors for coronary heart disease (CHD). In 676 (projected to 26.1 million) US persons from the National Health and Nutrition Examination Survey (NHANES) 2001-2002 with HTN, the authors estimated the preventable CHD events from statistical control of blood pressure (BP) and lipid levels. Using Framingham algorithms, the authors projected the CHD events that could be prevented from statistical control of BP, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol. If BP was controlled to nominal levels, the authors projected 19% of CHD events (37% if controlled to optimal) would be prevented. Improving lipid levels to nominal levels was estimated to prevent 27% of CHD events (62% if controlled to optimal). Combined control of BP and lipid levels to nominal levels was projected to prevent 38% of CHD events (76% if controlled to optimal). The authors' results demonstrate that combined control of BP and lipid levels may prevent the majority of CHD events in Americans with HTN.

The ASCOT-LLA and ALLHAT-LLT trials provide conflicting evidence of the efficacy of statins in decreasing cardiovascular (CV) morbidity and mortality in hypertensive patients. We performed a meta-analysis to compare the overall efficacy of statins in hypertensive and nonhypertensive patients enrolled in major randomized clinical trials. We systematically reviewed PubMed publications from 1985 onward for placebo-controlled randomized trials that examined the effect of statins on cardiac morbidity and mortality. Only trials that followed ≥1,000 patients for ≥2 years were included in the meta-analysis. Outcomes included cardiac or CV death, major coronary events, or major CV events. Pooled estimates of relative risk (RR) were calculated separately for hypertensive and nonhypertensive patients. The moderating effect of the percentage of hypertensive patients at baseline was tested using meta-regression. Besides the ASCOT-LLA and ALLHAT-LLT, 12 trials enrolling 69,984 patients met inclusion criteria. Overall, in these 12 trials, statin therapy decreased cardiac death by 24% (RR 0.76, 95% confidence interval [CI] 0.71 to 0.82). There was no evidence of difference in RR estimates for hypertensive (RR 0.78, 95% CI 0.72 to 0.84) and nonhypertensive (RR 0.76, 95% CI 0.72 to 0.80) patients. Similarly, meta-regression showed that the efficacy of statins was not moderated by the percentage of hypertensive patients at baseline (Q estimate 1.51, p = 0.22). In conclusion, statin therapy effectively decreases CV morbidity and mortality to the same extent in hypertensive and nonhypertensive patients.

This study determined the prevalence of primary prevention patients aged 40 to 79 years with uncontrolled hypertension (HTN) and low/moderate cholesterol levels, and the clinical and economic consequences of their cardiovascular risk levels stratified by additional cardiovascular risk factors. Prevalence was estimated from the 1999 to 2002 National Health and Nutrition Examination Survey (NHANES) datasets. Framingham risk equations were used to calculate the 4-year risk of coronary heart disease (CHD). HTN and cholesterol levels were then statistically "controlled" to ideal levels and risks were recalculated. Prevalence of uncontrolled hypertension was 15.2 million cases (13.7%). Of those, 12.9 million (84.8%) had low/moderate cholesterol levels, and 2.2 million (16.7%) had >/=3 additional risk factors with no history of CHD. Nearly 200,000 coronary events are expected to occur within 4 years, incurring over $2.5 billion in direct medical costs. Statistical estimation suggests that 64% of 4-year risk was attributable to uncontrolled blood pressure and lipids. The large number and high cost of CHD events expected to occur within the next 4 years in primary prevention patients with uncontrolled hypertension and >/=3 additional risk factors justifies aggressive screening to ensure that these patients are identified and properly managed.

BACKGROUND: Poorly controlled cardiovascular risk factors are common. Evaluating whether physicians respond appropriately to poor risk factor control in patients may better reflect quality of care than measuring proportions of patients whose conditions are controlled. OBJECTIVES: To evaluate therapy modifications in response to poor control of hypertension, dyslipidemia, or diabetes in a large clinical population. DESIGN: Retrospective cohort study within an 18-month period in 2002 to 2003. SETTING: Kaiser Permanente of Northern California. PATIENTS: 253,238 adult members with poor control of 1 or more of these conditions. MEASUREMENTS: The authors assessed the proportion of patients with poor control who experienced a change in pharmacotherapy within 6 months, and they defined "appropriate care" as a therapy modification or return to control without therapy modification within 6 months. RESULTS: A total of 64% of patients experienced modifications in therapy for poorly controlled systolic blood pressure, 71% for poorly controlled diastolic blood pressure, 56% for poorly controlled low-density lipoprotein cholesterol level, and 66% for poorly controlled hemoglobin A1c level. Most frequent modifications were increases in number of drug classes (from 70% to 84%) and increased dosage (from 15% to 40%). An additional 7% to 11% of those with poorly controlled blood pressure, but only 3% to 4% of those with elevated low-density lipoprotein cholesterol level or hemoglobin A1c level, returned to control without therapy modification. Patients with more than 1 of the 3 conditions, higher baseline values, and target organ damage were more likely to receive "appropriate care." LIMITATIONS: Patient preferences and suboptimal adherence to therapy were not measured and may explain some failures to act. CONCLUSIONS: As an additional measure of the quality of care, measuring therapy modifications in response to poor control in a large population is feasible. Many patients with poorly controlled hypertension, dyslipidemia, or diabetes had their therapy modified and, thus, seemed to receive clinically "appropriate care" with this new quality measure.

In this paper, a fuzzy case based reasoning approach to Web access path prediction is developed and tested. It is based on the assumption that new user's access patterns can be predicted by referencing to the behaviors of similar Web users in the past. This method has three phases. Firstly, a Web case base is constructed from the Web log data. This includes the pre-processing and cleaning of the Web log data so that a suitable format is developed. Secondly, contextual information is extracted from the Web pages, and this information is used to develop a similarity measurement between Web pages. This information is added to the Web case base. Finally, fuzzy association rule mining is used to discover the relationship between the browsing behavior (user navigations) and the Web contents using the Web case base. A set of predictive cases from the Web case base is then selected for the access path prediction. From the experimental evaluation, our approach has demonstrated better prediction accuracy than the existing approaches.

To examine challenges in forming accurate conclusions from claims data when comparing different patient groups, and to stress the need to adjust for confounding variables through application of statistical methods.Patients who were 60 or older and began amlodipine or felodipine in 1997 or 1998 were identified from a proprietary managed care claims database. Patients had 6 months of medical and outpatient pharmacy benefits coverage before and after initiating therapy. They were stratified on varying degrees of hypertension severity and on all-condition clinical complexity, and quantified with a proprietary Burden of Illness (BOI) score, defined as the expected resource use for the patient.s combined conditions during the 6 months before therapy.Of the 17,667 patients, 10,469 (59.3%) were female. The 12,389 amlodipine users were similar in age to felodipine users (n=5,278), 73 versus 74, respectively. More amlodipine users were assigned to the 2 most clinically complex quintiles of the BOI distribution (45.5% to 26.9%), with 24.3% of patients in the top quintile (9.7% for felodipine) and twice the prevalence of ischemic heart disease/angina (42.4% versus 19.4%). High-severity hypertension was found among 33.6% of amlodipine users, contrasted with 17.9% for felodipine. A significant difference in the mean average daily dose (ADD) between the amlodipine (5.93 mg) and felodipine (5.8 mg) groups (P=0.0007) was noted.These results stress the importance of assessing the impact of potentially confounding variables and the need to address differing patient characteristics through either risk adjustment or stratification in making head-to-head comparisons.

Paravalvular leak (PVL) is a seldomly covered aspect of structural heart disease. However, this is a condition that frequently presents after valvular replacement. This article will cover the diagnosising and treating PVL (i.e. imaging, access, and device selection). In addition, specific aspects of aortic and mitral PVL closure will be covered in this review.

OBJECTIVE: To evaluate the effectiveness of whole-genome array comparative genomic hybridization (aCGH) in prenatal diagnosis in Hong Kong. METHODS: Array CGH was performed on 220 samples recruited prospectively as the first-tier test study. In addition 150 prenatal samples with abnormal fetal ultrasound findings found to have normal karyotypes were analyzed as a 'further-test' study using NimbleGen CGX-135K oligonucleotide arrays. RESULTS: Array CGH findings were concordant with conventional cytogenetic results with the exception of one case of triploidy. It was found in the first-tier test study that aCGH detected 20% (44/220) clinically significant copy number variants (CNV), of which 21 were common aneuploidies and 23 had other chromosomal imbalances. There were 3.2% (7/220) samples with CNVs detected by aCGH but not by conventional cytogenetics. In the 'further-test' study, the additional diagnostic yield of detecting chromosome imbalance was 6% (9/150). The overall detection for CNVs of unclear clinical significance was 2.7% (10/370) with 0.9% found to be de novo. Eleven loci of common CNVs were found in the local population. CONCLUSION: Whole-genome aCGH offered a higher resolution diagnostic capacity than conventional karyotyping for prenatal diagnosis either as a first-tier test or as a 'further-test' for pregnancies with fetal ultrasound anomalies. We propose replacing conventional cytogenetics with aCGH for all pregnancies undergoing invasive diagnostic procedures after excluding common aneuploidies and triploidies by quantitative fluorescent PCR. Conventional cytogenetics can be reserved for visualization of clinically significant CNVs.

A 45-year-old man with primary systemic amyloidosis was found to have bilateral uveal effusions secondary to thickened sclera according to magnetic resonance imaging of the orbits. The patient was treated with bilateral sclerectomies and vortex vein decompression, and had an excellent outcome. Light microscopy of excised sclera revealed severe infiltration of the tissue by amyloid. To our knowledge, this is the first report of amyloid infiltration of the sclera leading to uveal effusion. Arch Ophthalmol. 2000;118:1293-1295

Thrombolysis remains an important reperfusion strategy for eligible patients with acute ST-segment elevation myocardial infarction (STEMI). Intracranial bleeding is a potentially fatal complication. A total of 342 Patients who received thrombolytic therapy in a University Hospital in Hong Kong for