The effect of idursulfase on growth in patients with Hunter syndrome: data from the Hunter Outcome Survey (HOS)

Hunter syndrome (mucopolysaccharidosis type II) is a rare and life-limiting multisystemic disorder with an X-linked recessive pattern of inheritance. Short stature is a prominent feature of this condition. This analysis aimed to investigate the effects of enzyme replacement therapy with idursulfase on growth in patients enrolled in HOS - the Hunter Outcome Survey which is a multinational observational database. As of Jan 2012, height data before treatment were available for 567 of 740 males followed prospectively after HOS entry. Cross-sectional analysis showed that short stature became apparent after approximately 8 years of age; before this, height remained within the normal range. Age-corrected standardized height scores (z-scores) before and after treatment were assessed using piecewise regression model analysis in 133 patients (8-15 years of age at treatment start; data available on ≥ 1 occasion within +/-24 months of treatment start; growth hormone-treated patients excluded). Results showed that the slope after treatment (slope=-0.005) was significantly improved compared with before treatment (slope=-0.043) (difference=0.038, p=0.004). Analysis of covariates (age at treatment start, cognitive involvement, presence of puberty at the start of ERT, mutation type, functional classification), showed a significant influence on growth of mutation type (height deficit in terms of z-scores most pronounced in patients with deletions/large rearrangements/nonsense mutations, p<0.0001) and age (most pronounced in the 12-15-year group, p<0.0001). Cognitive involvement, pubertal status at the start of ERT and functional classification were not related to the growth deficit or response to treatment. In conclusion, the data showed an improvement in growth rate in patients with Hunter syndrome following idursulfase treatment.

Improving Outcome After Major Surgery: Pathophysiological Considerations

Surgical and anesthesia-related techniques may reduce physical stress for patients undergoing high-risk surgery, but major surgery is increasingly performed in patients with substantial comorbidities. Strategies for improving the outcome for such patients include approaches that both increase tissue oxygen delivery and reduce metabolic demand. However, these strategies have produced conflicting results. To understand the success and failure of attempts to improve postoperative outcome, the pathophysiology of perioperative hemodynamic, metabolic, and immunological alterations should be analyzed. Our aim in this review is to provide a survey of fields of opportunities for improving outcome after major surgery. The issues are approached from 3 different angles: the view of the patient, the view of the surgical intervention, and the view of the anesthesia. Special attention is also given to what could be considered the result of the interaction among the 3: perioperative inflammation and immune response.

Survey of aspergillosis in non-neutropenic patients in Swiss teaching hospitals

Clin Microbiol Infect ABSTRACT: Invasive aspergillosis (IA) is a live-threatening opportunistic infection that is best described in haematological patients with prolonged neutropenia or graft-versus-host disease. Data on IA in non-neutropenic patients are limited. The aim of this study was to establish the incidence, disease manifestations and outcome of IA in non-neutropenic patients diagnosed in five Swiss university hospitals during a 2-year period. Case identification was based on a comprehensive screening of hospital records. All cases of proven and probable IA were retrospectively analysed. Sixty-seven patients were analysed (median age 60 years; 76% male). Sixty-three per cent of cases were invasive pulmonary aspergillosis (IPA), and 17% of these were disseminated aspergillosis. The incidence of IPA was 1.2/10?000 admissions. Six of ten cases of extrapulmonary IA affected the brain. There were six cases of invasive rhinosinusitis, six cases of chronic pulmonary aspergillosis, and cases three of subacute pulmonary aspergillosis. The most frequent underlying condition of IA was corticosteroid treatment (57%), followed by chronic lung disease (48%), and intensive-care unit stays (43%). In 38% of patients with IPA, the diagnosis was established at autopsy. Old age was the only risk factor for post-mortem diagnosis, whereas previous solid organ transplantation and chronic lung disease were associated with lower odds of post-mortem diagnosis. The mortality rate was 57%.

Infantile spasms: does season influence onset and long-term outcome?

To study whether onset of infantile spasms manifests seasonal variation, as previously reported, and whether any such seasonality is associated with treatment response and long-term outcome, data for 57 patients were retrospectively reviewed. The data were collected from hospital files and through a mail survey of children with infantile spasms born from 1980 to 2002 and monitored at the University Children's Hospital of Berne, Switzerland. The mean age at time of onset of infantile spasms was 7 months (range, 0.75-40), at diagnosis 8 months (range, 1-42) and at follow-up 11.3 years (range, 1-23 years). In 77% of participants, the etiology of infantile spasms was known (symptomatic); in the remaining 23% it was not known (nonsymptomatic). In contrast to previous findings, onset of infantile spasms was not associated with calendar month, photoperiod, or global solar radiation. Long-term prognosis was poor: 4 of the 57 (7%) children died; 49 (86%) had cognitive impairment and 40 (70%) had physical impairment; 31 (54%) had cerebral palsy, 37 had (65%) persistent seizures, and 9 (16%) had Lennox-Gastaut syndrome. Symptomatic infantile spasms were associated with worse cognitive outcome (P < 0.001), but treatment modality and overall duration of infantile spasms were not. There was no association of calendar month or photoperiod at onset with cognitive outcome or treatment response.

Use of linezolid in neonatal and pediatric inpatient facilities-results of a retrospective multicenter survey

The purpose of this investigation was to describe the use of linezolid in pediatric inpatient facilities. A retrospective multicenter survey including data from nine participating tertiary care pediatric inpatient facilities in Germany and Austria was undertaken. Data on 126 off-label linezolid treatment courses administered to 108 patients were documented. The survey comprises linezolid treatment in a broad spectrum of clinical indications to children of all age groups; the median age was 6.8 years (interquartile range 0.6-15.5 years; range 0.1-21.2 years; ten patients were older than 18 years of age but were treated in pediatric inpatient units). Of the 126 treatment courses, 27 (21%) were administered to preterm infants, 64 (51%) to pediatric oncology patients, and 5% to patients soon after liver transplantation. In 25%, the infection was related to a medical device. Linezolid iv treatment was started after intensive pre-treatment (up to 11 other antibiotics for a median duration of 14 days) and changed to enteral administration in only 4% of all iv courses. In 39 (53%) of 74 courses administered to children older than 1 week and younger than 12 years of age, the dose was not adjusted to age-related pharmacokinetic parameters. In only 17 courses (13%) was a pediatric infectious disease consultant involved in the clinical decision algorithm. Linezolid seemed to have contributed to a favorable outcome in 70% of all treatment courses in this survey. Although retrospective, this survey generates interesting data on the off-label use of linezolid and highlights several important clinical aspects in which the use of this rescue antibiotic in children might be improved.

Can level of education, accreditation and use of databases in cardiac rehabilitation be improved? Results from the European Cardiac Rehabilitation Inventory Survey

Professional skills, education and accreditation, along with clinical outcome assessment, are considered important factors to achieve comprehensive delivery and quality of cardiac rehabilitation (CR). This study assessed professional educational programmes, accreditation and use of databases in CR across the European countries.

Treatment of replacement resorption by intentional replantation, resection of the ankylosed sites, and Emdogain--results of a 6-year survey

The present clinical study investigated the outcome of intentional replantation using resection of the ankylosed sites of the root, extraoral endodontic treatment using titanium posts and Emdogain for periodontal healing following trauma-related ankylosis. During an evaluation period of 6 years, 16 ankylosed teeth affected by replacement resorption were treated as described. Evaluation parameters before treatment and during the follow-up period included Periotest scores, percussion sound and periapical radiographs. All findings were compared to those of the adjacent teeth. In a second accident, one tooth was lost after 7 months and was excluded as a dropout. Ankylosis did not recur in seven replanted teeth, which were observed for an average of 52.3 months (range: 24-68 months). Ankylosis recurred in eight teeth after an average period of 12 months (range: 4-26 months). An infraocclusion, normal or only slightly reduced Periotest scores and normal percussion sound were preoperatively found in six of seven successfully replanted teeth, which corresponded to a relatively small area of ankylosis. The majority of the teeth showing recurrent ankylosis preoperatively presented with normal position, negative Periotest scores and a high percussion sound which corresponded to an extended area of ankylosis. Statistically significant relationship between preoperative findings and the treatment outcome (P = 0.031) have become apparent. The results indicate that the treatment of minor areas of ankylosis by intentional replantation, resection of the ankylosed sites and Emdogain appeared to prevent or delay the recurrence of ankylosis in 7 of 15 teeth.

Thoracic endovascular aortic repair: impact of urgency on outcome and quality of life

OBJECTIVES: Endovascular repair of the descending thoracic aorta is a very promising technique in elective and, particularly, emergency situations. This study assessed the impact of urgency of the procedure on outcome and mid-term quality of life in surviving patients. METHODS: Post hoc analysis of prospectively collected data of 58 consecutive patients (January 2001-December 2005) with surgical pathologies of the descending thoracic aorta treated by endovascular means. Six patients were excluded due to recent operations on the ascending aorta before thoracic endovascular repair. The remaining patients (n=52) were 69+/-10 years old, and 43 were men (83%). Twenty-seven had been treated electively, and 25 for emergency indications. Reasons for emergency were acute type B aortic dissections with or without malperfusion syndrome in 14, and aortic ruptures in 11 cases. Follow-up was 29+/-16 months. Endpoints were perioperative and late morbidity and mortality rates and long-term quality of life as assessed by the short form health survey (SF-36) and Hospital Anxiety and Depression Scale questionnaires. RESULTS: Cohorts were comparable regarding age, sex, cardiovascular risk factors, and comorbidities. Perioperative mortality was somewhat higher in emergency cases (12% vs 4%, p=0.34). Paraplegia occurred in one patient in each cohort (4%). Overall quality of life after two and a half years was similar in both treatment cohorts: 72 (58-124) after emergency, and 85 (61-105) after elective endovascular aortic repair (p=0.98). Normal scores range from 85 to 115. Anxiety and depression scores were in the normal range and comparable. CONCLUSIONS: Thoracic endovascular aortic repair is an excellent and safe treatment option for the diseased descending aorta, particularly in emergency situations. Early morbidity and mortality rates can be kept very low. Mid-term quality of life was not affected by the urgency of the procedure. Similarly, mid-term anxiety and depression scores were not increased after emergency situations.

Outcome and quality of life after surgical and endovascular treatment of descending aortic lesions

BACKGROUND: Thoracic endovascular aortic repair (TEVAR) represents an attractive alternative to open aortic repair (OAR). The aim of this study was to assess outcome and quality of life in patients treated either by TEVAR or OAR for diseased descending thoracic aorta. METHODS: A post hoc analysis of a prospectively collected consecutive series of 136 patients presenting with surgical diseases of the descending aorta between January 2001 and December 2005 was conducted. Fourteen patients were excluded because of involvement of the ascending aorta. Assessed treatment cohorts were TEVAR (n = 52) and OAR (n = 70). Mean follow-up was 34 +/- 18 months. End points were perioperative and late mortality rates and long-term quality of life as assessed by the Short Form Health Survey (SF-36) and Hospital Anxiety and Depression Score questionnaires. RESULTS: Mean age was significantly higher in TEVAR patients (69 +/- 10 years versus 62 +/- 15 years; p = 0.002). Perioperative mortality rates were 9% (OAR) and 8% (TEVAR), respectively (p = 0.254). Accordingly, cumulative long-term mortality rates were similar in both cohorts. Overall quality-of-life scores were 93 (63-110, OAR) and 83 (60-112, TEVAR), respectively. Normal quality-of-life scores range from 85 to 115. Anxiety and depression scores were not increased after open surgery. CONCLUSIONS: Thoracic endovascular aortic repair and OAR both provide excellent long-term results in treatment of thoracic aortic disease. Long-term quality of life, however, is reduced after thoracic aortic repair. Interestingly, TEVAR patients did not score higher in overall quality of life despite all advantages of minimized access trauma. Similarly, anxiety and depression scores are not reduced by TEVAR, possibly reflecting a certain caution against the new technology.

Outcome and quality of life in patients treated for abdominal aortic aneurysms: a single center experience

BACKGROUND: Durability of protection and long-term quality of life (QoL) are critical outcome parameters of abdominal aortic aneurysm (AAA) repair. The aim of the present study was to compare results of endovascular and open aneurysm repair (EVAR and OR) with adjusted standard populations, including stratification for urgency of presentation. METHODS: Retrospective analysis of prospectively collected data of 401 consecutive patients presenting with AAA between January 1998 and December 2002. Cross-sectional follow up was 58 +/- 29 months. Patients were grouped into three cohorts: elective EVAR (n = 68), elective OR (n = 244), and emergency OR (including symptomatic and ruptured AAA, n = 89). Endpoints were perioperative (i.e., 30 days or in-hospital) and late mortality rates, as well as long-term QoL as assessed by the Short Form health survey questionnaire (SF-36). RESULTS: Mean age was lower in the elective OR cohort (66 +/- 10 years) than in the EVAR cohort (72 +/- 7 years; p < .05). Perioperative mortality rates were 4.4%, 0.4%, and 10.1%, for the EVAR, elective OR, and emergency OR cohorts, respectively (p < .05). Corresponding cumulative survival rates after 4 years were 67%, 89%, and 69%, respectively. Long-term QoL SF-36 scores were in all cohorts similar to age- and gender-adjusted standard populations, which score between 85 and 115: 99.6 +/- 35.8 (EVAR), 101.3 +/- 32.4 (elective OR), and 100.4 +/- 36.5 (emergency OR). CONCLUSIONS: Long-term QoL is not permanently impaired after AAA repair, but returns in long-term survivors to what would be expected in a standard population. In this respect, differences were found neither between EVAR and OR, nor between elective and emergency repair. Perioperative mortality rates were highest in patients undergoing emergency OR. The outlook for such patients after the perioperative period, however, was similar to that for patients undergoing elective repair.

Arterial access through the right subclavian artery in surgery of the aortic arch improves neurologic outcome and mid-term quality of life

BACKGROUND: We have shown that selective antegrade cerebral perfusion improves mid-term quality of life in patients undergoing surgical repair for acute type A aortic dissection and aortic aneurysms. The aim of the study was to assess the impact of continuous cerebral perfusion through the right subclavian artery on immediate outcome and quality of life. METHODS: Perioperative data of 567 consecutive patients who underwent surgery of the aortic arch using deep hypothermic circulatory arrest have been analyzed. Patients were divided into three groups, according to the management of cerebral protection. Three hundred eighty-seven patients (68.3%) had deep hypothermic circulatory arrest with pharmacologic protection with pentothal only, 91 (16.0%) had selective antegrade cerebral perfusion and pentothal, and 89 (15.7%) had continuous cerebral perfusion through the right subclavian artery and pentothal. All in-hospital data were assessed, and quality of life was analyzed prospectively 2.4 +/- 1.2 years after surgery with the Short Form-36 Health Survey Questionnaire. RESULTS: Major perioperative cerebrovascular injuries were observed in 1.1% of the patients with continuous cerebral perfusion through the right subclavian artery, compared with 9.8% with selective antegrade cerebral perfusion (p < 0.001) and 6.5% in the group with no antegrade cerebral perfusion (p = 0.007). Average quality of life after an arrest time between 30 and 50 minutes with continuous cerebral perfusion through the right subclavian artery was significantly better than selective antegrade cerebral perfusion (90.2 +/- 12.1 versus 74.4 +/- 40.7; p = 0.015). CONCLUSIONS: Continuous cerebral perfusion through the right subclavian artery improves considerably perioperative brain protection during deep hypothermic circulatory arrest. Irreversible perioperative neurologic complications can be significantly reduced and duration of deep hypothermic circulatory arrest can be extended up to 50 minutes without impairment in quality of life.

Psychosocial outcome in cardiovascular rehabilitation of peripheral artery disease and coronary artery disease patients

We investigated patients with a primary diagnosis of peripheral artery disease (n = 69) and coronary heart disease (CAD; n = 520) at baseline and on changes in psychosocial risk factors (depression, anxiety, quality of life, negative and positive affect) during a cardiovascular rehabilitation program. Patients completed psychosocial questionnaires at the beginning and at discharge of a 12-week rehabilitation program. Depression and anxiety were measured with the Hospital Anxiety and Depression Scale (HADS), positive and negative affect with the Global Mood Scale, and health-related quality of life with the SF-36 Health Survey. Patients with PAD showed improvements in anxiety (p < 0.001), negative affect (p < 0.001) and bodily pain (p < 0.001). Patients with CAD reported significant improvements in all measured dimensions (all p-values < 0.001).

Non-ignorable loss to follow-up: correcting mortality estimates based on additional outcome ascertainment

Loss to follow-up (LTFU) is a common problem in many epidemiological studies. In antiretroviral treatment (ART) programs for patients with human immunodeficiency virus (HIV), mortality estimates can be biased if the LTFU mechanism is non-ignorable, that is, mortality differs between lost and retained patients. In this setting, routine procedures for handling missing data may lead to biased estimates. To appropriately deal with non-ignorable LTFU, explicit modeling of the missing data mechanism is needed. This can be based on additional outcome ascertainment for a sample of patients LTFU, for example, through linkage to national registries or through survey-based methods. In this paper, we demonstrate how this additional information can be used to construct estimators based on inverse probability weights (IPW) or multiple imputation. We use simulations to contrast the performance of the proposed estimators with methods widely used in HIV cohort research for dealing with missing data. The practical implications of our approach are illustrated using South African ART data, which are partially linkable to South African national vital registration data. Our results demonstrate that while IPWs and proper imputation procedures can be easily constructed from additional outcome ascertainment to obtain valid overall estimates, neglecting non-ignorable LTFU can result in substantial bias. We believe the proposed estimators are readily applicable to a growing number of studies where LTFU is appreciable, but additional outcome data are available through linkage or surveys of patients LTFU. Copyright © 2013 John Wiley & Sons, Ltd.