Randomized trial of a computerized coronary heart disease risk assessment tool in HIV-infected patients receiving combination antiretroviral therapy.

BACKGROUND: Exposure to combination antiretroviral therapy (cART) can lead to important metabolic changes and increased risk of coronary heart disease (CHD). Computerized clinical decision support systems have been advocated to improve the management of patients at risk for CHD but it is unclear whether such systems reduce patients' risk for CHD. METHODS: We conducted a cluster trial within the Swiss HIV Cohort Study (SHCS) of HIV-infected patients, aged 18 years or older, not pregnant and receiving cART for >3 months. We randomized 165 physicians to either guidelines for CHD risk factor management alone or guidelines plus CHD risk profiles. Risk profiles included the Framingham risk score, CHD drug prescriptions and CHD events based on biannual assessments, and were continuously updated by the SHCS data centre and integrated into patient charts by study nurses. Outcome measures were total cholesterol, systolic and diastolic blood pressure and Framingham risk score. RESULTS: A total of 3,266 patients (80% of those eligible) had a final assessment of the primary outcome at least 12 months after the start of the trial. Mean (95% confidence interval) patient differences where physicians received CHD risk profiles and guidelines, rather than guidelines alone, were total cholesterol -0.02 mmol/l (-0.09-0.06), systolic blood pressure -0.4 mmHg (-1.6-0.8), diastolic blood pressure -0.4 mmHg (-1.5-0.7) and Framingham 10-year risk score -0.2% (-0.5-0.1). CONCLUSIONS: Systemic computerized routine provision of CHD risk profiles in addition to guidelines does not significantly improve risk factors for CHD in patients on cART.

A systematic review of glomerular hyperfiltration assessment and definition in the medical literature.

BACKGROUND AND OBJECTIVES: Evaluation of glomerular hyperfiltration (GH) is difficult; the variable reported definitions impede comparisons between studies. A clear and universal definition of GH would help in comparing results of trials aimed at reducing GH. This study assessed how GH is measured and defined in the literature. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Three databases (Embase, MEDLINE, CINAHL) were systematically searched using the terms "hyperfiltration" or "glomerular hyperfiltration". All studies reporting a GH threshold or studying the effect of a high GFR in a continuous manner against another outcome of interest were included. RESULTS: The literature search was performed from November 2012 to February 2013 and updated in August 2014. From 2013 retrieved studies, 405 studies were included. Threshold use to define GH was reported in 55.6% of studies. Of these, 88.4% used a single threshold and 11.6% used numerous thresholds adapted to participant sex or age. In 29.8% of the studies, the choice of a GH threshold was not based on a control group or literature references. After 2004, the use of GH threshold use increased (P<0.001), but the use of a control group to precisely define that GH threshold decreased significantly (P<0.001); the threshold did not differ among pediatric, adult, or mixed-age studies. The GH threshold ranged from 90.7 to 175 ml/min per 1.73 m(2) (median, 135 ml/min per 1.73 m(2)). CONCLUSION: Thirty percent of studies did not justify the choice of threshold values. The decrease of GFR in the elderly was rarely considered in defining GH. From a methodologic point of view, an age- and sex-matched control group should be used to define a GH threshold.

Assessment of cytomegalovirus-specific cell-mediated immunity for the prediction of cytomegalovirus disease in high-risk solid-organ transplant recipients: a multicenter cohort study.

BACKGROUND: Cytomegalovirus (CMV) disease remains an important problem in solid-organ transplant recipients, with the greatest risk among donor CMV-seropositive, recipient-seronegative (D(+)/R(-)) patients. CMV-specific cell-mediated immunity may be able to predict which patients will develop CMV disease. METHODS: We prospectively included D(+)/R(-) patients who received antiviral prophylaxis. We used the Quantiferon-CMV assay to measure interferon-γ levels following in vitro stimulation with CMV antigens. The test was performed at the end of prophylaxis and 1 and 2 months later. The primary outcome was the incidence of CMV disease at 12 months after transplant. We calculated positive and negative predictive values of the assay for protection from CMV disease. RESULTS: Overall, 28 of 127 (22%) patients developed CMV disease. Of 124 evaluable patients, 31 (25%) had a positive result, 81 (65.3%) had a negative result, and 12 (9.7%) had an indeterminate result (negative mitogen and CMV antigen) with the Quantiferon-CMV assay. At 12 months, patients with a positive result had a subsequent lower incidence of CMV disease than patients with a negative and an indeterminate result (6.4% vs 22.2% vs 58.3%, respectively; P < .001). Positive and negative predictive values of the assay for protection from CMV disease were 0.90 (95% confidence interval [CI], .74-.98) and 0.27 (95% CI, .18-.37), respectively. CONCLUSIONS: This assay may be useful to predict if patients are at low, intermediate, or high risk for the development of subsequent CMV disease after prophylaxis. CLINICAL TRIALS REGISTRATION: NCT00817908.

Prospective assessment of trocar-specific morbidity in laparoscopy.

BACKGROUND: The purpose of the present study was to challenge the hypothetical advantage of single port laparoscopy (SPL) over conventional laparoscopy by measuring prospectively the morbidity specifically related to conventional trocar sites (TS). METHODS: From November 2010 to December 2011, 300 patients undergoing various laparoscopic procedures were enrolled. Patient, surgery, and trocar characteristics were recorded. We evaluated at three time points (in-hospital and at 1 and 6 months postoperatively) specifically for each TS, pain (Visual Analog Scale), morbidity (infection, hematoma, hernia), and cosmesis (Patient Scar Assessment Score; PSAS). Patients designated their "worst TS," and a composite endpoint "bad TS" was defined to include any adverse outcome at a TS. RESULTS: We analyzed 1,074 TS. Follow-up was >90 %. Pain scores of >3/10 at 1 and 6 months postoperatively, were reported by 3 and 1 % of patients at the 5 mm TS and by 9 and 1 % at the larger TS, respectively (5 mm TS vs larger TS; p = 0.001). Pain was significantly lower for TS located in the lower abdomen than for the upper abdomen or the umbilicus (p = 0.001). The overall complication rate was <1 % and significantly lower for the 5 mm TS (hematoma p = 0.046; infection p = 0.0001). No hernia was found. The overall PSAS score was low and significantly lower for the 5 mm TS (p = 0.0001). Significant predictors of "bad TS" were larger TS (p = 0.001), umbilical position (p = 0.0001), emergency surgery (p = 0.0001), accidental trocar exit (p = 0.022), fascia closure (p = 0.006), and specimen extraction site (p = 0.0001). CONCLUSIONS: Specific trocar morbidity is low and almost negligible for 5 mm trocars. The umbilicus appears to be an unfavorable TS.

Assessment of panobacumab as adjunctive immunotherapy for the treatment of nosocomial Pseudomonas aeruginosa pneumonia.

The fully human anti-lipopolysaccharide (LPS) immunoglobulin M (IgM) monoclonal antibody panobacumab was developed as an adjunctive immunotherapy for the treatment of O11 serotype Pseudomonas aeruginosa infections. We evaluated the potential clinical efficacy of panobacumab in the treatment of nosocomial pneumonia. We performed a post-hoc analysis of a multicenter phase IIa trial (NCT00851435) designed to prospectively evaluate the safety and pharmacokinetics of panobacumab. Patients treated with panobacumab (n = 17), including 13 patients receiving the full treatment (three doses of 1.2 mg/kg), were compared to 14 patients who did not receive the antibody. Overall, the 17 patients receiving panobacumab were more ill. They were an average of 72 years old [interquartile range (IQR): 64-79] versus an average of 50 years old (IQR: 30-73) (p = 0.024) and had Acute Physiology and Chronic Health Evaluation II (APACHE II) scores of 17 (IQR: 16-22) versus 15 (IQR: 10-19) (p = 0.043). Adjunctive immunotherapy resulted in an improved clinical outcome in the group receiving the full three-course panobacumab treatment, with a resolution rate of 85 % (11/13) versus 64 % (9/14) (p = 0.048). The Kaplan-Meier survival curve showed a statistically significantly shorter time to clinical resolution in this group of patients (8.0 [IQR: 7.0-11.5] versus 18.5 [IQR: 8-30] days in those who did not receive the antibody; p = 0.004). Panobacumab adjunctive immunotherapy may improve clinical outcome in a shorter time if patients receive the full treatment (three doses). These preliminary results suggest that passive immunotherapy targeting LPS may be a complementary strategy for the treatment of nosocomial O11 P. aeruginosa pneumonia.

Outcome of unilateral ankle arthrodesis and total ankle replacement in terms of bilateral gait mechanics.

Previous studies assessed the outcome of ankle arthrodesis (AA) and total ankle replacement (TAR) surgeries; however, the extent of postoperative recovery towards bilateral gait mechanics (BGM) is unknown. We evaluated the outcome of the two surgeries at least 2 years post rehabilitation, focusing on BGM. 36 participants, including 12 AA patients, 12 TAR patients, and 12 controls were included. Gait assessment over 50 m distance was performed utilizing pressure insoles and 3D inertial sensors, following which an intraindividual comparison was performed. Most spatiotemporal and kinematic parameters in the TAR group were indicative of good gait symmetry, while the AA group presented significant differences. Plantar pressure symmetry among the AA group was also significantly distorted. Abnormality in biomechanical behavior of the AA unoperated, contralateral foot was observed. In summary, our results indicate an altered BGM in AA patients, whereas a relatively fully recovered BGM is observed in TAR patients, despite the quantitative differences in several parameters when compared to a healthy population. Our study supports a biomechanical assessment and rehabilitation of both operated and unoperated sides after major surgeries for ankle osteoarthrosis.

Propionic acidemia: clinical course and outcome in 55 pediatric and adolescent patients.

BACKGROUND: Propionic acidemia is an inherited disorder caused by deficiency of propionyl-CoA carboxylase. Although it is one of the most frequent organic acidurias, information on the outcome of affected individuals is still limited. STUDY DESIGN/METHODS: Clinical and outcome data of 55 patients with propionic acidemia from 16 European metabolic centers were evaluated retrospectively. 35 patients were diagnosed by selective metabolic screening while 20 patients were identified by newborn screening. Endocrine parameters and bone age were evaluated. In addition, IQ testing was performed and the patients' and their families' quality of life was assessed. RESULTS: The vast majority of patients (>85%) presented with metabolic decompensation in the neonatal period. Asymptomatic individuals were the exception. About three quarters of the study population was mentally retarded, median IQ was 55. Apart from neurologic symptoms, complications comprised hematologic abnormalities, cardiac diseases, feeding problems and impaired growth. Most patients considered their quality of life high. However, according to the parents' point of view psychic problems were four times more common in propionic acidemia patients than in healthy controls. CONCLUSION: Our data show that the outcome of propionic acidemia is still unfavourable, in spite of improved clinical management. Many patients develop long-term complications affecting different organ systems. Impairment of neurocognitive development is of special concern. Nevertheless, self-assessment of quality of life of the patients and their parents yielded rather positive results.

Status epilepticus: impact of therapeutic coma on outcome.

OBJECTIVES: Therapeutic coma is advocated in guidelines for management of refractory status epilepticus; this is, however, based on weak evidence. We here address the specific impact of therapeutic coma on status epilepticus outcome. DESIGN: Retrospective assessment of a prospectively collected cohort. SETTING: Academic hospital. PATIENTS: Consecutive adults with incident status epilepticus lasting greater than or equal to 30 minutes, admitted between 2006 and 2013. MEASUREMENTS AND MAIN RESULTS: We recorded prospectively demographics, clinical status epilepticus features, treatment, and outcome at discharge and retrospectively medical comorbidities, hospital stay, and infectious complications. Associations between potential predictors and clinical outcome were analyzed using multinomial logistic regressions. Of 467 patients with incident status epilepticus, 238 returned to baseline (51.1%), 162 had new disability (34.6%), and 67 died (14.3%); 50 subjects (10.7%) were managed with therapeutic coma. Therapeutic coma was associated with poorer outcome in the whole cohort (relative risk ratio for new disability, 6.86; 95% CI, 2.84-16.56; for mortality, 9.10; 95% CI, 3.17-26.16); the effect was more important in patients with complex partial compared with generalized convulsive or nonconvulsive status epilepticus in coma. Prevalence of infections was higher (odds ratio, 3.81; 95% CI, 1.66-8.75), and median hospital stay in patients discharged alive was longer (16 d [range, 2-240 d] vs 9 d [range, 1-57 d]; p < 0.001) in subjects managed with therapeutic coma. CONCLUSIONS: This study provides class III evidence that therapeutic coma is associated with poorer outcome after status epilepticus; furthermore, it portends higher infection rates and longer hospitalizations. These data suggest caution in the straightforward use of this approach, especially in patients with complex partial status epilepticus.

External assessment of the Early Mortality Risk Score in patients with adenocarcinoma undergoing pancreaticoduodenectomy.

BACKGROUND: Pancreaticoduodenectomies (PD) still have a substantial mortality rate. Recently, different scores have been published to predict the mortality risk pre-operatively after PD. This retrospective study was designed to perform an external assessment of an Early Mortality Risk Score (EMRS). METHODS: From 2000 to 2012, all PD cases performed at our institution were documented. Only patients treated for pancreatic head adenocarcinomas were included. Survival time and EMRS (based on age, tumour size, tumour differentiation and comorbidities) were calculated for every patient. Relative risks (RR) of early death 9 and 12 months after PD were then calculated. RESULTS: Of 270 PD for various aetiologies, 120 PD for adenocarcinomas were included. The median follow-up was 37 months, and the overall median survival was 19 months. EMRS of 4 showed a mortality RR of 5.1 at 9 months (P = 0.048) and of 4.5 at 12 months (P = 0.020). CONCLUSIONS: EMRS of 4 is a predictor of tumour-related mortality at 9 and 12 months after PD for adenocarcinoma. The EMRS was externally assessed in our patient cohort and can be implemented in clinical practice. Clinical implications of this score still need to be studied.

Childhood sexual and physical abuse: age at exposure modulates impact on functional outcome in early psychosis patients.

BACKGROUND: Evidence suggests a relationship between exposure to trauma during childhood and functional impairments in psychotic patients. However, the impact of age at the time of exposure has been understudied in early psychosis (EP) patients. METHOD: Two hundred and twenty-five patients aged 18-35 years were assessed at baseline and after 2, 6, 18, 24, 30 and 36 months of treatment. Patients exposed to sexual and/or physical abuse (SPA) were classified according to age at the time of first exposure (Early SPA: before age 11 years; Late SPA: between ages 12 and 15 years) and then compared to patients who were not exposed to such trauma (Non-SPA). The functional level in the premorbid phase was measured with the Premorbid Adjustment Scale (PAS) and with the Global Assessment of Functioning (GAF) scale and the Social and Occupational Functioning Assessment Scale (SOFAS) during follow-up. RESULTS: There were 24.8% of patients with a documented history of SPA. Late SPA patients were more likely to be female (p = 0.010). Comparison with non-SPA patients revealed that: (1) both Early and Late SPA groups showed poorer premorbid social functioning during early adolescence, and (2) while patients with Early SPA had poorer functional level at follow-up with lower GAF (p = 0.025) and lower SOFAS (p = 0.048) scores, Late SPA patients did not. CONCLUSION: Our results suggest a link between exposure to SPA and the later impairment of social functioning before the onset of the disease. EP patients exposed to SPA before age 12 may present long-lasting functional impairment, while patients exposed at a later age may improve in this regard and have a better functional outcome.

Call for uniform neuropsychological assessment after aneurysmal subarachnoid hemorrhage: Swiss recommendations.

BACKGROUND: In a high proportion of patients with favorable outcome after aneurysmal subarachnoid hemorrhage (aSAH), neuropsychological deficits, depression, anxiety, and fatigue are responsible for the inability to return to their regular premorbid life and pursue their professional careers. These problems often remain unrecognized, as no recommendations concerning a standardized comprehensive assessment have yet found entry into clinical routines. METHODS: To establish a nationwide standard concerning a comprehensive assessment after aSAH, representatives of all neuropsychological and neurosurgical departments of those eight Swiss centers treating acute aSAH have agreed on a common protocol. In addition, a battery of questionnaires and neuropsychological tests was selected, optimally suited to the deficits found most prevalent in aSAH patients that was available in different languages and standardized. RESULTS: We propose a baseline inpatient neuropsychological screening using the Montreal Cognitive Assessment (MoCA) between days 14 and 28 after aSAH. In an outpatient setting at 3 and 12 months after bleeding, we recommend a neuropsychological examination, testing all relevant domains including attention, speed of information processing, executive functions, verbal and visual learning/memory, language, visuo-perceptual abilities, and premorbid intelligence. In addition, a detailed assessment capturing anxiety, depression, fatigue, symptoms of frontal lobe affection, and quality of life should be performed. CONCLUSIONS: This standardized neuropsychological assessment will lead to a more comprehensive assessment of the patient, facilitate the detection and subsequent treatment of previously unrecognized but relevant impairments, and help to determine the incidence, characteristics, modifiable risk factors, and the clinical course of these impairments after aSAH.

Childhood sexual and physical abuse : age at exposure modulates impact on functional outcome in early psychosis patients

Introduction : La littérature suggère un lien entre l'exposition à des expériences traumatiques durant l'enfance et des déficits dans le niveau de fonctionnement chez des patients souffrant de psychose. Par contre, l'impact de l'âge au moment de l'exposition à ces expériences n'a pas été investigué chez des patients dans leur phase précoce de la psychose. Méthodes : Deux cents vingt-cinq patients âgés entre 18 et 35 ans ont été évalués au moment de leur entrée dans un programme thérapeutique spécialisé pour la psychose débutante (TIPP), et après 2, 6, 12, 18, 24, 30 et 36 mois de traitement. Les patients exposés à des abus sexuel et/ou physiques (SPA) ont été classifiés selon l'âge au moment de la première exposition (Early-SPA : avant 11 ans d'âge; Late-SPA : entre 12 et 15 ans d'âge) et ils ont été comparés à des patients qui n'ont jamais été exposés à une telle expérience (Non-SPA). Le niveau de fonctionnement dans la phase premorbide a été mesuré avec la Premorbid Adjustment Scale (PAS) et avec les échelles Global Assessment of Functioning (GAF) et Social and Occupational Functionning Assessment Scale (SOFAS) durant le suivi thérapeutique. Résultats : 24.8 % des patients ont été exposés à SPA. Les patients dans le groupe Late-SPA étaient plus souvent des femmes (p=0.010). Les comparaisons avec les patients dans le groupe Non-SPA ont révélé que : (1) Les patients dans le groupe Early et Late-SPA ont montré un moins bon niveau de fonctionnement social premorbide durant l'adolescence précoce, et (2) alors que les patients dans le groupe Early-SPA ont présenté un moins bon niveau de fonctionnement durant tout le suivi selon les scores de GAF (p=0.025) et SOFAS (p=0.048), les patients dans le groupe Late-SPA n'ont pas montré telles différences avec le groupe non exposé. Conclusion : Nos résultats suggèrent un lien entre l'exposition à SPA et une altération ultérieure de niveau de fonctionnement social, avant l'apparition de la maladie. Les patients dans leur phase précoce de la psychose exposés à SPA avant l'âge de 12 ans ont des altérations fonctionnelles durables, alors que les patients exposés à SPA plus tardivement semblent s'améliorer à ce niveau et montrent une meilleure capacité de récupération.

Inguinal hernias in patients of 50 years and above. Pattern and outcome

OBJECTIVE: to evaluate a one year experience with inguinal hernia repair, in patients of > 50years, with respect to the type of inguinal hernia, type of surgery, postoperative complications and recurrence. METHODS: a prospective descriptive study of patients (n=57) > 50 years operated for inguinal hernia during a one year period. Tension-free meshplasty and herniorrhaphy, using 3"x6" polypropylene mesh and 2-0 polypropylene suture, were performed in elective and emergency surgery respectively. Follow-up visits were scheduled at six weeks, three and six months postoperatively. RESULTS: the most representative age group was 61-70 years, and all patients were male. 52 (91.22%) patients had unilateral inguinal hernias, while five (8.77%) had bilateral hernias. In 50 (87.71%) patients, the hernia was uncomplicated, while seven (12.28%) patients presented with some complication such as obstruction or strangulation. Elective surgery was performed in 50 (87.71%) patients while seven (12.28%) patients were operated in emergency. Postoperatively, 50 (87.7%) patients had uneventful recovery, while seven (12.28%) patients developed some complications which were treated conservatively. Mean hospital stay was six days. One recurrence was observed and there was no peri/postoperative death. CONCLUSION: tension-free meshplasty and herniorrhaphy are safe, simple and applicable even in elderly patients after adequate pre-operative assessment and optimization. Although associated with longer hospital stay, the mortality rate is nil and complication as well as recurrence rate is low. Hence, timely repair is necessary in elderly patients even in those with comorbid conditions.

Uterine Doppler velocimetry of the uterine arteries in the second and third trimesters for the prediction of gestational outcome

PURPOSE: The aim of this longitudinal study was to investigate the value of uterine artery Doppler sonography during the second and third trimesters in the prediction of adverse pregnancy outcome in low-risk women. METHODS: From July 2011 to August 2012, a total of 205 singleton pregnant women presenting at our antenatal clinic were enrolled in this prospective study and were assessed for baseline demographic and obstetric data. They underwent ultrasound evaluation at the time of second and third trimesters, both included Doppler assessment of bilateral uterine arteries to determine the values of the pulsatility index (PI) and resistance index (RI) and presence of early diastolic notch. The endpoint of this study was assessing the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of Doppler ultrasonography of the uterine artery, for the prediction of adverse pregnancy outcomes including preeclampsia, stillbirth, placental abruption and preterm labor. RESULTS: The mean age of cases was 26.4±5.11. The uterine artery PI and RI values for both second (PI: 1.1±0.42 versus 1.53±0.59, p=0.002; RI: 0.55±0.09 versus 0.72±0.13, p=0.000 respectively) and third-trimester (PI: 0.77±0.31 versus 1.09±0.46, p=0.000; RI: 0.46±0.10 versus 0.60±0.14, p=0.010 respectively) evaluations were significantly higher in patients with adverse pregnancy outcome than in normal women. Combination of PI and RI >95th percentile and presence of bilateral notch in second trimester get sensitivity and specificity of 36.1 and 97% respectively, while these measures were 57.5 and 98.2% in third trimester. CONCLUSIONS: According to our study, it seems that uterine artery Doppler may be a valuable tool for the prediction of a variety of adverse outcomes in second and third trimesters.

Epidemiology, management and outcome of facial injuries

Dental injuries are common and the incidence of maxillofacial injuries has increased over the recent decades in Finland. Accidental injuries are the global leading cause of death among children over the age of one year and among adults under the age of 40 globally. Significant resources and costs are needed for the treatment of these patients. The prevention is the most economical way to reduce trauma rates and costs. For the prevention it is crucial to know the prevalences, incidences and risk factors related to injuries. To improve the quality of treatment, it is essential to explore the causes, trauma mechanisms and management of trauma. The above mentioned was the aim of this thesis. With a large epidemiological cohort study (5737 participants) it was possible to estimate lifetime prevalence of and risk factors for dental trauma in general population (Study I). The prevalence of dental fractures was 43% and the prevalence of dental luxations and avulsions was 14%. Male gender, a history of previous non-dental injuries, mental distress, overweight and high alcohol consumption were positively associated with the occurrence of dental injuries Study II was conducted to explore the differences in type and multiplicity of mandibular fractures in three different countries (Canada, Finland and Kuwait). This retrospective study showed that the differences in mandibular fracture multiplicity and location are based on different etiologies and demographic patterns. This data can be exploited for planning of measures to prevent traumatic facial fractures. The etiology, management and outcome of 63 pediatric skull base fracture (Study III) and 20 pediatric frontobasal fracture patients (Study IV) were explored. These retrospective studies showed that, both skull base fracture and frontobasa fracture are rare injuries in childhood and although intracranial injuries and morbidity are frequent, permanent neurological or neuropsychological deficits are infrequent. A systematic algorithm (Study V) for computer tomography (CT) image review was aimed at clinicians and radiologists to improve the assessment of patients with complex upper midface and cranial base trauma. The cohort study was cross sectional and data was collected in the Turku and Oulu University Hospitals. A novel image-reviewing algorithm was created to enhance the specificity of CT for the diagnosis of frontobasal fractures. The study showed that an image-viewing algorithm standardizes the frontobasal trauma detection procedure and leads to better control and assessment. The purpose of the retrospective subcranial craniotomy study (VI) was to review the types of frontobasal fractures and their management, complications and outcome when the fracture is approached subcranially. The subcranial approach appears to be successful and have a reasonably low complication rate. It may be recommended as the technique of choice in multiple and the most complicated frontal base fractures where the endoscopic endonasal approach is not feasible.