Georges Van Maele

Azithromycin for prevention of exacerbations in severe asthma (AZISAST): a multicentre randomised double-blind placebo-controlled trial

Background Patients with severe asthma are at increased risk of exacerbations and lower respiratory tract infections (LRTI). Severe asthma is heterogeneous, encompassing eosinophilic and non-eosinophilic (mainly neutrophilic) phenotypes. Patients with neutropilic airway diseases may benefit from macrolides. Methods We performed a randomised double-blind placebo-controlled trial in subjects with exacerbation-prone severe asthma. Subjects received low-dose azithromycin (n=55) or placebo (n=54) as add-on treatment to combination therapy of inhaled corticosteroids and long-acting β2 agonists for 6 months. The primary outcome was the rate of severe exacerbations and LRTI requiring treatment with antibiotics during the 26-week treatment phase. Secondary efficacy outcomes included lung function and scores on the Asthma Control Questionnaire (ACQ) and Asthma Quality of Life Questionnaire (AQLQ). Results The rate of primary endpoints (PEPs) during 6 months was not significantly different between the two treatment groups: 0.75 PEPs (95% CI 0.55 to 1.01) per subject in the azithromycin group versus 0.81 PEPs (95% CI 0.61 to 1.09) in the placebo group (p=0.682). In a predefined subgroup analysis according to the inflammatory phenotype, azithromycin was associated with a significantly lower PEP rate than placebo in subjects with non-eosinophilic severe asthma (blood eosinophilia ≤200/µl): 0.44 PEPs (95% CI 0.25 to 0.78) versus 1.03 PEPs (95% CI 0.72 to 1.48) (p=0.013). Azithromycin significantly improved the AQLQ score but there were no significant between-group differences in the ACQ score or lung function. Azithromycin was well tolerated, but was associated with increased oropharyngeal carriage of macrolide-resistant streptococci. Conclusions Azithromycin did not reduce the rate of severe exacerbations and LRTI in patients with severe asthma. However, the significant reduction in the PEP rate in azithromycin-treated patients with non-eosinophilic severe asthma warrants further study. ClinicalTrials.gov number NCT00760838.

Effects of Hemi-Portocaval Shunts For Inflow Modulation on the Outcome of Small-for-Size Grafts in Living Donor Liver Transplantation

Graft hyperperfusion in small‐for‐size grafts (SFSG) is considered the main causal factor of small‐for‐size syndrome (SFSS). We compared SFSG with a graft‐to‐recipient body ratio ≤0.8, with and without graft inflow modulation (GIM) by means of a hemi‐portocaval shunt (HPCS). Thirteen patients underwent adult‐to‐adult living donor liver transplantation (AALDLT): G1, n = 5 [4 right livers (RL) and 1 left liver (LL)] without GIM, and G2, n = 8 (4 RL and 4 LL) with GIM. In G2 patients, portal vein flow (PVF) was significantly reduced by HPCS: 190 ± 70 mL/min/100 g liver in G2 vs. 401 ± 225 ml/min in G1 (p = 0.002). One‐ and 6‐month post‐transplantation graft volume/standard liver volume (GV/SLV) ratio was of 72% and 79.5% in G1; 80% and 101% in G2 (p = ns). SFSS was observed in three G1 recipients (who were retransplanted), but in none of the G2 patients. At 1‐year, patient and graft survival was respectively of 40% and 20% in G1, 87.5% and 75% in G2 (p = 0.024 and 0.03).

Cryopreservation of human germinal vesicle stage and in vitro matured M II oocytes: influence of cryopreservation media on the survival, fertilization, and early cleavage divisions

OBJECTIVE To study the influence of low-sodium cryopreservation media (CPM) on the survival and development of frozen-thawed germinal vesicle (GV) stage and in vitro matured human oocytes. DESIGN Prospective experimental study. SETTING Academic hospital-based fertility center. PATIENT(S) Experimental groups: Oocytes cryopreserved at the GV (group A, n = 63 and group B, n = 64) or M II stage (group C, n = 62) with use of conventional (group A) or low-sodium CPM (groups B and C). Control groups: Sibling GV stage oocytes subjected to in vitro maturation (IVM; control group A, n = 64; control group B, n = 64). INTERVENTION(S) IVM, intracytoplasmic sperm injection and subsequent culture. MAIN OUTCOME MEASURE(S) Rates of survival, maturation, fertilization, and cleavage. RESULT(S) The postthaw survival was significantly lower in groups A (57.1%) and B (48.4%) compared to C (84.4%). In group A, maturation and cleavage rates were significantly lower, and fertilization rate was similar to controls (GVBD: 72.2% vs. 90.6%; progression to M II: 33.3% vs. 76.6%; cleavage: 42.9% vs. 88.2%; and fertilization: 58.3% vs. 69.4% in group A vs. control group A, respectively). There was no such difference in group B. In group C, despite a slight but significant lowering of the rate of 2 PN and an increase in that of 3 PN (2 PN: 47.4% vs. 70.2% and 3 PN: 15.8% vs. 3.2% in group C vs. total controls, respectively), embryonic cleavage per GV oocyte was significantly higher (25.8%) compared to group A (4.8%) but not to group B (15.6%). The rate of maturation and cleavage per surviving GV oocyte was significantly higher in group B than group A. CONCLUSION(S) Low-sodium-based CPM is beneficial for in vitro matured M II stage oocytes and is significantly better than the conventional sodium-based media for the GV stage oocytes.

Consequences of Scapular Anatomy for Reversed Total Shoulder Arthroplasty

The reverse total shoulder prosthesis provides successful functional outcome in many patients with rotator cuff tear arthropathy. However, scapular notching, a direct consequence of mechanical impingement between the humeral prosthesis and the glenoid, remains a major concern. We presumed a better knowledge of the anatomy of the scapula would enable design or placement modifications to minimize this phenomenon. After establishing a uniform spatial reference system using easy locatable surgical reference points and planes, we analyzed 200 dry bony scapulae and defined the glenoid and infraglenoid anatomy relative to the reference system. The bony rim of the two inferior quadrants of the glenoid forms a semicircle the center of which can be used perioperatively as an easy locatable bony reference point. The infraglenoid tubercle varies in width and length, and can interfere with the humeral part of the reverse prosthesis, creating scapular notching. To avoid notching, we suggest using a convex base plate with a smaller radius than currently used, placing it as low as possible with a 42-mm glenosphere eccentrically assembled to create a posterior offset. If prosthetic overhang cannot be obtained, we suggest removing part of the infraglenoid tubercle.

Shoulder Function after Harvesting a Thoracodorsal Artery Perforator Flap

Background: Converting the latissimus dorsi musculocutaneous flap to a thoracodorsal artery perforator flap has been reported for breast reconstruction. The goal of this article is to evaluate the donor site after harvesting a thoracodorsal artery perforator flap in patients who underwent breast surgery and to show the advantages of sparing the latissimus dorsi muscle on the function of the shoulder. Methods: Between 2002 and 2004, 22 patients who had a partial breast reconstruction using a pedicled thoracodorsal artery perforator flap were enrolled in a functional study to evaluate shoulder function postoperatively. Latissimus dorsi muscle strength, shoulder mobility, and latissimus dorsi thickness were measured by using the MicroFet2, a goniometer, and ultrasound examination, respectively. The measurements of the operated and contralateral (unoperated) sides were analyzed statistically. Results: When comparing the operated sides to the unoperated sides, latissimus dorsi strength seemed to be maintained after surgery. Shoulder mobility was also similar in all movements, but both active and passive forward elevation and passive abduction were reduced significantly after surgery, and latissimus dorsi thickness was not affected by harvesting the thoracodorsal artery perforator flaps. No seroma formation was found in any of the donor sites. Conclusions: Donor-site morbidity after harvesting a thoracodorsal artery perforator flap was reduced to a minimum. Therefore, perforator flaps should be considered in reconstruction whenever adequate perforators can be identified and safely dissected.

Seizures and epilepsy in patients with a spontaneous intracerebral haematoma

BACKGROUND Seizures occur more frequently in patients with an intracerebral haematoma (ICH) than in those with a cerebral infarct. However, the risk factors for seizures in association with an ICH are less well known. PURPOSE The characteristics of medically treated patients with spontaneous ICHs, who developed seizures, were retrospectively compared to those who did not. PATIENTS Fourteen patients were admitted to the Stroke Unit during 2004-2006 for seizures related to an ICH. Their characteristics were compared to those of 51 patients admitted during 2002-2004 for an ICH without subsequent seizures. RESULTS Early-onset seizures, occurring within 48 h of stroke onset, were observed in six patients with ICH related epileptic spells (42.9%). Late-onset ones occurred in eight patients, on average 8 months after the ICH. A focal onset of the seizures was documented in 75.7% of cases. Status epilepticus was observed in 21.4% of the patients. The seizures recurred in only 28.6% of the patients. Lobar haematomas were present in 78.6% of the seizure group, compared to 21.4% in the control group (P=0.008). In the former group a frontal lobe involvement was present in 57.1% compared to 9.8% in the latter group (P<0.001). On the post-ictal EEG, intermittent rhythmic delta activities were observed in 28.6% and periodic lateralized epileptic discharges in 21.4% of the seizure patients. CONCLUSIONS Seizures are more prone to occur in patients with frontal lobar haematomas. EEG can be helpful for the diagnosis of seizures in approximately 50% of the cases.

Levodopa-induced modifications of prosody and comprehensibility in advanced Parkinson's disease as perceived by professional listeners

The prosodic aspects of hypokinetic dysarthria in Parkinsons disease (PD) have been the focus of numerous reports. Few data on the effects of levodopa on prosody, more specifically on the effects on the variability of prosodic characteristics such as pitch, loudness and speech rate, are available in advanced PD. The relation between these characteristics and comprehensibility is currently unknown. These topics are the focus of the present report. Ten patients with advanced PD were evaluated, with and without medication, by four speech‐language pathologists during a reading task. A significant improvement of variability in pitch and loudness was demonstrated after medication intake. Comprehensibility improved following medication administration. Results are compared with previous studies.

Predicting Prognosis and Effect of Antibiotic Treatment in Rhinosinusitis

PURPOSE In evaluating complaints suggestive of rhinosinusitis, family physicians have to rely chiefly on the findings of a history, a physical examination, and plain radiographs. Yet, evidence of the value of signs, symptoms, or radiographs in the management of these patients is sparse. We aimed to determine whether clinical signs and symptoms or radiographic findings can predict the duration of the illness, the effect of antibiotic treatment, or both. METHODS We analyzed data from 300 patients with rhinosinusitis-like complaints participating in a randomized controlled trial comparing amoxicillin with placebo. We used Cox regression analysis to assess the association between the presence at baseline of rhinosinusitis signs and symptoms or an abnormal radiograph and the subsequent course of the illness. We then tested for interactions to assess whether the presence of any of these findings predicted a beneficial effect of antibiotic treatment. RESULTS Two factors at baseline were independently associated with a prolonged course of the illness: a general feeling of illness (hazard ratio = 0.77, 95% confidence interval, 0.60–0.99) and reduced productivity (hazard ratio = 0.68, 95% confidence interval, 0.53–0.88). Neither typical sinusitis signs and symptoms nor abnormal radiographs had any prognostic value. Prognosis remained unchanged whether or not patients were treated with antibiotics, no matter what symptoms patients had at baseline. CONCLUSIONS In a large group of average patients with rhinosinusitis, neither the presence of typical signs or symptoms nor an abnormal radiograph provided information with regard to the prognosis or the effect of amoxicillin. The time to recovery was longer in patients who felt ill at baseline or who did not feel able to work, but the course of their illness was not influenced by antibiotic treatment.

Evaluation of clinical pharmacist recommendations in the geriatric ward of a Belgian university hospital

Objective To evaluate the type, acceptance rate, and clinical relevance of clinical pharmacist recommendations at the geriatric ward of the Ghent university hospital. Methods The clinical pharmacist evaluated drug use during a weekly 2-hour visit for a period of 4 months and, if needed, made recommendations to the prescribing physician. The recommendations were classified according to type, acceptance by the physician, prescribed medication, and underlying drug-related problem. Appropriateness of prescribing was assessed using the Medication Appropriateness Index (MAI) before and after the recommendations were made. Two clinical pharmacologists and two clinical pharmacists independently and retrospectively evaluated the clinical relevance of the recommendations and rated their own acceptance of them. Results The clinical pharmacist recommended 304 drug therapy changes for 100 patients taking a total of 1137 drugs. The most common underlying drug-related problems concerned incorrect dose, drug–drug interaction, and adverse drug reaction, which appeared most frequently for cardiovascular drugs, drugs for the central nervous system, and drugs for the gastrointestinal tract. The most common type of recommendation concerned adapting the dose, and stopping or changing a drug. In total, 59.7% of the recommendations were accepted by the treating physician. The acceptance rate by the evaluators ranged between 92.4% and 97.0%. The mean clinical relevance of the recommendations was assessed as possibly important (53.4%), possibly low relevance (38.1%), and possibly very important (4.2%). A low interrater agreement concerning clinical relevance between the evaluators was found: kappa values ranged between 0.15 and 0.25. Summated MAI scores significantly improved after the pharmacist recommendations, with mean values decreasing from 9.3 to 6.2 (P < 0.001). Conclusion In this study, the clinical pharmacist identified a high number of potential drug-related problems in older patients; however, the acceptance of the pharmacotherapy recommendations by the treating physician was lower than by a panel of evaluators. This panel, however, rated most recommendations as possibly important and as possibly having low relevance, with low interrater reliability. As the appropriateness of prescribing seemed to improve with decreased MAI scores, clinical pharmacy services may contribute to the optimization of drug therapy in older inpatients.

Cost-effectiveness of telemonitoring for high-risk pregnant women

PURPOSE Cost-minimization is a main topic in present-day health care. Clinicians are urged to keep hospital stays as short as possible, also in Obstetrics and Gynaecology Departments. At present stabilized high-risk pregnant women stay in hospital for the sole purpose of being monitored. METHOD In this retrospective study the cost-effectiveness of telemonitoring of such high-risk pregnant women was calculated by analyzing the data of 456 episodes originating from 415 patients of the Ghent University Hospital. RESULTS AND CONCLUSIONS It was determined that telemonitoring made a cost-reduction of euro 145,822 per year possible. However, variables such as educational level, psychosocial situation, time-travel distance from home to the hospital, reimbursement system and actual clinical status were not included. Furthermore, the Belgian health authorities does not provide for a specific code to allow the billing of teleinterpretation of transmitted results.