Choice reaction time in patients with post-operative cognitive dysfunction

Background: Post‐operative cognitive dysfunction (POCD) is detected by administration of a neuropsychological test battery. Reaction time testing is at present not included as a standard test. Choice reaction time (CRT) data from the first International Study of Post‐operative Cognitive Dysfunction study were collected, but the association between POCD and reaction time has not been presented before. We hypothesized that CRT could be used as a screening tool for POCD. Methods: Patients aged 60 years or older scheduled for major surgery with general anaesthesia were recruited from 13 centres in nine countries. CRT was measured 52 times using the four boxes test. Patients performed the test before surgery (n=1083), at 1 week (n=926) and at 3 months (n=852) post‐operatively. CRT for the individual patient was determined as the median time of correct responses. The usefulness of the CRT as a screening tool for POCD was determined by the receiver–operator characteristic (ROC) curve. Results: Patients with POCD 1 week after surgery had a significantly longer reaction time compared with patients without POCD: 857 (221) vs. 762 (201) ms, respectively (P<0.0001). Also at 3 months, patients with POCD had a significantly longer CRT. ROC curves revealed that a reaction time of 813 ms was the most appropriate cut‐off at 1 week and 762 ms at 3 months but the positive predictive value for POCD was low: 34.4% and 14.7%, respectively. Conclusions: Post‐operative cognitive dysfunction is associated with impaired performance in the CRT test but the test is a poor predictor of POCD.     

Reliability and construct validity of the compatible MRI scoring system for evaluation of elbows in haemophilic children

Summary. We assessed the reliability and construct validity of the Compatible MRI scale for evaluation of elbows, and compared the diagnostic performance of MRI and radiographs for assessment of these joints. Twenty‐nine MR examinations of elbows from 27 boys with haemophilia A and B [age range, 5–17 years (mean, 11.5)] were independently read by four blinded radiologists on two occasions. Three centres participated in the study: (Toronto, n = 24 examinations; Atlanta, n = 3; Cuiaba, n = 2). The number of previous joint bleeds and severity of haemophilia were reference standard measures. The inter‐reader reliability of MRI scores was substantial (ICC = 0.73) for the additive (A)‐scale and excellent (ICC = 0.83) for the progressive (P)‐scale. The intrareader reliability was excellent for both P‐scores (ICC = 0.91) and A‐scores (ICC = 0.93). The total P‐ and A‐scores correlated poorly (r = 0.36) or moderately (r = 0.54), but positively, with clinical‐laboratory measurements. The total MRI scores demonstrated high accuracy for discrimination of presence or absence of arthropathy [P‐scale, area‐under‐the‐curve (AUC) = 0.94 ± 0.05; A‐scale, AUC = 0.89 ± 0.06], as did the soft tissue scores of both scales (P‐scale, AUC = 0.90 ± 0.06; A‐scale, AUC = 0.86 ± 0.06). Areas‐under‐the‐curve used to discriminate severe disease demonstrated high accuracy for both P‐MRI scores (AUC = 0.83 ± 0.09) and A‐MRI scores (AUC = 0.87 ± 0.09), but non‐diagnostic ability to discriminate mild disease. Similar results were noted for radiographic scales. In conclusion, both MRI scales demonstrated substantial to excellent reliability and accuracy for discrimination of presence/absence of arthropathy, and severe/non‐severe disease, but poor to moderate convergent validity for total scores and non‐diagnostic discriminant validity for mild/non‐mild disease. Compared with radiographic scores, MRI scales did not perform better for discrimination of severity of arthropathy.     

Viral safety of a pasteurized, monoclonal antibody-purified factor VIII concentrate in previously untreated haemophilia A patients

The efficacy and viral safety of a pasteurized, immunoaffinity-purified procoagulant factor VIII protein (FVIII:C; Monoclate-P) was studied in two multicentre, prospective, open-label trials in 30 previously untreated patients, 18 with severe (< 1% FVIII:C activity), and 12 with moderate (1% to 5% FVIII:C activity) haemophilia A. Clinical assessments, performed at screening and regularly thereafter for 6 to > 24 months (maximum 34 months), showed that none of 24 assessable patients acquired illnesses consistent with monitored transfusion-transmissible diseases. No patients acquired hepatitis B surface antigen, or antibodies against hepatitis B core antigen, hepatitis C, or human immunodeficiency virus. Likewise, no patients acquired treatment-related hepatitis A antibodies or sustained elevations of alanine aminotransferase levels. The safety profile for Monoclate-P is brought about by a multi-step safety system that incorporates viral inactivation (through a combination of immunoaffinity chromatography and pasteurization) plus donor screening, plasma testing, and quality assurance. The inhibitor development rate (13% low titre, 10% high titre) was similar to that reported in the literature for other FVIII concentrates (24% to 52%). The most frequently reported adverse events were related to typical infant and childhood diseases. Monoclate-P was effective in all patients treated according to protocol, except in two, who developed inhibitors.     

Automatic Sensor Adjustment in a Rate Modulated Pacemaker

A new feature (AutoSlope) has been introduced that can automatically adjust the sensor slope based on the chronic activity level of the patient. The algorithm adjusts the slope once per week so that 99% of the sensor response is maintained between the base rate and 23% of the difference between the programmed Base Rate and the Max Sensor Rate. Offsets are available for fine titration of sensor response in individual patients. The AutoSlope feature was evaluated in 93 patients with DDDR pacemakers (Trilogy DR+, Pacesetter). Patients were seen at 1, 3, and 6 months for a total of 178 evaluations. At each evaluation, the AutoSlope value was recorded. Patients then performed a brisk walk at sensor values equivalent to the AutoSlope value. Desired sensor rate was compared to the rate achieved by AutoSlope for the exercise period. Long-term sensor performance was evaluated by analyzing the sensor histogram. AutoSlope provided the desired sensor rate in most patients. Use of AutoSlope offsets allows fine titration of rate modulation in individual patients. Ongoing changes in sensor performance provided by AutoSlope allow patients to achieve a desired sensor rate from one evaluation to another without changes in permanent programmed settings. Programming a low maximum sensor rate may limit sensor response in some patients.     

Initial Experience with a New Single Chamber, Dual Sensor Rate Responsive Pacemaker

In August 1991, a new single chamber pacemaker became available that utilizes information from two sensors, activity and stimulus-to-T wave (QT) interval. We are reporting on the first 90 implants in 21 centers. T wave sensing was adequate at implantation in 88/90 patients, with a safety margin of > 100% in 86/90, Activity sensing was adequate in all patients. The contribution of each sensor fsensor blending) is programmable for each patient. Of 75 patients assessed at 1 month after implant, three have been programmed to "Activity-Only" mode, and 72 to dual sensor mode. Of these, 18 have been programmed to "QT < Activity," 48 to "QT = Activity," and 6 to "QT > Activity." Forty-five patients underwent exercise testing in dual sensor mode and a subgroup of 15 also underwent exercise testing in Activity-Only mode. The dual sensor mode produced a more gradual increase in pacing rate. Sensor Cross Checking^tmsatisfactorily prevented a sustained high pacing rate in tests of false-positive activity sensing (tapping, vibrating pacemaker, or static pressure). The maximum pacing rate on walking downstairs (94.2 ± 7.2 ppm) was similar to that produced by walking upstairs (91.6 ± 5.9 ppm). We conclude that initial assessment of this dual sensor, single chamber, rate responsive pacemaker confirms that the algorithm for combining data from two sensors functions satisfactorily. Dual sensor rate responsive pacing may offer significant advantages over single sensor devices, and further studies of this novel device are indicated.     

A Prospective, Randomized Evaluation of a Nonthoracotomy Implantable Cardioverter Defibrillator Lead System

Nonthoracotomy lead systems for ICDs have been developed that obviate the need for a thoracotomy and reduce the morbidity and mortality associated with implantation. However, an adequate DFT cannot be achieved in some patients using transvenous electrodes alone. Thus, a new subcutaneous "array" electrode was designed and tested in a prospective, randomized trial that compared the DFT obtained using monophasic shock waveforms with a single transvenous lead alone that has two defibrillating electrodes, the transvenous lead linked to a subcutaneous/submuscular patch electrode, and the transvenous lead linked to the investigational array electrode. There were 267 patients randomized to one of the three nonthoracotomy ICD lead systems. All had DFTs that met the implantation criterion of ≤ 25 J. The resultant study population was 82% male and 18% female, mean age of 63 ± 11 years. The indication for ICD implantation was monomorphic VT in 70%, VF in 19%, monomorphic VT/VF in 6%, and polymorphic VT in 4% of the patients, respectively. The mean LVEF was 0.33 ± 0.13. The mean DFT obtained with the transvenous lead alone was 17.5 ± 4.9 J as compared to 16.9 ± 5.5 J with the lead linked to a patch electrode (P = NS), and 14.9 ± 5.6 with the lead linked to the array electrode (array versus lead alone, P = 0.0001; array versus lead/patch, P = 0.007). The results of this investigation suggest that the subcutaneous array may be superior to the standard patch as a subcutaneous electrode to lower the DFT and increase the margin of safety for successful nonthoracotomy defibrillation.     

Once- versus twice-daily administration of controlled-release isosorbide-5-mononitrate 60 mg in the treatment of stable angina pectoris: A randomized, double-blind, cross-over study

Thirty-seven patients with chronic, stable angina pectoris wereincluded in a randomized, double-blind cross-over study to assessthe efficacy of once- and twice-daily dosage regimens of 60mg isosorbide-5-mononitrate, in a controlied release formulation(5-ISMN Durules^® Astra). After 2 weeks of treatment, duringa symptom-limited bicycle ergometer exercise test performed3 h after the dose, the time to 1 mm ST segment depression wasobserved to be longer by once-daily than by a twice-daily dosageregimen (614 ± 165 vs 561 ± 148 s, P<0·01).The time to the end of exercise was also significantly prolongedby once-daily dosage, as compared with placebo (693 ±158 and 645 ± 173 s, respectively; P<0·05),which was not observed with the twice-daily regimen. Both dosageregimens still had a significant effect on the prolongationof the time to onset of angina 9 h after the dose: 420 ±164 s by placebo, 492 ± 161 s by once-daily dosage; P<0·01and 466 ± 154 s by twice-daily dosage; P<0·05.Anginal attack rate and nitroglycerin consumption was significantlylower during the once-daily dosage period as compared with placebo;this difference was not evident during the twice-daily administrationof the drug. Controlled-release 5-ISMN 60 mg given once daily was effectivein angina pectoris patients for at least 9 h after the doseand showed no clinical signs of tolerance after 2 weeks of thetreatment. Attenuation of the clinical effect was observed withthe twice-daily (in 12 h intervals) dosage regimen, presumablycaused by constantly high 5-ISMN plasma concentration.