The 2001 Canadian recommendations for the management of hypertension: Part two--Therapy

OBJECTIVE: To provide updated, evidence-based recommendations for the therapy of hypertension in adults. OPTIONS: For patients with hypertension, a number of antihypertensive agents may control blood pressure. Randomized trials evaluating first-line therapy with thiazides, beta-adrenergic antagonists, angiotensin-converting enzyme inhibitors, calcium channel blockers, alpha-blockers, centrally acting agents or angiotensin II receptor antagonists were reviewed. OUTCOMES: The health outcomes that were considered were changes in blood pressure, cardiovascular morbidity, and cardiovascular and/or all-cause mortality rates. Economic outcomes were not considered due to insufficient evidence. EVIDENCE: MEDLINE was searched for the period March 1999 to October 2001 to identify studies not included in the 2000 revision of the Canadian Recommendations for the Management of Hypertension. Reference lists were scanned, experts were polled, and the personal files of the subgroup members and authors were used to identify other published studies. All relevant articles were reviewed and appraised, using prespecified levels of evidence, by content experts and methodological experts. VALUES: A high value was placed on the avoidance of cardiovascular morbidity and mortality. BENEFITS, HARMS AND COSTS: Various antihypertensive agents reduce the blood pressure of patients with sustained hypertension. In certain settings, and for specific classes of drugs, blood-pressure lowering has been associated with reduced cardiovascular morbidity and/or mortality. RECOMMENDATIONS: The present document contains detailed recommendations pertaining to treatment thresholds, target blood pressures, and choice of agents in various settings in patients with hypertension. The main changes from the 2000 Recommendations are the addition of a section on the treatment of hypertension in patients with diabetes mellitus, the amalgamation of the previous sections on treatment of hypertension in the young and old into one section, increased emphasis on the role of combination therapies over repeated trials of single agents and expansion of the section on the treatment of hypertension after stroke. Implicit in the recommendations for therapy is the principle that treatment for an individual patient should take into consideration global cardiovascular risk, the presence and/or absence of target organ damage, and comorbidities. VALIDATION: All recommendations were graded according to strength of the evidence and voted on by the Canadian Hypertension Recommendations Working Group. Individuals with potential conflicts of interest relative to any specific recommendation were excluded from voting on that recommendation. Only those recommendations achieving high levels of consensus are reported here. These guidelines will continue to be updated annually.     

Atypical presentation of pattern dystrophy in two families with peripherin/RDS mutations

PURPOSE: To describe the atypical clinical presentations of pattern dystrophy (PD) in two unrelated families with novel peripherin/RDS mutations. DESIGN: Observational case reports and family genetic study with review of peripherin/RDS mutations. PARTICIPANTS: Affected and unaffected members of two families with PD. METHODS: The probands of two families, as well as other family members, underwent an ophthalmologic assessment including slit-lamp biomicroscopy, applanation tonometry, and a dilated fundus examination. Goldmann visual fields and fluorescein angiography were performed, wherever appropriate. Blood samples were obtained from affected and selected unaffected members of the families for DNA analysis. RESULTS: The proband of family 1 had an acute onset of decreased vision and a yellowish lesion in both maculae that appeared inflammatory. However, resolution of the acute lesion ultimately resulted in fundus changes more typical for PD. Moreover, the proband's sister showed more classic-appearing PD lesions. Screening of the peripherin/RDS gene for sequence variations showed a 2-bp deletion, resulting in a translational frameshift at codon 290 in affected members of the family. The proband's father, who showed this sequence variation, did not have a macular lesion. The proband of family 2 was asymptomatic and showed a fundus phenotype similar to fundus flavimaculatus. The patient had normal visual acuity and did not demonstrate a "dark choroid" on fluorescein angiography. Molecular screening showed a Gln331stop variation in the peripherin/RDS gene. CONCLUSIONS: We describe two novel mutations in the peripherin/RDS gene in two unrelated families with PD. Clinicians should recognize the atypical features that may occur in patients with PD. A suspected diagnosis of PD may be confirmed by the identification of a mutation in the peripherin/RDS gene. In isolated family members with PD, a mutation in this gene may occur even in the absence of a clinically discernible macular lesion.     

Pharmacologic profile of the selective mitochondrial-K(ATP) opener BMS-191095 for treatment of acute myocardial ischemia

ATP-sensitive potassium channel (K(ATP)) openers as a class protect ischemic myocardium. The protective effects are independent of vasodilator activity and effects on action potential shortening, actions typically associated with sarcolemmal K(ATP) activation. BMS-191095 is a novel mitochondrial K(ATP) opener which protects ischemic myocardium while having no electrophysiologic or vasodilator effects (determined in vitro and in vivo). The cardioprotective effects were determined in isolated rat hearts subjected to ischemia and reperfusion. Protective effects were deduced from increased time to contracture formation during ischemia, improved reperfusion recovery of contractile function, and reduced reperfusion LDH release. The cardioprotective effects of BMS-191095 were observed at concentrations at which this compound selectively opened cardiac mitochondrial K(ATP) channels. This effect was consistent with the pharmacologic profile of this agent. The protective effects were abolished by mitochondrial K(ATP) inhibition. Unlike first-generation K(ATP) openers, BMS-191095 is expected to protect ischemic myocardium with little hemodynamic sequelae and without any proarrhythmic potential. BMS-191095 is potentially useful clinically as a cardioprotective agent. It is also a useful tool for basic research.     

Standard versus fiberoptic pulmonary artery catheterization for cardiac surgery in the Department of Veterans Affairs: a prospective, observational, multicenter analysis

BACKGROUND: Controversy exists regarding the utility of continuous monitoring of mixed venous oxygen saturation (STvo2) during cardiac surgery. During a multicenter, prospective, observational study in the Department of Veterans Affairs (Cooperative Study #5), frequency of use of standard pulmonary artery catheterization (PAC) and STvo2-PAC was recorded. Here the authors relate these data to clinical outcomes. METHODS: Logistic and Cox regression models evaluating the association of PAC type with mortality, one or more postoperative complications, cardiac complications, time to extubation, and intensive care unit length of stay were constructed. The number of thermodilution cardiac outputs and arterial blood gas analyses performed in the first 24 h postoperatively were compared. RESULTS: Data from 3,265 patients undergoing myocardial revascularization (81.7%) or valve replacement-repair (18.3%) were considered. STvo2-PAC was used in 49% and PAC in 51% of patients. In the 14 hospitals, STvo2-PAC was used in all patients in four, in some patients in four, and never in six. No association of STvo2-PAC use with outcome were observed aside from unexplained hospital level effects. A small but statistically significant reduction in the number of arterial blood gas analyses (8 +/- 3 vs. 10 +/- 4, P < 0.0001, STvo2-PAC vs. PAC, respectively) and thermodilution cardiac outputs (14 +/- 8 vs. 15 +/- 9, P < 0.0001, STvo2-PAC vs. PAC, respectively) was observed with use of STvo2-PAC. CONCLUSIONS: Despite higher cost, STvo2-PAC was commonly used in this cohort. Our analysis failed to detect associations with improved outcomes aside from a small reduction in resource utilization. The precise role of STvo2-PAC remains uncertain.     

Auditory function following spinal analgesia. Comparison of two spinal needles

BACKGROUND AND OBJECTIVE: Auditory impairment is among the lesser known complications of spinal analgesia. The aim of the present study was to determine the degree of vestibulocochlear dysfunction in patients undergoing spinal analgesia for lower abdominal surgery. METHODS: Eighty patients who had received spinal analgesia for lower abdominal surgery were studied. Males were undergoing inguinal herniorraphy and the females tubectomy. Audiograms were performed before operation and on the second and seventh postoperative days. Hearing levels were measured from 250 Hz-8 kHz. In Group 1 (n = 40) a 22-gauge, cutting type of spinal needle (Howard Jones) was used. In Group 2 (n = 40) a 25-gauge, non-cutting spinal needle (Whitacre) was used. RESULTS: Hearing loss >10 dB was noticed in three patients in Group 1 and none in Group 2. The mean hearing level was more reduced in Group 1 patients. CONCLUSIONS: Use of cutting type spinal needle is associated with a greater decrease in mean hearing levels compared to the non-cutting type.     

Evaluation of a decision aid and a personal risk profile in community pharmacy for patients considering options to improve cardiovascular health: the OPTIONS pilot study

Objective In a pilot study, to assess the feasibility and relevance of providing a community pharmacist consultation supplemented by a decision aid (DA) or a personal risk profile (PRP) to patients on lipid‐lowering or antihypertensive pharmacotherapy. Preliminary data on the clinical effectiveness of these interventions were collected. Method Patients were randomised to DA or PRP and evaluated before, two weeks after, and three months after a pharmacist consultation. No differences were observed between DA and PRP groups; results are reported for all patients combined. The quality of the patients' decision to initiate or maintain lifestyle change and/or pharmacological treatment was evaluated at baseline and two weeks after the consultation by measuring their knowledge, risk perception, decisional conflict and satisfaction with the decision process. The stage of change for various lifestyles and changes in cardiovascular disease (CVD)‐risk factors were evaluated at baseline and at three months. Setting Ten community pharmacies. Key findings Twenty‐six of 42 patients (62%) agreed to participate. Patients reported as excellent or very good the way the information was presented (79%), the amount of information (88%), and the usefulness of the tools (100%). The quality of the patients' decision at baseline was low; one‐third of participants correctly estimated their CVD risks and laboratory results, and 54% had high decisional conflict. After the intervention, the satisfaction scores for role in decision making, amount of information provided and pharmacist's attitude were 69%, 81% and 85% respectively, and the proportion of participants with high decisional conflict declined to 25% (P = 0.02). CVD knowledge and risk perception did not change after the intervention. Improvements in low‐density lipoprotein cholesterol (LDL)‐C, total‐C/high‐density lipoprotein (HDL)‐C ratio, body mass index, and estimated 10‐year CVD risk were observed. Conclusion Providing pharmacist consultation supplemented by a DA or a PRP in community pharmacies is feasible and relevant. However, it did not improve CVD knowledge or risk perception.     

The adverse effects of thalidomide in relapsed and refractory patients of multiple myeloma.

Thalidomide has shown efficacy in relapsed or refractory patients of multiple myeloma (MM). We present the adverse effect profile of thalidomide in 23 relapsed or refractory MM patients treated with this drug over a period of 15 months. Constipation (100% incidence) and sedation (87%) were the most common adverse effects. Neuropathy had low incidence and was late in onset (>12 months). Tolerance developed to sedation, constipation and skin lesions. All the adverse drug reactions were tolerable and did not warrant decrease or termination of therapy, except for peripheral neuropathy. Contrary to Western reports, peripheral neuropathy in Indian patients developed at a cumulative dose of 200 g or more after 10 months or more of therapy. Therapy was discontinued in one patient due to marked elevation of liver enzyme that was later attributed to acute hepatitis C infection. Only one patient dropped out of the trial for unknown reasons. Overall, thalidomide was found to be a relatively safe drug that can be used over a prolonged period of time.     

Juvenile nasopharyngeal angiofibromas: A study of recurrence pattern and role of pre-Operative embolization - ‘a decade’S experience’

This study is a retrospective analysis of 30 consecutive cases of Juvenile Nasopharyngeal Angiofibroma (JXA) operated at. Department of Head and Neck Surgery, Kidwai Memorial Institute of Oncology Bangalore, India: la tertiary referral centre) after prior emohilization by an interventional neuro-radiologisl (1996-2002). This study discusses critically the planning of surgical approach, based on anatomico-radiological factors and highlights the efficacy of preoperalive embolization in expediting total re moral of the tumor in 25 out of JO cases with advanced stage JNA. Objectives: To analyze the utility of pre-operatire embolisation in surgical extirpation of large JNAs; planning of the surgical approaches based on CT topography of the tumor; to study the various complications of embolisation and surgery associated with JXA & lastly to evaluate the puttern and location of recurrent tumor thus correlating with the original topography. Setting: Tertiary care cancer referral centre. Patients: Patients ranged in age from ’)- 24 years. all being males. Interventions: Majority of them were accessed by transfacial surgical approach(26). and in the recent past via midfacial degloving(4) within 4H hours of angioembolisation. Results: Complete removal of the tumor was achieved in 25 out of 30 cases with advanced stage JNA. Post surgical CT scans revealed tumor residua in 5 individuals, where the tumor was documented in - the temporal fossa 12), para-cavernous sinus region (I), cavernous sinus! I) and pterygo palatine fossa (I). Only the lesion in pterygopalaline fossa was successfully re-i>xcised & this alongwith the recurrence at para-cavernous & cavernous sinus & another were treated with radiotherapy; the 2 cases in the temporal fossa are under observation. The average blood loss during the procedure was 546.60 ml. Conclusions: Today, advances in radiologie imaging-complemented by interventional neuro-radiological expertise in angio-embolisation have expedited complète excision with minimal morbidity and acceptable recurrence rate. This study has justified pre-operative embolisation and M currently the standard of care for advanced JXA.