Telemedicine for genetic and neurologic evaluation in the neonatal intensive care unit.

OBJECTIVE: Evaluate whether telemedicine can be used to perform dysmorphology and neurologic examinations in the neonatal intensive care unit (NICU) by determining the examination accuracy, limitations and optimized procedures. STUDY DESIGN: Prospective evaluation of NICU patients referred for subspecialty consultation for dysmorphic features (n=10) or encephalopathy (n=10). A physician at bedside (bedside clinician) performed an in-person examination that was viewed in real time by a remote physician (remote consultant). Standardized examinations were recorded and compared. Subsequently, a qualitative approach established technique adjustments and optimization procedures necessary to improve visualization. RESULT: Telemedicine examinations identified 81 of 87 (93%) dysmorphology examination abnormalities and 37 of 39 (92%) neurologic examination abnormalities. Optimization of remote consultant visualization required an active bedside clinician assisting in camera and patient adjustments. CONCLUSION: Telemedicine can be used to perform accurately many components of the dysmorphology or neurologic examinations in NICU patients, but physicians must be mindful of specific limitations.

Simulated evaluation of a non-Luer safety connector system for use in neuraxial procedures.

BACKGROUND: Spinal syringes, needles, and other devices with connectors that will not also connect with Luer devices could substantially reduce wrong-route drug administration errors. This study aimed to evaluate a newly designed non-Luer safety connector system for neuraxial procedures in terms of clinical acceptability and cross-connectivity with conventional Luer devices. METHODS: A non-Luer safety connector system (BD UniVia-6 Safety Connector system), which included non-Luer spinal needles, syringes, and blunt fill filter needles, was evaluated in a prospective, simulated use, randomized study. Clinicians evaluated the acceptability and performance characteristics using a normal saline injectate on an artificial back model. RESULTS: Forty-nine clinicians participated in the study. For 93 of 98 spinal injection procedures, clinicians agreed that overall, the safety system was clinically acceptable (94.9%; 95% lower bound 89.6%). Forty-eight clinicians (98%; 95% lower bound: 90.7%) agreed that the safety system prevented or reduced the risk of misconnection between a conventional syringe and a safety spinal needle. A lower proportion (63.3%; 95% lower bound: 50.5%) agreed that the safety system would prevent or reduce the risk of misconnections between a safety syringe filled with medication intended for spinal injection and an i.v. Luer device. CONCLUSIONS: Our study demonstrated that study clinicians found the safety system to be acceptable with minimal impact on technique in a simulated-use setting. The non-Luer system also appeared to decrease the risk of administration of i.v. medications into the intrathecal space. Further modifications will be required to completely eliminate the risk of administering intrathecal medication i.v. and evaluation in a clinical setting will help determine the true impact of this non-Luer system on patient safety.

Anti-NMDA receptor encephalitis presenting with focal non-convulsive status epilepticus in a child.

A previously healthy 9-year-old girl presented to an emergency department (ED) with headache, dizziness, blurry vision, and abnormal visual perceptions. She was diagnosed with migraine, treated symptomatically, and discharged. Over the course of days, she became progressively somnolent, and returned to the ED, where she was found to have a right inferior quadrantanopsia and sixth nerve palsy. Magnetic resonance imaging (MRI) of the brain showed gyral swelling of the left parieto-occipital lobe. Continuous electroencephalogram (EEG) monitoring revealed focal non-convulsive status epilepticus (NCSE) in the left occipital region. Cerebrospinal fluid (CSF) was positive for antibodies directed against the N-methyl-d-aspartate receptor (NMDAR). This case is the first report of anti-NMDAR encephalitis presenting with focal non-convulsive status epilepticus (NCSE).

Renal failure five years after lung transplantation due to polyomavirus BK-associated nephropathy.

Polyomavirus-associated nephropathy (PyVAN) is rare in nonrenal solid organ transplantation and only limited information is available from single cases. We describe a 67-year-old female presenting with hypertension and progressive kidney failure due to PyVAN 60 months after lung transplantation. Plasma BK virus (BKV) loads were 4.85 log¹° copies/mL at diagnosis and cleared slowly over 14 months after switching from tacrolimus, mycophenolate and prednisone to low-dose tacrolimus, sirolimus and leflunomide, the latter being discontinued for anemia and diarrhea. BKV- and JC virus-specific immunoglobulins were detectable prior to transplantation. Only BKV-specific IgG and IgM increased during follow-up. BKV-specific T cells were detectable in blood following in vitro expansion, but cleared with reincreased sirolimus, yet BKV viremia remained undetectable. We identified eight other cases of PyVAN in nonrenal solid organ transplantation including lung (n = 1), heart (n = 6) and pancreas (n = 1). Overall, diagnosis was later than commonly seen in kidney transplants (median 18 months, interquartile range 10-29). Seven patients were male, five received triple immunosuppression consisting of tacrolimus, mycophenolate, prednisone. Immunosuppression was reduced in four cases and cidofovir and/or leflunomide administered in five and two cases, respectively. Renal function deteriorated in five requiring hemodialysis in four. We discuss mTOR inhibitors versus cidofovir and leflunomide as potential PyVAN rescue therapy.

Quality of life in patients treated with hemodialysis or peritoneal dialysis: what are the important determinants?

BACKGROUND: Patients with end-stage renal disease (ESRD) have significant impairments in health-related quality of life (HRQOL). In part, this is due to the intrusiveness of the treatment (hemodialysis or peritoneal dialysis) that is required. It is unclear whether hemodialysis or peritoneal dialysis is associated with a higher HRQOL. METHODS: 192 prevalent patients who self-selected treatment with hemodialysis (either in-center, satellite or home/self-care hemodialysis) or peritoneal dialysis were studied to determine whether treatment with hemodialysis or peritoneal dialysis is associated with a higher HRQOL. Demographic, laboratory and clinical information (including the presence of comorbid conditions using the Charlson comorbidity index) was assessed at baseline. The outcome of interest was HRQOL, which was measured using the Kidney Disease Quality of Life-Short Form (KDQOL-SF), the Short-Form 36 (SF-36) and the EuroQol EQ-5D at baseline and after 6 and 12 months of follow-up. RESULTS: There was no significant difference in HRQOL scores for the SF-36, the EQ-5D and for 9 of 11 KDQOL dimensions for patients treated with hemodialysis or peritoneal dialysis at baseline. As expected, HRQOL was significantly lower for patients who had more comorbid disease, required assistance with their daily care, and for patients with less than a grade 12 education. After controlling for the effect of other important variables, HRQOL (as measured by the EQ-5D visual analog or index scores) did not differ between hemodialysis and peritoneal dialysis patients. HRQOL was stable over time, both for patients who started on hemodialysis or peritoneal dialysis. CONCLUSIONS: There is no significant difference in HRQOL for prevalent ESRD patients treated with hemodialysis or peritoneal dialysis. It will be important to determine if this finding holds true for incident patients treated with hemodialysis or peritoneal dialysis.

An economic evaluation of early versus late referral of patients with progressive renal insufficiency.

Patients with progressive renal insufficiency (PRI) who start renal replacement therapy (RRT) within 4 months of seeing a nephrologist (late referral) have increased morbidity, mortality, and health care costs. We performed an economic evaluation of early versus late referral of patients with PRI to a multidisciplinary clinic. A decision analysis was performed from the perspective of the health care provider, using a Markov model to simulate progression of PRI and survival of patients on RRT. Our simulated patient cohort comprised 1,000 patients with PRI and estimated creatinine clearance of 20 mL/min. The study time horizon was 5 years. Clinical and cost data were taken from published Canadian and U.S. data, where available. Where published data were lacking, we used data from our prospectively maintained database. The study intervention was attendance at a PRI clinic where patients receive treatment to slow the rate of renal progression, receive treatment of complications of PRI, and are prepared for RRT. Endpoints were total cost of patient care, patient life-years, patient life-years free of RRT, and hospital admission days. Early referral resulted in cost savings and improved patient survival along with more life-years free of RRT and fewer hospital inpatient days. Cost-effectiveness was unaffected by univariate sensitivity analyses. Cost-effectiveness decreased as rates of renal function loss for patients referred early versus late approximated each other. In conclusion, early referral of patients with PRI to a multidisciplinary clinic appears cost-effective.

The Southern Alberta Renal Program database: a prototype for patient management and research initiatives.

The Southern Alberta Renal Program (SARP) database was developed to respond to an urgent need for local information on clinical outcomes, laboratory information, and health care costs, and to enable our local renal program to monitor the implementation of established clinical practice guidelines. The database captures detailed demographic, clinical, and laboratory information and is unique by also capturing comorbidity, health-related quality of life and costing information for patients with end-stage renal disease (ESRD) in southern Alberta, storing the information in one common database. By collecting information on patient comorbidity, health outcomes and costs, the SARP database has enabled many quality assurance initiatives as well as research opportunities for projects involving patients with ESRD. Due to the availability of links with other available local clinical and administrative databases, information is collected with a minimal need for manual data entry. This type of database is a method by which health programs could improve the quality of patient care. Programs caring for patients with chronic medical conditions such as ESRD should examine how computer databases could assist in clinical care and improve the efficiency with which that care is delivered to their patients.

Poor long-term survival after coronary angiography in patients with renal insufficiency.

Cardiovascular disease is common among dialysis patients, but much less is known regarding non-dialysis-dependent renal insufficiency (NDDRI) and its association with cardiac disease. We undertook a study to assess the impact of renal insufficiency on survival post-coronary angiography by comparing three groups of patients: dialysis-dependent patients, patients with NDDRI (creatinine > 2.3 mg/dL), and a reference group with creatinine levels less than 2.3 mg/dL and not on dialysis therapy. We used a prospective cohort that consisted of all patients undergoing coronary angiography in Alberta, Canada, from January 1, 1995, to December 31, 1997. Of the 16,989 patients, 196 patients (1.2%) were on dialysis therapy, 262 patients (1.5%) had NDDRI, and 16,531 patients (97.3%) formed the reference group. Mortality rates 1 year after angiography were 30.2% for patients with NDDRI, 15.8% for dialysis patients, and 4.1% for the reference group. Compared with the reference group, crude 4-year survival was significantly worse for dialysis patients and those with NDDRI, with hazard ratios of 4.05 (95% confidence interval, 3.02 to 5.42) and 7.32 (95% confidence interval, 5.97 to 8.97), respectively. Even after adjusting for clinical risk factors, survival remained worse for dialysis patients and those with NDDRI, with hazard ratios of 2.59 (95% confidence interval, 1.92 to 3.49) and 2.51 (95% confidence interval, 2.02 to 3.12), respectively. We conclude that renal insufficiency, both dialysis dependent and non-dialysis dependent, is an independent risk factor for increased mortality and poor long-term survival among patients undergoing coronary angiography.

Long-term knowledge retention following predialysis psychoeducational intervention.

BACKGROUND/AIMS: Early identification and predialysis psychoeducation are gaining acceptance. Although research supports the immediate value of predialysis interventions, long-term benefits remain unknown. We examined long-term knowledge retention following a psychoeducational intervention. METHODS: 47 progressive renal failure patients completed the Kidney Disease Questionnaire at baseline and 18, 30, 42, and 54 months after initiating renal replacement therapy (RRT; the 'longitudinal' sample). A larger cohort provided data at one or more of these points (n = 132, 117, 101, and 70 at 18, 30, 42, and 54 months, respectively; the 'cross-sectional' sample). RESULTS: Initial knowledge gains among psychoeducation recipients were followed by a significant knowledge advantage for three groups throughout follow-up. Patients who received predialysis psychoeducation either before or after starting dialysis demonstrated superior Kidney Disease Questionnaire scores as compared with those identified before the initiation of RRT who received the usual standard of practice. Patients identified after the initiation of RRT and who received standard education, however, demonstrated the same level of knowledge retention as produced by psychoeducation. The results were identical across the longitudinal and cross-sectional samples. CONCLUSIONS: Patient education produces important benefits in end-stage renal disease, but the incremental value of early intervention remains to be demonstrated.

Economic evaluation and end-stage renal disease: from basics to bedside.

Economic evaluation is the comparative analysis of alternative health care interventions in terms of their relative costs (resource use) and effectiveness (health effects). High-quality studies of economic evaluation have been increasingly published in medical journals and read by clinicians, although publication of these studies in nephrology journals has been a more recent phenomenon. This article shows how the basic principles of economics can be applied to health care through the use of economic evaluation. Different types of economic evaluation are discussed, and pitfalls common to such studies are identified. A simple framework is introduced that can be used to interpret the results of economic evaluations. Using this framework, selected therapies for patients with end-stage renal disease (ESRD) are categorized to highlight therapies that are very efficient, encourage their use, and draw attention to therapies in current use that are less effective and more expensive (ie, less efficient) than alternative therapy. Using examples pertinent to care of the patient with ESRD, we show how economic evaluation can be used to link medical outcomes, quality of life, and costs in a common index for multiple therapies with disparate outcome measures. This article highlights the need for clinical studies and economic evaluations of therapies in ESRD for which the effects of the therapy on health outcomes and/or costs are unknown.

Long-term safety and antihypertensive efficacy of irbesartan: pooled results of five open-label studies.

An analysis of 5 multicenter, open-label studies was conducted to evaluate the long-term safety and efficacy of irbesartan in 1,006 patients with seated diastolic blood pressure (SeDBP) 95-110 mm Hg. Irbesartan monotherapy was started at 75 mg and titrated to 300 mg at 2- to 4-week intervals to achieve normalized blood pressure (SeDBP <90 mm Hg). If normalized BP was not attained with irbesartan 300 mg alone, adjunctive medications could be added. At 12 months of therapy, the mean reduction in seated systolic blood pressure/SeDBP was 21.0/15.8 mm Hg, and 83% (684/821) of patients were normalized. Of those normalized, 64% were receiving irbesartan monotherapy and 86% were receiving irbesartan or irbesartan/hydrochlorothiazide only. No evidence of tachyphylaxis to the antihypertensive effect of irbesartan was noted. Thus, long-term irbesartan therapy, with or without other antihypertensives, achieved and maintained normalized BP in the majority of patients and was well tolerated.

The antihypertensive efficacy of the combination of irbesartan and hydrochlorothiazide assessed by 24-hour ambulatory blood pressure monitoring. Irbesartan Multicenter Study Group.

In a multicenter, double-blind, randomized trial, 178 patients with ambulatory diastolic blood pressure (BP) > or =85 mm Hg and seated diastolic BP (SeDBP) 95-110 mm Hg received either once-daily irbesartan 75 mg/hydrochlorothiazide (HCTZ) 12.5 mg, irbesartan 150 mg/HCTZ 12.5 mg, or placebo for 8 weeks to assess reductions in 24-hour ambulatory BP and office BP. Safety and tolerability of all treatment regimens were also evaluated. BP results and therapeutic response (trough SeDBP normalized to <90 mm Hg) were expressed as change from baseline to Week 8. Mean reductions in 24-hour ambulatory BP and office seated BP for irbesartan/HCTZ combinations were significantly greater compared with placebo (all, p<0.01). More patients were normalized with irbesartan/HCTZ (65%-69%) than placebo (24%, p<0.01). The frequency of adverse events was similar in all groups. Irbesartan/HCTZ given once-daily appears to be a well-tolerated, safe, and effective antihypertensive treatment.

Matrix study of irbesartan with hydrochlorothiazide in mild-to-moderate hypertension.

The purpose of this study was to assess the safety and antihypertensive dose-response effects of irbesartan and hydrochlorothiazide (HCTZ) in patients with mild-to-moderate hypertension. After a 4- to 5-week single-blind placebo lead-in period, 683 patients with seated diastolic blood pressure (SeDBP) between 95 and 110 mm Hg were randomized to receive once-daily dosing with one of 16 different double-blind, fixed combinations of irbesartan (0, 37.5, 100, and 300 mg irbesartan) and HCTZ (0, 6.25, 12.5, and 25 mg HCTZ) for 8 weeks. The primary efficacy variable was the change from baseline in trough SeDBP after 8 weeks of therapy. Data were analyzed by response surface modeling. At Week 8, mean changes from baseline in trough SeDBP (mm Hg) ranged from -3.5 for placebo, -7.1 to -10.2 for the irbesartan monotherapy groups, -5.1 to -8.3 for the HCTZ monotherapy groups, and -8.1 to -15.0 for the combination groups. Irbesartan plus HCTZ produced additive reductions in both SeDBP and seated systolic BP, with at least one combination producing greater BP reduction than either drug alone (P < .001). All treatments were well tolerated; there were no treatment-related serious adverse events. Irbesartan tended to ameliorate the dose-related biochemical abnormalities associated with HCTZ alone. In conclusion, the combination of HCTZ in doses up to 25 mg with irbesartan, in doses up to 300 mg, is safe and produces dose-dependent reductions in BP.

Safety of irbesartan in the treatment of mild to moderate systemic hypertension.

Nine multicenter, randomized, placebo-controlled studies were conducted to evaluate the safety and tolerability of the angiotensin II subtype 1 receptor blocker (AT1 blocker) irbesartan for the treatment of mild to moderate hypertension. After a 4- to 5-week placebo lead-in phase, patients were randomized to 4 to 12 weeks of double-blind therapy with either placebo (n = 641) or irbesartan (n = 1,965) at doses of 1 to 900 mg orally. All doses of irbesartan were well tolerated with no evidence of dose-related adverse effects. Across the full recommended clinical dose range, although not statistically significantly different, irbesartan use was associated with a lower incidence of adverse events, serious adverse events, and discontinuations due to adverse events compared with placebo. No clinically significant or unexpected changes in laboratory analyses were observed. Withdrawal of irbesartan therapy did not result in rebound hypertension or clinically important adverse events. Thus, irbesartan use in hypertensive patients was associated with a placebo-like safety and tolerability profile.

Comparative efficacy of two angiotensin II receptor antagonists, irbesartan and losartan in mild-to-moderate hypertension. Irbesartan/Losartan Study Investigators.

The primary objectives of this double-blind study were to compare the antihypertensive efficacy and tolerability of irbesartan and losartan, two angiotensin II (AT1 subtype) receptor antagonists with different pharmacokinetic profiles in patients with mild-to-moderate hypertension. Both drugs are approved for once-daily use (although losartan may also be prescribed twice-daily). After a placebo lead-in, 567 patients were randomized (1:1:1:1) to once-daily therapy with placebo, 100 mg losartan, 150 mg irbesartan, or 300 mg irbesartan for 8 weeks. Treatment groups had comparable demographic and baseline characteristics. After 8 weeks of treatment, reductions from baseline in trough seated diastolic blood pressure (SeDBP) and trough seated systolic blood pressure (SeSBP) with 300 mg irbesartan were greater than with 100 mg losartan (P < .01 for both comparisons), by 3.0 and 5.1 mm Hg, respectively; larger reductions were also demonstrated at weeks 1 and 4 (P < .01 and P = .017, respectively, for SeDBP). Throughout the study, the antihypertensive effect of 150 mg irbesartan did not differ significantly from that of 100 mg losartan. All therapies were well tolerated. The 300 mg dose of irbesartan was associated with the lowest incidence of adverse events (AE) and discontinuations because of AE. This study demonstrates that the maximally effective once-daily doses of two different AT1 receptor antagonists may result in clinically significant differences in blood pressure reductions, and therefore highlights the potential importance of the pharmacokinetic and pharmacodynamic differences between these two members of this class.

Dose-related antihypertensive effects of irbesartan in patients with mild-to-moderate hypertension.

Two multicenter, double-blind, placebo-controlled, parallel group studies were conducted to evaluate the efficacy, safety, pharmacokinetics, and pharmacodynamics of the angiotensin II receptor (AT1 subtype) antagonist irbesartan. The effect of irbesartan withdrawal and the effect of adding hydrochlorothiazide (HCTZ) to irbesartan were also assessed. After a placebo lead-in phase, all patients were randomized to 8 weeks of double-blind therapy with either placebo (n = 158) or irbesartan at doses of 1, 5, 10, 25, 50, 100, 200, or 300 mg (n = 731 total) orally once daily. Irbesartan reduced blood pressure in a dose-related manner. Reductions from baseline in trough seated diastolic blood pressure ranged from 7.5 mm Hg for 50 mg irbesartan to 11.6 mm Hg for 300 mg irbesartan. At week 8, statistically significant reductions over placebo were observed in trough seated blood pressure with all irbesartan doses > or = 50 mg. These reductions reached statistical significance versus placebo within 2 weeks with 100, 200, and 300 mg irbesartan. Plasma irbesartan concentrations correlated with dose. Angiotensin II and aldosterone levels generally showed dose-related changes, consistent with AT1 receptor blockade. In patients not controlled at 8 weeks, the addition of 12.5 mg HCTZ resulted in further dose-related reductions in blood pressure. Irbesartan demonstrated a placebo-like safety profile and no dose-related toxicity. Irbesartan, administered alone or in combination with HCTZ, was well tolerated. Withdrawal of irbesartan did not result in rebound hypertension or adverse events. Thus, once-daily irbesartan is both an effective and safe antihypertensive agent for the treatment of mild-to-moderate hypertension.

Dose-related efficacy of irbesartan for hypertension: an integrated analysis.

Results of eight multicenter, randomized, placebo-controlled, double-blind, parallel-group studies were pooled to assess the efficacy of the angiotensin II-receptor blocker irbesartan over the dose range of 1 to 900 mg. A total of 2955 adults with a seated diastolic blood pressure of 95 to 110 mm Hg were randomized to treatment with oral irbesartan once daily or placebo for 6 to 8 weeks. Office blood pressure was measured at trough (24+/-3 hours after the last dose) and peak (3+/-1 hours after the last dose) by mercury sphygmomanometry. Demographic characteristics (mean blood pressure; 151/101 mm Hg; mean age, 54 years; 63% male; and 82% white) were similar across all dose groups. After the groups were pooled, antihypertensive efficacy was assessed by therapeutic response (trough seated diastolic blood pressure <90 mm Hg or a reduction from baseline of > or = 10 mm Hg) and by modeling of the maximum reductions in trough and peak seated diastolic and systolic blood pressure. Antihypertensive effects increased with increasing doses and reached a plateau at > or = 300 mg. Irbesartan 150 mg provided placebo-subtracted reductions in trough seated systolic and diastolic blood pressure of approximately 8 and approximately 5 mm Hg, respectively, with 56% of patients displaying a favorable response. In conclusion, irbesartan provides clinically significant blood pressure lowering, with a clear relationship between (log) dose and antihypertensive effect.