Original Patient Data Research Articles

Review of the ICD Registry's Third Year, Expansion to include Lead Data and Pediatric ICD Procedures, and Role for Measuring Performance

ntroduction he National ICD Registry became the sole repository of CD implantation data for Medicare beneficiaries on April , 2006, and as of June 2009 had collected data from ,432 hospitals in the United States totaling over 380,000 mplants. The registry was developed through a partnership f the Heart Rhythm Society (HRS [www.HRSonline.org]) nd the American College of Cardiology Foundation ACCF [www.acc.org]) utilizing the expertise of the ational Cardiovascular Data Registry (NCDR [www. ccncdr.com]) and has made substantial progress toward everal predefined goals:

Review of the Registry's Second Year, Data Collected, and Plans to Add Lead and Pediatric ICD Procedures

esenc F d m l b t G t N d s Q o M N h a c p i t t i e r i e t a e y p c e t t b T t ntroduction he National ICD Registry became the sole repository of CD implantation data for Medicare beneficiaries April 1, 006 and as of June 2008 had collected data from 1,448 ospitals in the United States totaling over 270,373 imlants. This registry was developed through a partnership of he Heart Rhythm Society (HRS; www.HRSonline.org) and he American College of Cardiology Foundation (ACCF; ww.acc.org) utilizing the expertise of the National C iovascular Data Registry (NCDR; www.accncdr.com). he National ICD Registry is accruing ICD implants at the ate of 10,000 per month with 88% of implants being done n hospitals that enter all patients receiving ICDs including oth primary and secondary prevention indications in all ge groups. A rigorous Data Quality Reporting process is in lace to ensure data accuracy and hospital auditing will egin the summer of 2008. Six abstracts have been pr ed, and four manuscripts are in development utilizing ata generated from the National ICD Registry answering ey clinical questions elicited from the growing ICD imlant patient database ( http://www.accncdr.com). Funding or the Longitudinal ICD Registry Study has been procured, nd the study will begin in 2008. The scope of the National CD registry is being expanded to include data on new trial, ventricular, defibrillation, and left-heart leads placed t the time of ICD implant and whenever existing leads are epositioned, replaced, extracted or abandoned. These data ill assist the Food and Drug Administration (FDA) with urveillance of lead performance. Pediatric ICD implantaions will be followed in the Registry; and the Registry is eing positioned to serve as a performance reporting tool to ssist with quality measures.

Impact of clinical and molecular predictors of benefit from erlotinib in advanced non-small cell lung cancer on cost-effectiveness

6531 Background: Previously we have shown that the incremental cost effectiveness ratio (ICER) of erlotinib, in unselected patients with advanced non-small cell lung cancer (NSCLC) after chemotherapy failure, was $95,869 (2007 CAD), per life year gained (LYG), using original patient data from the NCIC CTG BR.21 trial of erlotinib versus placebo in advanced NSCLC. Here, we investigate the value of combining clinical and molecular predictors of outcome to identify more, and less cost- effective patient subgroups for treatment. Methods: Cost-effectiveness ranges of interest were identified a priori: group A ICER <$50,000/LYG, B $50,000- 75,000/LYG and C >$200,000/LYG CAD. Significant clinical and molecular predictors of outcome from the BR.21 trial were assessed to identify groups within these thresholds of cost-effectiveness, and to characterize patient characteristics of each group that had >50 patients. Due to small numbers, EGFR mutation status was not included. Results: The subgroup with lowest ICER ($22,564/LYG; n=52) consisted of patients with adenocarcinoma, never smoker status who had received one prior chemotherapy regimen. By contrast, past and present smokers with wild-type EGFR and K-ras gene mutation had the highest ICER for erlotinib treatment ($3,862,962/LYG; n=52). The presence of one of the following variables, never smoking status, high EGFR copy number or EGFR protein positive tumours (immunohistochemistry), predicted for lower ICERs in groups A and B, irrespective of histological subtype. Female gender was associated with higher ICERs in all three groups. Conclusions: Incorporation of molecular and clinical predictors into economic analyses has the potential to differentiate cost-effective versus cost-ineffective subgroups for treatment. We identified subsets of patients (e.g. smoking history, non-adenocarcinoma histology) who could be treated within a reasonable range of cost effectiveness. While subset analyses must be interpreted with caution, examining different methodological approaches in the economic analysis of novel agents is warranted and a parallel investigation using classification and regression tree methodology is underway. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Roche and OSIP Roche, Roche and OSIP

Outcome analysis of childhood low‐grade astrocytomas

We aimed to determine the long-term natural history of low-grade astrocytomas (LGA) in children, with respect to pathology, and to evaluate influence of treatment on survival. A consecutive cohort of patients < or =21 years with surgically confirmed LGA from 1965 to 1996 was assembled. All available pathology specimens were reviewed, masked to original diagnosis, patient data, and neuroimaging. Two hundred seventy-eight children (160 males; mean age 9.1 years; tumor location: 77 cerebrum, 62 cerebellum, 51 hypothalamic, 30 thalamus, 9 ventricle, 40 brainstem, and 9 spine) were assessed. Among 246 specimens reviewed, diagnoses were 135 pilocytic astrocytoma (PA), 27 diffuse astrocytoma (DA), 75 unclassifiable well-differentiated astrocytoma (NOS), and 9 subependymal giant cell astrocytoma. At 5 and 10 years from initial surgery, for all LGA overall survival (OS) was 87% and 83%, while progression-free survival (PFS) was 55% and 42%, respectively. Original pathology diagnoses did not predict PFS (P = 0.47), but reviewed diagnoses were significantly associated with PFS (P = 0.007). Reviewed diagnoses were highly associated with OS (P < 0.0001), with 5-year OS for PA 96%, DA 48%, and NOS 86%; these differences remained significant when stratified by location or extent of resection. Among patients with residual tumor after surgery, 5-year PFS was 48% with observation alone (n = 114), no different (P = 0.32) from that achieved with immediate irradiation (n = 86). LGA, particularly PA, have excellent long-term OS. While tumor location and resection extent affect outcome, pathologic diagnosis when carefully interpreted significantly influences long-term survival. Immediate postoperative irradiation does not confer an advantage in delaying first progression in children with residual PA.

Cortical dopamine D 2/D 3 receptors are a common site of action for antipsychotic drugs — An original patient data meta-analysis of the SPET and PET in vivo receptor imaging literature

Cortical dopamine D 2/D 3 receptors are a common site of action for antipsychotic drugs — An original patient data meta-analysis of the SPET and PET in vivo receptor imaging literature

Classification of neurovascular compression in typical hemifacial spasm: three-dimensional visualization of the facial and the vestibulocochlear nerves

In this paper, the authors introduce a method of noninvasive anatomical analysis of the facial nerve-vestibulocochlear nerve complex and the depiction of the variable vascular relationships by using 3D volume visualization. With this technique, a detailed spatial representation of the facial and vestibulocochlear nerves was obtained. Patients with hemifacial spasm (HFS) resulting from neurovascular compression (NVC) were examined. A total of 25 patients (13 males and 12 females) with HFS underwent 3D visualization using magnetic resonance (MR) imaging with 3D constructive interference in a steady state (CISS). Each data set was segmented and visualized with respect to the individual neurovascular relationships by direct volume rendering. Segmentation and visualization of the facial and vestibulocochlear nerves were performed with reference to their root exit zone (REZ), as well as proximal and distal segments including corresponding blood vessels. The 3D visualizations were interactively compared with the intraoperative situation during microvascular decompression (MVD) to verify the results with the observed microneurosurgical anatomy. Of the 25 patients, 20 underwent MVD (80%). Microvascular details were recorded on the affected and unaffected sides. On the affected sides, the anterior inferior cerebellar artery (AICA) was the most common causative vessel. The posterior inferior cerebellar artery, vertebral artery, internal auditory artery, and veins at the REZ of the facial nerve (the seventh cranial nerve) were also found to cause vascular contacts to the REZ of the facial nerve. In addition to this, the authors identified three distinct types of NVC within the REZ of the facial nerve at the affected sides. The authors analyzed the varying courses of the vessels on the unaffected sides. There were no bilateral clinical symptoms of HFS and no bilateral vascular compression of the REZ of the facial nerve. The authors discovered that the AICA is the most common vessel that interferes with the proximal and distal portions of the facial nerve without any contact between vessels and the REZ of the facial nerve on the unaffected sides. Three-dimensional visualization by direct volume rendering of 3D CISS MR imaging data offers the opportunity of noninvasive exploration and anatomical categorization of the facial nerve-vestibulocochlear nerve complex. Furthermore, it proves to be advantageous in establishing the diagnosis and guiding neurosurgical procedures by representing original MR imaging patient data in a 3D fashion. This modality provides an excellent overview of the entire neurovascular relationship of the cerebellopontine angle in each case.

Is the Superior Efficacy of New Generation Antipsychotics an Artifact of LOCF?

It has been argued that the efficacy superiority found in meta-analyses for some of the atypical antipsychotics is an artifact of higher dropout rates due to side effects in the haloperidol group combined with last-observation-carried-forward (LOCF) analyses. We therefore reanalyzed a number of pivotal studies comparing new generation antipsychotics (NGAs) and conventional antipsychotics (CAs). A total of 5 studies (n = 1271) comparing amisulpride and 3 studies (n = 2454) comparing olanzapine with CAs were reanalyzed using original patient data. We applied 4 different models: LOCF, completer analysis, LOCF but excluding dropouts due to adverse events, and LOCF but excluding all dropouts with the exception of dropouts related to efficacy. Effect sizes expressed as standardized mean differences between NGAs and CAs based on the 4 different analysis models were compared. The overall results were not different irrespective of the model used. Single studies, however, showed higher effect sizes when LOCF instead of other models was used. Overall, it does not seem that higher dropout rates due to side effects in the haloperidol groups together with LOCF analyses consistently biased the results in favor of amisulpride and olanzapine. Because the results of the single studies, however, showed that this may occasionally be the case, future studies should look at the data from different angles applying sensitivity analyses, and they may use alternative statistics such as mixed models, which need to be developed further. Ultimately, strategies to reduce dropout rates are needed.

A Comparison of Pain, Strength, Range of Motion, and Functional Outcomes After Hemiarthroplasty and Total Shoulder Arthroplasty in Patients with Osteoarthritis of the Shoulder

A systematic review of the literature was performed to estimate the impact of hemiarthroplasty compared with total shoulder arthroplasty on function and range of motion in patients suffering from osteoarthritis of the shoulder. We conducted an electronic search for relevant studies published in any language from 1966 to 2004, a manual search of the proceedings from five major orthopaedic meetings from 1995 to 2003, and a review of the reference lists from potentially relevant studies. Four randomized clinical trials, with similar eligibility criteria and surgical techniques, that compared hemiarthroplasty and total shoulder arthroplasty for the treatment of primary osteoarthritis of the shoulder were found to be eligible. Authors from three of the four studies provided original patient data. Analysis of covariance focused on the two-year outcome and included a comparison of the aggregate University of California at Los Angeles shoulder score, four University of California at Los Angeles domain scores, and range of motion. A total of 112 patients (fifty managed with hemiarthroplasty and sixty-two managed with total shoulder arthroplasty), who had a mean age of sixty-eight years, were included in this analysis. A significant moderate effect was detected in the function domain of the University of California at Los Angeles shoulder score (p < 0.001) in favor of total shoulder arthroplasty (mean [and standard deviation], 8.1 +/- 0.3) compared with hemiarthroplasty (mean, 6.6 +/- 0.3). A significant difference in the pain score was found in favor of the total shoulder arthroplasty group (p < 0.0001). However, the large degree of heterogeneity (p = 0.006, I(2) = 80.2%) among the studies decreased our confidence that total shoulder arthroplasty provides a true, consistent benefit with regard to pain. There was a significant difference in the overall change in forward elevation of 13 degrees (95% confidence interval, 0.5 degrees to 26 degrees ) in favor of the total shoulder arthroplasty group (p = 0.008). At a minimum of two years of follow-up, total shoulder arthroplasty provided better functional outcome than hemiarthroplasty for patients with osteoarthritis of the shoulder. Since continuous degeneration of the glenoid after hemiarthroplasty or glenoid loosening after total shoulder arthroplasty may affect the eventual outcome, longer-term (five to ten-year) results are necessary to determine whether these findings remain consistent over time.

The Relative Sensitivity of the Clinical Global Impressions Scale and the Brief Psychiatric Rating Scale in Antipsychotic Drug Trials

Although the Clinical Global Impression (CGI) and the Brief Psychiatric Rating Scale (BPRS) are both frequently used in drug trials for schizophrenia, their relative sensitivity in detecting differences between antipsychotics has not yet been examined. We therefore reanalyzed original patient data from all four pivotal, randomized controlled studies (n = 1205) that compared amisulpride with haloperidol in patients with schizophrenia. The sensitivity of the BPRS vs the CGI-improvement and the CGI-severity scales in detecting between-drug differences was estimated by calculating effect sizes and their 95% confidence intervals for both continuous (standardized mean differences) and dichotomous outcomes (odds ratios). The primary end points were the last observation carried forward results at study end points pooling all studies, but the results of the observed cases at different study weeks and the results of the single studies were also examined. The effect sizes derived from the BPRS and from the CGI were similar. When the single studies were pooled, all outcomes analyzed showed a statistically significant superiority of amisulpride compared to haloperidol as early as 2 weeks after initiation of treatment. The CGI may be as sensitive as the BPRS in detecting efficacy differences between antipsychotic drugs, although specific studies with truly independent ratings would be needed for confirmation. The fact that it takes only 1-2 min to fill in the CGI justifies its use in addition to more specific scales in drug trials for schizophrenia. Further development and evaluation of the CGI is warranted.

Cigarette Smoking and Risk of Non-Hodgkin Lymphoma: A Pooled Analysis from the International Lymphoma Epidemiology Consortium (InterLymph)

The International Lymphoma Epidemiology Consortium (InterLymph) provides an opportunity to analyze the relationship between cigarette smoking and non-Hodgkin lymphoma with sufficient statistical power to consider non-Hodgkin lymphoma subtype. The results from previous studies of this relationship have been inconsistent, likely due to the small sample sizes that arose from stratification by disease subtype. To clarify the role of cigarette smoking in the etiology of non-Hodgkin lymphoma, we conducted a pooled analysis of original patient data from nine case-control studies of non-Hodgkin lymphoma conducted in the United States, Europe, and Australia. Original data were obtained from each study and uniformly coded. Risk estimates from fixed-effects and two-stage random-effects models were compared to determine the impact of interstudy heterogeneity. Odds ratios (OR) and 95% confidence intervals (95% CI) were derived from unconditional logistic regression models, controlling for study center, age, sex, and race. In our pooled study population of 6,594 cases and 8,892 controls, smoking was associated with slightly increased risk estimates (OR, 1.07; 95% CI, 1.00-1.15). Stratification by non-Hodgkin lymphoma subtype revealed that the most consistent association between cigarette smoking and non-Hodgkin lymphoma was observed among follicular lymphomas (n = 1452). Compared with nonsmokers, current smokers had a higher OR for follicular lymphoma (1.31; 95% CI, 1.12-1.52) than former smokers (1.06; 95% CI, 0.93-1.22). Current heavy smoking (> or = 36 pack-years) was associated with a 45% increased OR for follicular lymphoma (1.45; 95% CI, 1.15-1.82) compared with nonsmokers. Cigarette smoking may increase the risk of developing follicular lymphoma but does not seem to affect risk of the other non-Hodgkin lymphoma subtypes we examined. Future research is needed to determine the biological mechanism responsible for our subtype-specific results.

Review: in people with schizophrenia, lithium is ineffective as sole therapy, while evidence on augmenting antipsychotics with lithium is inconclusive

Leucht S, Kissling W, McGrath J. Lithium for schizophrenia revisited: a systematic review and meta-analysis of randomized controlled trials. J Clin Psychiatry 2004;65:177–86.[OpenUrl][1][PubMed][2][Web of Science][3] Q Is lithium, as a...

Childbirth preferences after cesarean birth: a review of the evidence.

Conflicting evidence on maternal and fetal safety of vaginal and cesarean childbirth after a previous cesarean makes patients and practitioners uncertain about pursuing a trial of labor or an elective repeat cesarean delivery. This review systematically evaluated and summarized the evidence related to women's preference for delivery. The Cochrane Database of Systematic Reviews and Registry of Controlled Trials and the MEDLINE, HealthSTAR, PsycINFO, and CINAHL databases were searched from 1980 to August 2002. We reviewed controlled trials, case-control studies, and observational studies that contained original patient data on preference for women with a previous cesarean delivery and that were of "good" or "fair" quality. Women with a previous vaginal delivery were more likely to select trial of labor than women who did not have one. The most commonly cited reason for selecting trial of labor was ease of recovery and desire to return quickly to caring for other children (reported in 6 of 7 studies). Safety for the mother and/or infant was cited as an important reason for delivery choice in 4 of 11 studies. Important ethnic differences were reported. Nonwhite women were more likely to identify their provider as an important influence (39% vs 19%), and perceived labor as something to be avoided if another option resulted in a healthy baby compared with white women, who perceived labor as a challenge and an experience not to be missed. A woman's choice for delivery was often based on family obligations, such as the need for a shorter recovery so that she could care for her infant and children at home, rather than the safety of herself or her infant. It remains unclear if education on vaginal birth after cesarean increases the proportion of women who choose trial of labor. Future studies should evaluate the impact of education and timing of education on patient preference.

Lithium for Schizophrenia Revisited

Clinicians frequently use lithium to augment antipsychotic medication in schizophrenia. Therefore, we undertook a systematic review and meta-analysis of the use of lithium in the treatment of schizophrenia. Randomized controlled trials examining lithium (as a sole or an adjunctive compound) in participants with schizophrenia or related disorders were searched in the register of the Cochrane Schizophrenia Group. No language restrictions were applied. The Boolean phrase [lithium* or lithicarb or eskalith or lithobid or lithane or cibalith-s or quilonum or hypnorex] was used to locate articles. The search strategy initially identified 90 references. The authors of the included studies were contacted to obtain original patient data. The data were combined in a meta-analysis. The main outcome parameters were the number of patients with a clinically significant response and the number of patients leaving the studies early. The meta-analysis includes 20 studies (N = 611). The evidence shows that lithium as a sole agent is ineffective in the treatment of schizophrenia. Eleven trials examined the augmentation of antipsychotics with lithium. More patients who received lithium augmentation than those who received antipsychotics alone were classified as responders. However, the superiority was not consistent across different response thresholds, and when patients with prominent affective symptoms were excluded from the analysis, the advantage of lithium augmentation was not significant (p =.07). Significantly more patients taking lithium left the trials early, suggesting a lower acceptability of lithium augmentation compared with that of taking antipsychotics alone. Despite some evidence in favor of lithium augmentation, the overall results are inconclusive. A large trial of lithium augmentation of antipsychotic medications will be required in order to detect a benefit of small effect size in patients with schizophrenia who lack affective symptoms.

Carbamazepine augmentation for schizophrenia: how good is the evidence?

Augmentation strategies in schizophrenia treatment remain an important issue because despite the introduction of several new antipsychotics, many patients remain treatment resistant. The aim of this study was to undertake a systematic review and meta-analysis of the safety and efficacy of one frequently used adjunctive compound: carbamazepine. Randomized controlled trials comparing carbamazepine (as a sole or as an adjunctive compound) with placebo or no intervention in participants with schizophrenia or schizoaffective disorder were searched for by accessing 7 electronic databases, cross-referencing publications cited in pertinent studies, and contacting drug companies that manufacture carbamazepine. The identified studies were independently inspected and their quality assessed by 2 reviewers. Because the study results were generally incompletely reported, original patient data were requested from the authors; data were received for 8 of the 10 randomized controlled trials included in the present analysis, allowing for a reanalysis of the primary data. Dichotomous variables were analyzed using the Mantel-Haenszel odds ratio and continuous data were analyzed using standardized mean differences, both specified with 95% confidence intervals. Ten studies (total N = 283 subjects) were included. Carbamazepine was not effective in preventing relapse in the only randomized controlled trial that compared carbamazepine monotherapy with placebo. Carbamazepine tended to be less effective than perphenazine in the only trial comparing carbamazepine with an antipsychotic. Although there was a trend indicating a benefit from carbamazepine as an adjunct to antipsychotics, this trend did not reach statistical significance. At present, this augmentation strategy cannot be recommended for routine use. The most promising targets for future trials are patients with excitement, aggression, and schizoaffective disorder bipolar type.

Non-linear model for the kinetics of 10B in blood after BPA–fructose complex infusion

A numerical model with a memory effect was created to describe the kinetics of 10B in blood after a single 4-dihydroxyborylphenylalanine–fructose complex (BPA–F) infusion in boron neutron capture therapy (BNCT). The model formulation was based on the averaged data from 10 glioma patients from the Brookhaven National Laboratory (BNL) BNCT-trials. These patients received a 2 h i.v. infusion of a BPA–fructose complex that delivered 290 mg BPA/kg body weight. The model was validated by fitting the original BNL patient data and new patient data from the Finnish BNCT-trials. The new 3-parameter non-linear model provided mean absolute differences between the measured and estimated 10B concentrations in blood that were less than 3.9% when used to simulate actual patient irradiations that comprised two irradiation fields separated by a break to reposition the patient. The flexibility of the model was successfully tested with two different infusion protocols. The patient data were modelled with a two-compartment model and a bi-exponential fit for comparison. The 3-parameter model is better than previously described models in predicting the time course of blood 10B concentration after cessation of intravenous infusion of BPA–fructose.

A meta-analysis using individual patient data of trials comparing artemether with quinine in the treatment of severe falciparum malaria

We conducted a meta-analysis using individual patient data from randomized controlled trials comparing artemether and quinine in severe falciparum malaria. Eleven trials were identified, of which 8 were clearly randomized. Original individual patient data on 1919 patients were obtained from 7 trials, representing 85% of the patients in the original 11 studies. Overall there were 136 deaths among the 961 patients treated with artemether, compared with 164 in the 958 treated with quinine [14% vs 17%, odds ratio (95% confidence interval) 0·8 (0·62 to 1·02), P = 0·08]. There were no differences between the 2 treatment groups in coma recovery or fever clearance times, or the development of neurological sequelae. However, the combined ‘adverse outcome’ of either death or neurological sequelae was significantly less common in the artemether group [odds ratio (95% CI) 0·77 (0·62 to 0·96), P = 0·02], and treatment with artemether was associated with significantly faster parasite clearance [hazard ratio (95% CI) 0·62 (0·56 to 0·69), P < 0·001]. In subgroup analyses artemether was associated with a significantly lower mortality than quinine in adults with multisystem failure. In the treatment of severe falciparum malaria artemether is at least as effective as quinine in terms of mortality and superior to quinine in terms of overall serious adverse events. There was no evidence of clinical neurotoxicity or any other major side-effects associated with its use.

Low Molecular Weight Heparin and Unfractionated Heparin in Thrombosis Prophylaxis: Meta-Analysis Based on Original Patient Data

A meta-analysis (MA) based on original patient data has been performed comparing low molecular weight heparins (LMWH) with unfractionated heparin (UFH) in thrombosis prophylaxis after major surgical interventions. The analyses have been done for the following prespecified groups of studies: all studies, studies in orthopaedic surgery (OS) and studies in general surgery (GS, with further separation into low-dose studies [GS-LD] and high-dose studies [GS-HD]). Deep vein thrombosis (DVT, all locations) and wound haematoma were used as primary endpoints for efficacy and safety, respectively. The analysis confirms the results of previous publication-based meta-analyses. In GS there is no relevant difference between LMWH and UFH regarding efficacy; the safety results strongly depend on the dosage: under low-dose LMWH the risk of wound haematoma is significantly lower, under high-dose LMWH it is significantly higher than under UFH. However, most of the studies in the last group used regimens of LMWH that are not considered appropriate any more. In OS there is a trend towards a better efficacy and safety of LMWH. In addition, LMWHs are superior to UFH, in OS, with respect to the secondary endpoints proximal DVT and pulmonary embolism. The rates of proximal DVT and pulmonary embolism, respectively, are consistently lower under LMWH than under UFH, whereas slightly smaller rates of distal DVT are observed under UFH.

Meta-analysis of Two Randomized Controlled Trials Comparing Combined Zidovudine and Didanosine Therapy With Combined Zidovudine, Didanosine, and Nevirapine Therapy in Patients With HIV

To extend the range of CD4 counts in which a plasma viral load nadir (pVL) <20 copies/ml was known to be predictive of the duration of virologic response. To determine whether baseline pVL is predictive of virologic response during the study periods. A meta-analysis was conducted of the original individual patient data from two randomized controlled trials comparing zidovudine (ZDV)/didanosine (ddI) with ZDV/ddI/nevirapine (NVP). In total, 87 patients received ZDV/ddI and 83 received ZDV/ddI/NVP. Study subjects on triple therapy with baseline pVL <100,000 copies/ml were more likely to achieve a pVL <400 copies/ml (odds ratio [OR] = 2.49; p = .02) and <20 copies/ml (OR = 4.76; p = .001) during the trial than those with baseline pVL > 100,000 copies/ml. Among triple therapy patients, the relative risk of virologic failure was higher for patients with higher baseline pVL (rate ratio [RR] = 2.51/log10 copies/ ml; p = .01), after controlling for compliance and pVL nadir. The relative risks of virologic failure associated with pVL nadir <20 copies/ml and between 21 and 400 copies/ml were .04 (p = .0001) and .56 (p = .26), respectively, compared with patients with a pVL nadir >400 copies/ml. We have extended our earlier results that achieving a pVL nadir <20 copies/ml is important for maintaining virologic suppression. In particular, we have demonstrated that a pVL nadir <20 copies/ml is at least fivefold more protective against virologic failure than achieving a pVL nadir between 20 and 400 copies/ml. Baseline pVL is significantly associated with the probability of achieving and sustaining virologic suppression.

A systematic review of the evidence for hypodermoclysis to treat dehydration in older people.

The purpose of the study was to evaluate the evidence supporting the use of hypodermoclysis (i.e., subcutaneous infusion of fluids) to treat dehydrated elderly patients, and to discuss clinical applications of this mode of therapy in the long-term care setting. Articles reporting the use of hypodermoclysis were identified using a systematic MEDLINE search between January 1966 and May 1996. Articles were included in our sample if they contained original patient data that evaluated either the efficacy or adverse effects associated with the use of subcutaneous infusions to treat dehydration in adults, whether hyaluronidase was required to facilitate the absorption of subcutaneous fluid, or if potassium could be added to the solution. Eighteen articles met the inclusion criteria. Since we hypothesized that adverse effects associated with hypodermoclysis may have been related largely to the use of nonelectrolyte or hypertonic solutions, the studies were evaluated according to the type of fluid administered. Six hundred and eighty-five patients were described in 13 studies evaluating the efficacy and toxicity of subcutaneously administered fluid. Four studies evaluated hypodermoclysis using electrolyte-containing solutions in 25 patients. Two of these were randomized control trials (RCT) that compared hypodermoclysis to intravenous therapy. Both reported similar absorption of fluids. In the single RCT that evaluated adverse effects, 4 of 17 patients receiving hypodermoclysis reported minor side effects similar to those reported with intravenous therapy. Adverse effects were more severe when electrolyte-free or hypertonic solutions were evaluated. Of the 639 patients who may have received electrolyte-free solutions, 16 patients (2.5%) reported adverse effects, 8 of which were severe. Both patients reported to have received hypertonic solutions noted adverse effects, one of which was severe. The use of hyaluronidase to facilitate absorption was evaluated in 74 patients. These studies suggest that hyaluronidase improves the speed of fluid absorption but may not change the patient's comfort level. A single case report of 350 subcutaneous infusions in 67 patients investigated the administration of up to 34 mmol/L of potassium chloride (KCl) by hypodermoclysis. The only adverse reaction observed was discomfort at the infusion site. Hypodermoclysis can be used to most safely provide fluids when electrolyte-containing fluids are administered. Hypodermoclysis may have fallen into disuse because of reports of severe adverse reactions related to infusions of electrolyte-free or hypertonic solutions that would likely be considered inappropriate today. Whether or not hyaluronidase is required to promote subcutaneous fluid absorption remains unresolved. Limited evidence suggests that potassium chloride may, with caution, be safely added to subcutaneous infusions. The majority of the available studies evaluating hypodermoclysis are of poor quality. Because of the tremendous potential benefits of administering fluid subcutaneously, there is a need for good quality studies to evaluate the efficacy of hypodermoclysis.

A Comparison of Meta-analytic Results Using Literature vs Individual Patient Data

To compare the meta-analytic results from published literature vs those obtained from pooling original patient data. Individual patient data from 15 completed or ongoing trials on paternal white blood cell immunization as treatment for recurrent miscarriage were obtained through the American Society for Reproductive Immunology. Only randomized controlled trials were selected. Within these eight selected trials, 202 patients were from four published studies, 43 were added by the same investigators after publication, and 140 were from four unpublished trials. Individual patient data were collected using a standardized form and double data entry. Using the fixed treatment effect model, we found that the effect of immunization, denoted as the relative live-birth ratio (RR), was greater by pooling summary data from published articles (RR, 1.29; 95% confidence interval [CI], 1.03 to 1.60) than by pooling all individual patient data from the same investigators (RR, 1.17; 95% CI, 0.97 to 1.37) or when individual patient data were pooled from four unpublished trials (RR, 1.01; 95% CI, 0.74 to 1.28). A similar diminishing treatment effect for the same comparisons was observed using the random treatment effect model (RR, 1.38; 95% CI, 0.89 to 1.87 using published summary data; RR, 1.18; 95% CI, 0.98 to 1.42 using individual patient data; RR, 1.01; 95% CI, 0.74 to 1.28 using unpublished trials). Meta-analytic results may differ depending on the use of various data sources: whether the source was from summary statistics in the literature, from individual patient data provided by trialists, or from unpublished trials.