Biomedical subjects

D C Hoaglin

Publications and source records attributed to D C Hoaglin.

At least 19 recordsLinked to original sources

PubMed1997

Cancer incidence and mortality: the priority of screening frequency and population coverage.

In addition to the usual measures of screening-test performance, it is important to consider testing frequency when evaluating a screening program. Data on which to base recommendations for the timing of screening tests are urgently needed. For example, in the cases of cervical and colon cancer, when the target is a precursor lesion, research indicates that less frequent screening may be appropriate. This finding may not apply, however, to screening for breast cancer by mammography, which requires currently recommended intervals for the early detection of malignancies. Resources now allocated to breast cancer might more effectively be applied to the construction of tests that would permit longer intervals between screenings. To achieve the National Cancer Institute's goal of reducing cancer mortality in the United States by the year 2000, it will be important to review the balance between population coverage and individual screening for each cancer and to emphasize prevention strategies that maximize population coverage while minimizing expenditures.

Adult↗

PubMed1996

Simple robust procedures for combining risk differences in sets of 2 x 2 tables.

Meta-analyses often use a random-effects model to incorporate unexplained heterogeneity of study results. Trimmed versions of meta-analytic estimators for the risk difference, adapted from procedures designed for a random-effects analysis, can resist the impact of a few anomalous studies. A simulation study compared untrimmed and trimmed versions of four meta-analytic procedures that give weighted averages of risk differences. An adaptation of Winsorized estimates of components of variance gains some resistance to anomalous studies when estimating variability. The simulations found that a modified version of the DerSimonian-Laird estimator is attractive when risk differences reveal the added variability described by a random-effects model, and that a 20 per cent trimmed, weighted version of this procedure offers resistance against the impact of highly anomalous results. Among four trimmed procedures considered, the trimmed version of the modified DerSimonian-Laird estimator offers the best performance over a wide range of simulation designs and sample sizes. None of the methods, whether trimmed or untrimmed, is uniformly preferable. A published meta-analysis of a vaccination against TB provides data that serve to illustrate differences among the eight procedures.

BCG Vaccine↗

PubMed1996

Multiple-outcome meta-analysis of clinical trials.

When several clinical trials report multiple outcomes, meta-analyses ordinarily analyse each outcome separately. Instead, by applying generalized-least-squares (GLS) regression, Raudenbush et al. showed how to analyse the multiple outcomes jointly in a single model. A variant of their GLS approach, discussed here, can incorporate correlations among the outcomes within treatment groups and thus provide more accurate estimates. Also, it facilitates adjustment for covariates. In our approach, each study need not report all outcomes nor evaluate all treatments. For example, a meta-analysis may evaluate two or more treatments (one 'treatment' may be a control) and include all randomized controlled trials that report on any subset (of one or more) of the treatments of interest. The analysis omits other treatments that these trials evaluated but that are not of interest to the meta-analyst. In the proposed fixed-effects GLS regression model, study-level and treatment-arm-level covariates may be predictors of one or more of the outcomes. An analysis of rheumatoid arthritis data from trials of second-line drug treatments (used after initial standard therapies prove unsatisfactory for a patient) motivates and applies the method. Data from 44 randomized controlled trials were used to evaluate the effectiveness of injectable gold and auranofin on the three outcomes tender joint count, grip strength, and erythrocyte sedimentation rate. The covariates in the regression model were quality and duration of trial and baseline measures of the patients' disease severity and disease activity in each trial. The meta-analysis found that gold was significantly more effective than auranofin on all three treatment outcomes. For all estimated coefficients, the multiple-outcomes model produced moderate changes in their values and slightly smaller standard errors, to the three separate outcome models.

Antirheumatic Agents↗

PubMed1995

A random-effects regression model for meta-analysis.

Many meta-analyses use a random-effects model to account for heterogeneity among study results, beyond the variation associated with fixed effects. A random-effects regression approach for the synthesis of 2 x 2 tables allows the inclusion of covariates that may explain heterogeneity. A simulation study found that the random-effects regression method performs well in the context of a meta-analysis of the efficacy of a vaccine for the prevention of tuberculosis, where certain factors are thought to modify vaccine efficacy. A smoothed estimator of the within-study variances produced less bias in the estimated regression coefficients. The method provided very good power for detecting a non-zero intercept term (representing overall treatment efficacy) but low power for detecting a weak covariate in a meta-analysis of 10 studies. We illustrate the model by exploring the relationship between vaccine efficacy and one factor thought to modify efficacy. The model also applies to the meta-analysis of continuous outcomes when covariates are present.

BCG Vaccine↗

PubMed1995

Multiple-outcomes meta-analysis of treatments for periodontal disease.

The results of periodontal therapy vary by disease severity, outcome measure, and method of data analysis. Several clinical trials and a subsequent meta-analysis have demonstrated that, for teeth with severe disease, surgery decreases probing depth (PD) and increases attachment level (AL) more than non-surgical treatment. For other disease levels, the choice of therapy depends on the outcome measure. When clinical trials use two or more outcome measures (such as PD and AL), investigators ordinarily analyze each outcome separately. When the correlations are incorporated among the outcomes, a meta-analysis can use generalized-least-squares (GLS) regression to analyze multiple outcomes jointly. We applied the GLS multiple-outcomes model in a meta-analysis of 5 trials comparing surgical and non-surgical periodontal treatments, each assessing the outcomes PD and AL one year after treatment. The clinical conclusions are similar to those reported earlier, but our estimates of the relative benefits of surgical and non-surgical treatment should be more accurate, because the GLS method takes into account correlation between AL and PD. When correlations between the two outcomes rise, as they do with increasing severity of disease, the GLS estimates depart from those derived from separate analyses of PD and AL.

Dental Scaling↗

PubMed1993

Revising a display of multidimensional laboratory measurements to improve accuracy of perception.

To display multidimensional laboratory measurements, Hoeke et al. (1991) proposed a technique that uses plotting axes radiating from a point, assigns each test to a separate axis, and links the test results with line segments. A special nonlinear scaling ensures that a patient whose results all fall in the normal range is represented by a regular polygon of middle size, and colored zones emphasize more serious departures from the normal range. Results of research in graphical perception, however, point to potential difficulties in clinical applications. Those results also suggest a revision of the display that should overcome the difficulties. The new version plots the test results on parallel horizontal lines and links the points for adjacent tests by line segments, while retaining the special scaling and the colored bands.

Clinical Laboratory Techniques↗

PubMed1993

The effect of selective drainage positions on oxygen saturation in obese patients after upper abdominal surgery.

The obese patients undergoing upper abdominal surgery are at particularly high risk to develop postoperative pulmonary complications, and hypoxemia is one of the most common ones reported. During the initial postoperative period, they are often advised to maintain a semi-sitting position to optimize oxygenation. Although chest physical therapy usually avoids a Trendelenburg position, no published data indicate this position as being able to induce desaturation in obese patients following upper abdominal surgery. We studied fifteen adult obese patients without cardiopulmonary disease undergoing upper abdominal surgery. All patients were tested for 5 minutes during the first 3 postoperative days in each of 3 positions: semi-sitting, bed-flat lateral decubitus, and 15 degrees of Trendelenburg lateral decubitus positions. A statistically significant difference in oxygen saturation related to position was found only on the first postoperative day between semi-sitting and bed-flat lateral decubitus positions. The difference in mean SaO2 value between these 2 positions, however, was only 0.88%; and no significant correlation between the magnitude of obesity and the mean SaO2 difference was found. Although arterial oxygen saturation demonstrated statistically significant daily improvement during the first 3 postoperative days, the mean SaO2 values for any 2 consecutive days differed by less than 0.78%. Thus, in obese patients following upper abdominal surgery, 15 degrees of Trendelenburg lateral decubitus and bed-flat lateral decubitus positions do not induce clinically significant desaturation and can be used if necessary and appropriate. In obese patients with borderline oxygenation, supplemental oxygen used postoperatively can maintain adequate oxygenation and allow aggressive positioning.

Abdomen↗

PubMed1991

Oxygenated cardioplegia: the metabolic and functional effects of glucose and insulin.

Reports differ as to the efficacy of glucose and insulin as cardioplegic additives. Although deliberate oxygenation of crystalloid cardioplegic solutions improves myocardial protection, little is known about the protection afforded by glucose and insulin in such oxygenated solutions. In the isolated working rat heart, we studied the addition of oxygen, glucose, and insulin, separately and together, to a cardioplegic solution. The solution was equilibrated with O2 or N2, with glucose added as a substrate or sucrose as a nonmetabolizable osmotic control, with or without insulin. Hearts were arrested for 2 hours at 8 degrees C by multidose infusions. Oxygenation decreased lactate production and improved high-energy phosphate and glycogen preservation during arrest, prevented ischemic contracture, and improved functional recovery. The addition of glucose to the oxygenated solution increased the level of adenosine triphosphate at end-arrest from 10.5 +/- 0.5 to 13.9 +/- 0.6 nmol/mg dry weight and glycogen stores from 18.7 +/- 2.5 to 35.7 +/- 5.5 nmol/mg dry weight. The further addition of insulin did not better preserve these metabolites. Improvements in functional recovery due to glucose or insulin in the oxygenated solution attained statistical significance when both additives were included. Glucose increased lactate production significantly only when the solution was nitrogenated. Insulin added to the nitrogenated glucose-containing solution increased adenosine triphosphate and glycogen levels after 1 hour of arrest; and, although insulin did not prevent ischemic contracture from developing during the latter part of arrest with profound depletion of these metabolites, functional recovery was improved. The mechanism of improved functional recovery by insulin is not clear.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Diphosphate↗

PubMed1991

A brief introduction to influence diagnostics in regression.

Statistical analyses that involve regression methods often encounter data in which some observations have substantial influence. This article presents a nontechnical discussion of influence and of two techniques, based on leaving out each individual observation in turn, for diagnosing influential data. An example illustrates the techniques in an analysis of recurrence rates in endoscopic treatment of bleeding peptic ulcers.

Endoscopy↗

PubMed1991

Leukotrienes, thromboxane A2, and prostaglandins during systemic anaphylaxis in sheep.

We investigated the roles of eicosanoid mediators in acute systemic anaphylaxis in anesthetized sheep. Sheep were sensitized with dinitrophenylated Ascaris suum extract and were challenged with an intravenous injection of dinitrophenylated bovine serum albumin. During anaphylaxis, cyclooxygenase inhibitors eliminated the elevation of arterial plasma levels of thromboxane B2 and 6-ketoprostaglandin F 1 alpha but markedly elevated the levels of leukotriene E4 in lung lymph without significantly eliminating elevation of plasma levels of histamine. Most of the measured physiological abnormalities accompanying anaphylaxis were aggravated by cyclooxygenase blockade. Enhancement of this anaphylactic mediator response was associated with an accentuated and prolonged increase of airway pressure (P less than 0.05, compared with sensitized, antigen-challenged but otherwise untreated sheep), a more intense hypoxemia (P less than 0.0001), and leukopenia (P less than 0.001), changes that were largely eliminated by pretreating with the sulfidopeptide leukotriene (SPLT) antagonist FPL 55712, suggesting that the SPLTs were important mediators of these responses. In contrast, the prolonged, but less severe, systemic vascular collapse and the reduced pulmonary hypertension induced by cyclooxygenase inhibitors were not influenced by the SPLT antagonist. These results demonstrate that in sheep cyclooxygenase metabolites are mainly involved in the acute, but transient, systemic and pulmonary vascular response of systemic anaphylaxis, whereas SPLTs are primarily implicated in the airway and secondary cardiovascular response. SPLT may act either directly or by potentiating the release of and reactivity to histamine and other mediators. Our data therefore suggest that a combination of cyclooxygenase and lipoxygenase inhibition will be necessary to more effectively protect against the consequences of an anaphylactic reaction.

6-Ketoprostaglandin F1 alpha↗

PubMed1990

An empirical study of the possible relation of treatment differences to quality scores in controlled randomized clinical trials.

Meta-analytic investigations sometimes use assessments of research quality according to a formal protocol as a tool for improving research synthesis. We asked whether a particular quality scoring system could have a direct use in adjusting the summary estimates of a treatment difference. In an empirical study of the relation of quality scores to treatment differences in published meta-analyses of 7 groups of controlled randomized clinical trials comprising 107 primary studies, we found no relation between treatment difference and overall quality score. We also found no relation between quality score and variation in treatment difference. The level of quality scores has increased at a rate of 9% per decade for three decades, averaging 0.51 on a scale of 0 to 1 for the 1980s, and leaving much room for improvement. Nevertheless, attention to quality of studies by editors, reviewers, and authors may be raising both the level of research done and quality of the reports.

Meta-Analysis as Topic↗

PubMed1989

Alteration by burn injury of the pharmacokinetics and pharmacodynamics of cimetidine in children.

We have studied the mechanisms of the increased dosage requirements of the H2-receptor antagonist cimetidine in paediatric burned patients in a pharmacokinetic and pharmacodynamic study. Cimetidine (10-15 mg.kg-1) was given to 21 burned children and multiple blood samples were obtained for determination of plasma cimetidine concentrations and pharmacokinetic analysis. The relation of gastric pH to plasma cimetidine concentrations was studied in five of these children who had nasogastric tubes. In an additional four patients the effects of cimetidine on gastric pH were studied during a continuous infusion of cimetidine, which maintained steady-state plasma cimetidine concentrations above 0.5 microgram.ml-1. The mean (SEM) clearance of cimetidine in burned children was 16.22 ml.kg-1 and cimetidine half-life was 1.06 h. The cimetidine clearance and half-life values were significantly higher in burned children compared with our previously reported values for normal adult patients, 8.2 ml.min.kg-1 and 2.21 h respectively. Endogenous creatinine clearance normalized to 70 kg in burned children was 190 ml.min-1. In burned children 41% of the dose of intact cimetidine was excreted during 8 h of the study compared with 45% excretion during 24 h in healthy adult controls previously reported. The correlation coefficient between creatinine and cimetidine clearances was 0.93 (r2 = 0.85). The plasma concentration of cimetidine needed to increase gastric pH to greater than or equal to 4.0 was greater than or equal to 1.0 micron.ml-1, which contrasts with the value of greater than 0.5 micron.ml-1 required for adult burned patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

PubMed1989

Pulmonary vascular responses to hypercalcemia and hypocalcemia in the dog.

The pulmonary artery responses in the isolated whole-blood perfused canine lung to ionized calcium ([Ca++]) were quantified over a range of hypercalcemia and hypocalcemia values ([Ca++] = 0.23-1.88 mM) under conditions of controlled pulmonary blood flow and constant mean aortic and left atrial pressures. Calcium chloride, administered as bolus doses in the clinical range (5-15 mg.kg-1) at initial normocalcemia and without interventions producing vasoconstriction did not influence mean pulmonary artery pressure at constant pulmonary blood flow. Stable hypercalcemia ([Ca++] = 1.88 +/- 0.05 mM) did not influence the slope of the pulmonary artery pressure-flow plot. Because normal pulmonary vasomotor tone is low and cannot readily be lowered further, the possible vasodilator action of hypocalcemia was assessed by its ability to decrease the slope of the mean pulmonary artery pressure-flow plot, which had been first increased by alveolar hypoxia (AHX) or infusion of the prostaglandin endoperoxide analog U46619 (PG). During AHX (n = 5), a graded reduction from normocalcemia ([Ca++] = 1.08 +/- 0.02 mM) to moderate hypocalcemia ([Ca++] = 0.8 and 0.5 mM) did not alter the pulmonary artery pressure-flow plot, but severe hypocalcemia ([Ca++] = 0.26 +/- 0.01 mM) decreased the slope by 13 +/- 0.9 mmHg.l-1.min-1. The comparison of severe hypocalcemia ([Ca++] = 0.23-0.27 mM) versus a high dose of nifedipine (bolus of 10 micrograms/kg followed by continuous infusion at 40 micrograms.kg-1.h-1) on pulmonary vascular tone increased by either AHX or PG infusion indicated that both hypocalcemia and nifedipine decreased the slope of the relationship between mean pulmonary artery pressure and flow (during AHX: -16.1 +/- 1.38 and -23.3 +/- 1.73 mmHg.l-1.min-1, both P = 0.0001 vs. AHX alone, and during PG: -17.05 +/- 1.95 and -8.4 +/- 1.78 mmHg.l-1.min-1, P = 0.0001 vs. PG alone). Two principal conclusions emerge. First, the pulmonary vessels are minimally sensitive to changes in ionized calcium throughout the clinical hypercalcemia and hypocalcemia ranges; extreme hypocalcemia is required to produce vasodilation, which was reversed with calcium infusion. Second, whereas the pulmonary vasodilator effects of extreme hypocalcemia were independent of the intervention inducing pulmonary vasoconstriction (AHX vs. PG), those of nifedipine were much more pronounced with AHX.

Animals↗

PubMed1988

A single-blind study of pulse oximetry in children.

Oxygen saturation determined by pulse oximetry was monitored in 152 pediatric surgical patients divided into two groups. In one group, the oximeter data and alarms were available (N = 76) to the anesthesia team, and, in the other group, these data were unavailable (N = 76). A trained observer recorded all intraoperative hypoxic episodes and informed the anesthesia team of all major events (i.e., oxygen saturation less than or equal to 85% for greater than or equal to 30 s) (PaO2 approximately 52 mmHg). Thirty-five major events occurred: 24 in the unavailable group, and 11 in the available group (P = 0.021). A greater number of major events occurred in children less than or equal to 2 yr of age (P = 0.013). Hypoxic events diagnosed by the oximeter, but not by the anesthesiologist, were more frequent in the unavailable group (13) than in the available group (5) (P = 0.0495). ASA Physical Status 3 and 4 patients were more likely to suffer a major event (P = 0.009 available, 0.006 unavailable). The pulse oximeter diagnosed hypoxemia before the signs and symptoms of hypoxemia were apparent (i.e., prior to observed cyanosis or bradycardia). Major hypoxic events were unrelated to duration of anesthesia. Major events were evenly distributed among induction, maintenance, and awakening from anesthesia; a greater number of hypoxic events occurred during induction in the unavailable group (P = 0.031). No morbidity was documented in any patient who suffered an hypoxic event.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

PubMed1988

Neuromuscular dysfunction in burns and its relationship to burn size, hypermetabolism, and immunosuppression.

The etiology of neuromuscular (NM) dysfunction following burn injury has not been characterized. NM deficits, together with hypermetabolism and immunosuppression, are debilitating processes which play a key role in the morbidity and mortality of burned patients. This study examined the usefulness of the murine model to replicate clinically observed NM dysfunction. Systemic effects of graded increases in burn size were studied in the acute phase (3 weeks) of burn trauma. Metabolic rates, immune response to dinitrofluorobenzene (DNFB), maximum tension developed by gastrocnemius muscle, and the response of its NM junction to d-tubocurarine (dTc) were the parameters analyzed. Groups of male CF1 mice were given a 20%, 30%, and 50% total body surface area burn and compared to controls. By Day 21 postburn, all the burn groups showed elevated metabolic rates and immunosuppression to the inflammatory antigen DNFB. NM dysfunction evidenced as a significant depression of maximal tension development was observed in the 30% and 50% groups. A threefold increase in the effective dose (ED95) values of dTc was seen only in the 50% burn group. No NM junctional changes were seen in the 20% burn group. These findings are consistent with clinical observations. We conclude that the mouse is a useful model for evaluating NM dysfunction of burns.

Animals↗

PubMed1988

Ionized hypocalcemia after fresh frozen plasma administration to thermally injured children: effects of infusion rate, duration, and treatment with calcium chloride.

A number of cardiac arrests and severe hypotensive episodes have been witnessed associated with the intravenous infusion of fresh frozen plasma (FFP). To clarify the possible role of hypocalcemia, 28 thermally injured anesthetized pediatric patients with massive blood loss were studied to examine the cardiovascular responses (mean arterial pressure [MAP], heart rate, ECG) to 49 infusions of FFP. Rapid, statistically significant reductions in ionized calcium ([Ca2+]) followed each of four rates (1.0, 1.5, 2.0, and 2.5 ml.kg-1.min-1 for 5 minutes) of FFP infusion (P less than 0.0001). The slowest rate resulted in significantly less reduction in [Ca2+] than did the higher infusion rates (P less than 0.002). In five children MAP decreased greater than or equal to 20% below baseline levels, but this was not correlated with rate of FFP administration or decrease in [Ca2+]. The decreases in [Ca2+] and MAP were inversely related to age and unrelated to anesthetic technique. Changes in the Q-oTc interval were not related to [Ca2+]. Adverse cardiovascular responses and reduced [Ca2+] were not significantly different between 5- and 10-minute FFP infusions. Fewer fluctuations in MAP occurred when calcium chloride (CaCl2) was administered; the least fluctuation in [Ca2+] occurred when CaCl2 was administered during the plasma infusion. It is concluded that in thermally injured children 1-17 years old: 1) Rapid infusions of FFP produce sudden but evanescent decreases in [Ca2+]; more rapid infusions result in greater reductions in [Ca2+]. 2) There is no correlation between [Ca2+] and systemic hypotension. 3) Clinically important decreases in MAP occasionally accompany the rapid infusion of FFP.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

PubMed1988

The effect of nail polish on pulse oximetry.

A randomized, blind study examined the effect of nail polish color on measurement of oxygen saturation by pulse oximetry. Fourteen adult volunteers had blue, green, purple, black, and red nail polish applied to their finger nails. A strip-chart recording of oxygen saturation (Nellcor N100) was made in room air and later interpreted in a blinded fashion. The absorption spectra of the five polishes were determined by spectrophotometry. The spectra of nine other nail polishes and three intravenous dyes also were examined. Black, blue, and green nail polish significantly lowered oximeter readings of oxygen saturation. Blue and green produced greater decreases than purple and red; black produced an intermediate decrease. Some but not all nail polishes absorbed light at the wavelengths used by the pulse oximeter (660 nm and 940 nm). The degree of artifactual desaturation correlated best with the difference between absorbance at 660 nm and absorbance at 940 nm (r = 0.95). Spectrophotometric absorbance data suggest that other colors may interfere with pulse oximetry. On the basis of spectrophotometric data, brown-red nail polish was predicted to interfere with oximetry; subsequent pulse oximetry measurements confirmed the prediction. Nail polish should be removed routinely before pulse oximetry monitoring.

Adult↗

PubMed1987

Beta-adrenoceptor blockade, alpha-stimulation and changes in plasma potassium concentration after suxamethonium administration in dogs.

A study involving 20 mongrel dogs tested the hypotheses that beta-adrenoceptor blockade or alpha-adrenoceptor stimulation may potentiate and prolong the increase in plasma potassium concentration after suxamethonium administration, and that the beta effect is beta 2-receptor mediated. Propranolol 0.5 mg kg-1 altered the time to peak increase in plasma concentration of potassium after suxamethonium, but did not increase peak concentrations. In controls, the maximum change (0.83 mmol litre-1) occurred at 3 min, while in propranolol-treated dogs the peak change (0.96 mmol litre-1 occurred at 30 min. Similar results were obtained when metoprolol 0.25 mg kg-1 and ICI 118551 0.1 mg kg-1 were used, respectively, as selective beta 1- and beta 2-adrenoceptor blockers. The increases in potassium concentration following suxamethonium in the metoprolol group (0.98 mmol litre-1) and the ICI 118551 group (0.82 mmol litre-1) reached maximum concentrations at 30 min compared with the controls (0.79 mmol litre-1) which achieved a maximum at 3 min. Phenylephrine was infused at 8 micrograms kg-1 min-1 to produce alpha stimulation. The infusion alone altered plasma concentrations of potassium, but the haemodynamic changes were such that conclusions as to the effect of alpha-stimulation on release of potassium after suxamethonium could not be reached.

Adrenergic beta-Antagonists↗