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Statistical process control methods allow the analysis and improvement of anesthesia care.

PURPOSE: Quality aspects of the anesthetic process are reflected in the rate of intraoperative adverse events. The purpose of this report is to illustrate how the quality of the anesthesia process can be analyzed using statistical process control methods, and exemplify how this analysis can be used for quality improvement. METHODS: We prospectively recorded anesthesia-related data from all anesthetics for five years. The data included intraoperative adverse events, which were graded into four levels, according to severity. We selected four adverse events, representing important quality and safety aspects, for statistical process control analysis. These were: inadequate regional anesthesia, difficult emergence from general anesthesia, intubation difficulties and drug errors. We analyzed the underlying process using 'p-charts' for statistical process control. RESULTS: In 65,170 anesthetics we recorded adverse events in 18.3%; mostly of lesser severity. Control charts were used to define statistically the predictable normal variation in problem rate, and then used as a basis for analysis of the selected problems with the following results: Inadequate plexus anesthesia: stable process, but unacceptably high failure rate; Difficult emergence: unstable process, because of quality improvement efforts; Intubation difficulties: stable process, rate acceptable; Medication errors: methodology not suited because of low rate of errors. CONCLUSION: By applying statistical process control methods to the analysis of adverse events, we have exemplified how this allows us to determine if a process is stable, whether an intervention is required, and if quality improvement efforts have the desired effect.

Administration, Topical↗

Numbats and aardwolves--how low is low? A re-affirmation of the need for statistical rigour in evaluating regression predictions.

Many comparative physiological studies aim to determine if a particular species differs from a prediction based on a linear allometric regression for other species. However, the judgment as to whether the species in question conforms to this allometric relationship is often not based on any formal statistical analysis. An appropriate statistical method is to compare the new species' value with the 95% confidence limits for predicting an additional datum from the relationship for the other species. We examine the basal metabolic rate (BMR) of the termitivorous numbat (Myrmecobius fasciatus) and aardwolf (Proteles cristatus) to demonstrate the use of the 95% prediction limits to determine statistically if they have a lower-than-expected BMR compared to related species. The numbat's BMR was 83.6% of expected from mass, but fell inside the 95% prediction limits for a further datum; a BMR < 72.5% of predicted was required to fall below the one-tail 95% prediction limits. The aardwolf had a BMR that was only 74.2% of predicted from the allometric equation, but it also fell well within the 95% prediction limits; a BMR of only 41.8% of predicted was necessary to fall below the one-tail 95% prediction limits. We conclude that a formal statistical approach is essential, although it is difficult to demonstrate that a single species statistically differs from a regression relationship for other species.

Animals↗

SPBS: statistical programs for biological sciences. Minicomputer software for applying routine biostatistical methods.

The main routine statistical analyses can be carried out from start to finish on a minicomputer with basic language capability and greater than or equal to 32000 bytes of random access memory. However, no statistical software packs for minicomputers are ever complete enough for exhaustive analysis of most problems. Taking account of the requirements of statistical models, this paper gives an outline of how to set up a program. Examples are given from the package of statistical programs developed at this institute. The advantages and disadvantages of making these analyses on minicomputers are discussed, in comparison with the use of statistical programs requiring large computers.

Biometry↗

[Study of statistical test connections in non-orthogonal analysis of variance].

In the Analysis of Variance, we quite often split up the model to test different hypotheses about the model. However, when we analyse the results, we must not forget that the statistics used for the tests are not stochastically independent, either for an orthogonal design, because the test statistics have the same denominator, or for non-orthogonal design. In the latter case, test statistics have not only the same denominator but also not-independent numerators. The links between test statistics have been studied for orthogonal designs (Dall'Aglio, 1962) and for symmetrical Incomplete Block Design (Ballas and Webster, 1966). We shall give here results for the general case of the Analysis of Variance, treat more particularly the case of the Incomplete Block Design and show the joint distribution of two test statistics and, more simply, their correlation coefficient.

Analysis of Variance↗

Transgenic lambda/lacI mutagenicity assay: statistical determination of sample size.

Statistical analysis of the lambda/lacI transgenic mutagenicity assay was used to determine optimal sample size and resource allocation in terms of number of animals and number of recovered target genes (recovered phage) required to demonstrate a statistically significant induction in mutant frequency. Statistical assumptions as applied to mutagenicity data are discussed for a number of frequently used statistical analyses. Log transformations are suggested as a means of meeting statistical assumptions and examples are given on interpreting results of analyses of log transformed data. The data analyzed in this study indicate that 300,000 lambda plaques from each of five animals should be analyzed per treatment group in order to detect a doubling of mutant frequencies. Additional sensitivity is gained primarily through increase of animal number and not the number of phage rescued, due to inherent animal-to-animal variability.

Animals↗

BASIC computer program to summarize data using nonparametric and parametric statistics including Anderson-Darling test for normality.

Tools for calculating Gaussian parametric statistics are widely available in hand-held calculators and program packages for desktop as well as mainframe computers. The standard deviation calculated from non-Gaussian data may, however, be meaningless or even absurd. Furthermore, the standard error of the mean is frequently used as a descriptive statistic even if it really does not describe the variation in the observations themselves. However, comprehensive tools for calculating nonparametric descriptive statistics and judging whether observations have a Gaussian distribution are hard to come by. The present paper attempts to provide the essential statistical reasoning behind the calculation of descriptive statistics and introduces a computer program written in Microsoft BASIC that applies the methods described in the text.

Mathematical Computing↗

Exact statistical tests for any carcinogenic effect in animal bioassays. II. Age-adjusted tests.

Statistical methods are discussed for application in animal carcinogenesis bioassays that test a general null hypothesis that response frequencies are independent of the treatment level for all tumor endpoints, sexes, and species considered in the bioassay, conditional on survival. These methods are similar to those proposed earlier by Farrar and Crump (1988, Fundam, Appl. Toxicol. 11, 652-663) which involve test statistics that are functions of p values from multiple standard statistical hypothesis tests, and evaluation of significance using randomization. Refinements include the introduction of an exact incidental tumor test analogous to the asymptotic test of Hoel and Walburg (1972, J. Natl. Cancer Inst. 49, 361-372), which takes into account the possibility that any differences among treatment groups in response rates result from differences in survival that is independent of tumors. Additional consideration is given to selection of test statistics, and a test is proposed that is sensitive specifically to cases where the same tumor endpoints are affected in multiple sexes and species. Applications of the procedures to results of National Toxicology Program (NTP) bioassays concerning decabromodiphenyl oxide and iodinated glycerol illustrate the sensitivity of tests based on different test statistics to distinct alternative hypotheses. When compared with the qualitative conclusions of the NTP regarding the strength of evidence for a carcinogenic effect in the same bioassays, the results presented suggest that the methods can be useful in clarifying otherwise equivocal evidence for carcinogenicity. Various difficulties are discussed relevant to the construction of exact combined fatal and incidental tumor tests analogous to the tests of Peto et al. (1980, IARC Monogr. Suppl. 2).

Age Factors↗

The relationship between chi-square statistics from matched and unmatched analyses.

The McNemar chi-square statistic for testing the equality of proportions in matched pairs of binary data is expressed as a function of the Pearson chi-square statistic and a kappa statistic for measuring interrater agreement. Implications for data analysis and for sample size determination are discussed. The result is generalized to provide a similar relationship between Cochran's Q-statistic and the Pearson chi-square statistic for the comparison of proportions in matches of size m.

Chi-Square Distribution↗

Annual bed statistics give a misleading picture of hospital surge capacity.

STUDY OBJECTIVE: I describe how annual hospital surge capacity is affected by within-year variation in patient volume and bed supply. METHODS: Surge capacity was measured as the percentage and total number of hospital beds that are not occupied by patients. Administrative data were used to calculate these bed statistics for 78 hospitals in New Jersey--statewide and by emergency planning regions--in 2003. Annual bed statistics were compared to more refined calculations for each day of the year. Calculated numbers of empty beds were compared to federal disaster planning benchmarks. RESULTS: Annual bed statistics showed no major limitations on surge capacity. Statewide occupancy rates were well below 80% (ie, more than 20% of beds were empty), and the number of empty beds that were set up and staffed (ie, maintained) was well above federal disaster planning benchmarks. In contrast, daily bed statistics reveal long periods in 2003 when regional and statewide surge capacity was severely strained. Strained capacity was most likely to occur on Tuesdays through Fridays and least likely to occur on weekends. On 212 days, statewide occupancy of maintained beds met or exceeded 85%. This occupancy rate met or exceeded 90% and 95% on 88 and 4 days, respectively. On 288 days, the statewide number of empty maintained beds fell below the federal planning benchmark. CONCLUSION: Annual bed statistics give a misleading picture of hospital surge capacity. Analysis of surge capacity should account for daily variation in patient volume and within-year variation in bed supply.

Bed Occupancy↗

The application of statistical process control to horizontal strabismus surgery.

PURPOSE: Although originally developed to evaluate quality in manufacturing, statistical process control (SPC) techniques may be applicable to other frequently performed standardized processes. SPC analysis has rarely been used in medicine. We employed SPC charts to analyze the outcomes of one- and two-muscle horizontal strabismus surgery for esotropia and exotropia. METHODS: During a 33-month period between October 1, 1998 and July 1, 2001, we evaluated 95 patients undergoing strabismus surgery on either one or two previously unoperated eye muscles in one or both eyes. SPC charts were used to evaluate the success and validity of our surgical guidelines for horizontal recession and resection procedures. Data were divided into 2 groups, patients with esotropia and patients with exotropia, for computerized statistical analysis using QI Analyst (SPSS, Chicago, IL). RESULTS: Our results after horizontal strabismus surgery, both esotropia and exotropia repair, appear to follow the laws of statistical fluctuation or normal random variation. Our dose-response schedule produced a resultant ocular alignment or exit angle that appeared to be in statistical control, ie, variation from orthotropia that can be expected simply from normal random chance error with only a limited number of outliers. CONCLUSION: The resultant ocular alignment or exit angle after one- or two-muscle strabismus surgery may be described by standard models of statistical fluctuation. SPC may be a valuable method to analyze the variability of the results of many ophthalmologic procedures or treatments over time with the ultimate goal of producing better patient outcomes by decreasing variability.

Esotropia↗

Select Contemporary Statistical Concepts in Heart Failure Clinical Trials: Insights From the Heart Failure Collaboratory.

Evolving statistical concepts and innovative trial designs for heart failure (HF) clinical trials seek to improve the conduct, efficiency, and likelihood of meaningful evidence generation crucial for advancing therapeutic development and optimizing patient care. HF trials with conventional statistical frameworks often require large sample sizes, long follow-up times, and high cost to generate sufficient evidence. Novel statistical methodologies would be of interest if they could address these issues while retaining or enhancing the clinical relevance and reliability of results. The HFC (Heart Failure Collaboratory), comprising clinical investigators, clinicians, statisticians, patients, government representatives, payors, and industry collaborators, leads efforts to improve HF research methodologies. HFC discussions have included statistical concepts such as the estimand framework, HR drift, and analytic methods, including the win ratio and restricted mean survival time, that have not been used frequently in HF trials. The estimand framework encourages precise definition and alignment of trial objectives with trial design. The win ratio method attempts to incorporate and prioritize multiple clinically meaningful outcomes by using a hierarchy of clinical importance. The restricted mean survival time provides an alternative to the HR as a measure of therapeutic effect by quantifying the mean time gained or lost during a fixed time after randomization. This paper provides a critical review of some evolving HF trial design methodologies and statistical concepts for the HF community as discussed within the HFC. Our goal is to foster collaboration among diverse stakeholders and advance the development of effective treatments and improve patient care outcomes.

Heart Failure↗

Bladder stone formation after sigmoidocolocystoplasty: statistical analysis of risk factors.

PURPOSE: Bladder stone formation (BSF) after sigmoidocolocystoplasty (SCP) is a major source of morbidity. The authors identify risk factors and analyze them statistically. METHODS: Medical records of 106 patients who had SCP at our institute were reviewed to examine the incidence of post-SCP BSF, the stone removal method and length of follow-up. The primary underlying pathological conditions were myelomeningocele in 103 patients and other conditions in 3. Risk factors for BSF were statistically assessed by comparing cases with and without BSF. RESULTS: Bladder stone formation occurred in 20 (18.9%) of 106 patients (BSF group). The remaining 86 did not have stones (NBSF group). Mean age at SCP was 11.7 years in the BSF group and 10.2 years in the NBSF group. Mean follow-up was 12.0 years in the BSF group and 11.0 years in the NBSF group. BSF developed after a mean of 30.3 +/- 25.6 months after SCP. Twenty-two stone removal procedures were performed in the BSF group and spontaneous evacuation occurred in 4 instances. Once stone free, BSF recurred in 4 patients. Although differences between the 2 groups with respect to sex, age at SCP, follow-up period, bladder capacity, bladder compliance, incidence of gram-negative bacteriuria, incidence of gram-positive coccus bacteriuria, electrolytes, frequency of urinary catheterization, post-SCP incidence of vesicoureteric reflux, and incidence of ureteric reimplantation were not statistically significant, differences in the incidence of spontaneous micturition, bladder neck tightening procedures, or gram-positive bacillus bacteriuria, or frequency of bladder irrigation were all statistically significant (P < .05 in all, Fisher's Exact test). CONCLUSIONS: The authors are the first to statistically analyze a wide range of varying risk factors for BSF. BSF would appear to be common after SCP.

Adolescent↗

Statistical mapping of functional olfactory connections of the rat brain in vivo.

The olfactory pathway is a unique route into the brain. To better characterize this system in vivo, rat olfactory functional connections were mapped using magnetic resonance (MR) imaging and manganese ion (Mn2+) as a transport-mediated tracer combined with newly developed statistical brain image analysis. Six rats underwent imaging on a 1.5-T MR scanner at pre-administration, and 6, 12, 24, 36, 48, and 72 h and 5.5, 7.5, 10.5, and 13.5 days post-administration of manganese chloride (MnCl2) into the right nasal cavity. Images were coregistered, pixel-intensity normalized, and stereotactically transformed to the Paxinos and Watson rat brain atlas, then averaged across subjects using automated image analysis software (NEUROSTAT). Images at each time point were compared to pre-administration using a one-sample t statistic on a pixel-by-pixel basis in 3-D and converted to Z statistic maps. Statistical mapping and group averaging improved signal to noise ratios and signal detection sensitivity. Significant transport of Mn2+ was observed in olfactory structures ipsilateral to site of Mn2+ administration including the bulb, lateral olfactory tract (lo) by 12 h and in the tubercle, piriform cortex, ventral pallidum, amygdala, and in smaller structures such as the anterior commissure after 24 h post-administration. MR imaging with group-wise statistical analysis clearly demonstrated bilateral transsynaptic Mn2+ transport to secondary and tertiary neurons of the olfactory system. The method permits in vivo investigations of functional neuronal connections within the brain.

Amygdala↗

Direct determination of MUC5B promoter haplotypes based on the method of single-strand conformation polymorphism and their statistical estimation.

Haplotype-based human genome research is important in identifying disease susceptibility genes efficiently. Although haplotype reconstruction by statistical methods is widely used, direct haplotype determination by molecular techniques has also been developed as a complementary method for statistical estimation. In this study, we demonstrate a molecular haplotyping method making use of single-strand conformation polymorphism (SSCP) gels. We identified 10 common SNPs and a dinucleotide insertion/deletion polymorphism within 2-kb region upstream of the transcription initiation site of MUC5B and determined haplotype structure, dividing the region into two DNA fragments. Real haplotypes were determined unambiguously by our SSCP-based analysis with fragments longer than 1 kb. Haplotypes reconstructed from diploid genotypes in the same region by the statistical methods including EM algorithm were also evaluated. Direct comparison between statistical estimation and direct determination of haplotypes revealed that major haplotypes containing multiple marker sites showing strong LD are estimated in great accuracy but that a variety of haplotypes reflecting weak LD are not reconstructed precisely enough. Our data can be helpful in implementing molecular haplotyping or statistical estimation, since usage of these methods may be determined depending on the haplotype structures.

Base Sequence↗

Dynamic statistics of crayfish caudal photoreceptors.

Crayfish caudal photoreceptor units were monitored during transient and steady-state responses to light stimuli (step on, step off). A statistical analysis of interpulse interval distributions during quasi-stationary time periods was carried out. Firing statistics during transient conditions were superposable with statistics under whatever steady stimulation produced the same firing rate, indicating that mean firing rate is a sufficient statistic. Distributions encountered formed a continuum of possible shapes. Considerable variation in shape was found with temperature and also among species, with Orconectes clarkii tending to fire more regularly than Orconectes virilis. Some properties of O. virilis statistics are described, including a linear relation between mean and standard deviation, and a tendency for intervals to be nonindependent. The data are considered as constraints on closed form models of the photoreceptor nerve pulse generator.

Animals↗

A method for assessing the statistical significance of RNA folding.

We have developed a statistical method that is designed for analyzing potential RNA folded substructures. The statistical significance of RNA folding is assessed by the segment score. The segment score is defined as the difference between the lowest free energy calculated for the real biological sequence and the mean of the lowest free energies from random permutations of the real segment sequence, divided by the standard deviation of the random sample. This procedure was applied to the well-studied Escherichia coli 16S rRNA and potato spindle tuber viroid (PSTV) RNA. The results showed that the predictions of the locally significant secondary structures in these two molecules are in accord with the universally conserved local secondary structure elements (Gutell, Weiser & Noller, 1985, Prog. Nucl. Acid Res. molec. Biol. 32, 155-216; Riesner & Gross, 1985, A. Rev. Biochem. 54, 531-564). In addition, a statistical analysis indicated that the lowest free energies of a random sample set follow an approximately normal distribution. A reasonable size for the random sample set was determined statistically. Moreover, the statistical evaluation has been carried out using three different sets of energy rules--two sets (Salser, 1977, Cold Spring Harb. Symp. Quant Biol. 42, 985-1002; Freier, Kierzek, Jaeger, Sugimoto, Caruthers, Neilson & Turner, 1986, Proc. natn. Acad. Sci. U.S.A. 83, 9373-9377) take into account stacking energies and are based on experimental data and their computational extension (Salser, 1977)--the third set is a simplistic "unitary matrix" approach, where any base-pair is given a weight of "minus one" and an unpaired based is "zero". The Freier energy rules usually yield the strongest indication of significant folding region. However, the results derived from paired comparisons test don't provide sufficient evidence for concluding that a different set of energy rules is effective in changing the segment score level for local stem-loop structures in the 16S rRNA.

Analysis of Variance↗

Design and test of neural networks and statistical classifiers in computer-aided movement analysis: a case study on gait analysis.

OBJECTIVE: To describe the methods for designing and testing diagnostic systems in movement analysis and to verify the clinical usefulness of neural networks and statistical classifiers in a case study. DESIGN: Connectionist and statistical models trained and tested with measured data. BACKGROUND: A basic need in rehabilitation and related fields is to efficiently manage the vast information obtained from a movement analysis laboratory. Many studies have dealt with the interpretation of measured variables in order to correlate objective descriptors to the presence and/or severity of specific neuromusculoskeletal disorders or their consequences. This traditional analytical approach has been complemented in the last decade by new non-linear classification tools called neural networks. METHODS: A gait analysis study on 148 lower limb arthrosis patients and 88 age-matched control subjects. Pathological and healthy gait patterns obtained from force plates wer discriminated by means of multilayer perceptrons and statistical classifiers. RESULTS: Ten input features were enough to train a multilayer perceptron with six hidden neurons. The discrimination rate of the neural net was 80% after cross-validation, significantly higher (P<0.05) than the performance of a Bayes quadratic classifier (about 75%). A great variance due to a small cross-validation set could be demonstrated. CONCLUSIONS: Strict statistical requirements must be observed for designing a neural network. Although these models attain a better performance than conventional statistical approaches, the benefits they bring are sometimes not sufficient to justify their use. Furthermore, clinicians routinely involved in critical decisions may not consider such diagnostic systems reliable enough.

Journal Article↗

The validity of death certificates: routine validation of death certification and its effects on mortality statistics.

The 3478 death certificates (7.1% of all annual death certificates) of this study comprise those national death certificates in 1995 submitted for validation to the panel representing both medical and nosological expertise. As such, it is highly selected and represents, from the nosological point of view, the most inconsistently filled-in portion of Finnish death certificates. The routine validation procedure is essentially based on exploitation of the extra medical information, i.e. the case history, on the Finnish death certificate form. Altogether, 2813 (80.9%) out of 3478 certificates could be adjusted at the primary panel session; the rest required further clarification. The re-assignment of cause of death by the panel and the impact of panel adjustments on the national mortality statistics is assessed here by comparing the initial death certification and the finally registered underlying cause of death grouped into ICD-9 major categories with special reference to the subcategories of neoplasm, cardiovascular disease (HVD) and unnatural death. A statistically significant decline (p<0.0001) in deaths, both in the category of symptoms, signs and ill-defined conditions and in the pulmonary circulation disease subcategory of HVD with 37.6 and 35.1%, respectively, was observed. The decrease of 11.1% in the benign or NUD neoplasm subcategory and the increase of 8.6 and 7.0% in the categories of endocrine disease, and musculo-skeletal and connective tissue disease, respectively, are essential observations as to the quality of the cause of death register. The effect on the HVD major category was practically nil. At the HVD-subcategorial level, a decrease of 14.0% for diseases of the veins and lymphatics and other circulatory diseases and an increase of 3.5% for hypertensive diseases (HYP) were the two next most obvious alterations to the diseases of the pulmonary circulation, but were without statistical significance. For ischaemic heart disease and other subcategories, the effects were minor. The unnatural deaths as a whole increased in the final statistics with only 0.9%. In the study data, categorial changes ranged from the decrease of 75.2% for symptoms, signs and ill-defined conditions to the increase of 77.3% for endocrine diseases. In conclusion, the Finnish death certificate form, death certification practices and cause of death validation procedure seem to serve the coding of causes of death for mortality statistics appropriately. The results of the study form a relevant reference background to evaluation of epidemiological studies on mortality.

Abstracting and Indexing↗