Pulmonary vein reconnection and repeat ablation characteristics following cryoballoon-compared to radiofrequency-based pulmonary vein isolation.

BACKGROUND: Despite advances in efficacy and safety of pulmonary vein isolation (PVI), atrial fibrillation (AF) recurrence after PVI remains common. PV-reconnection is the main finding during repeat PVI procedures performed to treat recurrent AF. OBJECTIVE: To analyze pulmonary vein (PV) reconnection patterns during repeat ablation procedures in a large cohort of consecutive patients undergoing radio frequency or cryoballoon-based PVI. METHODS: Retrospective analysis of PV-reconnection patterns and analysis of re-ablation strategies in consecutive index RF- and CB-based PVI and their respective re-ablation procedures during concomitant usage of both energy sources at a single high-volume center in Germany. RESULTS: A total of 610 first (06/2015-10/2022) and 133 s (01/2016-11/2022) repeat ablation procedures after 363 (60%) RF- and 247 (40%) CB-based index PVIs between 01/2015 and 12/2021 were analyzed. PV-reconnection was found in 509/610 (83%) patients at first and 74/133 (56%) patients at second repeat procedure. 465 of 968 (48%) initially via CB isolated PVs were reconnected at first re-ablation but 796 of 1422 initially RF-isolated PV (56%) were reconnected (OR: 0.73 [95% CI: 0.62-0.86]; p < .001). This was driven by fewer reconnections of the left PVs (LSPV: OR: 0.60 [95% CI: 0.42-0.86]; p = .005 and LSPV: 0.67 [0.47-0.95]; p = .026). PV-reconnection was more likely after longer, RF-based index PVI and in older females. Repeat procedures were shorter after CB-compared to after RF-PVI. CONCLUSIONS: Reconnection remains the most common reason for repeat AF ablation procedures after PVI. Our data suggest to preferentially use of the cryoballoon during index PVI, especially in older women.

The Swiss Canine Cancer Registry: a retrospective study on the occurrence of tumours in dogs in Switzerland from 1955 to 2008.

Diagnostic records are a key feature of any cancer epidemiology, prevention or control strategy for man and animals. Therefore, the information stored in human and animal cancer registries is essential for undertaking comparative epidemiological, pathogenic and therapeutic research. This study presents the Swiss Canine Cancer Registry, containing case data compiled between 1955 and 2008. The data consist of pathology diagnostic records issued by three veterinary diagnostic laboratories in Switzerland. The tumours were classified according to the guidelines of the International Classification of Oncology for Humans on the basis of tumour type, malignancy and body location. The dogs were classified according to breed, age, sex, neuter status and place of residence. The diagnostic data were correlated with data on the Swiss general dog population and the incidence of cancer in dogs was thus investigated. A total of 67,943 tumours were diagnosed in 121,963 dogs and 47.07% of these were malignant. The most common tumour location was the skin (37.05%), followed by mammary glands (23.55%) and soft tissue (13.66%). The most common tumour diagnoses were epithelial (38.45%), mesenchymal (35.10%) and lymphoid tumours (13.23%). The results are compared with data in other canine registries and similarities in tumour distribution and incidence are noted. It is hoped that this study will mark the beginning of continuous registration of dog tumours in Switzerland, which, in turn, will serve as a reference for research in the fields of animal and human oncology.

Hyperglycaemia is associated with impaired pulsatile insulin secretion: effect of basal insulin therapy.

AIM: Postprandial insulin pulsatility is impaired in patients with type 2 diabetes, but the effects of exogenous insulin therapy on pulsatile insulin secretion are not known. We addressed, whether pulsatile insulin secretion is related to glycaemic control, whether basal insulin supplementation increases postprandial insulin secretion, and if so, is this accomplished by a specific improvement in pulsatile insulin secretion? METHODS: Fourteen patients with type 2 diabetes underwent a mixed meal test before and after an 8-week treatment period with insulin glargine. Glucose, insulin and C-peptide levels were measured, and insulin pulsatility was determined by deconvolution analysis. RESULTS: Insulin treatment lowered fasting glycaemia from 179.6 ± 7.5 mg/dl to 117.6 ± 6.5 mg/dl (p < 0.001). Postprandial insulin and C-peptide levels increased significantly after the treatment period (p < 0.0001). The total calculated insulin secretion rate increased with insulin treatment (p = 0.0039), with non-significant increases in both pulsatile and non-pulsatile insulin secretion. Insulin pulse frequency was unchanged by the intervention. There was an inverse relationship between fasting and postprandial glycaemia and insulin pulse mass (r(2) = 0.51 and 0.56, respectively), whereas non-pulsatile insulin secretion was unrelated to either fasting or postprandial glucose concentrations (r(2) = 0.0073 and 0.031). CONCLUSIONS: Hyperglycaemia in type 2 diabetes is associated with a reduction in postprandial insulin secretion, specifically through a reduction in insulin pulsatility. Reducing chronic hyperglycaemia by basal insulin therapy enhances endogenous ß-cell function in the postprandial state. These data support the use of basal insulin regimens in the pharmacotherapy of overtly hyperglycaemic patients with type 2 diabetes.

Reduced minicolumns in the frontal cortex of patients with autism.

Cell minicolumns were shown to be narrower in frontal regions in brains of autistic patients compared with controls. This was not found in primary visual cortex. Within the frontal cortex, dorsal and orbital regions displayed the greatest differences while the mesial region showed the least change. We also found that minicolumns in the brain of a 3-year-old autistic child were indistinguishable from those of the autistic adult in two of three frontal regions, in contrast to the control brains. This may have been due to the small size of the columns in the adult autistic brain rather than to an accelerated development. The presence of narrower minicolumns supports the theory that there is an abnormal increase in the number of ontogenetic column units produced in some regions of the autistic brain during corticoneurogenesis.

The effects of recall on reporting injury and poisoning episodes in the National Health Interview Survey.

OBJECTIVE: To examine effects of length of time between injury or poisoning and interview on the number of reported injury and poisoning episodes in the National Health Interview Survey (NHIS). (Hereinafter, both injuries and poisonings will be referred to as "injuries".) DESIGN: The NHIS collects data continuously on medically attended injuries occurring to family members during the three months before interview. Time between injury and interview was established by subtracting the reported injury date from the interview date. Values were multiply imputed for the 25% of the episodes for which dates were only partially reported. MAIN OUTCOME MEASURES: An analysis of mean square error (MSE) was used to quantify the extent of errors in estimated annual numbers of injuries and to compare the contributions of bias and variance to these errors. RESULTS: The lowest estimated MSEs for annualized estimates for all injuries and for less severe injuries were attained when the annualized estimates were based on 3--6 elapsed cumulative weeks between injury and interview. The average weighted number of injuries reported per week per year was 8% lower in later weeks (weeks 6--13) than in earlier weeks (weeks 1--5) for all episodes, and 24% lower in later weeks than in earlier weeks for contusions/superficial injuries, with both differences being statistically significant. For fractures, however, the averages in the two periods were statistically similar. CONCLUSIONS: The error associated with the estimated annual number of injuries was large with a three month reference period for all injuries and for less severe injuries. Limiting analysis to episodes with up to five weeks between injury and interview has statistical, intuitive, and analytic appeal for all injuries and for less severe injuries.

Humans and great apes share a large frontal cortex.

Some of the outstanding cognitive capabilities of humans are commonly attributed to a disproportionate enlargement of the human frontal lobe during evolution. This claim is based primarily on comparisons between the brains of humans and of other primates, to the exclusion of most great apes. We compared the relative size of the frontal cortices in living specimens of several primate species, including all extant hominoids, using magnetic resonance imaging. Human frontal cortices were not disproportionately large in comparison to those of the great apes. We suggest that the special cognitive abilities attributed to a frontal advantage may be due to differences in individual cortical areas and to a richer interconnectivity, none of which required an increase in the overall relative size of the frontal lobe during hominid evolution.

Analysing the effects of anaemia on local recurrence of head and neck cancer when covariate values are missing.

We present a case study in the analysis of the prognostic effects of anaemia and other covariates on the local recurrence of head and neck cancer in patients who have been treated with radiation therapy. Because it is believed that a large fraction of the patients are cured by the therapy, we use a failure time mixture model for the outcomes, which simultaneously models both the relationship of the covariates to cure and the relationship of the covariates to local recurrence times for subjects who are not cured. A problematic feature of the data is that two covariates of interest having missing values, so that only 75 per cent of the subjects have complete data. We handle the missing-data problem by jointly modelling the covariates and the outcomes, and then fitting the model to all of the data, including the incomplete cases. We compare our approach to two traditional methods for handling missingness, that is, complete-case analysis and the use of an indicator variable for missingness. The comparison with complete-case analysis demonstrates gains in efficiency for joint modelling as well as sensitivity of some results to the method used to handle missing data. The use of an indicator variable yields results that are very similar to those from joint modelling for our data. We also compare the results obtained for the mixture model with results obtained for a standard (non-mixture) survival model. It is seen that the mixture model separates out effects in a way that is not possible with a standard survival model. In particular, conditional on other covariates, we find strong evidence of an association between anaemia and cure, whereas the evidence of an association between anaemia and time to local recurrence for patients who are not cured is weaker.

Fitting the log-F accelerated failure time model with incomplete covariate data.

Data obtained from studies in the health sciences often have incompletely observed covariates as well as censored outcomes. In this paper, we present methods for fitting the log-F accelerated failure time model with incomplete continuous and/or categorical time-independent covariates using the Gibbs sampler. A general location model that allows different covariance structures across cells is specified for the covariates, and ignorable missingness of the covariates is assumed. Techniques that accommodate standard assumptions of ignorable censoring as well as certain types of nonignorable censoring are developed. We compare our approach to traditional complete-case analysis in an application to data obtained from a study of melanoma. The comparison indicates that substantial gains in efficiency are possible with our approach.

Multiple imputation for threshold-crossing data with interval censoring.

Medical statistics often involve measurements of the time when a variable crosses a threshold value. The time to threshold crossing may be the outcome variable in a survival analysis, or a time-dependent covariate in the analysis of a subsequent event. This paper presents new methods for analysing threshold-crossing data that are interval censored in that the time of threshold crossing is known only within a specified interval. Such data typically arise in event-history studies when the threshold is crossed at some time between data-collection points, such as visits to a clinic. We propose methods based on multiple imputation of the threshold-crossing time with use of models that take into account values recorded at the times of visits. We apply the methods to two real data sets, one involving hip replacements and the other on the prostate specific antigen (PSA) assay for prostate cancer. In addition, we compare our methods with the common practice of imputing the threshold-crossing time as the right endpoint of the interval. The two examples require different imputation models, but both lead to simple analyses of the multiply imputed data that automatically take into account variability due to imputation.

Analyses of public use decennial census data with multiply imputed industry and occupation codes.

"This paper gives a brief introduction to multiple imputation for handling non-response in surveys. We then describe a recently completed project in which multiple imputation was used to recalibrate industry and occupation codes in 1970 U.S. census public use samples to the 1980 standard. Using analyses of data from the project, we examine the utility of analysing a large data set having imputed values compared with analysing a small data set having true values, and we provide examples of the amount by which variability is underestimated by using just one imputation rather than multiple imputations."

Multiple imputation in health-care databases: an overview and some applications.

Multiple imputation for non-response replaces each missing value by two or more plausible values. The values can be chosen to represent both uncertainty about the reasons for non-response and uncertainty about which values to impute assuming the reasons for non-response are known. This paper provides an overview of methods for creating and analysing multiply-imputed data sets, and illustrates the dramatic improvements possible when using multiple rather than single imputation. A major application of multiple imputation to public-use files from the 1970 census is discussed, and several exploratory studies related to health care that have used multiple imputation are described.

[Handling missing data in coverage estimation, with application to the 1986 Test of Adjustment Related Operations].

"This paper discusses methods used to handle missing data in post-enumeration surveys for estimating census coverage error, as illustrated for the 1986 Test of Adjustment Related Operations (Diffendal 1988). The methods include imputation schemes based on hot-deck and logistic regression models as well as weighting adjustments. The sensivity of undercount estimates from the 1986 test to variations in the imputation models is also explored." The test was carried out in Central Los Angeles County, California.