SUMMARY Standard techniques for selecting the bandwidth of a kernel estimator from the data in a nonparametric regression model perform badly when the errors are correlated. In this paper we propose a modified version of an existing plug-in bandwidth selector. The method is generalized to stationary error variables by estimating a functional of the residual covariance function. The proposed bandwidth selector shows good properties in asymptotic theory and in simulations without assuming a parametric model for the error process.

Choice of bandwidth for kernel regression when residuals are correlated

Gastric acid is of central importance in the pathogenesis of duodenal ulcer, gastric ulcer, and gastroesophageal reflux disease. Pharmacological reduction of acid secretion is, therefore, the mainstay of current treatment, but the optimal degree of acid suppression remains incompletely understood. This paper considers the ideal ways of assessing and reporting the pharmacological effectiveness of acid-inhibiting drugs and relating such data to clinical efficacy. Twenty-four-hour intragastric pH measurements are widely used for this purpose, although this technique cannot measure secretion quantitatively. Data on suppression of 24-hr intragastric acidity for groups of subjects have been successfully correlated with healing rates for duodenal ulcer, gastric ulcer, and gastroesophageal reflux disease. Three primary determinants of healing have been derived from antisecretory data. These are the degree of suppression of acidity, the duration of suppression of acidity, and the duration of treatment. The order of importance of these determinants varies depending on the disease. Data on 24-hr intragastric acidity should be accompanied whenever possible by data on 24-hr plasma gastrin levels, as the relationship between suppression of acidity and a rise in gastrin varies widely between individuals. It is not possible to predict the plasma gastrin level from the intragastric pH or any other measurement of intragastric acidity. Comparative data sets in groups of subjects may provide useful information. Proton pump inhibitors produce a greater and longer-lasting degree of suppression of acidity than conventional doses of H2-receptor antagonists. For this reason, they are more effective in healing duodenal ulcer and gastric ulcer. However, in view of the importance of duration of treatment, healing rates with the H2-receptor antagonists approach those obtained with proton pump inhibitors if treatment is continued for a longer time. In gastroesophageal reflux disease in particular, although the optimal degree of acid suppression is not yet defined, the consistently superior performance of proton pump inhibitors demonstrates that increased suppression of acidity is clinically beneficial.

Optimizing Acid Suppression for Treatment of Acid-Related Diseases

To carry out a simultaneous comparison of the 24-h in vivo performance of antimony and glass electrodes and the findings of intermittent gastric aspiration, a triple-probe system with closely adjacent tips was positioned in the gastric corpus of 10 subjects representing different clinical and pharmacologic conditions. We showed that pH values measured with the antimony and the glass units were well correlated to those assessed in gastric aspirates (rs = 0.87; b = 1.079; a = -0.33; and rs = 0.85; b = 1.121; a = -0.38, respectively). A proportional correlation (rs = 0.86; b = 0.97; a = 0.02) was also found between the two intraluminal pH measurements. With regard to the error frequency distributions obtained by comparing the three measuring systems two at a time, the pH pairs differed by no more than 1 pH unit in most cases (>90%). It can be concluded that antimony and glass pH electrodes can be used interchangeably in 24-h intragastric acidity studies in man.

Gastric aspiration versus antimony and glass ph electrodes: A simultaneous comparative in vivo study

Antimony and glass pH electrodes show almost identical experimental errors in continuously measuring buffer solutions at constant temperature over 24 hr. These errors are lower than the nominal quantization error of the instruments and are not properly described by the 24- hr drift determination. The addition of food particles to the solutions can induce severe reading artifacts. The longer response time reported in vitroof antimony electrodes when moving from pH 1 to pH 7 (3.4 sec vs 0.8 sec with glass electrodes) is irrelevant during in vivopH-metry studies, because we found that the greatest absolute difference between raw fast acquired (4–6 sec) consecutive pH readings of two commonly used devices was 0.7 pH units in circadian profiles obtained from 413 subjects with various clinical conditions. In our in vivo studies, gastric acidity was monitored continuously with two side-by-side minielectrodes, which were variously combined (antimony-glass, A-G; antimony-antimony A1–A2; glass-glass, G1–G2) and applied on groups of 27 subjects matched for clinical condition. The 24-hr pH means and the 24-hr [H+] means calculated from the acidity profiles obtained with the three electrode combinations, lie on the identity line in each group. Using the Bland-Altman technique for assessing measurement agreement, the differences between the 24- hr pH means and the 24-hr [H+] means obtained with the three combined systems are similar (P=.903 and P=0.824, respectively) and their 95% confidence limits are comprised within the range (±) of the reading error of the measuring systems (namely, ±0.3 pH units and ±12 mmolliter in terms of [H+]). These data show that the 24-hr acidity indexes calculated from gastric pH recordings performed with two closely adjacent antimony and glass electrodes are similar, irrespective of their possible combinations. It can be concluded that antimony and glass electrodes provide equivalent results in vivo and can be used interchangeably in the clinical setting.

Antimony and glass pH electrodes can be used interchangeably in 24-hour studies of gastric acidity.

While smoothing methods are commonly applied to noisy signals, this is not true for differentiation. Derivatives are often of intrinsic interest when analyzing biological dynamics, and as will be illustrated, they are useful for determining characteristic points (local extrema, inflection, and saddle points) in the curve, in the presence of noise. There are inherent difficulties in computing derivatives which might have inhibited wider usage. Kernel estimation is a statistical approach to nonparametric regression (i.e., without specifying a functional model for the signal), which allows detertining the signal itself and its derivatives from noisy data. This method is presented, together with its properties. The influence and the choice of the weight function (kernel) of the smoothing parameter and the treatment of boundary points deserve particular attention.

The Analysis of Noisy Signals by Nonparametric Smoothing and Differentiation

The interaction between smoking and the effect of histamine H2-antagonists on intragastric acidity was examined in a double blind double dummy placebo controlled study. Healthy volunteers, 11 smokers and 10 non-smokers, were given, on four separate days at least one week apart, either placebo or cimetidine 800 mg nocte or ranitidine 2 X 150 mg per day or ranitidine 300 mg nocte. Tablets were taken at 2115 and 0900 h. Smokers smoked a cigarette hourly from 0700 to 2300 h. Breakfast, lunch, and dinner were standardised. Intragastric acidity was measured with a combined intragastric glass electrode and a solid state recorder. The subjects were fully ambulatory. The three histamine H2-receptor antagonist regimens were less effective (p = 0.04) in smokers than in non-smokers, but the difference between acidity of smokers and non-smokers was small. Means of medians of pH during a 24-h period with placebo, cimetidine 800 mg, ranitidine 2 X 150 mg and ranitidine 300 mg were 1.6, 2.3, 3.1, and 2.7 in smokers and 1.5, 2.7, 3.2, and 3.1 in non-smokers, respectively. In a second part of the study seven chronic smokers were reexamined after acutely stopping smoking: inhibition of gastric acidity by histamine H2-receptor antagonists was similar before and after withdrawal. Smoking does not affect intragastric acidity in untreated volunteers and only slightly decreases the effectiveness of histamine H2-receptor antagonists on intragastric acidity. This effect best in part explains the unfavourable effect of smoking on healing of peptic ulcer in patients treated with these drugs.

https://gut.bmj.com/content/gutjnl/28/5/549.full.pdf

Does smoking interfere with the effect of histamine H2-receptor antagonists on intragastric acidity in man?

Doessmoking interfere withtheeffect ofhistamine H2-receptor antagonists onintragastric acidity inman?

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Does smoking interfere with the effect of histamine H2-receptor antagonists on intragastric acidity in man?

Doessmoking interfere withtheeffect ofhistamine H2-receptor antagonists onintragastric acidity inman?