A new diagnostic work-up for defining anemia etiologies: a cohort study in patients ≥ 50 years in general practices.

BACKGROUND: To study etiologies of anemia using an extensive laboratory analysis in general practices. METHOD: An extensive laboratory analysis was performed in blood of newly diagnosed anemia patients aged ≥50 years from the general population in the city of Dordrecht area, the Netherlands. Eight laboratory-orientated etiologies of anemia were defined. Patients were assigned one or more of these etiologies on the basis of their test results. RESULTS: Blood of 4152 patients (median age 75 years; 49% male) was analyzed. The anemia etiology was unclear in 20%; a single etiology was established in 59%; and multiple etiologies in 22% of the patients. The most common etiologies were anemia of chronic disease (ACD) (54.5%), iron deficiency anemia (IDA) (19.1%) and renal anemia (13.8%). The most common single etiologies were IDA (82%) and ACD (68%), while the multiple etiologies most commonly included folic acid deficiency (94%) and suspected bone marrow disease (88%). Older age was associated with a lower incidence of IDA and a higher incidence of renal anemia. Mild anemia was more often associated with ACD and uncertain anemia, while severe anemia was mainly seen in patients with IDA. CONCLUSION: Extensive laboratory analysis in anemic patients from the general population helped clarify the etiology of anemia and revealed many various combinations of etiologies in a significant proportion of patients. Age, sex and the severity of anemia are predictive of the underlying etiology.

Decision-making by the NICE Interventional Procedures Advisory Committee.

BACKGROUND: This study explored the evidence base for recommendations by the National Institute of Health and Care Excellence (NICE) Interventional Procedures Advisory Committee, the only NICE committee not to consider cost. The four potential recommendations are: Standard Arrangements (can be performed as routine practice in the NHS); Special Arrangements (can be done under certain conditions); Research Only; and Do Not Do. METHODS: Quantitative content analysis of data extracted from all published Interventional Procedure Guidance (IPG) for 2003-2018 (n = 496) was undertaken. All data were extracted independently by two researchers; disagreements were clarified by consensus. Data were tabulated, descriptive statistics produced, and regression analyses performed. RESULTS: The proportion of IPGs by recommendation was: 50·0 per cent Standard Arrangements; 37·2 per cent Special Arrangements; 11·1 per cent Research Only; and 1·6 per cent Do Not Do. There was a clear trend over time: the proportion of recommendations for Standard Arrangements decreased, whereas the evidence threshold increased. Adjusted mean numbers of patients in the evidence base by recommendation type were: Standard, 4867; Special, 709; Research Only, 386. Regression analyses confirmed that the year of recommendation, numbers of patients and levels of evidence all affected the likely recommendation. CONCLUSION: This study suggests that the likelihood of achieving the most positive recommendation (Standard Arrangements) is decreasing, and that this is most likely due to evidential requirements becoming more demanding. These findings are distinct from those reported for other NICE committees, for which the cost and statistical superiority of new therapies are among the drivers of recommendations.

ANTECEDENTES: Este estudio analiza los niveles de evidencia de las recomendaciones propuestas por el Interventional Procedures Advisory Committee del National Institute of Health and Care Excellence (NICE), el único comité NICE que no tiene en consideración los costes en la guía para los procedimientos de intervención. Las cuatro recomendaciones potenciales son: disposiciones estándar (se pueden efectuar sin restricciones en el marco del NHS); disposiciones especiales (se pueden efectuar bajo ciertas condiciones), en el ámbito de la investigación solo; y no intervenir. MÉTODOS: Se realizó un análisis cuantitativo del contenido de todas las Interventional Procedure Guidance (IPG) publicadas entre 2003-2018 (n = 496). Se obtuvieron todos los datos de forma independiente por dos investigadores y los desacuerdos entre ellos se decidieron por consenso. Se tabularon los datos y se realizaron estadísticas descriptivas y análisis de regresión. RESULTADOS: La proporción de las IPG según el tipo de recomendación eran estándar en el 50% de los casos, especial en el 37%, solo investigación en el 11% y no intervenir en el 2%. Se observó una clara tendencia a lo largo del tiempo: la proporción de recomendaciones del tipo de disposiciones estándar disminuía, mientras que el umbral para la evidencia aumentaba. La media ajustada del número de pacientes para cada tipo de recomendación (estándar, específica y solo investigación) fue de 4.867, 709 y 386, respectivamente. Los análisis de regresión confirmaron que el año de la recomendación, el número de pacientes y los niveles de evidencia afectaban el tipo de recomendación. Estos resultados son diferentes a los relativos a otros comités de NICE, en los que el coste y la superioridad estadística de las nuevas terapias son los motores de las recomendaciones. CONCLUSIÓN: Este estudio sugiere que la probabilidad de lograr la recomendación más positiva (disposición estándar) está disminuyendo, y ello con toda probabilidad es debido a que los requerimientos relacionados con la evidencia son cada vez más exigentes.

[Tick-borne disease or not? Do not let yourself be fooled]. / Tekenbeetziekte ofniet? Laat u niet beetnemen.

Confusion among physicians and patients is increasing regarding the diagnosis and treatment ofLyme borreliosis due to the enormous amount ofambiguous information available and media attention. Some of the dilemmas that physicians encounter are illustrated by 3 patients with a range of symptoms, one of whom was convinced she had Lyme borreliosis. However none of these patients had significant evidence that suggested Lyme borreliosis. Physicians should follow the guidelines developed by the Dutch Institute for Health Care Improvement (CBO) or the Infectious Diseases Society of America rather than 'alternative' guidelines, which are not evidence-based.

High-conductance anion channels in embryonic chick osteogenic cells.

Patch-clamp measurements done on excised membrane patches obtained from 1-5 day cultured embryonic chick osteoblasts, osteocytes, and periosteal fibroblasts revealed the existence of a high-conductance anion channel: 371 +/- 63 pS when measured under symmetrical 158 mM Cl- conditions. The channel frequently displayed subconductance levels. The ion selectivity of the channel expressed as the (an)ion to chloride permeability ratio was as follows: Cl- (1.0) greater than methylsulfate- (0.71) greater than gluconate- (0.25) greater than glutamate- (0.17) greater than Na+ = K+ (0.10). In addition, the channel had a significant permeability for inorganic phosphate ions. The channel was found in about 1% of the cell-attached patches, which indicates that the channel is under the control of as yet unknown intracellular factors. Once activated by patch excision, the channel was voltage dependent and active at potentials close to 0 mV. At potentials outside the range of +/- 10 mV channel activity decreased. This process proceeded faster at increasing membrane potentials of either polarity. Returning to potentials close to 0 mV caused reopening of the channels within seconds if the preceding voltage step led to complete closure of the channels. Channel activity did not depend noticeably on intracellular and extracellular CA2+ ions. The channel is not unique to (chick) osteogenic cells but has been demonstrated in excised patches obtained from excitable and other nonexcitable cells. Although its presence in a wide variety of cell types suggests that the channel plays a general role in as yet unknown cell physiologic processes, the channel may also have specific functions in osteogenic cells, for example providing a pathway for phosphate ions during mineralization.

Identification of Ca(2+)-activated K+ channels in cells of embryonic chick osteoblast cultures.

Primary cultures of embryonic chick osteoblasts consist of a heterogeneous cell population. Patch clamp measurements were done on 1- to 5-day-old osteoblasts, osteocytes, fibroblastlike cells, and cells that could not be classified on morphologic criteria. The measurements showed the omnipresence of depolarization-activated high-conductance channels in cell-attached patches. The whole-cell experiments showed an outward rectifying conductance activating at positive membrane potentials. Channels underlying the latter conductance were found to be K+ conducting in outside-out membrane patches. The activation potential of the outward rectifying K+ conductance shifted to negative membrane potentials upon increasing the intracellular Ca2+ concentration within the range of 10(-8)-10(-3.2) M. The same happened with the activation potential of the K+ channels found in outside-out patches. Finally, inside-out patch experiments directly demonstrated the dependency of the activation potential of K+ channels on Ca2+ ions. Thus the identity and main characteristics of Ca2(+)-activated K+ channels expressed by the various cell types present in chick osteoblast cultures have now been established. Decreased input resistances were found in cells of cultures more than 2 days old. This is consistent with the establishment of electrical coupling between the cells. Functions in which Ca2(+)-activated K+ channels could play a role are discussed.

Histopathological findings in Becker-type muscular dystrophy.

Muscle biopsy specimens from 14 patients with Becker-type muscular dystrophy were analyzed to investigate possible neurogenic factors underlying the histopathological changes. Group atrophy, pyknotic nuclear clumps, and angular small fibers were seen respectively in 71%, 85%, and 100% of the cases. In one biopsy specimen, notable type grouping was observed. A prominent finding was the appearance of groups of regenerating fibers in biopsy specimens from younger patients. Fiber degeneration was present in only 57% of the cases. While myopathic features predominated in some biopsy specimens, others were compatible with denervation. It is not possible to give an answer to the question whether the changes are basically myopathic or neurogenic (or both), but evidence is growing that a neurogenic component may play a part in the pathogenesis of the disease.

Late effects of locally delivered mitomycin C on formation of neointima and on vasomotor response to acetylcholine.

BACKGROUND: Balloon angioplasty damages endothelial cells and stimulates smooth muscle cell proliferation. The effects of local cytotoxic drug therapy on formation of neointima and late endothelial function are not known. This study was designed to determine whether direct infusion of mitomycin C via a microporous balloon catheter could significantly reduce formation of neointima after angioplasty. Furthermore, we investigated whether endothelial cell function is normal 7 weeks after the initial microporous angioplasty procedure. METHODS: In 34 New Zealand white rabbits, bilateral external iliac arteries underwent balloon angioplasty, followed by either high-dose (0.66 mg/kg) or low-dose (0.025 mg/kg) mitomycin C in one iliac artery and saline infusion in the contralateral artery, and a control group was given saline in both vessels. Formation of neointima was measured in the iliac arteries after 7 weeks by morphometry. Before sacrifice of 17 'angioplasty' rabbits and three undamaged rabbits, graded doses of acetylcholine and isosorbide dinitrate were infused in the distal aorta, and the iliac artery diameter was measured by computerized quantitative angiography. RESULTS: No significant differences in the absolute area of the intima or the intima: media ratio were demonstrated between control arteries and arteries that were directly infused with either high-dose or low-dose mitomycin. However, within the high-dose group, the mitomycin-treated vessel had a significantly lesser extent of formation of intimal hyperplasia (0.17 +/- 0.03 versus 0.27 +/- 0.03 mm2, P < 0.03) and lower intima: media area ratio (0.60 +/- 0.31 versus 1.09 +/- 0.42, P < 0.03) than the contralateral saline-treated vessel. Significant increases in mean luminal iliac artery diameter [0.18 mm (10.5%) at 1 min and 0.23 mm (13%) at 3 min, P < 0.05)] from baseline values following acetylcholine were observed in previously damaged iliac arteries. This vasodilatory response was not different from that in undamaged arteries. CONCLUSIONS: Local delivery of mitomycin C had no favorable effect on the inhibition of intimal hyperplasia compared with control saline-treated arteries. Normal endothelial function, determined on the basis of dilatory response to acetylcholine, can be demonstrated 7 weeks after balloon angioplasty injury.

The effects of a specific prompting sign on speed reduction.

The purpose of this experiment was to determine whether a specifically worded prompting sign ("BEGIN SLOWING HERE") could reduce speeding where a highway entered an urban area with a residential speed limit. Speed measurements were obtained on vehicles at the start of the residential speed limit zone. Following a baseline period the prompting sign was introduced, removed and reintroduced. The results indicated that the prompting sign produced clear reductions in the percentage of motorists travelling 10, 15 and 20 km or more over the speed limit. These results suggest the importance of more specific road signs in influencing the behavior of motorists.

The influence of signs prompting motorists to yield before marked crosswalks on motor vehicle-pedestrian conflicts at crosswalks with flashing amber.

The purpose of this experiment was to evaluate the effects of signs reading "STOP HERE FOR PEDESTRIANS" alone and in conjunction with advance stop lines on pedestrian safety at multilane crosswalks with pedestrian-activated amber flashing lights. Motorist and pedestrian behaviors measured throughout this experiment included the occurrence of various types of motor vehicle-pedestrian conflicts; the distance that motorists stopped before the crosswalk when yielding to pedestrians; and the percentage of motorists yielding to pedestrians. The introduction of the sign alone 50 feet (15.15 m) before the crosswalk increased the distance before the crosswalk that motorists yielded to pedestrians and reduced the percentage of motor vehicle-pedestrian conflicts whether the flashing light was activated or not. The addition of the advance stop line was associated with further improvements in both measures.

The use of feedback signs to increase observed daytime seat belt use in two cities in North Carolina.

Well publicized enforcement programs in North Carolina have raised seat belt use to about 80%. In an effort to find techniques to raise belt use further, signs providing feedback to drivers on belt use rates were introduced in two communities, Asheboro (population 18,000) and Greensboro (population 183,000). Feedback signs remind motorists about belt use and imply a constant and vigorous enforcement presence. The signs were prominently posted by the roadside at high volume locations; belt use information was changed weekly based on observational surveys. Observed daytime driver belt use in Asheboro increased from an average of 75% before the signs to 89% after the signs were established. At urban sites in Greensboro, driver belt use increased from 80% to 86%. Right front passenger belt use increased significantly in Asheboro but not in Greensboro. There were no changes in belt use at two interstate exit sites in Greensboro. Reasons for the differential success rates may relate to differences in initial belt use rates, community size, amount of publicity, and numbers of encounters with the signs. It is clear, however, that feedback signs can be an important supplement to belt use enforcement programs.

Auditory stimulus control in pigeons: Jenkins and Harrison (1960) revisited.

Pigeons were trained to peck a key in the presence of a 1000-Hz tone on a variable-interval one-minute schedule of reinforcement. One group was trained with an illuminated key; the other was trained in a totally dark chamber. During a generalization test on tonal frequency, subjects trained and tested with the key illuminated produced rather shallow gradients around the training value; subjects trained and tested in the dark produced steeper generalization gradients. These data replicate Jenkins and Harrison's (1960) finding that tone acquires relatively little control over responding and demonstrate that this absence of control is a function of the presence of the keylight.

The development of stimulus control with and without a lighted key.

In two experiments, the effect of an illuminated response key on the acquisition of stimulus control by an airflow stimulus was assessed. In the first experiment, pigeons were given nondifferential training with airflow emerging from behind the response key in one of three conditions of illumination: trained to peck a lighted key, trained to peck an unlighted key with a houselight present, trained to peck a key in total darkness. After 10 days of training on a variable-interval schedule of reinforcement, all subjects were given a generalization test on airflow velocity. The gradients for subjects trained in the dark were sharp, while those for subjects trained in lighted conditions were shallow. In the second experiment, the effect of an irrelevant keylight on the acquisition of an airflow velocity discrimination was assessed. Two groups of pigeons were trained to discriminate two airflow velocities. One group was trained with a lighted response key and the other was trained to peck the response key in total darkness. The dark-trained subjects acquired the discrimination more rapidly. The results demonstrate that the acquisition of stimulus control by airflow with either a differential or nondifferential training procedure can be overshadowed by keylight.

Summation of punishment suppression.

In two experiments, eight rats were trained to lever press with food on a variable-interval schedule. Bar pressing produced shock on a variable-interval schedule in the presence of two independently presented stimuli, a light and a tone. Two rats in each experiment received alternative presentations of the light and the tone and were consequently always in the presence of a stimulus that signalled variable-interval punishment. The other two rats in each experiment were treated similarly except that they received periods in which neither light nor tone was present. During these periods, bar pressing was not punished. The two stimuli that signalled punishment were then presented simultaneously to evaluate the effect of stimulus compounding on response suppression. The subjects trained without punishment-free periods did not show summation to the compound stimulus; the subjects trained with punishment-free periods showed summation of suppression. The major difference between the two experiments was the longer mean interval of variable-interval punishment used in the second experiment. This manipulation made the summation effect more resistant to extinction and thus increased its magnitude.

Airflow as a discriminative stimulus.

In one experiment, pigeons were taught to discriminate airflow by having availability of reinforcement signalled by its presence and extinction signalled by its absence. After they reached criterion, some were trained on a discrimination reversal. Others were trained on an intradimensional discrimination with a low airflow velocity associated with reinforcement and a higher airflow velocity associated with extinction. All discriminations were learned rapidly, indicating that airflow velocity can function as a discriminative stimulus. In the second and third experiments, naive pigeons were trained to discriminate the presence of a compound stimulus (one of three tonal intensities paired with one of three airflow velocities) from its absence. These pigeons were subsequently given a component stimulus test during extinction on four stimulus values; the two training values, the tone alone, and the airflow alone. High or moderate velocity airflow controlled more responding than any of the three tone intensities. However, low velocity airflow controlled more responding only when a low intensity tone was employed.

Summation of conditioned suppression.

Four rats were trained to suppress responses in the presence of two separately presented stimuli that signalled shock in a conditioned-suppression paradigm. The two stimuli that signalled shock were then presented simultaneously to evaluate the effect of stimulus compounding on conditioned suppression. Two rats were tested by presenting the compound conditioned stimulus while conditioned suppression was being maintained to the individual conditioned stimuli. The other two rats were tested by giving them random presentations of the compound conditioned stimulus and the single conditioned stimuli during extinction of conditioned suppression. All four rats showed greater suppression to the compound stimulus than to either stimulus presented alone.

Treatment of constipation-caused encopresis by a negative reinforcement procedure.

During a baseline condition soiling and the cumulative number of bowel movements of a child suffering from retentive encopresis were recorded. Following this, a DRO (differential reinforcement of other behavior) alone, a DRO plus overcorrection procedure, and a negative reinforcement procedure were each evaluated using a reversal design. The negative reinforcement procedure, which involved having the child sit on the toilet three times a day for increasing time periods if no bowel movement occurred, suppressed soiling and led to regular unprompted daily bowel movements in a very brief period of time. The DRO alone and DRO plus overcorrection conditions produced only a small decline in soiling.

The use of a brief movement restriction procedure to eliminate severe inappropriate behavior.

The effect of a brief movement restriction (BMR) procedure on the maladaptive behavior of two severely mentally retarded persons was evaluated using a multiple baseline research design. Following a functional analysis of the maladaptive behaviors, baseline data were collected on the frequency of smearing in a six year old boy and the frequency of aggression-destruction and stereotypic behavior in a 24 year old man. Following the baseline period a treatment package that included reinforcement for alternative behavior and BMR were first introduced for feces smearing. After feces smearing had shown a reduction with the first client the treatment package was introduced for aggression and destruction with the second client. After aggression and destruction had been reduced, the treatment package was added for stereotypy. The treatment package completely eliminated each of the target behaviors and they remained absent during a long follow-up period.

A comparison of the recognition distance of several types of pedestrial signals with low-vision pedestrians.

Although approximately 80-85% of the legally blind population has some residual vision, little research has examined the relative conspicuity of various types of visual pedestrian signals currently used by cities with this group of pedestrians. This research compared the relative conspicuity of an incandescent WALK sign, a white LED WALK sign, a blue LED WALK sign, and white and blue LED WALK signs that included an animated "eyes" display with legally blind participants who had some vision. All WALK signals were equated for brightness with the use of a N.I.S.T.-certified illuminance meter. Participants had to discriminate whether the test stimulus was a blue/white WALK sign or a blue/white DON'T WALK sign. Test stimuli were presented in randomized blocks of trials, and recognition distances were determined by having participants approach the test stimuli until they could identify them. Results indicated that there were no significant differences between the incandescent and LED signals without the animated eyes or between the blue and white LED signals. However, Tukey's method showed a significant contrast between the signals with the animated eyes display and signals without this display (F=149.88, P value<0.0001). Participants could identify the Walk signal 62% further away when it also contained the animated "eyes" display. These results show that the addition of an animated "eyes" display to the WALK sign significantly improves recognition distance for a large segment of persons with visual impairment.

Operant extinction in the treatment of severe maladaptive behavior: adapting research to practice.

Operant extinction involves termination of reinforcement for a previously reinforced response. As a clinical intervention for severe maladaptive behavior operant extinction is often repudiated because of intensity of side effects, length of treatment time required, and implementation difficulties. This article discusses both theoretical and practical aspects of extinction, including components of the extinction process and the importance of functional assessment to its effective use. Potential strategies for increasing the effectiveness of extinction while diminishing intrusiveness are recommended. Based on recent research innovations, a technology is emerging for effective use of operant extinction in the treatment of severe maladaptive behavior.

The effects of low alcohol beverages on alcohol consumption and impairment.

We examined the effects of providing drinks with half the alcohol level on alcohol consumption and blood alcohol concentration (BAC) of 4 patrons of a private club. Alcohol consumption was measured by observers and level of impairment was determined from breath samples obtained by digitalized ALERT (Alcohol Level Evaluation Road Tester) breath testing devices. An alternating treatments design was employed to compare the sessions during which people drank mixed drinks with their usual alcohol concentration with sessions during which they drank mixed drinks with half the alcohol concentration that cost half as much as the regular drinks. All 4 participants consumed less alcohol during sessions when they received drinks with the lower alcohol content. BAC was also less on all but two sessions during the low alcohol condition.