Health-related quality of life and appropriateness of cholecystectomy

OBJECTIVE: To evaluate the relationship among appropriateness of the use of cholecystectomy and outcomes. SUMMARY BACKGROUND DATA: The use of cholecystectomy varies widely across regions and countries. Explicit appropriateness criteria may help identify suitable candidates for this commonly performed procedure. This study evaluates the relationship among appropriateness of the use of cholecystectomy and outcomes. METHODS: Prospective observational study in 6 public hospitals in Spain of all consecutive patients on waiting lists to undergo cholecystectomy for nonmalignant disease. Explicit appropriateness criteria for the use of cholecystectomy were developed by a panel of experts using the RAND appropriateness methodology and applied to recruited patients. Patients were asked to complete 2 questionnaires that measure health-related quality of life-the Short Form 36 (SF-36) and the Gastrointestinal Quality of Life Index (GIQLI)-before the intervention and 3 months after it. RESULTS: Patients judged as being appropriate candidates for cholecystectomy, using the panel's explicit appropriateness criteria, had greater improvements in the bodily pain, vitality, and social function domains of the SF-36 than those judged to be inappropriate candidates. They also demonstrated improvements in the GIQLI's physical impairment domain. Interventions judged as inappropriate were performed primarily among patients without symptoms of cholelithiasis. Those asymptomatic had a lower improvement in the bodily pain, social functioning, and physical summary scale of the SF-36 and in the symptomatology, physical impairment, and total score domains of the GIQLI. CONCLUSIONS: These results suggest a direct relationship between the application of explicit appropriateness criteria and better outcomes, as measured by health-related quality of life. They also indicate that patients without symptoms are not good candidates for cholecystectomy.     

In vivo demonstration of the absorptive function of the middle ear epithelium

The present study investigated in vivo fluid and ion transport across the middle ear epithelium. The tympanic membrane of rats was punctured under general anesthesia. A capillary tube was fitted to the external auditory canal and the bulla filled with various solutions. Middle ear (ME) fluid volume variations were then measured at constant pressure.

When saline was used, a linear decrease of fluid volume was apparent. Replacement of sodium with a non-permeable cation (N-methyl-d-glucamin) reduced the absorption rate from 0.065 ± 0.008 to 0.019 ± 0.003 μl/min (P < 0.05, n = 6). Similarly, amiloride (10⁻³ M), a sodium channel antagonist, reduced the absorption rate to 0.027 ± 0.006 μl/min (P < 0.05, n = 6). Net absorption was abolished when chloride was substituted with gluconate: −0.008 ± 0.004 μl/min (P < 0.02, n = 6), which might have been related (i) to the role of chloride as a diffusible anion through the paracellular pathway, or (ii) to the secretion of chloride through apical channels. However in this condition, 4,4′-diisothiocyanostilbene-2,2′-disulfonic acid, a chloride channel blocker, did not affect the rate of fluid exchange −0.008 ± 0.007 μl/min (P = 0.75, n = 6).

This model provides the first in vivo evidence for the absorptive function of the ME. Fluid introduced into the ME cavity disappears due to active transport through the mucosa. This process is sodium-dependent and can be hindered by high concentration of amiloride. The rate of absorption is high enough to allow total clearance of fluid from the cavity of the middle ear within 13 h. This process might play a role in the maintaining a fluid-free and gas-filled middle ear cavity.     

Experimental model for investigating trans-mucosal gas exchanges in the middle ear of the rat

OBJECTIVE: The total pressure in the middle ear depends on the air composition of this gas pocket, i.e. on gas exchanges occurring through either the Eustachian tube (ET) or mucosa. The aim of this study was to develop an experimental model to investigate the exclusive role of trans-mucosal gas exchanges in the middle ear (ME). MATERIAL AND METHODS: Both tympanic membranes of 20 Sprague-Dawley rats were punctured under general anesthesia. Rats were divided into two equal groups. Group 1 had no ET obstruction. In Group 2, the ET was blocked, after velar incision, by cauterization and application of cyanoacrylate glue into the lumen. One open transparent glass tube containing a droplet of colored water was placed horizontally and connected hermetically to each ear canal. The ME was then flushed with room air through the tube. Variations in ME gas volume were measured by reading the displacement of the liquid droplet in the horizontal tube. The kinetics of variations in gas volume between groups were displayed and statistically compared using a two-sided t-test. RESULTS: The pattern of variations in ME gas volume with time was similar in the two groups. Both were characterized by a decrease with three phases and an elimination rate of approximately 0.152 +/- 0.026 microl/min. There was no significant difference in the mean rate of ME volume changes between the two groups. CONCLUSION: This experimental model allows investigation of trans-mucosal gas exchanges. These exchanges exhibit an absorptive function resulting in a negative pressure that must be compensated, under physiological conditions, by air flow through the ET.     

The KARTAN study: a postmarketing assessment of Irbesartan in patients with hypertension

BACKGROUND: An important purpose of postmarketing surveillance of drugs is to better characterize the safety profile of drug therapy in the clinical setting. Another goal is to confirm the effectiveness of these drugs in patients who are candidates for antihypertensive therapy and who may have been excluded from Phase III studies. Irbesartan is a long-acting angiotensin II-receptor blocker specific for the angiotensin 1-receptor subtype that, in clinical trials in patients with hypertension, reduces blood pressure. OBJECTIVES: The KARTAN (this word was derived from the first and last syllables of Karvea [trademark of Bristol-Myers Squibb Group, Madrid, Spain] and irbesartan) study was designed to confirm and extend the findings from previous clinical trials using data from a large number of patients with hypertension treated with irbesartan in routine clinical practice. The primary goal was to assess the types and incidences of adverse drug reactions (ADRs) occurring at a low frequency (<0.05%) with irbesartan. The secondary objectives were to study the effect of irbesartan as an antihypertensive agent, to assess the types and incidences of the most frequent ADRs (>/=0.05%) occurring in routine clinical practice, and to detect possible interactions between irbesartan and other drugs frequently used in the primary care setting. METHODS: This 6-month, observational, open-label, uncontrolled, national, longitudinal, prospective study was conducted by 852 primary care physicians across Spain. Men and women aged >/=18 years with mild to moderate hypertension who, in their physicians' opinion, should have been treated with irbesartan were included. Each patient was followed up for 6 months, attending visits at baseline (ie, the start of treatment) and 1, 3, and 6 months after the start of treatment. A sample size of 3219 patients was calculated for the detection of >/=1 low-incidence (<0.05%) ADR. After the baseline visit, therapy typically was begun with irbesartan 150 mg/d. The initial dose was titrated up, at 300-mg increments based on the patient's response, at each visit as needed to achieve the treatment goals (systolic blood pressure, <140 mm Hg; diastolic blood pressure, <90 mm Hg). Information regarding ADRs was collected on case-report forms designed for each visit and analyzed by the scientific committee of the study. All recruited patients were included in the tolerability analysis. RESULTS: A total of 4887 patients were enrolled (2165 men, 2 772 women; mean [SD] age, 61.1 [11.0] years [range, 19-94 years]; 23.3% of patients were aged >70 years); 4612 were assessable for efficacy. One hundred eight patients (2.2%) experienced ADRs over the 6-month treatment period; 3 of these patients (0.1%) experienced >1 ADR. Of the total number of clinical manifestations of ADRs, 24 occurred at an incidence <0.05%. Irbesartan produced reductions in blood pressure that were statistically significant from the first visit (all p < 0.001), and 39.9% of the patients achieved the treatment goal at the end of the follow-up period. CONCLUSION: In this postmarketing surveillance study of patients with hypertension treated in routine clinical practice, irbesartan showed a satisfactory tolerability profile that was consistent with that seen in randomized, controlled trials.     

Effect of glucomannan and the dosage form on ethinylestradiol oral absorption in rabbits

To the beneficial properties of dietary fiber in human health, several disadvantages can be added as the possible modification of the bioavailability of other drugs when administered by the oral route. In this study, the influence of glucomannan in the oral bioavailability of ethinyl estradiol (EE), when administered to female rabbits in two different dosage forms (enteric capsules and dispersed in water), was established. To carry out the study, three groups of six animals each were used. All animals received 1 mg kg(-1) oral EE, and rabbits in groups 2 and 3 received 1.5 g glucomannan dispersed in water or in enteric capsules, respectively, immediately before EE. When comparing the results obtained after the administration of EE/glucomannan dispersed in water with those obtained after the administration of this estrogen without fiber, we can see that Cmax is 1.4 times lower, AUC 1.9 times lower and that tmax is identical (10 min). However, after the administration of fiber in enteric capsules, AUC and Cmax are higher (4.1 and 7.8 times, respectively) than when the estrogen was administered alone, and also, there is a delay in tmax (20 min). After the administration of glucomannan in the enteric capsule, the fiber forms, as in the stomach, a highly viscous solution in the gut that would limit EE access to the mucosal surface delaying its absorption. However, this effect could be compensated by a reduction of EE metabolism in the intestinal wall, leading to a higher absorption of the estrogen.     

Community participation and social control in the health system

In Colombia, the 1991 Constitution established the obligation of promoting social participation. However, the discussion regarding the significance and scope of social participation is far from being over with the promulgation of the Constitution since social participation has a high political component, i.e., social participation requires the transfer of a part of power to sectors previously excluded from decision taking. As long as the State has conceived the market strategy as the best way to allocate resources and the receptors of social policy are considered as consumers, the challenge is to establish a balance between supply and demand in order to guarantee efficiency and efficacy in the application of resources and transparency in the public administration. Thus, the community of users has the mission of monitoring the correct allocation of State resources. Upon evaluating some of the results of the application of this strategy of social participation in health, three features can be highlighted: there are important advances in the promotion of social participation but not in social control; social control is dispersed and atomized, and participation as institutional policy is weak. Regarding the first aspect, it can be concluded that there has been a favorable response of the municipalities to the obligation of promoting the organizational forms of the community as far as health is concerned. When the actions carried out for social control are taken into account, the outlook varies. The convoking capacity of the institutions of the system to community organizations is considerably low, as well as the discussion of the reports presented by such organizations. On the other hand, the lack of communication between the different instances involved in both promotion of participation and social control became evident, situation which reflects the presence of relationships of bilateral nature, i.e., only the most direct interlocutor is known.