Randomised clinical trial: early assessment after 2 weeks of high-dose mesalazine for moderately active ulcerative colitis - new light on a familiar question.

BACKGROUND: Rapid resolution of rectal bleeding and stool frequency are important goals for ulcerative colitis therapy and may help guide therapeutic decisions. AIM: To explore patient diary data from ASCEND I and II for their relevance to clinical decision making. METHODS: Data from two randomised, double-blind, Phase III studies were combined. Patients received mesalazine (mesalamine) 4.8 g/day (Asacol 800 mg MR) or 2.4 g/day (Asacol 400 mg MR). Time to improvement or resolution of rectal bleeding and stool frequency was assessed and the proportion of patients experiencing symptom improvement or resolution at day 14 evaluated using survival analysis. Symptoms after 14 days were compared to week 6. A combination of prespecified and post hoc analyses were used. RESULTS: Median times to resolution and improvement of both rectal bleeding and stool frequency were shorter with 4.8 g/day than 2.4 g/day (resolution, 19 vs. 29 days, P = 0.020; improvement, 7 vs. 9 days, P = 0.024). In total, 73% of patients experienced improvement in both rectal bleeding and stool frequency by day 14 with 4.8 g/day, compared to 61% with 2.4 g/day. More patients achieved symptom resolution by day 14 with 4.8 g/day than 2.4 g/day (43% vs. 30%; P = 0.035). Symptom relief after 14 days was associated with a high rate of symptom relief after 6 weeks. CONCLUSIONS: High-dose mesalazine 4.8 g/day provides rapid relief of the cardinal symptoms of moderately active ulcerative colitis. Symptom relief within 14 days was associated with symptom relief at 6 weeks in the majority of patients. Day 14 is a practical timepoint at which response to treatment may be assessed and decisions regarding therapy escalation made (Clinicaltrials.gov: NCT00577473, NCT00073021).

Cosmic transcendence, loneliness, and exchange of emotional support with adult children: a study among older parents in The Netherlands.

Gerotranscendence defines a shift in meta-perspective from earlier materialistic and pragmatic concerns, toward more cosmic and transcendent ones in later life. Population-based studies that have empirically examined this concept using Tornstam's gerotranscendence scale, highlight cosmic transcendence as a core component, which includes a sense of belongingness with past and future generations. Such generative concerns may increase expectations regarding the quality of the bond with one's children in later life. This study examined whether the association between emotional support exchanged with children and feelings of loneliness later in life varied by the degree of cosmic transcendence of the older parent. Data from 1,845 older parents participating in a population-based study living in The Netherlands were analyzed from the 1995/1996 cycle of the Longitudinal Aging Study Amsterdam. Interviews included self-report measures of cosmic transcendence, loneliness, emotional support exchanged with children, health indicators, and marital status. Results indicated that a negative association between loneliness and level of emotional support exchanged with children was more pronounced among older parents with higher cosmic transcendence scores, in particular among the married. It is argued that cosmic transcendence reflects a sense of generativity and an increased emotional dependency on children in later life. Under favorable social conditions (supportive relationships with children and being married) cosmic transcendent views had a positive impact on social well-being in later life. When children no longer met emotional needs of older parents, cosmic transcendence increased feelings of loneliness.

Successful treatment of Staphylococcus epidermidis prosthetic valve endocarditis with linezolid after failure of treatment with oxacillin, gentamicin, rifampicin, vancomycin, and fusidic acid regimens.

We present a 49-y-old male, with a history of Marfan's disease and aortic and mitral valve replacement surgery, who was operated for a type III thoracoabdominal aneurysm. The postoperative course was compromised by a Staphylococcus epidermidis mitral valve endocarditis, which was successfully treated only after intravenous linezolid was included in the therapy.

[The hot summer of 2003: heat stroke in Maastricht]. / De hete zomer van 2003: hitteberoerte in Maastricht.

Two male patients, 46 and 62 years of age, were brought to the emergency department on a hot summer's day. Both wore excessive clothing. The first patient had a temperature of 43 degrees C and was comatose. Heteroanamnesis indicated that he was suffering from schizophrenia. Although the prognosis seemed to be poor, his condition improved after treatment in intensive care, consisting of cooling and supportive treatment, but the patient had considerable permanent neurological impairment. The second patient had a temperature of 40.3 degrees C, was confused and had an atactic gait. He was cooled immediately and recovered swiftly without complications. Heat stroke is a life-threatening illness, which is defined as a body temperature above 40 degrees C and central nervous-system dysfunction. Heat stroke may be attended by many serious complications, including multi-organ failure and residual brain damage. Prompt recognition and rapid treatment, consisting of adequate cooling, are required.

Successful treatment of severe bleeding with recombinant factor VIIa after kidney transplantation.

Recombinant factor VIIa (rFVIIa, NovoSeven) has been registered for the treatment of bleeding episodes in patients with inherited or acquired hemophilia A or B with inhibitors. Furthermore, rFVIIa has been used successfully for the treatment of bleeding in patients with thrombocytopenia, and acquired and congenital platelet dysfunction. The definite spectrum of indications for rFVIIa has not yet been established. We describe a case of severe intra-abdominal bleeding 3 days after non-heart beating kidney transplantation in a patient with severe coronary artery disease in which rFVIIa (a single intravenous bolus injection 70 microg/kg bodyweight) was successfully used. No thrombotic complications occurred. This report demonstrates that rFVIIa might be safe and effective after recent renal transplantation.

Successful aging in the oldest old: Who can be characterized as successfully aged?

BACKGROUND: Successful aging is a worldwide aim, but it is less clear which indicators characterize elderly persons as successfully aged. We explored the meaning of successful aging from 2 perspectives. METHODS: Analysis of data from the first cross-sectional part of the longitudinal Leiden 85-plus Study, conducted in Leiden, the Netherlands. All inhabitants of Leiden aged 85 years were eligible. Data were obtained from 599 participants (response rate, 87%). Successful aging from a public health perspective was defined as a state of being. All participants were classified as successful or not successful based on optimal scores for physical, social, and psychocognitive functioning and on feelings of well-being, using validated quantitative instruments. Qualitative indepth interviews on the perspectives of elderly persons were held with a representative group of 27 participants. RESULTS: Although 45% (267/599) of the participants had optimal scores for well-being, only 13% (79/599) had optimal scores for overall functioning. In total, 10% (58/599) of the participants satisfied all the criteria and could be classified as successfully aged. The qualitative interviews showed that most elderly persons viewed success as a process of adaptation rather than a state of being. They recognized the various domains of successful aging, but valued well-being and social functioning more than physical and psychocognitive functioning. CONCLUSIONS: If successful aging is defined as an optimal state of overall functioning and well-being, only a happy few meet the criteria. However, elderly persons view successful aging as a process of adaptation. Using this perspective, many more persons could be considered to be successfully aged.

"No strength": sex and old age in a rural town in Ghana.

This article is part of a larger project on social and cultural meanings of growing old in a rural community of Ghana, the fieldwork for which was carried out between 1994 and 2000. It deals with ideas and practices concerning sex among the elderly. Informal conversations were held with individual elders and with groups of people that were, middle-aged and young. Sex was generally regarded as a matter of "strength", which was diminishing at old age. For men the concept of strength specifically referred to sexual potency, whereas for women "strength" was part of a more general feeling of physical power and the ability to perform the many activities expected from being a man's sexual partner. Sex at old age is looked at with a considerable amount of ambivalence. On the one hand, it is something that the elderly should have left behind them. On the other hand, sex confirms the vitality and status of the elder. If sex is practised at old age, it should be orderly and restrained, "respectful".

The development of ventilator-associated pneumonia does not change aspects of mechanical ventilation.

OBJECTIVE: To evaluate whether the development of ventilator-associated pneumonia (VAP) is associated with changes in ventilation parameters. DESIGN: Matched case-control study. SETTING: Mixed intensive care unit of a university hospital. PATIENTS: From a large database we selected 33 patients with VAP, diagnosed with quantitative cultures of bronchoscopically obtained specimens. In addition, 33 other mechanically ventilated patients who did not develop VAP were selected (controls). Patients with VAP and controls were matched on seven variables representing severity of illness: duration of ventilation until matching, diagnosis on admission, renal function, liver function, preceding infection, preceding surgery and immunosuppressive therapy. Each patient with VAP was matched to a single control. Variables regarding type and mode of ventilation and interpretation of chest radiographs were not included in the matching procedure. MEASUREMENTS AND RESULTS: Characteristics of mechanical ventilation (mode of ventilation, tidal volume, expired minute ventilation, peak airway pressures, mean airway pressures, level of positive end-expiratory pressure, arterial oxygen tension(PaO2)/fractional inspired oxygen (FIO2) ratio), were compared on the day of diagnosis of VAP (or matching for controls) and 2 and 4 days before. Although there was a significant difference in PaO2/FIO2 ratios between cases and controls on the day of diagnosis of VAP, the change in PaO2/FIO2 ratios during the days of study were not statistically different between patients developing VAP and controls. No significant differences were found for any of the other variables of ventilation at any of the three time points studied, nor were there significant differences in changes of these parameters within individual patients. CONCLUSIONS: Characteristics and parameters of mechanical ventilation are not influenced by the development of VAP. It is, therefore, unlikely that these variables are useful in the diagnostic work-up of VAP.

Prevention of ventilator-associated pneumonia by oral decontamination: a prospective, randomized, double-blind, placebo-controlled study.

UNLABELLED: Colonization of the intestinal tract has been assumed to be important in the pathogenesis of ventilator-associated pneumonia (VAP), but relative impacts of oropharyngeal, gastric, or intestinal colonization have not been elucidated. Our aim was to prevent VAP by modulation of oropharyngeal colonization, without influencing gastric and intestinal colonization and without systemic prophylaxis. In a prospective, randomized, placebo-controlled, double-blind study, 87 patients received topical antimicrobial prophylaxis (gentamicin/ colistin/vancomycin 2% in Orabase, every 6 h) in the oropharynx and 139 patients, divided over two control groups, received placebo (78 patients were studied in the presence of patients receiving topical prophylaxis [control group A] and 61 patients were studied in an intensive care unit where no topical prophylaxis was used [control group B]). Baseline characteristics were comparable in all three groups. Topical prophylaxis eradicated colonization present on admission in oropharynx (75% in study group versus 0% in control group A [p < 0.00001] and 9% in control group B patients [p < 0.00001]) and in trachea (52% versus 22% in A [p = 0.03] and 7% in B [p = 0.004]). Moreover, topical prophylaxis prevented acquired oropharyngeal colonization (10% versus 59% in A [p < 0.00001] and 63% in B [p < 0.00001]). Colonization rates in stomach and intestine were not affected. Incidences of VAP were 10% in study patients, 31% in Group A, and 23% in Group B patients (p = 0.001 and p = 0.04, respectively). This was not associated with shorter durations of ventilation or ICU stay or better survival. Oropharyngeal colonization is of paramount importance in the pathogenesis of VAP, and a targeted approach to prevent colonization at this site is a very effective method of infection prevention. KEYWORDS: cross infection, prevention and control; respiration, artificial, adverse effects; antibiotics, administration and dosage infection control methods; pneumonia, etiology, prevention and control; intubation, intratracheal, adverse effects

Steady-state pharmacokinetics of twice-daily dosing of saquinavir plus ritonavir in HIV-1-infected individuals.

OBJECTIVE: To compare the steady state plasma pharmacokinetics of 1000 mg of saquinavir (SQV) in a soft-gel capsule (SGC) formulation in combination with 100 mg of ritonavir (RTV) (capsules) in a twice-daily dosing regimen in HIV-1-infected individuals with historical controls who used 400 mg of SQV in a hard-gel capsule (HGC) formulation in combination with 400 mg of RTV and to investigate the plasma pharmacokinetics of the 1000 mg/100 mg regimen after normal and high-fat breakfasts. DESIGN: Open-label, crossover, steady-state pharmacokinetic study. METHODS: Six HIV-1-infected individuals who used either 1200 mg of SQV (SGC or HGC) three times daily or 400 mg twice daily in combination with 400 mg of RTV twice daily were included. Each patient was switched to 1000 mg of SQV SGC twice daily in combination with 100 mg of RTV twice daily. After 14 days, the patients came to the hospital for assessment of a pharmacokinetic profile during 12 hours. Patients were randomized to receive a high-fat (+/-45 g of fat) or normal (+/-20 g of fat) breakfast. After 7 days, a second pharmacokinetic profile was assessed after ingestion of the drugs with the alternate breakfast. A noncompartmental pharmacokinetic method was used to calculate the area under the plasma concentration versus time curve (AUC0-12h), the maximum plasma concentration (Cmax), the plasma trough concentration (C12h), and the elimination half-life in plasma (t1/2). The obtained pharmacokinetic parameters were compared with those of 12 patients using SQV HGC (400 mg twice daily) in combination with RTV (400 mg twice daily). RESULTS: The median values of the pharmacokinetic parameters for SQV SGC (1000 mg twice daily, normal breakfast) were: AUC0-12h, 18.84 h*mg/L; Cmax, 3.66 mg/L; C12h, 0.40 mg/L; and t1/2, 3.0 hours. The median values of the pharmacokinetic parameters for SQV HGC (400 mg twice daily, normal breakfast) were: AUC0-12h, 6.99 h*mg/L; Cmax, 1.28 mg/L; C12h, 0.23 mg/L; and t1/2, 3.9 hours. The exposure to SQV in the dosing regimen of 1000 mg twice daily in combination with 100 mg of RTV twice daily was significantly higher than the exposure to SQV in a dosing regimen of 400 mg twice daily in combination with 400 mg of RTV twice daily. The pharmacokinetic parameters of SQV SGC in the dosing regimen of 1000 mg twice daily in combination with 100 mg of RTV twice daily were not significantly different after ingestion of a high-fat or normal breakfast (p >.35). CONCLUSIONS: The combination of 1000 mg of SQV SGC twice daily and 100 mg of RTV twice daily resulted in a higher exposure to SQV compared with the exposure to SQV obtained when SQV is used in the 400 mg/400 mg twice-daily combination with RTV. In this small number of patients, no significant differences in exposure were seen after ingestion of either a normal or high-fat breakfast. From a pharmacokinetic perspective, the combination of 1000 mg of SQV SGC twice daily and 100 mg of RTV twice daily seems to be a good option for further clinical evaluation.

User fees and drugs: what did the health reforms in Zambia achieve?

The article reports on exploratory research into the effects and prospects of health reforms in Zambia. The research, which was qualitative, was carried out in two rural and two urban health centres and their surrounding catchment populations. The authors focus on four principles of health reform: community involvement (including cost sharing), prevention, equity and quality of care. One of their main conclusions is that many people criticize the introduction of cost sharing because it does not improve the quality of care, by which they first of all mean the availability of drugs. The authors plead for a humane implementation of user fees in public health care that is directly linked to a more efficient provision of essential medicines.

Colonization with Pseudomonas aeruginosa in patients developing ventilator-associated pneumonia.

To determine routes of colonization and genotypic variation of Pseudomonas aeruginosa leading to ventilator-associated pneumonia, colonization of the rectum, stomach, oropharynx, and trachea was studied chronologically in 10 patients. Ninety-one isolates of P aeruginosa were genotyped; seven different genotypes were identified. Patients developing ventilator-associated pneumonia caused by P aeruginosa were colonized at multiple body sites and may be colonized with multiple genotypes. The upper respiratory tract is the predominant initial site of colonization with P aeruginosa.

[Reciprocity and care of the elderly. An anthropologic comparison between Ghana and the Netherlands]. / Reciprociteit en zorg voor ouderen. Een antropologische vergelijking tussen Ghana en Nederland.

The author compares the lives of elderly people in Ghana and the Netherlands from the perspective of reciprocity. As a rule, the Ghanaian government does not provide social security for the elderly. Their security is entirely in the hands of their relatives and depends on reciprocity. As a result, some elderly find themselves in a stressful situation, both in material and in emotional terms. A remarkable similarity is that the principle of reciprocity is applied in both societies; in Ghana openly, in the Netherlands in a more subtle and concealed way.

The fake patient: a research experiment in a Ghanaian hospital.

The authors report on a research experiment involving the admission of one of them as a pseudo-patient in a rural Ghanaian hospital. The experiment was meant to assess the feasibility of carrying out unobtrusive participant observation in a hospital setting. Practical, methodological and ethical implications are discussed.

Cross-colonisation with Pseudomonas aeruginosa of patients in an intensive care unit.

BACKGROUND: Ventilator-associated pneumonia (VAP) caused by Pseudomonas aeruginosa is usually preceded by colonisation of the respiratory tract. During outbreaks, colonisation with P aeruginosa is mainly derived from exogenous sources. The relative importance of different pathways of colonisation of P aeruginosa has rarely been determined in non-epidemic settings. METHODS: In order to determine the importance of exogenous colonisation, all isolates of P aeruginosa obtained by surveillance and clinical cultures from two identical intensive care units (ICUs) were genotyped with pulsed field gel electrophoresis. RESULTS: A total of 100 patients were studied, 44 in ICU 1 and 56 in ICU 2. Twenty three patients were colonised with P aeruginosa, seven at the start of the study or on admission and 16 of the remaining 93 patients became colonised during the study. Eight patients developed VAP due to P aeruginosa. The incidence of respiratory tract colonisation and VAP with P aeruginosa in our ICU was similar to that before and after the study period, and therefore represents an endemic situation. Genotyping of 118 isolates yielded 11 strain types: eight in one patient each, two in three patients each, and one type in eight patients. Based on chronological evaluation and genotypical identity of isolates, eight cases of cross-colonisation were identified. Eight (50%) of 16 episodes of acquired colonisation and two (25%) of eight cases of VAP due to P aeruginosa seemed to be the result of cross-colonisation. CONCLUSIONS: Even in non-epidemic settings cross-colonisation seems to play an important part in the epidemiology of colonisation and infection with P aeruginosa.

Yebisa Wo Fie: growing old and building a house in the Akan Culture of Ghana.

'House' (ofie) in the Akan culture of Ghana is the most common metonym for people living together. Mefie (my house) means 'my family'. A house is someone's identity, it is a sign of security and happiness. A house is the concretisation of social relations and the sentiments accompanying them. A house, not least of all, is a status symbol. Building a house is building a powerful symbol. A house is something to which people attach some of the most cherished virtues of their culture: respect, love, memory, 'home' and beauty. In this article, building a house is seen as one of the most important achievements in a person's life. It provides elderly people with respect and security. The article is based on anthropological research in the rural Ghanaian town of Kwahu-Tafo.

Implementation of bronchoscopic techniques in the diagnosis of ventilator-associated pneumonia to reduce antibiotic use.

In intensive care units, a large proportion of antibiotics are prescribed for presumed episodes of ventilator-associated pneumonia (VAP). VAP is usually diagnosed on a combination of clinical, radiographic, and microbiologic criteria with a high sensitivity but low specificity for VAP. As a result, patients may receive antibiotics unnecessarily. Specificity can be increased by the addition of quantitative cultures of samples of protected specimen brush (PSB) and bronchoalveolar lavage (BAL) to the diagnostic criteria. We prospectively analyzed the effects of implementation of PSB and BAL in the diagnosis of VAP on antibiotic prescription. PSB and/or BAL were performed in patients who fulfilled the clinical, radiographic, and microbiologic criteria for VAP. Based on quantitative cultures of PSB and/or BAL, patients were categorized into three groups: VAP microbiologically proven (Group 1; n = 72); clinical suspicion of VAP not confirmed microbiologically (Group 2; n = 66); and patients in whom bronchoscopy could not be performed (Group 3; n = 17). In Group 1, antibiotic therapy was instituted empirically in 40 patients (56%) (Group 1a) and after obtaining culture results in the other 32 patients (Group lb). Adjustment of therapy, based on culture results, occurred in 14 (35%) patients in Group la. In Group 2 empiric therapy was instituted in 34 (52%) patients (Group 2a) and dIscontinued within 48 h in 17 of them (50%). In Group 3, 17 (100%) patients were treated with antibiotics. Among the 66 patients in whom a clinical suspicion of VAP was not confirmed, only 18 (27%) were treated with antibiotics, and antibiotic therapy was withheld in 48 (35%) of 138 patients who underwent bronchoscopy. Withholding of antibiotic therapy had no negative effect on the recurrence of a clinical suspicion of VAP or on mortality rates. We conclude that addition of bronchoscopic techniques to the criteria for VAP may help to reduce antibiotic use. However, the definite benefits and cost-effectiveness of these techniques should be analyzed in a randomized study.