Corianne A.J.M. de Borgie

Cranberries vs antibiotics to prevent urinary tract infections: a randomized double-blind noninferiority trial in premenopausal women

BACKGROUND The increasing prevalence of uropathogens resistant to antimicrobial agents has stimulated interest in cranberries to prevent recurrent urinary tract infections (UTIs). METHODS In a double-blind, double-dummy noninferiority trial, 221 premenopausal women with recurrent UTIs were randomized to 12-month prophylaxis use of trimethoprim-sulfamethoxazole (TMP-SMX), 480 mg once daily, or cranberry capsules, 500 mg twice daily. Primary end points were the mean number of symptomatic UTIs over 12 months, the proportion of patients with at least 1 symptomatic UTI, the median time to first UTI, and development of antibiotic resistance in indigenous Escherichia coli. RESULTS After 12 months, the mean number of patients with at least 1 symptomatic UTI was higher in the cranberry than in the TMP-SMX group (4.0 vs 1.8; P = .02), and the proportion of patients with at least 1 symptomatic UTI was higher in the cranberry than in the TMP-SMX group (78.2% vs 71.1%). Median time to the first symptomatic UTI was 4 months for the cranberry and 8 months for the TMP-SMX group. After 1 month, in the cranberry group, 23.7% of fecal and 28.1% of asymptomatic bacteriuria E coli isolates were TMP-SMX resistant, whereas in the TMP-SMX group, 86.3% of fecal and 90.5% of asymptomatic bacteriuria E coli isolates were TMP-SMX resistant. Similarly, we found increased resistance rates for trimethoprim, amoxicillin, and ciprofloxacin in these E coli isolates after 1 month in the TMP-SMX group. After discontinuation of TMP-SMX, resistance reached baseline levels after 3 months. Antibiotic resistance did not increase in the cranberry group. Cranberries and TMP-SMX were equally well tolerated. CONCLUSION In premenopausal women, TMP-SMX, 480 mg once daily, is more effective than cranberry capsules, 500 mg twice daily, to prevent recurrent UTIs, at the expense of emerging antibiotic resistance. TRIAL REGISTRATION isrctn.org Identifier: ISRCTN50717094.

Cost utility analysis of co-prescribed heroin compared with methadone maintenance treatment in heroin addicts in two randomised trials

Abstract Objective To determine the cost utility of medical co-prescription of heroin compared with methadone maintenance treatment for chronic, treatment resistant heroin addicts. Design Cost utility analysis of two pooled open label randomised controlled trials. Setting Methadone maintenance programmes in six cities in the Netherlands. Participants 430 heroin addicts. Interventions Inhalable or injectable heroin prescribed over 12 months. Methadone (maximum 150 mg a day) plus heroin (maximum 1000 mg a day) compared with methadone alone (maximum 150 mg a day). Psychosocial treatment was offered throughout. Main outcome measures One year costs estimated from a societal perspective. Quality adjusted life years (QALYs) based on responses to the EuroQol EQ-5D at baseline and during the treatment period. Results Co-prescription of heroin was associated with 0.058 more QALYs per patient per year (95% confidence interval 0.016 to 0.099) and a mean saving of €12 793 (£8793,

Lactobacilli vs Antibiotics to Prevent Urinary Tract Infections: A Randomized, Double-blind, Noninferiority Trial in Postmenopausal Women

16 122) (€1083 to €25 229) per patient per year. The higher programme costs (€16 222; lower 95% confidence limit €15 084) were compensated for by lower costs of law enforcement (- €4129; upper 95% confidence limit - €486) and damage to victims of crime (- €25 374; upper 95% confidence limit - €16 625). The results were robust for the use of national EQ-5D tariffs and for the exclusion of the initial implementation costs of heroin treatment. Completion of treatment is essential; having participated in any abstinence treatment in the past is not. Conclusions Co-prescription of heroin is cost effective compared with treatment with methadone alone for chronic, treatment resistant heroin addicts.

Long-term prevalence of post-traumatic stress disorder symptoms in patients after secondary peritonitis

BACKGROUND Growing antibiotic resistance warrants studying nonantibiotic prophylaxis for recurrent urinary tract infections (UTIs). Use of lactobacilli appears to be promising. METHODS Between January 2005 and August 2007, we randomized 252 postmenopausal women with recurrent UTIs taking part in a double-blind noninferiority trial to receive 12 months of prophylaxis with trimethoprim-sulfamethoxazole, 480 mg, once daily or oral capsules containing 109 colony-forming units of Lactobacillus rhamnosus GR-1 and Lactobacillus reuteri RC-14 twice daily. Primary end points were the mean number of symptomatic UTIs, proportion of participants with at least 1 UTI during 12 months, time to first UTI, and development of antibiotic resistance by Escherichia coli. RESULTS The mean number of symptomatic UTIs in the year preceding randomization was 7.0 in the trimethoprim-sulfamethoxazole group and 6.8 in the lactobacilli group. In the intention-to-treat analysis, after 12 months of prophylaxis, these numbers were 2.9 and 3.3, respectively. The between-treatment difference of 0.4 UTIs per year (95% CI, -0.4 to 1.5) was outside our noninferiority margin. At least 1 symptomatic UTI occurred in 69.3% and 79.1% of the trimethoprim-sulfamethoxazole and lactobacilli participants, respectively; median times to the first UTI were 6 and 3 months, respectively. After 1 month of trimethoprim-sulfamethoxazole prophylaxis, resistance to trimethoprim-sulfamethoxazole, trimethoprim, and amoxicillin had increased from approximately 20% to 40% to approximately 80% to 95% in E coli from the feces and urine of asymptomatic women and among E coli causing a UTI. During the 3 months after trimethoprim-sulfamethoxazole discontinuation, resistance levels gradually decreased. Resistance did not increase during lactobacilli prophylaxis. CONCLUSIONS In postmenopausal women with recurrent UTIs, L rhamnosus GR-1 and L reuteri RC-14 do not meet the noninferiority criteria in the prevention of UTIs when compared with trimethoprim-sulfamethoxazole. However, unlike trimethoprim-sulfamethoxazole, lactobacilli do not increase antibiotic resistance. TRIAL REGISTRATION isrctn.org Identifier: ISRCTN50717094.

Costs of relaparotomy on-demand versus planned relaparotomy in patients with severe peritonitis: an economic evaluation within a randomized controlled trial

IntroductionThe aim of this study was to determine the long-term prevalence of post-traumatic stress disorder (PTSD) symptomology in patients following secondary peritonitis and to determine whether the prevalence of PTSD-related symptoms differed between patients admitted to the intensive care unit (ICU) and patients admitted only to the surgical ward.MethodA retrospective cohort of consecutive patients treated for secondary peritonitis was sent a postal survey containing a self-report questionnaire, namely the Post-traumatic Stress Syndrome 10-question inventory (PTSS-10). From a database of 278 patients undergoing surgery for secondary peritonitis between 1994 and 2000, 131 patients were long-term survivors (follow-up period at least four years) and were eligible for inclusion in our study, conducted at a tertiary referral hospital in Amsterdam, The Netherlands.ResultsThe response rate was 86%, yielding a cohort of 100 patients; 61% of these patients had been admitted to the ICU. PTSD-related symptoms were found in 24% (95% confidence interval 17% to 33%) of patients when a PTSS-10 score of 35 was chosen as the cutoff, whereas the prevalence of PTSD symptomology when borderline patients scoring 27 points or more were included was 38% (95% confidence interval 29% to 48%). In a multivariate analyses controlling for age, sex, Acute Physiology and Chronic Health Evaluation II (APACHE II) score, number of relaparotomies and length of hospital stay, the likelihood of ICU-admitted patients having PTSD symptomology was 4.3 times higher (95% confidence interval 1.11 to 16.5) than patients not admitted to the ICU, using a PTSS-10 score cutoff of 35 or greater. Older patients and males were less likely to report PTSD symptoms.ConclusionNearly a quarter of patients receiving surgical treatment for secondary peritonitis developed PTSD symptoms. Patients admitted to the ICU were at significantly greater risk for having PTSD symptoms after adjusting for baseline differences, in particular age.

Psychosocial adjustment of children and adults with port wine stains.

IntroductionResults of the first randomized trial comparing on-demand versus planned-relaparotomy strategy in patients with severe peritonitis (RELAP trial) indicated no clear differences in primary outcomes. We now report the full economic evaluation for this trial, including detailed methods, nonmedical costs, further differentiated cost calculations, and robustness of different assumptions in sensitivity analyses.MethodsAn economic evaluation was conducted from a societal perspective alongside a randomized controlled trial in 229 patients with severe secondary peritonitis and an acute physiology and chronic health evaluation (APACHE)-II score ≥11 from two academic and five regional teaching hospitals in the Netherlands. After the index laparotomy, patients were randomly allocated to an on-demand or a planned-relaparotomy strategy. Primary resource-utilization data were used to estimate mean total costs per patient during the index admission and after discharge until 1 year after the index operation. Overall differences in costs between the on-demand relaparotomy strategy and the planned strategy, as well as relative differences across several clinical subgroups, were evaluated.ResultsCosts were substantially lower in the on-demand group (mean, €65,768 versus €83,450 per patient in the planned group; mean absolute difference, €17,682; 95% CI, €5,062 to €29,004). Relative differences in mean total costs per patient (approximately 21%) were robust to various alternative assumptions. Planned relaparotomy consistently generated more costs across the whole range of different courses of disease (quick recovery and few resources used on one end of the spectrum; slow recovery and many resources used on the other end). This difference in costs between the two surgical strategies also did not vary significantly across several clinical subgroups.ConclusionsThe reduction in societal costs renders the on-demand strategy a more-efficient relaparotomy strategy in patients with severe peritonitis. These differences were found across the full range of healthcare resources as well as across patients with different courses of disease.Trial RegistrationISRCTN51729393

Medical-grade honey does not reduce skin colonization at central venous catheter-insertion sites of critically ill patients: a randomized controlled trial

OBJECTIVES To assess the impact of a facial port wine stain (PWS) on behavioural problems in children and on health related quality of life in adults applying for laser treatment. DESIGN A survey by questionnaire of patients with PWS not previously treated. OUTCOME MEASURES Two standard general instruments and a more specific PWS questionnaire were used. Adolescents and adults (13-31 years) received a short version of the RAND Health Insurance Questionnaire from the Medical Outcome Study (MOS-24). Childrens (4-12 years) parents received the Child Behaviour Checklist (CBCL). A specific PWS questionnaire was sent to both age groups. ANALYSIS The results of the MOS-24 were compared with those of a reference population without chronic illness. Observed behaviour in children was compared with data from a Dutch reference group, from children with constipation and from another group of children with a PWS. RESULTS 41 MOS-24 and 41 CBCL were returned (91% and 95% response rates, respectively). Adolescents and adults reported little effect on role and social functioning, but showed low scores for mental health, self-perceived health and vitality/health. Childrens parents reported no clinically significant problem behaviour (T-score > 70). Adults experienced more negative psychosocial consequences of having a PWS than children (specific PWS questionnaire). CONCLUSIONS Children with PWS do not show significant problem behaviour. Adolescents and adults reported less vitality/energy than was expected in this age group. Adolescents and adults showed statistically significant negative consequences of their PWS in social contacts compared to children (P < or = 0.01, Mann-Whitney).

Assessing Preferences Regarding Healthcare Interventions that Involve Non-Health Outcomes: An Overview of Clinical Studies.

IntroductionCatheter-related bloodstream infections (CRBSIs) associated with short-term central venous catheters (CVCs) in intensive care unit (ICU) patients are a major clinical problem. Bacterial colonization of the skin at the CVC insertion site is an important etiologic factor for CRBSI. The aim of this study was to assess the efficacy of medical-grade honey in reducing bacterial skin colonization at insertion sites.MethodsA prospective, single-center, open-label randomized controlled trial was performed at the ICU of a university hospital in The Netherlands to assess the efficacy of medical-grade honey to reduce skin colonization of insertion sites. Medical-grade honey was applied in addition to standard CVC-site dressing and disinfection with 0.5% chlorhexidine in 70% alcohol. Skin colonization was assessed on a daily basis before CVC-site disinfection. The primary end point was colonization of insertion sites with >100 colony-forming units at the last sampling before removal of the CVC or transfer of the patient from the ICU. Secondary end points were quantitative levels of colonization of the insertion sites and colonization of insertion sites stratified for CVC location.ResultsColonization of insertion sites was not affected by the use of medical-grade honey, as 44 (34%) of 129 and 36 (34%) of 106 patients in the honey and standard care groups, respectively, had a positive skin culture (P = 0.98). Median levels of skin colonization at the last sampling were 1 (0 to 2.84) and 1 (0 to 2.70) log colony-forming units (CFUs)/swab for the honey and control groups, respectively (P = 0.94). Gender, days of CVC placement, CVC location, and CVC type were predictive for a positive skin culture. Correction for these variables did not change the effect of honey on skin-culture positivity.ConclusionsMedical-grade honey does not affect colonization of the skin at CVC insertion sites in ICU patients when applied in addition to standard disinfection with 0.5% chlorhexidine in 70% alcohol.Trial registrationNetherlands Trial Registry, NTR1652.

Providing Genetic Risk Information to Parents of Newborns with Sickle Cell Trait: Role of the General Practitioner in Neonatal Screening

Decision making in healthcare often involves decision alternatives that vary on different dimensions in conflicting ways, such as health benefits and costs. In such cases, it is not always easy to identify the best option, as a tradeoff has to be made. In preference studies, patients evaluate health states or healthcare strategies reflecting this trade-off. A focus that is restricted to only health outcomes in decision making may be too narrow. Patients also derive utility, or experience disutility, from healthcare processes themselves. A range of techniques is available for eliciting valuations of patients for these processes and other non-health outcomes. At present, it is unclear to what extent, and how, clinical evaluation studies have taken into account non-health outcomes. We performed a systematic review of trade-off and valuation studies to assess the extent to which valuations of process and non-health outcomes have actually been elicited from patients, in what specialty areas, and what techniques were used.We identified 567 articles that addressed patients’ preferences involving non-health outcomes. The main therapeutic fields were oncology (17%), gynecology/obstetrics (11%), pulmonology (11%), cardiology (7%), gastroenterology (6%), and infectious diseases (6%). There was an absolute increase from the early 1980s (a handful of studies published each year) to recent years (almost 100 publications per year). We noticed a strong increase in elicitation techniques aimed at identification of determinants of patients’ preferences.The number of studies addressing preferences for medical dilemmas involving non-health outcomes is steadily increasing and covers the whole spectrum of health-related interventions across all medical fields. A diversification in application fields as well as in research methods was observed, reflecting a lack of standardization. There is a need for methodological standards and evidence-based criteria to evaluate the methodological quality and clinical validity of studies that address preferences for dilemmas involving non-health outcomes.

Evaluating the Psychological Effects of Genetic Testing in Symptomatic Patients: A Systematic Review

PURPOSE In 2007, the neonatal screening program in the Netherlands was expanded to include hemoglobinopathies. Newborns with sickle cell disease (SCD), as well as SCD carriers are identified. The benefit of reporting SCD carriers includes detection of more couples at risk (both parents are carriers) who can be informed about future reproductive choices, a responsibility of their general practitioner (GP). We evaluated knowledge, ideas, and actions of GPs after reporting SCD carriers and explored and analyzed potential barriers. METHODS A questionnaire study. RESULTS A total of 139 GPs responded to our questionnaire (49%). Ninety GPs (90%) stated they informed parents of the test result. In only 23 cases (23%) both parents had themselves tested for hemoglobinopathies. Eighty-one GPs (64%) stated that they did not have enough clinical experience with SCD. Almost half of the GPs indicated that they did not experience any barriers in counseling patients (n=60, 48%). CONCLUSION At the moment, the goal of the neonatal screening for SCD carriers has not been achieved as the majority of parents were not tested for hemoglobinopathies after disclosure of carrier status in their newborn. With GPs reporting few barriers in counseling parents and only indicating a lack of knowledge and clinical experience, more effort is required to provide better information to GPs to help facilitate their work.