Consensus on the definition and criteria for failure of surgical treatment in bacterial arthritis of a native joint: An international Delphi study.

PURPOSE: The literature presents a wide range of success rates for a single surgical intervention of bacterial-septic-arthritis, and there is a lack of clear criteria for identifying treatment failure and making decisions about reintervention. This Delphi study aims to establish a consensus among an international panel of experts regarding the definition of treatment failure and the criteria for reintervention in case of bacterial arthritis. METHODS: The conducting and reporting Delphi studies (CREDES) criteria were used. Data from a systematic review was provided as the basis for the study. A list of 100 potential experts were identified. The study was designed and conducted as follows: (I) identification and invitation of an expert panel, (II) informing the participating expert panel on the research question and subject, and (III) conducting two or three Delphi rounds to reach consensus on explicit research items. Potential criteria were rated on a five-point Likert scale. RESULTS: Sixty orthopaedic experts from nine countries participated in this Delphi study, with 55 completing all three rounds. The mean experience as an orthopaedic surgeon was 15 years (SD ± 9). Strong (96%) consensus was reached on the definition of treatment failure: the persistence of physical signs of arthritis (e.g., pain and swelling) and/or systemic inflammation (e.g., fever and no improvement in CRP) despite surgical and antibiotic treatment. Furthermore, consensus (>80%) was reached on six criteria influencing the decision for reintervention; pain (81%), sepsis (98%), fever (88%), serum CRP (93%), blood culture (82%), and synovial fluid culture (84%). CONCLUSION: The definition of treatment failure for bacterial arthritis after a single surgical intervention was established through a three-round Delphi study. Additionally, consensus was reached on six criteria that are helpful for determining the need for reintervention. This definition and these criteria may help in the development of clinical guidelines, and will empower physicians to make more precise and consistent decisions regarding reintervention for patients, ultimately aiming to reduce over- and undertreatment and improve patient outcomes. LEVEL OF EVIDENCE: Level V.

Dutch injection versus surgery trial in patients with carpal tunnel syndrome (DISTRICTS): protocol of a randomised controlled trial comparing two treatment strategies.

INTRODUCTION: Carpal tunnel syndrome (CTS) is the most common peripheral neuropathy. The optimal treatment strategy is still unknown. The objective of the Dutch Injection versus Surgery TRIal in patients with CTS (DISTRICTS) is to investigate if initial surgery of CTS results in a better clinical outcome and is more cost-effective when compared with initial treatment with corticosteroid injection. METHODS AND ANALYSIS: The DISTRICTS is an ongoing multicenter, open-label randomised controlled trial. Participants with CTS are randomised to treatment with surgery or with a corticosteroid injection. If needed, any additional treatments after this first treatment are allowed and these are not dictated by the study protocol. The primary outcome is the difference between the groups in the proportion of participants recovered at 18 months. Recovery is defined as having no or mild symptoms as measured with the 6-item carpal tunnel symptoms scale. Secondary outcome measurements are among others: time to recovery, hand function, patient satisfaction, quality of life, additional treatments, adverse events, and use of care and health-related costs. ETHICS AND DISSEMINATION: The study was approved by the Medical Ethical Committee of the Amsterdam University Medical Centers (study number 2017-171). Study results will be disseminated in peer-reviewed journals and conferences. TRIAL REGISTRATION NUMBER: ISRCTN Registry: 13164336.

Clinical value of a screening tool for tumor predisposition syndromes in childhood cancer patients (TuPS): a prospective, observational, multi-center study.

Recognizing a tumor predisposition syndrome (TPS) in a child with cancer is of clinical relevance. Earlier we developed a screening tool to increase diagnostic accuracy and clinical efficiency of identifying TPSs in children with cancer. Here we report on the value of this tool in clinical practice. TuPS is a prospective, observational, multi-center study including children newly diagnosed with cancer from 2016 to 2019 in the Netherlands. Children in whom a TPS had been diagnosed before the cancer diagnosis were excluded. The screening tool consists of a checklist, 2D and 3D photographic series and digital assessment of these by a clinical geneticist. If a TPS was suspected, the patient was assessed positive and referred for routine genetic consultation. Primary aim was to assess the clinical value of this new screening tool. Of the 363 included patients, 57% (208/363) were assessed positive. In 15% of patients (32/208), the 2D photographic series with (n = 12) or without (n = 20) 3D photographs were decisive in the positive assessment. In 2% (4/208) of positive assessed patients, a TPS was diagnosed, and in an additional 2% (4/208) a germline variant of uncertain significance was found. Thirty-five negatively assessed patients were evaluated through routine genetic consultation as controls, in none a TPS was detected. Using the screening tool, 57% of the patients were assessed as suspected for having a TPS. No false negative results were identified in the negative control group in the clinical care setting. The observed prevalence of TPS was lower than expected, due to selection bias in the cohort.

RELAx - REstricted versus Liberal positive end-expiratory pressure in patients without ARDS: protocol for a randomized controlled trial.

BACKGROUND: Evidence for benefit of high positive end-expiratory pressure (PEEP) is largely lacking for invasively ventilated, critically ill patients with uninjured lungs. We hypothesize that ventilation with low PEEP is noninferior to ventilation with high PEEP with regard to the number of ventilator-free days and being alive at day 28 in this population.  METHODS/DESIGN: The "REstricted versus Liberal positive end-expiratory pressure in patients without ARDS" trial (RELAx) is a national, multicenter, randomized controlled, noninferiority trial in adult intensive care unit (ICU) patients with uninjured lungs who are expected not to be extubated within 24 h. RELAx will run in 13 ICUs in the Netherlands to enroll 980 patients under invasive ventilation. In all patients, low tidal volumes are used. Patients assigned to ventilation with low PEEP will receive the lowest possible PEEP between 0 and 5 cm H2O, while patients assigned to ventilation with high PEEP will receive PEEP of 8 cm H2O. The primary endpoint is the number of ventilator-free days and being alive at day 28, a composite endpoint for liberation from the ventilator and mortality until day 28, with a noninferiority margin for a difference between groups of 0.5 days. Secondary endpoints are length of stay (LOS), mortality, and occurrence of pulmonary complications, including severe hypoxemia, major atelectasis, need for rescue therapies, pneumonia, pneumothorax, and development of acute respiratory distress syndrome (ARDS). Hemodynamic support and sedation needs will be collected and compared. DISCUSSION: RELAx will be the first sufficiently sized randomized controlled trial in invasively ventilated, critically ill patients with uninjured lungs using a clinically relevant and objective endpoint to determine whether invasive, low-tidal-volume ventilation with low PEEP is noninferior to ventilation with high PEEP. TRIAL REGISTRATION: ClinicalTrials.gov , ID: NCT03167580 . Registered on 23 May 2017.

Effect of On-Demand vs Routine Nebulization of Acetylcysteine With Salbutamol on Ventilator-Free Days in Intensive Care Unit Patients Receiving Invasive Ventilation: A Randomized Clinical Trial.

Importance: It remains uncertain whether nebulization of mucolytics with bronchodilators should be applied for clinical indication or preventively in intensive care unit (ICU) patients receiving invasive ventilation. Objective: To determine if a strategy that uses nebulization for clinical indication (on-demand) is noninferior to one that uses preventive (routine) nebulization. Design, Setting, and Participants: Randomized clinical trial enrolling adult patients expected to need invasive ventilation for more than 24 hours at 7 ICUs in the Netherlands. Interventions: On-demand nebulization of acetylcysteine or salbutamol (based on strict clinical indications, n = 471) or routine nebulization of acetylcysteine with salbutamol (every 6 hours until end of invasive ventilation, n = 473). Main Outcomes and Measures: The primary outcome was the number of ventilator-free days at day 28, with a noninferiority margin for a difference between groups of -0.5 days. Secondary outcomes included length of stay, mortality rates, occurrence of pulmonary complications, and adverse events. Results: Nine hundred twenty-two patients (34% women; median age, 66 (interquartile range [IQR], 54-75 years) were enrolled and completed follow-up. At 28 days, patients in the on-demand group had a median 21 (IQR, 0-26) ventilator-free days, and patients in the routine group had a median 20 (IQR, 0-26) ventilator-free days (1-sided 95% CI, -0.00003 to ∞). There was no significant difference in length of stay or mortality, or in the proportion of patients developing pulmonary complications, between the 2 groups. Adverse events (13.8% vs 29.3%; difference, -15.5% [95% CI, -20.7% to -10.3%]; P < .001) were more frequent with routine nebulization and mainly related to tachyarrhythmia (12.5% vs 25.9%; difference, -13.4% [95% CI, -18.4% to -8.4%]; P < .001) and agitation (0.2% vs 4.3%; difference, -4.1% [95% CI, -5.9% to -2.2%]; P < .001). Conclusions and Relevance: Among ICU patients receiving invasive ventilation who were expected to not be extubated within 24 hours, on-demand compared with routine nebulization of acetylcysteine with salbutamol did not result in an inferior number of ventilator-free days. On-demand nebulization may be a reasonable alternative to routine nebulization. Trial Registration: clinicaltrials.gov Identifier: NCT02159196.

Validation of a clinical screening instrument for tumour predisposition syndromes in patients with childhood cancer (TuPS): protocol for a prospective, observational, multicentre study.

INTRODUCTION: Recognising a tumour predisposition syndrome (TPS) in patients with childhood cancer is of significant clinical relevance, as it affects treatment, prognosis and facilitates genetic counselling. Previous studies revealed that only half of the known TPSs are recognised during standard paediatric cancer care. In current medical practice it is impossible to refer every patient with childhood cancer to a clinical geneticist, due to limited capacity for routine genetic consultation. Therefore, we have developed a screening instrument to identify patients with childhood cancer with a high probability of having a TPS. The aim of this study is to validate the clinical screening instrument for TPS in patients with childhood cancer. METHODS AND ANALYSIS: This study is a prospective nationwide cohort study including all newly diagnosed patients with childhood cancer in the Netherlands. The screening instrument consists of a checklist, two- and three-dimensional photographic series of the patient. 2 independent clinical geneticists will assess the content of the screening instrument. If a TPS is suspected based on the instrument data and thus further evaluation is indicated, the patient will be invited for full genetic consultation. A negative control group consists of 20% of the patients in whom a TPS is not suspected based on the instrument; they will be randomly invited for full genetic consultation. Primary outcome measurement will be sensitivity of the instrument. ETHICS AND DISSEMINATION: The Medical Ethical Committee of the Academic Medical Centre stated that the Medical Research Involving Human Subjects Act does not apply to this study and that official approval of this study by the Committee was not required. The results will be offered for publication in peer-reviewed journals and presented at International Conferences on Oncology and Clinical Genetics. The clinical data gathered in this study will be available for all participating centres. TRIAL REGISTRATION NUMBER: NTR5605.

Endoscopic sinus surgery in adult patients with chronic rhinosinusitis with nasal polyps (PolypESS): study protocol for a randomised controlled trial.

BACKGROUND: Chronic rhinosinusitis with nasal polyps is a chronic disease frequently seen in otorhinolaryngological practice. Along with its chronic disease burden it creates high societal costs. Therapy consists of long-term use of medication and, if insufficient, endoscopic sinus surgery. No consensus exists on the right timing and extent of disease that warrants surgery. Furthermore, there is lack of clinical knowledge about the benefit of surgery over medication only. The current trial evaluates the clinical effectiveness and cost-effectiveness of endoscopic sinus surgery in addition to drug treatment versus medication exclusively in the adult patient group with nasal polyps. METHODS: A prospective, multicentre, superiority, randomised controlled (PolypESS) trial in 238 patients aged 18 years or older selected for primary or revision endoscopic sinus surgery by the otorhinolaryngologist was designed. Patients will be randomised to either endoscopic sinus surgery in addition to medication or medical therapy only. Relevant data will be collected prior to randomisation, at baseline and 3, 6, 12, 18 and 24 months after start of treatment. Complete follow-up will be 24 months. Primary outcome is disease-specific Health-related Quality of Life quantified by the SNOT-22 after 12-month follow-up. Secondary outcomes are generic Health-related Quality of Life, cost-effectiveness, objective signs of disease and adverse effects of treatment. Subgroup analyses will be performed to verify whether treatment effects differ among patient phenotypes. DISCUSSION: The PolypESS trial will investigate tailored care in adult patients with chronic rhinosinusitis with nasal polyps and will result in improved clinical pathways to help to determine in which circumstances to perform surgery. TRIAL REGISTRATION: Dutch Trial Register, NTR4978 . Registered on 27 November 2014.

Continuous Postoperative Pericardial Flushing: A Pilot Study on Safety, Feasibility, and Effect on Blood Loss.

BACKGROUND: Prolonged or excessive blood loss is a common complication after cardiac surgery. Blood remnants and clots, remaining in the pericardial space in spite of chest tube drainage, induce high fibrinolytic activity that may contribute to bleeding complications. Continuous postoperative pericardial flushing (CPPF) with an irrigation solution may reduce blood loss by preventing the accumulation of clots. In this pilot study, the safety and feasibility of CPPF were evaluated and the effect on blood loss and other related complications was investigated. METHODS: Between November 2011 and April 2012 twenty-one adult patients undergoing surgery for congenital heart disease (CHD) received CPPF from sternal closure up to 12 h postoperative. With an inflow Redivac drain that was inserted through one of the chest tube incision holes, an irrigation solution (NaCl 0.9% at 38 °C) was delivered to the pericardial cavity using a volume controlled flushing system. Safety aspects, feasibility issues and complications were registered. The mean actual blood loss in the CPPF group was compared to the mean of a retrospective group (n = 126). RESULTS: CPPF was successfully completed in 20 (95.2%) patients, and no method related complications were observed. Feasibility was good in this experimental setting. Patients receiving CPPF showed a 30% (P = 0.038) decrease in mean actual blood loss 12 h postoperatively. CONCLUSIONS: CPPF after cardiac surgery was found to be safe and feasible in this experimental setting. The clinically relevant effect on blood loss needs to be confirmed in a randomized clinical trial.

Preventive nebulization of mucolytic agents and bronchodilating drugs in invasively ventilated intensive care unit patients (NEBULAE): study protocol for a randomized controlled trial.

BACKGROUND: Preventive nebulization of mucolytic agents and bronchodilating drugs is a strategy aimed at the prevention of sputum plugging, and therefore atelectasis and pneumonia, in intubated and ventilated intensive care unit (ICU) patients. The present trial aims to compare a strategy using the preventive nebulization of acetylcysteine and salbutamol with nebulization on indication in intubated and ventilated ICU patients. METHODS/DESIGN: The preventive nebulization of mucolytic agents and bronchodilating drugs in invasively ventilated intensive care unit patients (NEBULAE) trial is a national multicenter open-label, two-armed, randomized controlled non-inferiority trial in the Netherlands. Nine hundred and fifty intubated and ventilated ICU patients with an anticipated duration of invasive ventilation of more than 24 hours will be randomly assigned to receive either a strategy consisting of preventive nebulization of acetylcysteine and salbutamol or a strategy consisting of nebulization of acetylcysteine and/or salbutamol on indication. The primary endpoint is the number of ventilator-free days and surviving on day 28. Secondary endpoints include ICU and hospital length of stay, ICU and hospital mortality, the occurrence of predefined pulmonary complications (acute respiratory distress syndrome, pneumonia, large atelectasis and pneumothorax), and the occurrence of predefined side effects of the intervention. Related healthcare costs will be estimated in a cost-benefit and budget-impact analysis. DISCUSSION: The NEBULAE trial is the first randomized controlled trial powered to investigate whether preventive nebulization of acetylcysteine and salbutamol shortens the duration of ventilation in critically ill patients. TRIAL REGISTRATION: NCT02159196, registered on 6 June 2014.

The development of a clinical screening instrument for tumour predisposition syndromes in childhood cancer patients.

BACKGROUND: Identification of tumour predisposition syndromes in patients who have cancer in childhood is paramount for optimal care. A screening instrument that can help to identify such patients will facilitate physicians caring for children with cancer. The complete screening instrument should consist of a standardised series of pictures and a screening form for manifestations not visible in the pictures. Here we describe the development of such a screening form based on an international two-stage Delphi process and an initial validation of the complete instrument. PATIENTS AND METHODS: We identified manifestations that may contribute to the diagnosis of a tumour predisposition syndrome through the Winter-Baraitser Dysmorphology Database and the textbook "Gorlin's Syndromes of the Head and Neck". In a two-round Delphi process, eight international content-experts scored the contribution of each of these manifestations. We performed a clinical validation of the instrument in a selected cohort of 10 paediatric cancer patients from another centre. RESULTS: In total, 49 manifestations were found to contribute to the diagnosis of a tumour predisposition syndrome and were included in the screening form. The pilot validation study showed that patients suspected of having a tumour predisposition syndrome were recognised. Excellent correlation for indications of patient's referral between the screening instrument and the reference standard (personal evaluation by an experienced clinical geneticist) was found. CONCLUSIONS: The Delphi process performed by international specialists with a function as opinion leaders in their field of expertise, has led to a screening instrument for childhood cancer patients. Patients who may have a tumour predisposition syndrome and thus have an indication to be referred for further genetic analysis, can be identified using the screening instrument.

Lactobacilli vs antibiotics to prevent urinary tract infections: a randomized, double-blind, noninferiority trial in postmenopausal women.

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.

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.

Providing genetic risk information to parents of newborns with sickle cell trait: role of the general practitioner in neonatal screening.

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.

A multicenter randomized clinical trial investigating the cost-effectiveness of treatment strategies with or without antibiotics for uncomplicated acute diverticulitis (DIABOLO trial).

BACKGROUND: Conservative treatment of uncomplicated or mild diverticulitis usually includes antibiotic therapy. It is, however, uncertain whether patients with acute diverticulitis indeed benefit from antibiotics. In most guidelines issued by professional organizations antibiotics are considered mandatory in the treatment of mild diverticulitis. This advice lacks evidence and is merely based on experts' opinion. Adverse effects of the use of antibiotics are well known, including allergic reactions, development of bacterial resistance to antibiotics and other side-effects. METHODS: A randomized multicenter pragmatic clinical trial comparing two treatment strategies for uncomplicated acute diverticulitis. I) A conservative strategy with antibiotics: hospital admission, supportive measures and at least 48 hours of intravenous antibiotics which subsequently are switched to oral, if tolerated (for a total duration of antibiotic treatment of 10 days). II) A liberal strategy without antibiotics: admission only if needed on clinical grounds, supportive measures only. Patients are eligible for inclusion if they have a diagnosis of acute uncomplicated diverticulitis as demonstrated by radiological imaging. Only patients with stages 1a and 1b according to Hinchey's classification or "mild" diverticulitis according to the Ambrosetti criteria are included. The primary endpoint is time-to-full recovery within a 6-month follow-up period. Full recovery is defined as being discharged from the hospital, with a return to pre-illness activities, and VAS score below 4 without the use of daily pain medication. Secondary endpoints are proportion of patients who develop complicated diverticulitis requiring surgery or non-surgical intervention, morbidity, costs, health-related quality of life, readmission rate and acute diverticulitis recurrence rate. In a non-inferiority design 264 patients are needed in each study arm to detect a difference in time-to-full recovery of 5 days or more with a power of 85% and a confidence level of 95%. With an estimated one percent of patients lost to follow up, a total of 533 patients will be included. CONCLUSION: A clinically relevant difference of more than 5 days in time-to-full recovery between the two treatment strategies is not expected. The liberal strategy without antibiotics and without the strict requirement for hospital admission is anticipated to be more a more cost-effective approach. TRIAL REGISTRATION NUMBER: NCT01111253.

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

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 trade-off 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.

Low uptake of prenatal diagnosis after established carrier status of a balanced structural chromosome abnormality in couples with recurrent miscarriage.

OBJECTIVE: To evaluate to what extent couples carrying a balanced structural chromosome abnormality follow up the advice to opt for invasive prenatal diagnosis (PND) in subsequent pregnancies. DESIGN: Index-control study. SETTING: Six centers for Clinical Genetics in The Netherlands. PATIENT(S): Couples referred for chromosome analysis after recurrent miscarriage between 1992 and 2001 and with at least one pregnancy after disclosure; 239 carrier couples and 389 noncarrier couples. INTERVENTION(S): Questionnaire, medical record checking. MAIN OUTCOME MEASURE(S): Uptake of invasive PND. RESULT(S): Only 53 of 239 (22%) carrier couples underwent a PND procedure (CVS or amniocentesis) in all subsequent pregnancies. A relatively high number, 105 (44%) carrier couples, refrained from PND in all subsequent pregnancies. More carrier couples with maternal age >or=36 years (20/33 = 61%) refrained from PND, compared with carrier couples with maternal age <36 years (85/206 = 41%). In women >or=36 years, an equal proportion of carrier and noncarrier couples refrained from PND (61% vs. 54%). CONCLUSION(S): The advice to opt for invasive PND in carrier couples is poorly followed, especially in carrier couples with maternal age >or=36 years. The motivations of carrier couples to opt for or refrain from invasive PND procedures should be the topic for further research to optimize clinical care and informative decision making.

Evaluating the psychological effects of genetic testing in symptomatic patients: a systematic review.

Most research on the effects of genetic testing is performed in individuals at increased risk for a specific disease (presymptomatic subjects) but not in patients already affected by disease. If results of these studies in presymptomatic subjects can be applied to patients is unclear. We performed a systematic review to evaluate the effects of genetic testing in patients and describe the methodological instruments used. About 2611 articles were retrieved and 16 studies included. Studies reported great variety in designs, methods, and patient outcomes. In total, 2868 participants enrolled of which 62% were patients. Patients appeared to have a lower perceived general health and higher levels of anxiety and depression than presymptomatic subjects before genetic testing. In the long term no psychological impairment was shown. We conclude that patients differ from presymptomatic subjects and may be more vulnerable to negative effects of genetic testing. Conclusions from earlier research on presymptomatic genetic testing cannot be generalized to patients, and more standardized research is needed.

Factors associated with posttraumatic stress symptoms in a prospective cohort of patients after abdominal sepsis: a nomogram.

OBJECTIVE: To determine to what extent patients who have survived abdominal sepsis suffer from symptoms of posttraumatic stress disorder (PTSD) and depression, and to identify potential risk factors for PTSD symptoms. DESIGN AND SETTING: PTSD and depression symptoms were measured using the Impact of Events Scale-Revised (IES-R), the Post-Traumatic Symptom Scale 10 (PTSS-10) and the Beck Depression Inventory II (BDI-II). PATIENTS AND PARTICIPANTS: A total of 135 peritonitis patients were eligible for this study, of whom 107 (80%) patients completed the questionnaire. The median APACHE-II score was 14 (range 12-16), and 89% were admitted to the ICU. MEASUREMENTS AND RESULTS: The proportion of patients with "moderate" PTSD symptom scores was 28% (95% CI 20-37), whilst 10% (95% CI 6-17) of patients had "high" PTSD symptom scores. Only 5% (95% CI 2-12) of the patients expressed severe depression symptoms. Factors associated with increased PTSD symptoms in a multivariate ordinal regression model were younger age (0.74 per 10 years older, p=0.082), length of ICU stay (OR=1.4 per doubling of duration, p=0.003) and having some (OR=4.9, p=0.06) or many (OR=55.5, p<0.001) traumatic memories of the ICU or hospital stay. CONCLUSION: As many as 38% of patients after abdominal sepsis report elevated levels of PTSD symptoms on at least one of the questionnaires. Our nomogram may assist in identifying patients at increased risk for developing symptoms of PTSD.