"Rescue" of Nonparticipants in Colorectal Cancer Screening: A Randomized Controlled Trial of Three Noninvasive Test Options.

Few studies have directly targeted nonparticipants in colorectal cancer screening to identify effective engagement strategies. We undertook a randomized controlled trial that targeted nonparticipants in a previous trial of average-risk subjects which compared participation rates for mailed invitations offering a fecal test, a blood test or a choice of either. Nonparticipants (n = 899) were randomized to be offered a kit containing a fecal immunochemical test (FIT), directions on how to arrange a blood DNA test, or the option of doing either. Screening participation was assessed 12 weeks after the offer. To assess the cognitive and attitudinal variables related to participation and invitee choice, invitees were surveyed after 12 weeks, and associations were investigated using multinomial logistic regression. Participation rates were similar between groups (P = 0.88): 12.0% for FIT (35/292), 13.3% for the blood test (39/293), and 13.4% for choice (39/290). Within the choice group, participation was significantly higher with FIT (9.7%, 28/290) compared with the blood test (3.8%, 11/290, P = 0.005). The only variable significantly associated with participation was socioeconomic status when offered FIT, and age when offered choice but there was none when offered the blood test. Survey respondents indicated that convenience, time-saving, comfort, and familiarity were major influences on participation. There was no clear advantage between a fecal test, blood test, or choice of test although, when given a choice, the fecal test was preferred. Differences in variables associated with participation according to invitation strategy warrant consideration when deciding upon an invitation strategy for screening nonparticipants. PREVENTION RELEVANCE: This trial of screening for those at average risk for colorectal cancer targeted past fecal-test nonparticipants and compared participation rates for mailed invitations offering a fecal test, blood test, or choice of either. Although there was no clear advantage between strategies, factors associated with participation differed between each strategy.

Prevalence and Potential Correlates of Family Refusal to Organ Donation for Brain-Dead Declared Patients: A 12-Year Retrospective Screening Study.

BACKGROUND: This study was designed to determine prevalence and potential correlates of family refusal to organ donation for patients declared brain dead thorough a 12-year retrospective data analysis. METHODS: Of 111 cases declared brain dead by our hospital within a 12-year period between 2008 and 2019, a total of 82 potentially brain-dead organ donors were included in this retrospective study. Data on sociodemographic characteristics, length of intensive care unit stay, cause of death, decedent's wishes, interview time, family decision, and reasons for refusal were recorded. RESULTS: The rate of family refusal to organ donation was 51.2% and because of religious concerns (64.3%) in most of cases. The likelihood of family consent to organ donation was significantly higher for an adult vs a child (60.0% vs 25.9%, P = .004) and for a schooler and adolescent age vs a younger child (55.6 vs 22.5%, P = .004). Patients who were declared brain dead after nontraumatic intracranial hemorrhage (60.4%) vs encephalitis (18.2%) had higher rates of family consent to organ donation (P = .023). CONCLUSIONS: In conclusion, our findings revealed family refusal to organ donation in at least half of cases and higher likelihood of family consent to organ donation depending on age of patient (adult vs children) and cause of death (brain injury vs encephalitis). The religious concerns and distrust in the health care system were the 2 major causes of family refusal, whereas no significant difference was noted across different family refusal reasons in terms of sociodemographic factors, length of intensive care unit stay, awareness of decedent's wishes, or time of family interview.

Characteristics Associated With Consent and Reasons for Declining in a Randomized Trial in Pregnancy.

OBJECTIVE: To evaluate the maternal characteristics associated with consent to a randomized trial of labor induction in pregnancy. METHODS: This is a secondary analysis of low-risk nulliparous women randomized to induction of labor at 39 weeks or expectant management. During the trial, the Data and Safety Monitoring Committee requested additional fields on the screening log, which already included race and ethnicity: maternal age, type of insurance, and the reason for declining consent if declined. RESULTS: From August 2016 (start of additional data collection) to August 2017, 1,965 (28%) of the 7,112 eligible women consented to the trial. Consent was more likely for Black women (41%, adjusted odds ratio [aOR] 1.47, 95% CI 1.24-1.74), and less likely for Asian women (15%, aOR 0.64, 95% CI 0.48-0.84), compared with White women (24%). Women without private insurance were more likely to consent (38%, aOR 1.55, 95% CI 1.34-1.79), compared with those with private insurance (22%). Younger women were also more likely to consent. Among eligible women who declined participation and provided a reason (68%), preference to be expectantly managed (85%) was most common, a response more common in Asian women (aOR 1.75, 95% CI 1.31-2.33) and less common in women without private insurance (aOR 0.60, 95% CI 0.51-0.70). Not wanting to participate in research was more common in Asian women (aOR 2.41, 95% CI 1.44-4.03). Declining consent because family or friends objected was more common in Asian women (aOR 2.51, 95% CI 1.27-4.95) and women without private insurance (aOR 1.68, 95% CI 1.10-2.59). CONCLUSION: Frequency of consent and reasons for declining consent were associated with age, type of insurance, and race and ethnicity. These findings should be considered when developing recruitment strategies that promote diverse participant representation. CLINICAL TRIAL REGISTRATION: ClinialTrials.gov, NCT01990612.

Decision-Making And Selection Bias in Four Observational Studies on Duchenne and Becker Muscular Dystrophy.

BACKGROUND: Natural history data are essential for trial design in Duchenne (DMD) and Becker muscular dystrophy (BMD), but recruitment for observational studies can be challenging. OBJECTIVE: We reviewed reasons why patients or caregivers declined participation, and compared characteristics of participants and non-participants to assess possible selection bias in four observational studies, three on DMD and one on BMD. METHODS: Three pediatric DMD studies focused on cross-sectional cognitive function and brain MRI (DMDbrain, n = 35 and DMDperfusion, n = 12), and on longitudinal upper extremity function and muscle MRI (DMDarm, n = 22). One adult BMD study assessed longitudinal functioning (n = 36). Considerations for non-participation were retrospectively reviewed from screening logs. Age, travel-time, DMD gene mutations and age at loss of ambulation (DMDarm and BMD study only), of participants and non-participants were derived from the Dutch Dystrophinopathy Database and compared using nonparametric tests (p < 0.05). RESULTS: The perceived burden of the protocol (38.2%), use of MRI (30.4%), and travel-time to the study site (19.1%) were the most frequently reported considerations for non-participation. Only few patients reported lack of personal gain (0.0- 5.9%). Overall, participating patients were representative for the studied sub-populations, except for a younger age of DMDarm study participants and a complete lack of participants with a mutation beyond exon 63. CONCLUSION: Optimizing patient involvement in protocol design, improving MRI experiences, and integrating research into clinics are important factors to decrease burden and facilitate participation. Nationwide registries are essential to compare participants and non-participants and ensure representative observational research. Specific effort is needed to include patients with distal mutations in cognitive studies.

Non-response in a national health survey in Germany: An intersectionality-informed multilevel analysis of individual heterogeneity and discriminatory accuracy.

BACKGROUND: Dimensions of social location such as socioeconomic position or sex/gender are often associated with low response rates in epidemiological studies. We applied an intersectionality-informed approach to analyze non-response among population strata defined by combinations of multiple dimensions of social location and subjective health in a health survey in Germany. METHODS: We used data from the cross-sectional sample of the German Health Interview and Examination Survey for Adults (DEGS1) conducted between 2008 and 2011. Information about non-responders was available from a mailed non-responder questionnaire. Intersectional strata were constructed by combining all categories of age, sex/gender, marital status, and level of education in scenario 1. Subjective health was additionally used to construct intersectional strata in scenario 2. We applied multilevel analysis of individual heterogeneity and discriminatory accuracy (MAIHDA) to calculate measures of discriminatory accuracy, proportions of non-responders among intersectional strata, as well as stratum-specific total interaction effects (intersectional effects). Markov chain Monte Carlo methods were used to estimate multilevel logistic regression models. RESULTS: Data was available for 6,534 individuals of whom 36% were non-responders. In scenario 2, we found weak discriminatory accuracy (variance partition coefficient = 3.6%) of intersectional strata, while predicted proportions of non-response ranged from 20.6% (95% credible interval (CI) 17.0%-24.9%) to 57.5% (95% CI 48.8%-66.5%) among intersectional strata. No evidence for intersectional effects was found. These results did not differ substantially between scenarios 1 and 2. CONCLUSIONS: MAIHDA revealed that proportions of non-response varied widely between intersectional strata. However, poor discriminatory accuracy of intersectional strata and no evidence for intersectional effects indicate that there is no justification to exclusively target specific intersectional strata in order to increase response, but that a combination of targeted and population-based measures might be appropriate to achieve more equal representation.

Refusal of viral testing during the SARS-CoV-2 pandemic.

Widespread testing for the respiratory syndrome coronavirus-2 (SARS-CoV-2) will represent an important part of any strategy designed to safely reopen societies from lockdown. Healthcare settings have the potential to become reservoirs of infectivity, and therefore many hospital trusts are beginning to carry out routine screening of staff and patients. This could promote the effective cohorting of patients and reduce the rate of nosocomial infection. However, for various reasons, some individuals may refuse this testing. Here we highlight this as an emergent ethicolegal issue which we expect to become increasingly relevant as testing becomes ubiquitous. We explore this position from an ethical and legal perspective, determining whether refusal of testing is acceptable under UK law. Individual patients refusing testing could undermine a hospital's testing strategy; therefore clinicians and policy makers must prospectively determine the best course of action if this were to occur.

Which orthopaedic trauma patients are likely to refuse to participate in a clinical trial? A latent class analysis.

OBJECTIVE: The study aimed to assess systematic differences in the characteristics of patients that consented for the trial compared with the broader pool of eligible patients in a large, pragmatic orthopaedic trauma trial. DESIGN: A retrospective observational study performed from April 2017 to March 2018. SETTING: Academic trauma centre in Baltimore, USA. PARTICIPANTS: There were 642 eligible adult trial participants with an operative fracture to the appendicular skeleton and were indicated for blood clot prophylaxis. The median age of the sample was 50 years (IQR: 31-63), and 60% were male. PRIMARY OUTCOME MEASURE: The primary outcome was the refusal to enrol in the trial. Demographic and injury covariates were included in iterations of latent class models. The final model was selected based on a minimum Bayesian information criterion. RESULTS: The final model identified three clusters with five covariates predictive of cluster membership (age, neighbourhood-based socioeconomic status, alcohol use, multiple fractures, multiple surgeries). The three clusters were associated with 22% (Cluster 1), 38% (Cluster 2) and 62% (Cluster 3) refusal rates, respectively. Members of Cluster 3 (n=84) were most commonly between 66 and 80 years of age (49% vs 6% (Cluster 1) and 21% (Cluster 2)), of high neighbourhood-based socioeconomic status (85% vs 63% (Cluster 1) and 8% (Cluster 2)), with isolated fractures (100% vs 80% (Cluster 1) and 92% (Cluster 2)), and were less likely to have multiple surgeries compared with the other clusters (28% vs 47% (Cluster 1) and 35% (Cluster 2)). CONCLUSION: In this study, the likelihood of refusing to participate in the trial ranged from 22% to 62% in the three identified clusters. Elderly age, high socioeconomic status, and less severe injuries defined the cluster that was most likely to refuse trial participation. TRIAL REGISTRATION NUMBER: NCT02984384.

Cost and efficacy comparison of prenatal recall and reflex DNA screening for trisomy 21, 18 and 13.

OBJECTIVE: To compare costs and efficacy of reflex and recall prenatal DNA screening for trisomy 21, 18 and 13 (affected pregnancies). In both methods women have Combined test markers measured. With recall screening, women with a high Combined test risk are recalled for counselling and offered a DNA blood test or invasive diagnostic testing. With reflex screening, a DNA analysis is automatically performed on plasma collected when blood was collected for measurement of the Combined test markers. METHODS: Published data were used to estimate, for each method, using various unit costs and risk cut-offs, the cost per woman screened, cost per affected pregnancy diagnosed, and for a given number of women screened, numbers of affected pregnancies diagnosed, unaffected pregnancies with positive results, and women with unaffected pregnancies having invasive diagnostic testing. RESULTS: Cost per woman screened is lower with reflex v recall screening: £37 v £38, and £11,043 v £11,178 per affected pregnancy diagnosed (DNA £250, Combined test markers risk cut-off 1 in 150). Reflex screening results in similar numbers of affected pregnancies diagnosed, with 100-fold fewer false-positives and 20-fold fewer women with unaffected pregnancies having invasive diagnostic testing. CONCLUSIONS: Reflex DNA screening is less expensive, more cost-effective, and safer than recall screening.

Hispanic representation in diabetes cardiovascular outcomes trials.

Objective: To examine Hispanic/Latino representation in diabetes cardiovascular outcomes trials for novel antidiabetic drugs. Research design and methods: We compared Hispanic/Latino representation, age, gender and body mass index in diabetes cardiovascular outcomes trials published from January 2008 to October 2018 to Hispanic adults with diabetes in the National Health Examination and Nutrition Survey over the same time period. Results: Hispanics/Latinos comprised 18.5 % of trial subjects, which was similar to the proportion of US adults with diabetes who identify as Hispanic. Trial subjects were significantly younger, more likely to be female, and more obese than US Hispanics/Latinos. At least 10 different Latin American countries and territories were represented across the 10 trials. Conclusions: US Hispanics/Latinos differ from subjects in diabetes cardiovascular outcomes trials, which may limit generalizability of trial results.

Who says "no" to participating in stroke clinical trials and why: an observational study from the Vancouver Stroke Program.

BACKGROUND: Successful stroke trials require adequate recruitment. In this observational study, we assessed reasons for refusal to provide informed consent in eligible patients approached for clinical trial participation at the Vancouver Stroke Program. METHODS: We assessed screening logs from four trials that were actively recruiting at our center: three randomized trials, two of which investigated different antithrombotic strategies for secondary prevention (NAVIGATE-ESUS, NCT02313909 12/2014; DATAS-II, NCT02295826 11/2014) and one that investigated surgery plus medical management versus medical management alone for primary prevention (CREST-2, NCT02089217 03/2014). The fourth study was observational and non-randomized; all participants received an external monitoring device (PROPHECY, NCT03712865 10/2018). Screening logs from June 2015 to April 2017 were reviewed retrospectively. Subsequently, we used a prospective structured case report form for screening (May 2017-March 2018). We assessed and compared refusal rates between trials, demographics of those refusing consent, and their reasons for doing so. We used descriptive statistics, chi-square and Fisher's exact tests as appropriate for non-parametric data, and t-tests for parametric data. We examined likelihood of refusal by sex using multivariable logistic regression models including age and trial intervention as co-variables. RESULTS: A total of 235 patients (43% women) were approached for consent. More patients refused the surgical (59%) and antithrombotic trials (53%) compared with the non-randomized external monitoring device study (13%) (p < 0.001). Surgical trial refusals were primarily due to a desire for certainty in receiving a particular intervention (39%), with the majority of those patients wanting surgery. Refusals for the antithrombotic trials were mainly due to concerns with the potential side effects of the study drug (41%); refusals in the device trial were mainly due to disinterest (46%). Women refused participation more often than men (48% vs 33%). Women remained less likely to consent than men, even after adjustment for age and trial intervention (OR 0.46, 95% CI 0.26-0.82, p = 0.009). CONCLUSIONS: Concern surrounding drug safety, randomization, and disinterest were the chief deterrents to enrolment; there were also differences in rates of consent by gender. A better understanding of why patients refuse participation in stroke trials may help to develop future patient-directed communication strategies to improve enrolment. Further research is required to better understand the reasons underlying gender disparities in consent rates.

Attitude towards deceased donation in Ho Chi Minh City, Vietnam.

Describe the current state of deceased kidney donation in Southern Vietnam and to explore the knowledge, attitude and behaviour towards kidney donation after death. Factors associated with the decision to donate among selective populations in HoChi Minh city were explored. Self-administered questionnaire of 30 questions to people over 18 years in three different communities were studied, n = 1068; 77% and 63.8% agreed they would donate their own kidney and that of their relatives respectively after death. Factors associated with positive donation wishes were knowledge of the national shortage of organs and brain death as well as positive previous family conversations. Main reason for refusal was lack of agreement within families about donation. The desire for equitable distribution of organs was frequently expressed. The majority of people interviewed in this large study agreed with deceased organ donation. Despite this, few deceased donor kidney transplants are performed in adults and none in children in Southern Vietnam, therefore greater efforts in the donation process and coordination of deceased donor lists is required. Given the correlation between positive donation wishes and knowledge with desire to donate, widespread public education campaigns are critical to the promotion and development of a successful deceased organ donation programme in Southern Vietnam.

Understanding how, why, for whom, and under what circumstances opt-out blood-borne virus testing programmes work to increase test engagement and uptake within prison: a rapid-realist review.

BACKGROUND: Prisons represent a unique opportunity to diagnose blood-borne viruses. Opt-out testing is receiving increasing interest, as a result of mounting evidence to suggest that the manner in which a test offer is delivered, affects test uptake. Although the effectiveness of opt-out testing within the prison setting has been established, robust explanations are required for the variation in outcomes reported. METHODS: Rapid-realist review methodology was used to synthesise the literature on prison-based opt-out testing. The review was carried out in three phases. Phase one: An expert panel provided literature relevant to the implementation of opt-out testing within the English prison estate. Unstructured searches were also conducted to identify other social programmes where "opt-out" had been used to increase uptake. Phase two: a systematic search of six peer-review and five grey literature databases was carried out to identify empirical data on opt-out testing within the prison setting. Phase three: Additional non-exhaustive searches were carried out to identify literature that reinforced emergent concepts. The development of programme theory took place with each iteration and was validated in consultation with stakeholders. RESULTS: Programme theory was constructed for two outcomes: the proportion of intake offered a test and the proportion offered that accepted testing. The proportion of intake offered testing was influenced by the timing of the test offer, which was often delayed due to barriers to prisoner access. The decision to accept testing was influenced by concerns about confidentiality, fear of a positive diagnosis, a prisoner's personal interpretation of risk, discomfort with invasive procedures, trust in healthcare, and the fidelity of the opt-out offer. CONCLUSIONS: This review identified important implementation considerations that moderate the effectiveness of opt-out testing programmes. It also highlighted a lack of appreciation for the theoretical underpinnings of opt-out programmes and tension around how to implement testing in a manner that adheres to both default theory and informed consent. It is anticipated that results will be used to inform the design and implementation of subsequent versions of these programmes, as well as catalyse further in-depth analysis into their operation within the unique context of prison. REVIEW REGISTRATION: CRD42017068342 .

[Discontinuation of Orthodontic Treatment: what are the early predictive factors?] / Abandons de traitement orthodontique : quels sont les facteurs predictifs precoces ?

INTRODUCTION: Discontinuation of orthodontic treatment has iatrogenic, psychological, ergonomic and financial consequences. The objective of this study was to investigate early risk factors (prior to installation) of discontinuation of orthodontic treatment. MATERIALS AND METHODS: We performed a case-control study between a group of patients who dropped their orthodontic treatment ("A") and a randomly selected group of patients who had completed their orthodontic treatment ("NA"). The two groups were compared, with descriptive, uni and multivariate analyzes. The risk factors assessed were age, gender, socioeconomic status, type of treatment, dysmorphism, malocclusion, need for treatment, compliance. RESULTS: In the dropout group 55 patients were included ("A") and 100 in the non-abandoned ("NA") group randomly selected. The subject at risk of abandonment was a girl of less than 11 years of age with a low socio-economic level with antero-posterior and vertical skeletal dysmorphisms, a molar class II, a teeth crowding, a small aesthetic prejudice or, on the contrary, very important, complex treatment (with extractions or with surgery) and having delays or missed appointments before the installation of the orthodontic appliance. CONCLUSION: Patients' motivation needs to be strengthened for both extremes: treatments that appear simple and conversely for complex cases requiring strong cooperation.

A Randomized Controlled Trial of Opt-in Versus Opt-Out Colorectal Cancer Screening Outreach.

OBJECTIVES: METHODS:: RESULTS:: Patients randomized to opt-in agreed to participate 23.1% of the time, and only 2.5% of those in opt-out chose not to participate. FIT kits were mailed to 22.4% and 93% of patients in opt-in and opt-out arms, respectively. In intention-to-screen analysis, patients in the opt-out arm had a higher FIT completion rate (29.1%) than in the opt-in arm (9.6%) (absolute difference 19.5%; 95% confidence interval, 10.9-27.9%; P < .001). Results were similar in subgroup analysis of those sent initial messaging through the EHR portal (9.5% opt-in versus 37.5% in opt-out). CONCLUSIONS: .

[Parents avoiding child vaccination in the neonatal period - an analysis of attitudes].

OBJECTIVE: Parents' avoidance of vaccination is a growing phenomenon and leads to the deterioration of the epidemiological situation regarding diseases included in active prevention programs. The aim of the study was to analyze the attitudes of parents who avoid vaccination in newborns. PATIENTS AND METHODS: Material and methods: The study included parents who refused to perform vaccination in theirnewborn. A survey analyzing the attitudes of parents avoiding vaccination in newborns was performed in a tertiary referral hospital in the years 2015-2017. We gathered information concerning their demographic data, comprising the reasons for their decision, information sources and the implementation of vaccination in a child after six months.. RESULTS: Results: We observed an increase in the number of parents avoiding vaccination in the years 2015-2017 (1.58%, 2.54%, 2.83% respectively). The parents were mature (age 31.5-34.5 years), usually with university education (93%). 63% had more than one child. In large families, 67% of the parents had vaccinated their older children. The lack of honest medical information from the personnel, negative opinions from the Internet and other parents were the reasons for avoiding vaccination. CONCLUSION: Conclusions: The insufficient activity of the medical personnel and the strong influence of anti-vaxxers' opinions, which is easily accessible on social media, are the reasons for the nonoptimal implementation of the vaccination program. It is necessary to spread honest knowledge about the epidemiological threats concerning vaccine-preventable diseases and develop a skillful way of distributing it through all the possible ways of communication.

Informing future research for carriage of multiresistant Gram-negative bacteria: problems with recruiting to an English stool sample community prevalence study.

OBJECTIVES: This study aims to highlight problems with recruiting to an English stool sample community prevalence study. It was part of a larger cross-sectional research to determine the risk factors for the presence of extended-spectrum beta-lactamase and carbapenemase-producing coliforms in stool samples of the asymptomatic general English population. SETTING: Four National Health Service primary care trusts (PCTs) of England representing a different section of the population of England: Newham PCT; Heart of Birmingham Teaching PCT; Shropshire County PCT; and Southampton City PCT. PARTICIPANTS: Sixteen general practices across the four PCTs were purposefully selected. After stratification of GP lists by age, ethnicity and antibiotic use, 58 337 randomly selected patients were sent a postal invitation.Patients who had died, moved to a different surgery, were deemed too ill by their General Practitioner or hospitalised at the time of mailing were excluded. RESULTS: Stool and questionnaire returns varied by area, age, gender and ethnicity; the highest return rate of 27.3% was in Shropshire in the age group of over 60 years; the lowest, 0.6%, was in Birmingham in the age group of 18-39 years. Whereas only 3.9%(2296) returned a completed questionnaire and stool sample, 94.9% of participants gave permission for their sample and data to be used in future research. CONCLUSION: Researchers should consider the low stool specimen return rate and wide variation by ethnicity and age when planning future studies involving stool specimen collection. This is particularly pertinent if the study has no health benefit to participants. Further research is needed to explore how to improve recruitment in multicultural communities and in younger people.

Predictors of activity involvement in dementia care homes: a cross-sectional study.

BACKGROUND: Despite the finding that involvement in activities is one of the most important needs of residents with dementia living in care homes, care facilities struggle to fulfill this need. Over the years, various factors are suggested which may contribute to or disable activity provision in dementia care homes. These include limited financial resources, task oriented staff and disease-related characteristics of residents. This study aims to further clarify which of these factors predict higher activity involvement. METHODS: Data were derived from the second measurement (2011) of the Living Arrangements for people with Dementia study. One thousand two hundred eighteen people residing in 139 dementia care homes were involved. Forty predictors of higher involvement were studied. Multilevel backward regression analyses were performed. RESULTS: The most important predictors of higher involvement were: absence of agitation, less ADL dependency, and a higher cognitive status of the residents, higher staff educational level, lower experienced job demands by care staff and a smaller number of residents living in the dementia care wards of a facility. More social supervisor support as perceived by staff was found to predict less activity involvement. CONCLUSIONS: To increase the activity involvement of care home residents with dementia it seems vital to: 1) reduce staff's experienced job demands; 2) elevate their overall educational level; 3) train staff to provide suitable activities, taking account of the behavior and preserved capabilities of residents; and 4) foster transition towards small-scale care. In order to achieve these aims, care organizations might need to evaluate the use of their financial means.

Selection bias and subject refusal in a cluster-randomized controlled trial.

BACKGROUND: Selection bias and non-participation bias are major methodological concerns which impact external validity. Cluster-randomized controlled trials are especially prone to selection bias as it is impractical to blind clusters to their allocation into intervention or control. This study assessed the impact of selection bias in a large cluster-randomized controlled trial. METHODS: The Improved Cardiovascular Risk Reduction to Enhance Rural Primary Care (ICARE) study examined the impact of a remote pharmacist-led intervention in twelve medical offices. To assess eligibility, a standardized form containing patient demographics and medical information was completed for each screened patient. Eligible patients were approached by the study coordinator for recruitment. Both the study coordinator and the patient were aware of the site's allocation prior to consent. Patients who consented or declined to participate were compared across control and intervention arms for differing characteristics. Statistical significance was determined using a two-tailed, equal variance t-test and a chi-square test with adjusted Bonferroni p-values. Results were adjusted for random cluster variation. RESULTS: There were 2749 completed screening forms returned to research staff with 461 subjects who had either consented or declined participation. Patients with poorly controlled diabetes were found to be significantly more likely to decline participation in intervention sites compared to those in control sites. A higher mean diastolic blood pressure was seen in patients with uncontrolled hypertension who declined in the control sites compared to those who declined in the intervention sites. However, these findings were no longer significant after adjustment for random variation among the sites. After this adjustment, females were now found to be significantly more likely to consent than males (odds ratio = 1.41; 95% confidence interval = 1.03, 1.92). CONCLUSIONS: Though there appeared to be a higher consent rate for females than for males, the overall impact of potential selection bias and refusal to participate was minimal. Without rigorous methodology, selection bias may be a threat to external validity in cluster-randomized trials. TRIAL REGISTRATION: NCT01983813 . Date of registration: Oct. 28, 2013.

Trends in Personal Belief Exemption Rates Among Alternative Private Schools: Waldorf, Montessori, and Holistic Kindergartens in California, 2000-2014.

OBJECTIVES: To evaluate trends in rates of personal belief exemptions (PBEs) to immunization requirements for private kindergartens in California that practice alternative educational methods. METHODS: We used California Department of Public Health data on kindergarten PBE rates from 2000 to 2014 to compare annual average increases in PBE rates between schools. RESULTS: Alternative schools had an average PBE rate of 8.7%, compared with 2.1% among public schools. Waldorf schools had the highest average PBE rate of 45.1%, which was 19 times higher than in public schools (incidence rate ratio = 19.1; 95% confidence interval = 16.4, 22.2). Montessori and holistic schools had the highest average annual increases in PBE rates, slightly higher than Waldorf schools (Montessori: 8.8%; holistic: 7.1%; Waldorf: 3.6%). CONCLUSIONS: Waldorf schools had exceptionally high average PBE rates, and Montessori and holistic schools had higher annual increases in PBE rates. Children in these schools may be at higher risk for spreading vaccine-preventable diseases if trends are not reversed.