How to Determine if a Project Is Human Subjects Research, a Quality Improvement Project, or Both.

Background: Before undertaking a research project, investigators must determine if the planned activity is human subjects research or a quality improvement project because specific regulations govern the conduct of human subjects research. Making this determination, however, can be confusing because human subjects research and quality improvement projects share similar characteristics. Methods: The definitions, questions, and examples provided in this article will help investigators decide between quality improvement projects and human subjects research or determine when to seek regulatory guidance. Results: While quality improvement and human subjects research are both rigorous processes and at times involve similar methods, the two types of studies have distinctly different overall aims. Quality improvement projects use data-driven methods to improve health delivery and quality. Such projects examine changes in human behavior and are largely experiential learning processes. Research is a systematic investigation designed to develop or contribute to generalizable knowledge. Conclusion: In most instances, the goals of human subjects research and quality improvement projects do not intersect, and quality improvement projects are generally not subject to US Department of Health and Human Services (HHS) regulatory protections. However, some projects are both quality improvement and human subjects research, and sometimes, a quality improvement project develops into a human subjects research project. Investigators must be aware of the criteria defining human subjects research to ensure that HHS regulations for the protection of human subjects are applied when necessary.

Understanding Broad Consent.

Background: The 2018 revisions to the Common Rule that were effective in January 2019 introduced a new category of informed consent: broad consent. Methods: Investigators and institutional review board (IRB) members need to understand (1) what broad consent is, (2) the role of broad consent under the revised Common Rule, (3) how and when broad consent can be used, (4) exempt research categories that relate to broad consent, and (5) the scope of limited IRB review as it relates to broad consent. Results: Under the prior regulations, researchers had two consent options: obtain study-specific informed consent or request the IRB to waive the requirement to obtain informed consent. The revision to the Common Rule introduced the third option of broad consent, but its applicability is limited. Broad consent can only be used to obtain an individual's consent for the storage, maintenance, and secondary research use of identifiable private information or identifiable biospecimens. The regulatory authority for broad consent is at 45 CFR §46.116(d). None of the required elements of broad consent can be omitted or altered because each element is considered essential. Broad consent shares many of the requirements for study-specific informed consent, but several elements are unique: a description of the types of secondary research that may be conducted; statements describing the private information or biospecimens that might be used in research, whether sharing of the information or biospecimens might occur, and the types of institutions or researchers that might conduct research with the information or biospecimens; information on how long the information or biospecimens may be stored, maintained, and used; a statement that subjects will or will not be informed of the details of any subsequent research; a statement that research results will or will not be disclosed to subjects; and contact information for obtaining answers to questions about the subjects' rights regarding storage and use of information or biospecimens and whom to contact regarding research-related harm. Conclusion: Broad consent provides flexibility that did not exist prior to the revision, giving researchers the option to obtain broad consent for the storage, maintenance, and secondary research use of identifiable private information or identifiable biospecimens. With an understanding of the regulations, an investigator can plan how best to organize his or her research plan and decide whether to obtain study-specific informed consent, to apply for a waiver of consent, or to obtain broad consent.

Teaching Medical Students to Help Patients Quit Smoking: Outcomes of a 10-School Randomized Controlled Trial.

BACKGROUND: Early in medical education, physicians must develop competencies needed for tobacco dependence treatment. OBJECTIVE: To assess the effect of a multi-modal tobacco dependence treatment curriculum on medical students' counseling skills. DESIGN: A group-randomized controlled trial (2010-2014) included ten U.S. medical schools that were randomized to receive either multi-modal tobacco treatment education (MME) or traditional tobacco treatment education (TE). SETTING/PARTICIPANTS: Students from the classes of 2012 and 2014 at ten medical schools participated. Students from the class of 2012 (N = 1345) completed objective structured clinical examinations (OSCEs), and 50 % (N = 660) were randomly selected for pre-intervention evaluation. A total of 72.9 % of eligible students (N = 1096) from the class of 2014 completed an OSCE and 69.7 % (N = 1047) completed pre and post surveys. INTERVENTIONS: The MME included a Web-based course, a role-play classroom demonstration, and a clerkship booster session. Clerkship preceptors in MME schools participated in an academic detailing module and were encouraged to be role models for third-year students. MEASUREMENTS: The primary outcome was student tobacco treatment skills using the 5As measured by an objective structured clinical examination (OSCE) scored on a 33-item behavior checklist. Secondary outcomes were student self-reported skills for performing 5As and pharmacotherapy counseling. RESULTS: Although the difference was not statistically significant, MME students completed more tobacco counseling behaviors on the OSCE checklist (mean 8.7 [SE 0.6] vs. mean 8.0 [SE 0.6], p = 0.52) than TE students. Several of the individual Assist and Arrange items were significantly more likely to have been completed by MME students, including suggesting behavioral strategies (11.8 % vs. 4.5 %, p < 0.001) and providing information regarding quitline (21.0 % vs. 3.8 %, p < 0.001). MME students reported higher self-efficacy for Assist, Arrange, and Pharmacotherapy counseling items (ps ≤0.05). LIMITATIONS: Inclusion of only ten schools limits generalizability. CONCLUSIONS: Subsequent interventions should incorporate lessons learned from this first randomized controlled trial of a multi-modal longitudinal tobacco treatment curriculum in multiple U.S. medical schools. NIH Trial Registry Number: NCT01905618.

Epidemiology of acute pancreatitis in hospitalized children in the United States from 2000-2009.

BACKGROUND: Single-center studies suggest an increasing incidence of acute pancreatitis (AP) in children. Our specific aims were to (i) estimate the recent secular trends, (ii) assess the disease burden, and (iii) define the demographics and comorbid conditions of AP in hospitalized children within the United States. METHODS: We used the Healthcare Cost and Utilization Project Kids' Inpatient Database, Agency for Healthcare Research and Quality for the years 2000 to 2009. Extracted data were weighted to generate national-level estimates. We used the Cochrane-Armitage test to analyze trends; cohort-matching to evaluate the association of AP and in-hospital mortality, length of stay, and charges; and multivariable logistic regression to test the association of AP and demographics and comorbid conditions. RESULTS: We identified 55,012 cases of AP in hospitalized children (1-20 years of age). The incidence of AP increased from 23.1 to 34.9 (cases per 10,000 hospitalizations per year; P<0.001) and for all-diagnoses 38.7 to 61.1 (P<0.001). There was an increasing trend in the incidence of both primary and all-diagnoses of AP (P<0.001). In-hospital mortality decreased (13.1 to 7.6 per 1,000 cases, P<0.001), median length of stay decreased (5 to 4 days, P<0.001), and median charges increased ($14,956 to $22,663, P<0.001). Children with AP compared to those without the disease had lower in-hospital mortality (adjusted odds ratio, aOR 0.86, 95% CI, 0.78-0.95), longer lengths of stay (aOR 2.42, 95% CI, 2.40-2.46), and higher charges (aOR 1.62, 95% CI, 1.59-1.65). AP was more likely to occur in children older than 5 years of age (aORs 2.81 to 5.25 for each 5-year age interval). Hepatobiliary disease was the comorbid condition with the greatest association with AP. CONCLUSIONS: These results demonstrate a rising incidence of AP in hospitalized children. Despite improvements in mortality and length of stay, hospitalized children with AP have significant morbidity.

Serum markers for severe Clostridium difficile infection in immunosuppressed hospitalized patients.

Clostridium difficile infection (CDI) has emerged as the leading cause of nosocomial diarrhea in the developed world. The prompt recognition of severe CDI is essential in providing early aggressive therapy. Though previous studies have identified leukocytosis, azotemia, and hypoalbuminemia as markers to differentiate severe from non-severe CDI in the general patient population, there is little data in immunosuppressed patients. We conducted a retrospective chart review of immunosuppressed patients with CDI to identify serum markers associated with severe CDI. Twenty-nine immunosuppressed patients with CDI (nine with severe disease) were identified. Those with severe disease were older and had evidence of renal dysfunction. The white blood cell count, platelet, and albumin levels were the same in the severe and non-severe immunosuppressed CDI patients. Therefore, recognized serum markers of severe CDI are not universally useful in immunosuppressed patients. Moreover, the clinician must be aware that immunosuppressed patients can develop severe CDI while remaining leukopenic.

Low levels of hydrogen sulfide in the blood of diabetes patients and streptozotocin-treated rats causes vascular inflammation?

Hydrogen sulfide (H(2)S) is emerging as a physiological neuromodulator as well as a smooth muscle relaxant. We submit the first evidence that blood H(2)S levels are significantly lower in fasting blood obtained from type 2 diabetes patients compared with age-matched healthy subjects, and in streptozotocin-treated diabetic rats compared with control Sprague-Dawley rats. We further observed that supplementation with H(2)S or an endogenous precursor of H(2)S (l-cysteine) in culture medium prevents IL-8 and MCP-1 secretion in high-glucose-treated human U937 monocytes. These first observations led to the hypothesis that lower blood H(2)S levels may contribute to the vascular inflammation seen in diabetes.

Langerhans cell histiocytosis, a case of Letterer Siwe disease.

An 8-month-old male infant presented with a progressively worsening generalized rash of 5-6 months duration, fever, poor feeding, and abdominal distension. An initial laboratory workup revealed anemia, thrombocytopenia, and hepatosplenomegaly. The patient was started on i.v. antibiotics, and a working diagnosis of Langerhans cell histiocytosis was reached that was later confirmed with a skin biopsy. Subsequently, the patient received first-round chemotherapy with vinblastine and prednisone, on which he appeared to improve clinically; however, he soon relapsed. He then received combination salvage therapy with cladribine (2CdA) and cytarabine (Ara-C) for three cycles. The patient responded well to this regimen with resolution of his condition. The patient was then referred for a bone marrow transplant.

Preprinted order sets as a safety intervention in pediatric sedation.

OBJECTIVES: Implement preprinted packets for pediatric procedural sedations to increase documentation compliance and decrease medication ordering errors. STUDY DESIGN: Retrospective chart review of pediatric inpatients undergoing procedural sedation before and after implementation of a preprinted packet including an order set, consent form, and sedation monitoring form. Patient charts before and after the intervention were reviewed for completeness of medical documentation, correct medication dosages, and adverse events. Chi2 or Fisher exact test was used to determine preintervention vs postintervention differences. RESULTS: Forty-two charts preintervention and 42 postintervention were reviewed. Documentation compliance increased on consent forms (P < .001), procedure notes (P = .113), and sedation monitoring forms (P = .003), while dating and timing of order forms decreased. Ordering of resuscitation equipment (P = .12), documentation of American Society of Anesthesiologists' (ASA) physical status classification (P < .001) and allergies (P < .001), and postsedation orders (P < .001) also increased. Medications ordered using unit/kg increased 43% (P < .05). Medication ordering errors for sedation agents decreased 64% (P < .001). Ordering of appropriate reversal agents increased 73% (P = .02). CONCLUSIONS: Implementing preprinted physician orders, consent forms, and prepared packets increased documentation compliance and ordering of reversal agents and resuscitation equipment. Medication dosage ordering errors decreased.

Improving patient understanding of prescription drug label instructions.

BACKGROUND: Patient misunderstanding of instructions on prescription drug labels is common and a likely cause of medication error and less effective treatment. OBJECTIVE: To test whether the use of more explicit language to describe dose and frequency of use for prescribed drugs could improve comprehension, especially among patients with limited literacy. DESIGN: Cross-sectional study using in-person, structured interviews. PATIENTS: Three hundred and fifty-nine adults waiting for an appointment in two hospital-based primary care clinics and one federally qualified health center in Shreveport, Louisiana; Chicago, Illinois; and New York, New York, respectively. MEASUREMENT: Correct understanding of each of ten label instructions as determined by a blinded panel review of patients' verbatim responses. RESULTS: Patient understanding of prescription label instructions ranged from 53% for the least understood to 89% for the most commonly understood label. Patients were significantly more likely to understand instructions with explicit times periods (i.e., morning) or precise times of day compared to instructions stating times per day (i.e., twice) or hourly intervals (89%, 77%, 61%, and 53%, respectively, p < 0.001). In multivariate analyses, dosage instructions with specific times or time periods were significantly more likely to be understood compared to instructions stating times per day (time periods--adjusted relative risk ratio (ARR) 0.42, 95% Confidence Interval (CI) 0.34-0.52; specific times--ARR 0.60, 95% CI 0.49-0.74). Low and marginal literacy remained statistically significant independent predictors of misinterpreting instructions (low--ARR 2.70, 95% CI 1.81-4.03; marginal--ARR 1.66, 95% CI 1.18-2.32). CONCLUSIONS: Use of precise wording on prescription drug label instructions can improve patient comprehension. However, patients with limited literacy were more likely to misinterpret instructions despite use of more explicit language.

Provider and patient intervention to improve weight loss: a pilot study in a public hospital clinic.

OBJECTIVE: To assess the efficacy of a literacy-appropriate weight loss intervention targeting providers and patients in improving physicians' weight loss counseling and patients' self-reported beliefs, and self-efficacy. METHODS: The study took place in a public hospital nephrology clinic. The intervention included two physician workshops and a small group patient education. Physician-patient communication was observed and coded. Structured interviews assessed patient recall of weight loss recommendations, weight-related beliefs, and self-efficacy. RESULTS: 64 patient visits were observed before and after the intervention. 75% of patients were African American, 96% lacked private insurance, 71% had low literacy skills; mean body mass index (BMI) of 35 kg/m(2). Physician counseling improved significantly post-intervention, particularly in assessing, supporting and advising patients about weight loss and exercise. Patients reported increases in recall of weight loss recommendations and were more likely to report greater confidence about losing weight (52% vs. 70%, p<0.01). CONCLUSIONS: This pilot study offers promising directions to address provider and patient barriers to weight loss education and counseling in a public hospital. PRACTICE IMPLICATIONS: Hospital-based weight loss interventions need to target both physicians and patients.

Measuring adult literacy in health care: performance of the newest vital sign.

OBJECTIVE: To compare performance of the newest vital sign (NVS) with existing literacy measures. METHODS: We administered the NVS and REALM to 129 patients, and NVS and S-TOFHLA to 119 patients all in public clinics. RESULTS: The NVS demonstrated high sensitivity for detecting limited literacy and moderate specificity (area under the receiver operating characteristic [AUROC] curve 0.71-0.73). The NVS was less effective than the S-TOFHLA for predicting health outcomes. CONCLUSION: The NVS is able to identify patients with limited literacy skills, but may misclassify those with adequate literacy according to the REALM and S-TOFHLA. NVS scores were not associated with health outcomes.

To err is human: patient misinterpretations of prescription drug label instructions.

OBJECTIVE: To examine the nature and cause of patients' misunderstanding common dosage instructions on prescription drug container labels. METHODS: In-person cognitive interviews including a literacy assessment were conducted among 395 patients at one of three primary care clinics in Shreveport, Louisiana, Jackson, Michigan and Chicago, Illinois. Patients were asked to read and demonstrate understanding of dosage instructions for five common prescription medications. Correct understanding was determined by a panel of blinded physician raters reviewing patient verbatim responses. Qualitative methods were employed to code incorrect responses and generate themes regarding causes for misunderstanding. RESULTS: Rates of misunderstanding for the five dosage instructions ranged from 8 to 33%. Patients with low literacy had higher rates of misunderstanding compared to those with marginal or adequate literacy (63% versus 51% versus 38%, p<0.001). The 374 (19%) incorrect responses were qualitatively reviewed. Six themes were derived to describe the common causes for misunderstanding: label language, complexity of instructions, implicit versus explicit dosage intervals, presence of distractors, label familiarity, and attentiveness to label instructions. CONCLUSION: Misunderstanding dosage instructions on prescription drug labels is common. While limited literacy is associated with misunderstanding, the instructions themselves are awkwardly phrased, vague, and unnecessarily difficult. PRACTICE IMPLICATIONS: Prescription drug labels should use explicit dosing intervals, clear and simple language, within a patient-friendly label format. Health literacy and cognitive factors research should be consulted.

Literacy and misunderstanding prescription drug labels.

BACKGROUND: Health literacy has increasingly been viewed as a patient safety issue and may contribute to medication errors. OBJECTIVE: To examine patients' abilities to understand and demonstrate instructions found on container labels of common prescription medications. DESIGN: Cross-sectional study using in-person, structured interviews. SETTING: 3 primary care clinics serving mostly indigent populations in Shreveport, Louisiana; Jackson, Michigan; and Chicago, Illinois. PATIENTS: 395 English-speaking adults waiting to see their providers. MEASUREMENT: Correct understanding of instructions on 5 container labels; demonstration of 1 label's dosage instructions. RESULTS: Correct understanding of the 5 labels ranged from 67.1% to 91.1%. Patients reading at or below the sixth-grade level (low literacy) were less able to understand all 5 label instructions. Although 70.7% of patients with low literacy correctly stated the instructions, "Take two tablets by mouth twice daily," only 34.7% could demonstrate the number of pills to be taken daily. After potential confounding variables were controlled for, low (adjusted relative risk, 2.32 [95% CI, 1.26 to 4.28]) and marginal (adjusted relative risk, 1.94 [CI, 1.14 to 3.27]) literacy were significantly associated with misunderstanding. Taking a greater number of prescription medications was also statistically significantly associated with misunderstanding (adjusted relative risk, 2.98 [CI, 1.40 to 6.34] for > or =5 medications). LIMITATIONS: The study sample was at high risk for poor health literacy and outcomes. Most participants were women, and all spoke English. The authors did not examine the association between misunderstanding and medication error or evaluate patients' actual prescription drug-taking behaviors. CONCLUSIONS: Lower literacy and a greater number of prescription medications were independently associated with misunderstanding the instructions on prescription medication labels.

Low literacy impairs comprehension of prescription drug warning labels.

BACKGROUND: Adverse events resulting from medication error are a serious concern. Patients' literacy and their ability to understand medication information are increasingly seen as a safety issue. OBJECTIVE: To examine whether adult patients receiving primary care services at a public hospital clinic were able to correctly interpret commonly used prescription medication warning labels. DESIGN: In-person structured interviews with literacy assessment. SETTING: Public hospital, primary care clinic. PARTICIPANTS: A total of 251 adult patients waiting for an appointment at the Louisiana State University Health Sciences Center in Shreveport (LSUHSC-S) Primary Care Clinic. MEASUREMENTS: Correct interpretation, as determined by expert panel review of patients' verbatim responses, for each of 8 commonly used prescription medication warning labels. RESULTS: Approximately one-third of patients (n=74) were reading at or below the 6th-grade level (low literacy). Patient comprehension of warning labels was associated with one's literacy level. Multistep instructions proved difficult for patients across all literacy levels. After controlling for relevant potential confounding variables, patients with low literacy were 3.4 times less likely to interpret prescription medication warning labels correctly (95% confidence interval: 2.3 to 4.9). CONCLUSIONS: Patients with low literacy had difficulty understanding prescription medication warning labels. Patients of all literacy levels had better understanding of warning labels that contained single-step versus multiple-step instructions. Warning labels should be developed with consumer participation, especially with lower literate populations, to ensure comprehension of short, concise messages created with familiar words and recognizable icons.

Recommendations for effective newborn screening communication: results of focus groups with parents, providers, and experts.

OBJECTIVES: The aims of this study were to determine parent and provider knowledge and awareness of newborn screening; to gather opinions from parents, providers, and newborn screening professionals about the content and timing of newborn screening education; and to use consensus data to formulate recommendations and to develop educational materials for parents and providers. METHODS: We conducted 22 focus groups and 3 individual interviews between October 2003 and May 2004, with English- and Spanish-speaking parents of infants <1 year of age who had experience with initial testing, retesting, or false-positive screenings; health professionals who provide prenatal care or health care for newborns; and state newborn screening program health professionals. RESULTS: Parents and providers had limited knowledge and awareness about newborn screening practices. Parents wanted brief to-the-point information on newborn screening and its benefits, including the possible need for retesting and the importance of returning promptly for retesting if initial results are abnormal. Parents wanted the information orally from the primary care provider. Parents, providers, and newborn screening professionals all thought that an accompanying concise, easy-to-read brochure with contact information would be helpful. All focus group participants thought that parents should receive this information before the birth of the infant, preferably in the third trimester of pregnancy. Providers wanted a brief checklist of information and resources to prepare them to educate parents effectively. CONCLUSIONS: We recommend prenatal and primary care providers be more involved in educating parents about newborn screening. Professional societies and state health officials should work together to encourage parent and provider education. User-friendly patient and provider education materials, such as those we developed, could form the basis for this educational approach.

Infant hearing screening: stakeholder recommendations for parent-centered communication.

OBJECTIVES: The purpose of this study was to identify what stakeholders considered best practices for parent-provider communication regarding newborn hearing screening and diagnosis. We used consensus data to develop educational materials for parents. METHODS: We conducted 29 focus groups and 23 individual interviews between October 2003 and May 2004. Participants included (1) English- and Spanish-speaking parents of infants <18 months of age who had experience with hospital-based newborn hearing screening; (2) parents of children with hearing loss; (3) primary care providers who provide prenatal care or care for newborns; and (4) audiologists, audiology technicians, and hospital nurses. RESULTS: Communication to parents about hospital-based newborn hearing screening was limited. Most parents first learned about the screening in the hospital, but all stakeholders thought a more opportune time for education was before the birth. For parents of infants who did not pass the newborn hearing screening, stakeholders recommended direct communication about the urgency of diagnostic testing. They also indicated that primary care providers needed current information regarding hearing screening, diagnostic testing, and early intervention. All stakeholders thought that a brief brochure for parents to take home would be helpful for hospital-based screening and, if necessary, subsequent diagnostic testing. Primary care providers requested basic, to-the-point information. CONCLUSIONS: The most opportune time to begin discussion of newborn hearing screening is before the birth. Providers need up-to-date information on current standards of hearing screening, diagnosis, and intervention. User-friendly patient education materials, such as those we developed, could assist providers in educating parents.

Misunderstanding of prescription drug warning labels among patients with low literacy.

PURPOSE: The common causes for misunderstanding prescription drug warning labels (PWLs) among adults with low literacy were studied. METHODS: A total of 74 patients reading at or below the sixth-grade level and receiving care at the primary care clinic at the Louisiana State University Health Sciences Center in Shreveport were recruited to participate in structured interviews. Patients were asked to interpret and comment on eight commonly used warning labels found on prescription medications. Correct interpretation was determined by expert panel review of patients' verbatim responses. Qualitative methods were employed to code responses and generate themes regarding the misunderstanding of these PWLs. RESULTS: Among this sample of patients with low literacy skills, rates of correct interpretation for the eight warning labels ranged from 0% to 78.7%. With the exception of the most basic label, less than half of all patients were able to provide adequate interpretations of the warning label messages. Five themes were derived to describe the common causes for misunderstanding the labels: single-step versus multiple-step instructions, reading difficulty of text, use of icons, use of color, and message clarity. Labels were at greater risk for being misunderstood if they included multiple instructions, had a greater reading difficulty, included unfamiliar terms, or used confusing icons that were discordant with text messages. Participants also frequently imposed an incorrect meaning on label colors, which led to further confusion. CONCLUSION: Patients with low literacy skills demonstrated a lower rate of correct interpretation of the eight most commonly used PWLs than did those with higher literacy skills. Multiple-step instructions, reading difficulty of text, the use of icons, the use of color, and message clarity were the common causes of label misinterpretation.

Are continuity clinic patients less satisfied when the resident is postcall?

Due to recent public debate and newly imposed resident work hour restrictions, we decided to investigate the relationship of resident call status to their ambulatory patients' satisfaction. Resident continuity clinic patients were asked to rate their level of satisfaction on a 10-point Likert-type scale. Using multiple regression approaches, these data were then assessed as a function of resident call status. We found that in 646 patient encounters, patient satisfaction scores were significantly less when the resident was postcall, 8.99 +/- 1.8, than when not postcall, 9.31 +/- 1.3. We herein discuss etiologies and implications of these findings for both patient care and medical education.