Kira Bona

Diagnosis and management of adults with pharyngitis. A cost-effectiveness analysis.

Pharyngitis is a common and costly condition in adults. The National Ambulatory Medical Care Survey estimated that 18 million patients sought care for a sore throat in the United States in 1996, making it the sixth leading cause of visits to physicians (1). As many as four to six times more individuals may not seek care for a sore throat (2, 3). Many organisms cause sore throat. Chief among them are group A -hemolytic streptococcus (GAS), nongroup A streptococcus, Mycoplasma pneumoniae, Chlamydia pneumoniae, and several respiratory viruses (4). With rare exceptions, such as with Neisseria gonorrhoeae infection or the acute antiretroviral syndrome, no compelling data indicate treatment for patients with pharyngitis not caused by group A streptococcus (5). Nevertheless, although only about 10% of adults with pharyngitis seen in primary care settings have group A streptococcal infection (6), 75% of patients seen by physicians receive antibiotics (7). The potential morbidity of both allergic reactions and antibiotic resistance must be considered in decisions about management of pharyngitis (8, 9). Thus far, GAS has remained sensitive to penicillin, which therefore remains the recommended treatment (10). However, despite expert recommendations, physicians prescribe broad-spectrum antibiotics to 70% to 75% of adults (7, 11). Widespread resistance to macrolides has already been documented in GAS (12-14). Evidence for the effectiveness of GAS treatment has also become less compelling in recent years. Acute rheumatic fever, a sequelae of GAS pharyngitis, has become exceedingly rare in adults in industrial societies outside of sporadic outbreaks (15-17); as a result, prevention of that illness is not an important rationale for treatment. Little evidence suggests that treatment prevents glomerulonephritis (18-20). Pharyngitis treatment does shorten symptom duration and reduce the risk for infectious sequelae (21, 22), but the clinical significance of these benefits continues to be argued (22). Clinicians have several tools to determine whether a patient with pharyngitis is likely to have GAS. Rapid diagnostic assays with excellent operating characteristics are available (23-33). Furthermore, clinical criteria or decision rules can help clinicians predict the likelihood of a positive throat culture (6, 34); a recent systematic review and clinical guideline (35, 36) recommended several strategies for diagnosis and management of pharyngitis based on one such decision rule (34). Cost-effectiveness and decision analyses incorporating medical costs are useful in assessing management strategies when no definitive randomized clinical trials have compared these strategies (37). We performed a costutility analysis to examine five common strategies for testing and treatment in pharyngitis care. We also examined the effect of a decision rule (34) on those strategies. Methods Decision Analytic Model We developed a decision model [Appendix Figure 1] to evaluate common strategies for managing adult patients with pharyngitis. We constructed this model to examine the short-term cost-effectiveness of five strategies: 1) observation onlyneither test nor treat [observation]; 2) empirical antibiotic treatment of all patients without any testing [empirical therapy]; 3) throat culture for all patients, with antibiotic treatment for positive results [culture]; 4) optical immunoassay (OIA) followed by culture to confirm negative OIA test result only, with antibiotic treatment for positive results on either test [OIA/culture]; 5) OIA alone for all patients, with antibiotic treatment for positive results (OIA alone). Our model examines several possible outcomes of pharyngitis, and we discuss the probabilities of each in the following section. In brief, we examined the effect of the preceding strategies for diagnosis or treatment with a 10-day course of penicillin (with erythromycin substituted in case of an allergic reaction to penicillin [10, 35, 36, 38, 39]) on each of four outcomes: acute rheumatic fever, peritonsillar abscess, duration of symptoms, and allergic reactions to antibiotics. All outcomes were appropriately treated, and the costs and effects of treatment were included in our model. We made several simplifying conditions in creating our decision model. We considered only patients without a history of acute rheumatic fever or glomerulonephritis. Because a patient with a history of penicillin allergy would not receive penicillin and therefore would have no risk for allergic reaction, such patients were not included in our base-case model. We assumed that no patient would develop acute rheumatic fever with another complication (abscess or allergic reaction) and that patient adherence and follow-up (including ability to contact patients with culture results) were 100%. Finally, we assumed that all tests were done in an on-site reference laboratory; we did not consider the cost of transporting specimens for either culture or OIA, and we assumed that OIA results would be available before the patient left the office. In accordance with recent recommendations by an expert panel (40), the base-case analysis takes the societal perspective. We considered all outcomes and direct costs incurred within the first year of diagnosis except (as recommended for base-case analyses using quality-adjusted life-years [QALYs]) for costs such as work lost because of short-term illness (40, 41). These losses are assumed to be included in the decreased preference for illness, estimated as part of the utility for short-term illness. Three studies of adult pharyngitis that examined work days lost (42-44) did not find a significant difference between lost work days in patients treated and those not treated with penicillin; therefore, inclusion of lost productivity costs would probably not have affected our results appreciably. We limited our analysis to the first year after diagnosis. Most of the costs associated with GAS pharyngitis occur within the first several weeks. A few patients will have late complications, such as rheumatic valve deformities, and will require treatments such as heart valve replacement 20 or more years after their episode of pharyngitis. Because these complications are rare and because discounting would eliminate most of these downstream costs, we joined pediatric investigators in limiting our analysis to health care costs incurred in the first year (45, 46). The model output was quality-adjusted loss of life expectancy, measured as quality-adjusted life-days. Incremental cost-effectiveness analyses were performed by rank ordering all five competing strategies by increasing effectiveness, then calculating incremental cost-effectiveness strategies for each strategy (Appendix). All analyses were performed by using a decision analysis software program (DATA, versions 3.5 and 4.0, TreeAge, Williamstown, Massachusetts). Data Sources We searched the published literature for probabilities, utilities, and costs, as described in the following section (and in more detail in the Appendix). The Clinical Examination We examined the incorporation of the clinical examination into our strategies for management of pharyngitis. A recent systematic review of the clinical examination in adult pharyngitis (47) found that no individual element of the history or physical examination for a patient with pharyngitis is accurate enough to diagnose streptococcal pharyngitis (Appendix). However, several clinical prediction rules have combined key findings as a tool in predicting the probability of sore throat in adults (6, 34, 48-50). The pharyngitis decision rule by Centor and colleagues (34) (Appendix Figure 2) is the only rule validated in several populations (47, 51-53). It is based on four clinical findings (tonsillar exudates, tender anterior cervical lymphadenopathy, absence of cough, and history of fever); each risk factor is weighted equally to give a score of 0 to 4 points. It can then be used as a likelihood ratio by applying it to a population with a known GAS pharyngitis prevalence (such as the patients seen in a practice) to determine the individual patients probability of GAS pharyngitis. Because this new probability estimate can be considered a prevalence of GAS pharyngitis for an individual patient, we examined the incorporation of the decision rule into our strategies (as described in the Results section under the heading Application of a Clinical Decision Rule). Prevalence of GAS Pharyngitis The prevalence of GAS pharyngitis in adults, defined as the proportion of throat cultures that grow GAS, varies between 5% and 26% in primary care and emergency department settings (6, 34, 54). It can also vary with the season of the year, exposure to children, and other factors (10). On the basis of a study done in Boston, Massachusetts, we used a GAS pharyngitis prevalence of 10% (6) for our model (Table 1). Table 1. Baseline Probabilities, Utilities, and Costs for Cost-Effectiveness Analysis of Management of Group A -Hemolytic Streptococcal Pharyngitis GAS Test Characteristics We modeled two-plate culture in the reference laboratory as the gold standard with 100% sensitivity and specificity. Although this is not an ideal gold standard, other possibilities (such as antibody titers) cannot be obtained when a treatment decision must be made. Culture is therefore generally considered the criterion standard (10, 46, 55, 56). We identified studies of rapid antigen testing in September 2000 using the MEDLINE subject heading terms pharyngitis and streptococcal infections, diagnosis and found that most studies of OIA were of relatively good quality and used similar gold standards. Therefore, we averaged the sensitivity findings of the studies of OIA with weighting for the number of patients in each study to estimate an overall sensitivity of 0.884 (23-33) and specificity of 0.944 (23-33). We incorporated these test characteristics into our model by using Bayesian a

Unmeasured Costs of a Child's Death: Perceived Financial Burden, Work Disruptions, and Economic Coping Strategies Used by American and Australian Families Who Lost Children to Cancer

PURPOSE Financial concerns represent a major stressor for families of children with cancer but remain poorly understood among those with terminally ill children. We describe the financial hardship, work disruptions, income loss, and coping strategies of families who lost children to cancer. METHODS Retrospective cross-sectional survey of 141 American and 89 Australian bereaved parents whose children died between 1990 and 1999 and 1996 to 2004, respectively, at three tertiary-care pediatric hospitals (two American, one Australian). Response rate: 63%. RESULTS Thirty-four (24%) of 141 families from US centers and 34 (39%) of 88 families from the Australian center reported a great deal of financial hardship resulting from their childrens illness. Work disruptions were substantial (84% in the United States, 88% in Australia). Australian families were more likely to report quitting a job (49% in Australia v 35% in the United States; P = .037). Sixty percent of families lost more than 10% of their annual income as a result of work disruptions. Australians were more likely to lose more than 40% of their income (34% in Australia v 19% in the United States; P = .035). Poor families experienced the greatest income loss. After accounting for income loss, 16% of American and 22% of Australian families dropped below the poverty line. Financial hardship was associated with poverty and income loss in all centers. Fundraising was the most common financial coping strategy (52% in the United States v 33% in Australia), followed by reduced spending. CONCLUSION In these US and Australian centers, significant household-level financial effects of a childs death as a result of cancer were observed, especially for poor families. Interventions aimed at reducing the effects of income loss may ease financial distress.

Assessment of Financial Burden as a Standard of Care in Pediatric Oncology.

Family financial hardship has emerged as a burden of pediatric cancer treatment with negative implications for family well‐being. As part of an extensive project to create evidence‐based standards for the psychosocial care of children with cancer, we performed a literature review of pediatric cancer‐associated financial hardship utilizing six databases, and identified 24 publications for incorporation into this review. Financial hardship during childhood cancer was found to affect a significant proportion of the population and to negatively impact family well‐being. Existing literature supports a strong recommendation for assessment of financial hardship as a component of comprehensive psychosocial care in pediatric oncology. Pediatr Blood Cancer

Impact of Socioeconomic Status on Timing of Relapse and Overall Survival for Children Treated on Dana-Farber Cancer Institute ALL Consortium Protocols (2000–2010)

Population‐based evidence suggests that lower socioeconomic status (SES) negatively impacts the overall survival (OS) of children with leukemia; however, the relationships between SES and treatment‐related mortality, relapse, and timing of relapse remain unclear.

Trajectory of Material Hardship and Income Poverty in Families of Children Undergoing Chemotherapy: A Prospective Cohort Study

Poverty is correlated with negative health outcomes in pediatric primary care, and is emerging as a negative prognostic indicator in pediatric oncology. However, measures of poverty amenable to targeted intervention, such as household material hardship (HMH)—including food, energy, and housing insecurity—have not been described in pediatric oncology. We describe the trajectory of family reported HMH and income poverty at a pediatric oncology referral center in New England with high psychosocial supports.

Adolescent and Young Adult Patient Engagement and Participation in Survey-Based Research: A Report From the "Resilience in Adolescents and Young Adults With Cancer" Study.

Conducting patient‐reported outcomes research with adolescents and young adults (AYAs) is difficult due to low participation rates and high attrition. Forty‐seven AYAs with newly diagnosed cancer at two large hospitals were prospectively surveyed at the time of diagnosis and 3–6 and 12–18 months later. A subset participated in 1:1 semistructured interviews. Attrition prompted early study closure at one site. The majority of patients preferred paper–pencil to online surveys. Interview participants were more likely to complete surveys (e.g., 93% vs. 58% completion of 3–6 month surveys, P = 0.02). Engaging patients through qualitative methodologies and using patient‐preferred instruments may optimize future research success.

Prevalence and impact of financial hardship among New England pediatric stem cell transplantation families.

Poverty is correlated with negative health outcomes in pediatric primary care and subspecialties; its association with childhood hematopoietic stem cell transplantation (HSCT) patterns of care and clinical outcomes is not known. We describe family-reported financial hardship at a primary referral center in New England and explore the relationship between measures of poverty and patterns of care and clinical outcomes. Forty-five English-speaking parents of children after allogeneic HSCT in the prior 12 months completed a 1-time survey (response rate 88%). Low-income families, defined as ≤200% federal poverty level (FPL), were compared with all others. Eighteen (40%) families reported pre-HSCT incomes ≤200% FPL. Material hardship, including food, housing, or energy insecurity was reported by 17 (38%) families in the cohort. Low-income families reported disproportionate transplantation-related income losses, with 7 (39%) reporting annual income losses of >40% compared with 2 (18%) wealthier families (P = .02). In univariate analyses, 11 (61%) low-income children experienced graft-versus-host disease (GVHD) of any grade in the first 180 days after HSCT compared with 2 (7%) wealthier children (P = .004). We conclude that low income and, in particular, material hardship, are prevalent in a New England pediatric HSCT population and represent targets for improvement in quality of life. The role of poverty in mediating GVHD deserves further investigation in larger studies that can control for known risk factors and may provide a targetable source of transplantation-associated morbidity.

Hope, distress, and later quality of life among adolescent and young adults with cancer

ABSTRACT We aimed to explore the predictive value of screening for distress alone, hope alone, or a combination of both. In a multicenter prospective study, 37 English-speaking adolescents and young adults with cancer and 40 parents completed validated instruments at diagnosis (“baseline”) and 3–6 months later (“follow-up”). Correlated regression models described associations. Within each instrument, baseline and follow-up scores were associated. However, only a composite hope/distress score predicted all three patient-centered outcomes. Multidimensional screens incorporating positive and negative psychosocial constructs may predict patient-centered outcomes better than isolated, single-construct instruments.

Disparities in Pediatric Palliative Care: An Opportunity to Strive for Equity

* Abbreviations: EOL — : end of life PPC — : pediatric palliative care The importance of pediatric palliative care (PPC) for children with cancer has been broadly embraced over the last 2 decades in response to compelling evidence of high symptom burden and suffering throughout the continuum of care.1–3 Yet, how best to evaluate the impact of PPC remains a methodological challenge in a field focused on patient-reported outcomes, including symptom alleviation and goal-concordant care. In adult oncology, the benchmarking of palliative care has been facilitated by data demonstrating that end-of-life (EOL) care intensity (which is evaluable with administrative data, such as hospitalization and receipt of ICU care) is discordant with the wishes of adult patients with cancer.4,5 Similar benchmarking in pediatrics has been limited by an unknown correlation of care intensity with family goals and an absence of methodology for pediatric-specific administrative data. In this issue of Pediatrics , Johnston et al6 provide the first US population-based data … Address correspondence to Kira Bona, MD, MPH, Department of Pediatric Oncology, Dana-Farber Cancer Institute, 450 Brookline Ave, Boston, MA 02115. E-mail: kira.bona{at}childrens.harvard.edu

Household material hardship in families of children post-chemotherapy

Poverty is an important patient‐reported outcome of therapy and a potential predictor of outcome disparities in pediatric cancer. We previously identified that nearly 30% of pediatric cancer families experience household material hardship (HMH), a concrete measure of poverty including food, energy, or housing insecurity, during the first 6 months of chemotherapy. We conducted a follow‐up survey in a subcohort of these families at least 1 year off‐therapy and found that 32% reported HMH in early survivorship. Persistently high concrete resource needs off‐therapy may have significance for child health and quality of life, and thus represent targets for future investigation.