Joan M. Neuner

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

Relationship Between Number of Breast Cancer Operations Performed and 5-Year Survival After Treatment for Early-Stage Breast Cancer

OBJECTIVES We examined the association between number of breast cancer operations performed in a hospital (hospital volume) and all-cause and breast cancer-specific mortality using a national database and statistical methods appropriate for clustering and reducing confounding. METHODS In a retrospective cohort study, we linked Surveillance, Epidemiology, and End Results tumor registry data with Medicare claims data. The cohort included 11225 Medicare patients who had undergone surgery for early-stage breast cancer from 1994 to 1996 in 457 different hospitals. Primary outcomes were all-cause and breast cancer-specific survival rates at a mean follow-up time of 62.5 months. RESULTS In comparison with treatment in a low-volume hospital, treatment in a high-volume hospital was associated with hazard ratios of 0.83 (95% confidence interval [CI]=0.75, 0.92) for all-cause mortality and 0.80 (CI=0.66, 0.97) for breast cancer-specific mortality. CONCLUSIONS An association between the volume of breast cancer operations performed in a hospital and 5-year survival rates was observed for both all-cause and breast cancer-specific mortality. Further work investigating the aspects of hospital volume that contribute to increased survival is warranted.

A framework for health numeracy: how patients use quantitative skills in health care.

Our objective of this study is to develop a conceptual framework for the construct of health numeracy based on patient perceptions, using a cross-sectional, qualitative design. Interested participants (n = 59) meeting eligibility criteria (age 40–74, English speaking) were assigned to one of six focus groups stratified by gender and educational level (low, medium, high). Fifty-three percent were male, and 47% were female. Sixty-one percent were white non-Hispanic, and 39% were of minority race or ethnicity. Participants were randomly selected from three primary care sites associated with an academic medical center. Focus group discussions were held in May 2004 and focused on how numbers are used in the health care setting. Data were presented from clinical trials to further explore how quantitative information is used in health communication and decision making. Focus groups were audio and videotaped; verbatim transcripts were prepared and analyzed. A framework of health numeracy was developed to reflect the themes that emerged. Three broad conceptual domains for health numeracy were identified: primary numeric skills, applied health numeracy, and interpretive health numeracy. Across domains, results suggested that numeracy contains an emotional component, with both positive and negative affect reflected in patient numeracy statements. We conclude that health numeracy is a multifaceted construct that includes applied and interpretive components and is influenced by patient affect.

Diagnosis and treatment of osteoporosis in patients with vertebral compression fractures.

OBJECTIVES: To determine whether patients with vertebral compression fractures are diagnosed with or treated for osteoporosis.

The association of robotic surgical technology and hospital prostatectomy volumes: increasing market share through the adoption of technology.

Despite limited and conflicting evidence for the efficacy of newly developed robotic technology for laparoscopic prostatectomy, this technology is spreading rapidly. Because the newer technology is more costly, reasons for this rapid adoption are unclear. The authors of this report sought to determine whether hospital acquisition of robotic technology was associated with volume of prostate cancer surgery.

Risk reduction and survival benefit of prophylactic surgery in BRCA mutation carriers, a systematic review.

BACKGROUND Mutations in BRCA1 or BRCA2 genes results in an elevated risk for developing both breast and ovarian cancers over the lifetime of affected carriers. General surgeons may be faced with questions about surgical risk reduction and survival benefit of prophylactic surgery. METHODS A systematic literature review was performed using the electronic databases PubMed, OVID MEDLINE, and Scopus comparing prophylactic surgery vs observation with respect to breast and ovarian cancer risk reduction and mortality in BRCA mutation carriers. RESULTS Bilateral risk-reducing mastectomy provides a 90% to 95% risk reduction in BRCA mutation carriers, although the data do not demonstrate improved mortality. The reduction in ovarian and breast cancer risks using risk-reducing bilateral salpingo-oophorectomy has translated to improvement in survival. CONCLUSIONS Clinical management of patients at increased risk for breast cancer requires consideration of risk, patient preference, and quality of life.

Heightened Attention to Medical Privacy: Challenges for Unbiased Sample Recruitment and a Possible Solution

Subject recruitment for epidemiologic studies is associated with major challenges due to privacy laws now common in many countries. Privacy policies regarding recruitment methods vary tremendously across institutions, partly because of a paucity of information about what methods are acceptable to potential subjects. The authors report the utility of an opt-out method without prior physician notification for recruiting community-dwelling US women aged 65 years or older with incident breast cancer in 2003. Participants (n = 3,083) and possibly eligible nonparticipants (n = 2,664) were compared using characteristics derived from billing claims. Participation for persons with traceable contact information was 70% initially (2005-2006) and remained over 90% for 3 follow-up surveys (2006-2008). Older subjects and those living in New York State were less likely to participate, but participation did not differ on the basis of socioeconomic status, race/ethnicity, underlying health, or type of cancer treatment. Few privacy concerns were raised by potential subjects, and no complaints were lodged. Using opt-out methods without prior physician notification, a population-based cohort of older breast cancer subjects was successfully recruited. This strategy may be applicable to population-based studies of other diseases and is relevant to privacy boards making decisions about recruitment strategies acceptable to the public.

Bone Density Testing in Older Women and Its Association with Patient Age

OBJECTIVES: To measure the early adoption of bone density testing and examine the association between older age and such testing.

Meaningful Use and the Patient Portal Patient Enrollment, Use, and Satisfaction With Patient Portals at a Later-Adopting Center

Many physicians are adopting patient portals in response to governmental incentives for meaningful use (MU), but the stage 2 requirements for portal use may be particularly challenging for newer electronic health record (EHR) users. This study examined enrollment, use based on MU requirements, and satisfaction in a recently adopting fee-for-service multispecialty system. Between 2010 and 2012, overall portal enrollment increased from 13.2% to 23.1% but varied substantially by physician specialty. In 2013, more than 97% of physicians would have met requirements for a stage 2 MU utilization measure requiring that patients download personal health information, but only 38% of all physicians (87% of primary care physicians [PCPs] and 37% of other specialists) would have met e-mail requirements. Satisfaction with the portal overall and with portal-based e-mails was high. These results suggest that later-adopting PCPs can succeed in providing satisfactory record and e-mail access but specialists may find reaching e-mail thresholds more difficult.

Determining the Clinical Significance of Monoclonal Gammopathy of Undetermined Significance: A SEER–Medicare Population Analysis

BACKGROUND Clinical guidelines have recommended annual follow-up examinations of most patients with monoclonal gammopathy of undetermined significance (MGUS); however, evidence supporting this practice is lacking. We performed a population-based study to examine the patterns of disease presentation and outcomes of patients with multiple myeloma, Waldenström macroglobulinemia, and lymphoplasmacytic lymphoma (monoclonal gammopathy-associated malignancies) comparing those with or without a previous MGUS follow-up examination. MATERIALS AND METHODS Patients with monoclonal gammopathy-associated malignancy from 1994 through 2007 were identified using the Surveillance, Epidemiology, and End Results-Medicare linked database and divided into 2 cohorts: those with follow-up (MGUS follow-up examination preceding the diagnosis) and those with no follow-up (no such follow-up examination). We compared the outcomes, including the rates of major complications at cancer diagnosis (acute kidney injury, cord compression, dialysis use, fracture, and hypercalcemia) and survival using propensity score adjustment and Cox proportional hazard models. All statistical tests were 2-sided. RESULTS Of the 17,457 study patients, 6% had undergone MGUS follow-up. After multivariable modeling, the follow-up group had significantly fewer major complications at diagnosis (odds ratio 0.68; 95% confidence interval [CI], 0.57-0.80) and better disease-specific (median, 38 vs. 29 months, P < .001; hazard ratio [HR] 0.85; 95% CI, 0.76-0.94) and overall (median, 23 vs. 19 months, P < .001; HR 0.87; 95% CI, 0.80-0.95) survival. CONCLUSION Patients with MGUS follow-up preceding the diagnosis of a monoclonal gammopathy-associated malignancy can experience fewer major complications and have longer survival than those without such follow-up examinations. Future studies replicating our findings in the non-Medicare population and determining the optimal schedule and cost-effectiveness of MGUS follow-up are warranted.