Comorbid status in patients with osteomyelitis is associated with long-term incidence of extremity amputation.

INTRODUCTION: Osteomyelitis is associated with significant morbidity, including amputation. There are limited data on long-term amputation rates following an osteomyelitis diagnosis. We sought to determine the incidence of amputation in patients with osteomyelitis over 2 years. RESEARCH DESIGN AND METHODS: Observational cohort study of 1186 inpatients with osteomyelitis between 2004 and 2015 and stratified by osteomyelitis location status to evaluate the impact on amputation, mortality rates, readmission data, and inpatient days. RESULTS: Persons with diabetes had 3.65 times greater probability of lower extremity amputation (p<0.001), readmission (p<0.001), and longer inpatient stay (p<0.001) and had higher 2-year mortality (relative risk (RR) 1.23, p=0.0027), adjusting for risk factors. Male gender (RR 1.57, p<0.001), black race (RR 1.41, p<0.05), former smoking status (RR 1.38, p<0.01), myocardial infarction (RR 1.72, p<0.001), congestive heart failure (RR 1.56, p<0.001), peripheral vascular disease (RR 2.25, p<0.001) and renal disease (RR 1.756, p<0.001) were independently associated with amputation. Male gender (RR 1.39, p<0.01), black race (RR 1.27, p<0.05), diabetes (RR 2.77, p<0.001) and peripheral vascular disease (RR 1.59, p<0.001) had increased risk of lower, not upper, extremity amputation. CONCLUSIONS: Patients with osteomyelitis have higher rates of amputation and hospitalization. Clinicians must incorporate demographic and comorbid risk factors to protect against amputation.

Utility of a Telephone Triage Hotline in Response to the COVID-19 Pandemic: Longitudinal Observational Study.

BACKGROUND: During the initial months of the COVID-19 pandemic, rapidly rising disease prevalence in the United States created a demand for patient-facing information exchanges that addressed questions and concerns about the disease. One approach to managing increased patient volumes during a pandemic involves the implementation of telephone-based triage systems. During a pandemic, telephone triage hotlines can be employed in innovative ways to conserve medical resources and offer useful population-level data about disease symptomatology and risk factor profiles. OBJECTIVE: The aim of this study is to describe and evaluate the COVID-19 telephone triage hotline used by a large academic medical center in the midwestern United States. METHODS: Michigan Medicine established a telephone hotline to triage inbound patient calls related to COVID-19. For calls received between March 24, 2020, and May 5, 2020, we described total call volume, data reported by callers including COVID-19 risk factors and symptomatology, and distribution of callers to triage algorithm endpoints. We also described symptomatology reported by callers who were directed to the institutional patient portal (online medical visit questionnaire). RESULTS: A total of 3929 calls (average 91 calls per day) were received by the call center during the study period. The maximum total number of daily calls peaked at 211 on March 24, 2020. Call volumes were the highest from 6 AM to 11 AM and during evening hours. Callers were most often directed to the online patient portal (1654/3929, 42%), nursing hotlines (1338/3929, 34%), or employee health services (709/3929, 18%). Cough (126/370 of callers, 34%), shortness of breath (101/370, 27%), upper respiratory infection (28/111, 25%), and fever (89/370, 24%) were the most commonly reported symptoms. Immunocompromised state (23/370, 6%) and age >65 years (18/370, 5%) were the most commonly reported risk factors. CONCLUSIONS: The triage algorithm successfully diverted low-risk patients to suitable algorithm endpoints, while directing high-risk patients onward for immediate assessment. Data collected from hotline calls also enhanced knowledge of symptoms and risk factors that typified community members, demonstrating that pandemic hotlines can aid in the clinical characterization of novel diseases.

Culture-Negative and Culture-Positive Sepsis: A Comparison of Characteristics and Outcomes.

BACKGROUND: The primary objective of this study was to compare the characteristics of culture-positive and culture-negative status in septic patients. We also determined whether culture status is associated with mortality and whether unique variables are associated with mortality in culture-positive and culture-negative patients separately. METHODS: Utilizing patient records from intensive care units, emergency department, and general care wards in a large academic medical center, we identified adult patients with suspected infection and ≥2 systemic inflammatory response syndrome criteria between January 1, 2007, and May 31, 2014. We compared the characteristics between culture-positive and culture-negative patients and used binary logistic regression to identify variables independently associated with culture status and mortality. We also did sensitivity analyses using patients with Sequential Organ Failure Assessment and quick Sequential Organ Failure Assessment criteria for sepsis. RESULTS: The study population included 9288 culture-negative patients (89%) and 1105 culture-positive patients (11%). Culture-negative patients received more antibiotics during the 48 hours preceding diagnosis but otherwise demonstrated similar characteristics as culture-positive patients. After adjusting for illness severity, a positive culture was not independently associated with mortality (odds ratio = 1.01 [95% CI, 0.81-1.26]; P = .945). The models predicting mortality separately in culture-negative and culture-positive patients demonstrated very good and excellent discrimination (C-statistic ± SD, 0.87 ± 0.01 and 0.92 ± 0.01), respectively. In the sensitivity analyses using patients with sepsis by Sequential Organ Failure Assessment and quick Sequential Organ Failure Assessment criteria, after adjustments for illness severity, positive cultures were still not associated with mortality (odds ratio = 1.13 [95% CI, 0.86-1.43]; P = .303; and odds ratio = 1.05 [95% CI, 0.83-1.33]; P = .665), respectively. In all models, physiological derangements were associated with mortality. CONCLUSIONS: While culture status is important for tailoring antibiotics, culture-negative and culture-positive patients with sepsis demonstrate similar characteristics and, after adjusting for severity of illness, similar mortality. The most important factor associated with negative cultures is receipt of antibiotics during the preceding 48 hours. The risk of death in patients suspected of having an infection is most associated with severity of illness. This is aligned with the Sepsis-3 definition using Sequential Organ Failure Assessment score to better identify those suspected of infection at highest risk of a poor outcome.

Ordering Stains That Aren't Indicated.

The pathologist rarely interacts with patients face-to-face, but he or she nonetheless maintains a crucial relationship with the patient (i.e., the patient-pathologist relationship). A more tangible relationship, the pathologist-clinician relationship, is typically augmented by the patient-pathologist relationship, but at times the two distinct relationships are at odds, creating ethical dilemmas for the pathologist. This case study and discussion highlight some of these potential ethical questions and underscore the need for pathologists and clinicians to have cooperative, collaborative, and professional relationships. Pathologists should feel empowered to guide the clinician's use of appropriate clinical testing to ensure proper management of the patient and responsible use of health care resources.

Implementation and Operational Research: A Cost-Effective, Clinically Actionable Strategy for Targeting HIV Preexposure Prophylaxis to High-Risk Men Who Have Sex With Men.

BACKGROUND: Preexposure prophylaxis (PrEP) is effective at preventing HIV infection among men who have sex with men (MSM), but there is uncertainty about how to identify high-risk MSM who should receive PrEP. METHODS: We used a mathematical model to assess the cost-effectiveness of using the HIV Incidence Risk Index for MSM (HIRI-MSM) questionnaire to target PrEP to high-risk MSM. We simulated strategies of no PrEP, PrEP available to all MSM, and eligibility thresholds set to HIRI-MSM scores between 5 and 45, in increments of 5 (where a higher score predicts greater HIV risk). Based on the iPrEx, IPERGAY, and PROUD trials, we evaluated PrEP efficacies from 44% to 86% and annual costs from $5900 to 8700. We designate strategies with incremental cost-effectiveness ratio (ICER) ≤$100,000/quality-adjusted life-year (QALY) as "cost-effective." RESULTS: Over 20 years, making PrEP available to all MSM is projected to prevent 33.5% of new HIV infections, with an ICER of $1,474,000/QALY. Increasing the HIRI-MSM score threshold reduces the prevented infections, but improves cost-effectiveness. A threshold score of 25 is projected to be optimal (most QALYs gained while still being cost-effective) over a wide range of realistic PrEP efficacies and costs. At low cost and high efficacy (IPERGAY), thresholds of 15 or 20 are optimal across a range of other input assumptions; at high cost and low efficacy (iPrEx), 25 or 30 are generally optimal. CONCLUSIONS: The HIRI-MSM provides a clinically actionable means of guiding PrEP use. Using a score of 25 to determine PrEP eligibility could facilitate cost-effective use of PrEP among high-risk MSM who will benefit from it most.

Bartonella henselae infections in solid organ transplant recipients: report of 5 cases and review of the literature.

Bartonella henselae is the causative agent of cat scratch disease and bacillary angiomatosis-peliosis. The spectrum of disease, diagnosis, and management of B. henselae infection in solid organ transplant recipients has not been well characterized. We identified 29 cases of solid organ transplant recipients who had Bartonella infection, 24 by a review of the English-language literature and 5 from our institution. Localized cat scratch disease was found in 8 patients (28%), and disseminated infection was found in 21 patients (72%). The mean time after transplantation to development of Bartonella infection among those with cat scratch disease was 5.6 ± 5.3 years, and among those with disseminated infection was 2.7 ± 2.4 years. Prominent clinical features included cat exposure in 26 patients (90%), fever in 27 patients (93%), lymphadenopathy in 12 patients (41%), and skin lesions in 7 patients (24%). Methods used in establishing the diagnosis of Bartonella infection included culture, polymerase chain reaction (PCR) assay, serologic assays, and histopathologic examination. Culture was positive in 2 of only 4 patients in whom this was performed, and PCR was positive in 12 of 14 patients (86%) in whom this test was performed. Serologic assays were positive in all 23 patients who were tested. Histopathologic examination of tissues in all 8 patients who had cat scratch disease revealed granulomatous inflammation in 4 (50%) and bacillary angiomatosis-peliosis in 2 (25%). Among the 15 patients who had disseminated infection and who had tissue examined, 8 (53%) had only granulomatous inflammation, 4 had only bacillary angiomatosis-peliosis (27%), and 2 had both granulomas and bacillary angiomatosis-peliosis (13%). A positive Warthin-Starry or Steiner stain was noted in 12 of 19 patients (63%) who had 1 of these stains performed. All 8 patients with cat scratch disease and 19 of 21 patients with disseminated bartonellosis were cured with antimicrobial therapy. Two patients, both of whom had endocarditis, died. Among solid organ transplant recipients, infection with B. henselae is uncommon and has diverse disease manifestations including disseminated disease. Persistent fevers or lymphadenopathy in a transplant recipient who has been exposed to cats should prompt clinicians to maintain a high index of suspicion for B. henselae infection. Identifying B. henselae as the causative organism often requires multiple diagnostic studies. Once the diagnosis is established, most solid organ transplant recipients respond appropriately to antimicrobial treatment.

Association Between Follow-Up Magnetic Resonance Imaging and Clinical Status Among Patients With Spinal Infections.

BACKGROUND: Spinal infections, including paraspinal and/or epidural abscesses and vertebral discitis and osteomyelitis, can have devastating consequences. The diagnostic imaging modality of choice has traditionally been magnetic resonance imaging (MRI) given the very high sensitivity and specificity, although the role of MRI in follow-up of spinal infections and how this relates to follow-up clinical status is poorly understood. We sought to understand the relationship between follow-up MRI and clinical status. METHODS: We conducted a retrospective review of adults with spinal infection to assess the relationship between follow-up MRI and clinical course. The degree of agreement between MRI and clinical follow-up was assessed using the Cohen kappa coefficient. A multinomial logistic regression model was applied to assess the impact of covariates in affecting the clinical outcome and MRI at follow-up independently. RESULTS: Ninety-eight patients met inclusion criteria during a 13-year period. We observed a lack of correlation between clinical follow-up status and MRI (κ = 0.065, P = 0.322). The McNemar-Bowker test for symmetry revealed that this disagreement was asymmetric (P < 0.001). Notably, clinical worsening was never associated with an improved MRI, and clinical improvement was overall not predictive of MRI result and vice versa. CONCLUSIONS: Routine follow-up MRI does not seem to correlate with clinical follow-up among patients with spinal infections. The use of MRI without new clinical indications in routine follow-up testing should be interpreted with caution.

Developing a fully online course for senior medical students.

In 2002 the University of Michigan Medical School created a one-month course in advanced medical therapeutics (AMT). All senior medical students were required to complete the course. To provide some flexibility for students who were interviewing for residency positions the AMT course was created using a distance-learning model, and in the 2008-2009 academic year it was offered in a fully online format. The components of the course are weekly case-based modules, a weekly online seminar, quizzes based on modules and seminars, and a research project based on a therapeutic question. The paper discusses the development and components of the AMT course, a survey of fourth-year medical students who participated in the course between 2007 and 2010, and how the course evolved over three years.

Bacterial pneumonias during an influenza pandemic: how will we allocate antibiotics?

We are currently in the midst of the 2009 H1N1 pandemic, and a second wave of flu in the fall and winter could lead to more hospitalizations for pneumonia. Recent pathologic and historic data from the 1918 influenza pandemic confirms that many, if not most, of the deaths in that pandemic were a result of secondary bacterial pneumonias. This means that a second wave of 2009 H1N1 pandemic influenza could result in a widespread shortage of antibiotics, making these medications a scarce resource. Recently, our University of Michigan Health System (UMHS) Scarce Resource Allocation Committee (SRAC) added antibiotics to a list of resources (including ventilators, antivirals, vaccines) that might become scarce during an influenza pandemic. In this article, we summarize the data on bacterial pneumonias during the 1918 influenza pandemic, discuss the possible impact of a pandemic on the University of Michigan Health System, and summarize our committee's guiding principles for allocating antibiotics during a pandemic.

HIV-infected patients with anal carcinoma who subsequently developed oral squamous cell carcinoma: report of 2 cases.

We describe 2 patients who had human immunodeficiency virus (HIV) infection and who first developed human papillomavirus (HPV)-related anal squamous cell carcinoma and later, oral squamous cell carcinoma. At the time each patient developed oral cancer, they were responding well to antiretroviral therapy with undetectable viral loads. Careful screening for oral cancers may be indicated in HIV-infected patients with HPV-associated anal cancer.

Non-AIDS-defining cancers: should antiretroviral therapy be initiated earlier?

Non-AIDS-defining cancers have recently gained more attention, and it appears that several of these cancers may be more common the the HAART era. By most accounts in the literature, the overall risk of non-AIDS-defining cancer in HIV-infected persons is 2 to 3 times that in the general population. In this article, we review the literature on 5 of the most common non-AIDS-defining cancers (Hodgkin disease, anal cancer, hepatocellular carcinoma, oral cancer, and lung cancer) in the pre- and post-HAART periods. It remains unclear whether earlier initiation (CD4+ cell count above 350/microL) of antiretroviral therapy may be beneficial in preventing non-AIDS-defining cancer. Further large-scale, randomized, prospective studies on this question are warranted.

Pandemic influenza and acute care centers: taking care of sick patients in a nonhospital setting.

The ongoing spread of H5N1 avian influenza in Southeast Asia has raised concern about a worldwide influenza pandemic and has made clear the need to plan in advance for such an event. The federal government has stressed the importance of planning and, in particular, has asked hospitals and public health agencies to develop plans to care for patients outside of traditional healthcare settings. These alternative or acute care centers (ACCs) would be opened when hospitals, emergency departments (EDs), and clinics are overwhelmed by an influenza pandemic. The University of Michigan Hospital System (UMHS), a large tertiary care center in southeast Michigan, has been developing a model for offsite care of patients during an influenza pandemic. This article summarizes our planning efforts and the lessons learned from 2 functional exercises over the past 3 years.

An elderly patient with fluoroquinolone-associated achilles tendinitis.

BACKGROUND: Due to their broad-spectrum activity and oral bioavailability, fluoroquinolone antibiotics are commonly prescribed to adults aged >60 years for many common community-acquired infections. The association between fluoroquinolone use and Achilles tendinitis is well established but sometimes missed in clinical practice. Older patients and patients with renal dysfunction are at particularly increased risk for this complication. CASE SUMMARY: We present a case of Achilles tendinitis in a 77-year-old patient with renal dysfunction and a urinary tract infection (UTI) treated with ciprofloxacin 250 mg PO QD. Tendinitis developed within several days of the start of treatment and improved within 2 days of treatment cessation, without the need for intervention. The likelihood of ciprofloxacin having caused this reaction was probable (Naranjo score, 7). Early diagnosis and treatment cessation might have prevented tendon rupture, and the tendinitis resolved completely with subsequent physical therapy. CONCLUSION: Based on this outcome in this patient with UTI, fluoroquinolones should be used with caution, particularly in patients with risk factors predisposing to tendinitis, including advanced age and renal dysfunction.

Magnitude and duration of elevated gastric pH in patients infected with human immunodeficiency virus after administration of chewable, dispersible, buffered didanosine tablets.

STUDY OBJECTIVES: To test the hypothesis that gastric pH would be elevated above pH 3.0 for at least 2 hours after administration of chewable, dispersible, buffered didanosine tablets. Doses tested were 200 mg (two 100-mg tablets) and 400 mg (two 200-mg tablets). We also sought to compare these doses with regard to maximum gastric pH (pHmax), time to pHmax (TpH-max), time that gastric pH exceeds 3.0 (TpH>3), and area under the gastric pH versus time curve for pH greater than 3.0 (AUCT>pH 3). DESIGN: Prospective, parallel-group, dose-comparison, gastric pH study. SETTING: General Clinical Research Center, University of Michigan Hospitals, Ann Arbor, Michigan. PATIENTS: Nineteen patients infected with human immunodeficiency virus, aged 30-62 years, and receiving long-term didanosine therapy. INTERVENTION: Patients underwent continuous gastric pH monitoring, using the Heidelberg capsule radiotelemetric pH monitoring device. After documentation of a fasting baseline gastric pH below 3.0, patients were given 180 ml of water (control phase), and gastric pH was allowed to return to baseline. After administration of a single, oral dose of didanosine 200 mg or 400 mg with 180 ml of water, gastric pH was recorded until pH remained below 3.0 for 10 minutes. MEASUREMENTS AND MAIN RESULTS: A mean pHmax of 8.6 (range 6.3-9.5) was achieved with a TpH-max of 4.1 minutes (range 1-12.0 min). Mean TpH>3 was 24.9 minutes (range 15-55 min), with an AUCT>pH 3 of 2.6 pH x min(-1) (range 1.2-6.9 pH x min(-1)). The two doses of didanosine tested did not differ significantly in mean gastric pH parameters. CONCLUSIONS: After administration of chewable, dispersible, buffered didanosine tablets, 200 or 400 mg, the mean duration of elevated gastric pH (TpH>3) was less than 30 minutes, with a range of 15-55 minutes. Characterization of the magnitude and duration of elevated gastric pH may allow for earlier administration of other pH-sensitive drugs. The short duration of elevated gastric pH may help explain the wide variability in didanosine bioavailability observed clinically.

Differentiating inhalational anthrax from other influenza-like illnesses in the setting of a national or regional anthrax outbreak.

The workup of a febrile patient who presents with an influenza-like illness in the setting of a national or regional anthrax outbreak presents a unique challenge to the physicians who initially evaluate this patient, and the diagnostic challenge can be even more profound during the influenza season. Based on information gathered from the recent inhalational anthrax cases, we have developed an algorithm to be used by physicians in the emergency department to evaluate patients with influenza-like illnesses during a national or regional anthrax outbreak. The algorithm necessitates stays no longer than 24 hours in the emergency department or hospital.