Infectious Complications After Deployment Trauma: Following Wounded US Military Personnel Into Veterans Affairs Care.

Background: Infectious complications related to deployment trauma significantly contribute to the morbidity and mortality of wounded service members. The Trauma Infectious Disease Outcomes Study (TIDOS) collects data on US military personnel injured in Iraq and Afghanistan in an observational cohort study of infectious complications. Patients enrolled in TIDOS may also consent to follow-up through the Department of Veterans Affairs (VA). We present data from the first 337 TIDOS enrollees to receive VA healthcare. Methods: Data were collected from the Department of Defense (DoD) Trauma Registry, TIDOS infectious disease module, DoD and VA electronic medical records, and telephone interview. Cox proportional hazard analysis was performed to identify predictors of post-discharge infections related to deployment trauma. Results: Among the first 337 TIDOS enrollees who entered VA healthcare, 111 (33%) had 244 trauma-related infections during their initial trauma hospitalization (2.1 infections per 100 person-days). Following initial discharge, 127 (38%) enrollees had 239 trauma-related infections (170 during DoD follow-up and 69 during VA time). Skin and soft-tissue infections and osteomyelitis were predominant during and after the initial trauma hospitalization. In a multivariate model, a shorter time to development of a new infection following discharge was independently associated with injury severity score ≥10 and occurrence of ≥1 inpatient infection during initial trauma hospitalization. Conclusions: Incident infections related to deployment trauma continue well after initial hospital discharge and into VA healthcare. Overall, 38% of enrolled patients developed a new trauma-related infection after their initial hospital discharge, with 29% occurring after the patient left military service.

Mental and Physical Health-Related Quality of Life Following Military Polytrauma.

INTRODUCTION: The long-term impact of deployment-related trauma on mental and physical health-related quality of life (HRQoL) among military personnel is not well understood. We describe the mental and physical HRQoL among military personnel following deployment-related polytrauma after their discharge from the hospital and examine factors associated with HRQoL and longitudinal trends. MATERIALS AND METHODS: The U.S. military personnel with battlefield-related trauma enrolled in the Trauma Infectious Diseases Outcomes Study were surveyed using SF-8 Health Surveys at 1 month post-discharge (baseline) and at follow-up intervals over 2 years. Inclusion in the longitudinal analysis required baseline SF-8 plus responses during early (3 and/or 6 months) and later follow-up periods (12, 18, and/or 24 months). Associations of demographics, injury characteristics, and hospitalization with baseline SF-8 scores and longitudinal changes in SF-8 scores during follow-up were examined. Survey responses were used to calculate the Mental Component Summary score (MCS) and the Physical Component Summary score (PCS). The MCS focuses on vitality, mental health, social functioning, and daily activity limitations, whereas PCS is related to general health, bodily pain, physical functioning, and physical activity limitations. Longitudinal trends in SF-8 scores were assessed using chi-square tests by comparing the median score at each timepoint to the median 1-month (baseline) score, as well as comparing follow-up scores to the immediately prior timepoint (e.g., 6 months vs. 3 months). Associations with the 1-month baseline SF-8 scores were assessed using generalized linear regression modeling and associations with longitudinal changes in SF-8 were examined using generalized linear regression modeling with repeated measures. RESULTS: Among 781 enrollees, lower baseline SF-8 total scores and PCS were associated with spinal and lower extremity injuries (P < .001) in the multivariate analyses, whereas lower baseline MCS was associated with head/face/neck injuries (P < .001). Higher baseline SF-8 total was associated with having an amputation (P = .009), and lower baseline SF-8 total was also associated with sustaining a traumatic brain injury (TBI; P = .042). Among 524 enrollees with longitudinal follow-up, SF-8 scores increased, driven by increased PCS and offset by small MCS decreases. Upward SF-8 total score and PCS trends were associated with time post-hospital discharge and limb amputation (any) in the multivariate analyses (P < .05), whereas downward trends were independently associated with spinal injury and developing any post-discharge infection (P ≤ .001). Patients with lower extremity injuries had lower-magnitude improvements in PCS over time compared to those without lower extremity injuries (P < .001). Upward MCS trend was associated with higher injury severity (P = .003) in the multivariate analyses, whereas downward trends were independently associated with having a TBI (P < .001), time post-hospital discharge (P < .001), and occurrence of post-discharge infections (P = .002). CONCLUSIONS: Overall, HRQoL increased during the 2-year follow-up period, driven by PCS improvement. Increasing HRQoL was associated with time since hospital discharge and limb amputation, whereas a downward trend in HRQoL was associated with spinal injury and post-discharge infection. The longitudinal decline in MCS, driven by TBI occurrence, time since hospital discharge, and developing post-discharge infections, emphasizes the importance of longitudinal mental health care in this population.

Greater variability in kidney function is associated with an increased risk of death.

Intra-individual variability in kidney function is a common phenomenon; however, predictors of kidney function variability and its prognostic significance are not known. To examine this question, we assembled a cohort of 51,304 US veterans with an estimated glomerular filtration rate (eGFR) <60 ml/min at the end of the study period and who had at least two eGFR measurements during the previous 3 years. Variability in kidney function was defined for each patient as the coefficient of variation of the regression line fitted to all outpatient measures of eGFR during this time frame. In adjusted analyses, blacks, women, and those with Current Procedural Terminology and ICD-9-CM diagnostic codes for hypertension, diabetes, cardiovascular disease, peripheral artery disease, chronic lung disease, hepatitis C, dementia, acute kidney injury, and those with a greater number of hospitalizations had greater variability in eGFR. After a median follow-up of 4.9 years, there were 23.66%, 25.68%, and 31.23% deaths among patients in the lowest, intermediate, and highest tertiles of eGFR variability, respectively. Compared with the referent (those in the lowest tertile), patients in the highest tertile had a significantly increased risk of death with a hazard ratio of 1.34 (1.28-1.40), an association consistently present in all sensitivity analyses. Thus, our results demonstrate that greater variability in kidney function is independently associated with increased risk of death.

Mitigating COVID-19 Vaccine Waste Through a Multidisciplinary Inpatient Vaccination Initiative.

ABSTRACT: A multidisciplinary team at a tertiary care Veterans Health Administration medical center created a standardized process to identify medically stable inpatients, to notify inpatient staff of available COVID-19 vaccine doses, and to coordinate inpatient vaccine administration. The team's goals were to mitigate vaccine waste while safely vaccinating as many patients as possible. Using a unique set of exclusion criteria and clinical judgment, a quality improvement team reviewed patients admitted to medicine teams to determine medical stability. Eligible, interested patients were listed in a secure shared file, and outpatient vaccine clinic staff communicated with inpatient nurse leaders regarding the availability of unadministered doses. Doses were transported to the hospital from the clinic and administered by inpatient nurses. Between January 8 and April 26, 2021, 105 patients were vaccinated with either the Moderna or the Pfizer-BioNTech COVID-19 vaccine during admission. Sixty-nine percent of the patients received a first dose, 27% received a second dose, and 4% received both doses. Forty-two percent of the patients vaccinated while inpatient identified as Black or African American compared with 28% of the vaccinated outpatients. No vaccine-related safety events were reported. This process demonstrates a viable approach to mitigating waste of COVID-19 vaccines and safely, efficiently, and equitably vaccinating an inpatient population.

Universal masking to control healthcare-associated transmission of severe acute respiratory coronavirus virus 2 (SARS-CoV-2).

OBJECTIVES: To assess extent of a healthcare-associated outbreak of severe acute respiratory coronavirus virus 2 (SARS-CoV-2) and to evaluate the effectiveness of infection control measures, including universal masking. DESIGN: Outbreak investigation including 4 large-scale point-prevalence surveys. SETTING: Integrated VA healthcare system with 2 facilities and 330 beds. PARTICIPANTS: Index patient and 250 exposed patients and staff. METHODS: We identified exposed patients and staff and classified them as probable and confirmed cases based on symptoms and testing. We performed a field investigation and an assessment of patient and staff interactions to develop probable transmission routes. Infection prevention interventions included droplet and contact precautions, employee quarantine, and universal masking with medical and cloth face masks. We conducted 4 point-prevalence surveys of patient and staff subsets using real-time reverse-transcriptase polymerase chain reaction for SARS-CoV-2. RESULTS: Among 250 potentially exposed patients and staff, 14 confirmed cases of coronavirus disease 2019 (COVID-19) were identified. Patient roommates and staff with prolonged patient contact were most likely to be infected. The last potential date of transmission from staff to patient was day 22, the day universal masking was implemented. Subsequent point-prevalence surveys in 126 patients and 234 staff identified 0 patient cases and 5 staff cases of COVID-19, without evidence of healthcare-associated transmission. CONCLUSIONS: Universal masking with medical face masks was effective in preventing further spread of SARS-CoV-2 in our facility in conjunction with other traditional infection prevention measures.

Risk of non-melanoma skin cancer in a national cohort of veterans with rheumatoid arthritis.

OBJECTIVE: To determine the incidence of and risk factors for non-melanoma skin cancer (NMSC) in a national cohort of veterans with RA. METHODS: We examined skin cancer risk in a cohort of 20 648 patients with RA derived from the Department of Veterans' Affairs (VA) national administrative databases. The cohort was divided into two medication groups: patients treated with non-biologic and TNF-α antagonist DMARDs. We defined skin cancer as the first occurrence of an International Classification of Disease, Version 9, Clinical Modification (ICD-9-CM) code for NMSC after initiation of a DMARD. Outcome risk was described using hazard ratios (HRs) with Cox proportional hazards regression for time-to-event analysis and logistic regression. We performed medical record review to validate the diagnosis of NMSC. RESULTS: Incidence of NMSC was 18.9 and 12.7 per 1000 patient-years in patients on TNF-α antagonists and non-biologic DMARDs, respectively. Patients on TNF-α antagonists had a higher risk of developing NMSC (HR 1.42; 95% CI 1.24, 1.63). Risk factors for NMSC included older age, male gender, NSAID and glucocorticoid use and a history of prior malignancies. There was substantial agreement between ICD-9-CM diagnosis of NMSC and medical record validation (κ = 0.61). CONCLUSION: TNF-α antagonist therapy in veterans with RA may be associated with an increased risk of NMSC, compared with therapy with non-biologic DMARDs. Rheumatologists should carefully screen patients receiving TNF-α antagonists for pre-cancerous skin lesions and skin cancer.

Rate of kidney function decline associates with mortality.

The effect of rate of decline of kidney function on risk for death is not well understood. Using the Department of Veterans Affairs national databases, we retrospectively studied a cohort of 4171 patients who had rheumatoid arthritis and early stage 3 chronic kidney disease (CKD; estimated GFR 45 to 60 ml/min) and followed them longitudinally to characterize predictors of disease progression and the effect of rate of kidney function decline on mortality. After a median of 2.6 years, 1604 (38%) maintained stable kidney function; 426 (10%), 1147 (28%), and 994 (24%) experienced mild, moderate, and severe progression of CKD, respectively (defined as estimated GFR decline of 0 to 1, 1 to 4, and >4 ml/min per yr). Peripheral artery disease predicted moderate progression of CKD progression. Black race, hypertension, diabetes, cardiovascular disease, and peripheral artery disease predicted severe progression of CKD. After a median of 5.7 years, patients with severe progression had a significantly increased risk for mortality (hazard ratio 1.54; 95% confidence interval 1.30 to 1.82) compared with those with mild progression; patients with moderate progression exhibited a similar trend (hazard ratio 1.10; 95% confidence interval 0.98 to 1.30). Our results demonstrate an independent and graded association between the rate of kidney function decline and mortality. Incorporating the rate of decline into the definition of CKD may transform a static definition into a dynamic one that more accurately describes the potential consequences of the disease for an individual.

Inpatient versus outpatient intravenous diuresis for the acute exacerbation of chronic heart failure.

BACKGROUND: We established an IV outpatient diuresis (IVOiD) clinic and conducted a quality improvement project to evaluate safety, effectiveness and costs associated with outpatient versus inpatient diuresis for patients presenting with acute decompensated heart failure (ADHF) to the emergency department (ED). METHODS: Patients who were clinically diagnosed with ADHF in the ED, but did not have high-risk features, were either diuresed in the hospital or in the outpatient IVOiD clinic. The dose of IV diuretic was based on their home maintenance diuretic dose. The outcomes measured were the effects of diuresis (urine output, weight, hemodynamic and laboratory abnormalities), 30-90 day readmissions, 30-90 day death and costs. RESULTS: In total, 36 patients (22 inpatients and 14 outpatients) were studied. There were no significant differences in the baseline demographics between groups. The average inpatient stay was six days and the average IVOiD clinic days were 1.2. There was no significant difference in diuresis per day of treatment (1159 vs. 944 ml, p = 0.46). There was no significant difference in adverse outcomes, 30-90 day readmissions or 30-90 day deaths. There was a significantly lower cost in the IVOiD group compared to the inpatient group ($839.4 vs. $9895.7, p=<0.001). CONCLUSIONS: Outpatient IVOiD clinic diuresis may be a viable alternative to accepted clinical practice of inpatient diuresis for ADHF. Further studies are needed to validate this in a larger cohort and in different sites.

Herpes zoster risk factors in a national cohort of veterans with rheumatoid arthritis.

BACKGROUND: Herpes zoster occurs more commonly in patients taking immunosuppressive medications, although the risk associated with different medications is poorly understood. METHODS: We conducted a retrospective cohort study involving 20,357 patients who were followed in the Veterans Affairs healthcare system and treated for rheumatoid arthritis from October 1998 through June 2005. Cox proportional hazards regression was used to determine risk factors for herpes zoster and herpes zoster-free survival. Chart review was performed to validate the diagnosis of herpes zoster. RESULTS: The incidence of herpes zoster was 9.96 episodes per 1000 patient-years. In time-to-event analysis, patients receiving medications used to treat mild rheumatoid arthritis were less likely to have an episode of herpes zoster than patients receiving medications used to treat moderate and severe rheumatoid arthritis (P < .001). Independent risk factors for herpes zoster included older age, prednisone use, medications used to treat moderate and severe rheumatoid arthritis, malignancy, chronic lung disease, renal failure, and liver disease. Among patients receiving tumor necrosis factor-alpha antagonists, etanercept (hazard ratio, 0.62) and adalimumab (hazard ratio, 0.53) were associated with a lower risk of herpes zoster. There was excellent agreement between the International Classification of Diseases, Version 9, Clinical Modification diagnosis of herpes zoster and diagnosis by chart review (kappa = 0.92). CONCLUSIONS: Risk factors for herpes zoster included older age, prednisone use, medications used to treat moderate and severe rheumatoid arthritis, and several comorbid medical conditions. These results demonstrate that the Department of Veterans Affairs' national administrative databases can be used to study rare adverse drug events.

Current recommendations in the management of osteomyelitis of the hand and wrist.

Management of osteomyelitis of the hand and wrist is a multidisciplinary and individualized process. A rational approach to management includes careful consideration of the pathogenesis, microbiology, diagnostic options, and surgical and medical treatment of this disease.

Urinary Tract Infections after Combat-Related Genitourinary Trauma.

Background: We examined clinical outcomes among combat casualties with genitourinary injuries after blast trauma. Methods: Characteristics, clinical care, urologic complications, and infections for subjects enrolled in the Trauma Infectious Disease Outcomes Study (TIDOS) were collected from Department of Defense (DOD) and Department of Veterans Affairs (VA) sources. Logistic regression identified predictors for urinary tract infections (UTIs) after genitourinary trauma. Results: Among 530 TIDOS enrollees who entered VA care, 89 (17%) sustained genitourinary trauma. The majority of subjects (93%) were injured via a blast and 27% had a dismounted complex blast injury (DCBI). Sexual dysfunction was reported with 36% of subjects, whereas 14% had urinary retention/incontinence and 8% had urethral stricture. Urologic complications were comparable between patients with and without DCBIs. Nineteen (21%) subjects had one or more UTI with a total of 40 unique UTI events (25% during initial hospitalization and 75% during subsequent DOD or VA care). The UTI incidence rate was 0.89 per patient-year during initial hospitalization, 0.05 per patient-year during DOD follow-up, and 0.07 per patient-year during VA healthcare. Subjects with UTIs had a higher proportion of bladder injury (53% vs. 13%; p < 0.001), posterior urethral injury (26% vs. 1%; p = 0.001), pelvic fracture (47% vs. 4%; p < 0.001), soft-tissue infection of the pelvis/hip (37% vs. 4%; p = 0.001), urinary catheterization (47% vs. 11%; p < 0.001), urinary retention or incontinence (42% vs. 6%; p < 0.001), and stricture (26% vs. 3%; p = 0.004) compared with patients with genitourinary trauma and no UTI. Independent UTI risk factors were occurrence of a soft-tissue infection at the pelvis/hip, trauma to the urinary tract, and transtibial amputation. Conclusions: Among combat casualties with genitourinary trauma, UTIs are a common complication, particularly with severe blast injury and urologic sequelae. Episodes of UTIs typically occur early after the initial injury while in DOD care, however, recurrent infections may continue into long-term VA care.

Association between 16S-23S internal transcribed spacer sequence groups of Mycobacterium avium complex and pulmonary disease.

Organisms within the Mycobacterium avium complex (MAC) may have differential virulence. We compared 33 subjects with MAC pulmonary disease to 75 subjects with a single positive culture without disease. M. avium isolates were significantly more likely to be associated with MAC pulmonary disease (odds ratio = 5.14, 95% confidence interval = 1.25 to 22.73) than M. intracellulare.

Measuring acceptable treatment failure rates for community-acquired pneumonia: potential for reducing duration of treatment and antimicrobial resistance.

OBJECTIVE: This study was designed to establish the rates of treatment failure for community-acquired pneumonia that are acceptable to knowledgeable and experienced physicians, in order to facilitate the interpretation of existing studies and the design of new studies aimed at optimizing the duration of antibiotic therapy. Reducing the duration of antibiotic therapy is one strategy for reducing antibiotic exposure and thereby minimizing the potential for the emergence of antimicrobial resistance. DESIGN: Survey soliciting the acceptable failure rate for treatment given to an adult patient with uncomplicated community-acquired pneumonia treated with standard-of-care therapy in the outpatient setting. Analysis was performed using a modification of established methods of contingent valuation analysis. PARTICIPANTS: Six hundred eighty infectious diseases physicians in North America who were also members of the Emerging Infections Network of the Infectious Diseases Society of America. RESULTS: Three hundred seventy-five (55.1%) of 680 physicians responded to the survey. The median acceptable failure rate for treatment was 13.5%. Five hundred ten respondents (75.0%) found a failure rate of 7.3% acceptable, and 170 respondents (25.0%) found a failure rate of 19.8% acceptable. CONCLUSIONS: This study identified the failure rates for treatment of community-acquired pneumonia that were acceptable to infectious disease physicians. This range of acceptable treatment failure rates may facilitate the design of studies aimed at optimizing the duration of antimicrobial therapy for community-acquired pneumonia.

Osteomyelitis: approach to diagnosis and treatment.

Osteomyelitis is a common disease with a variety of clinically and microbiologically distinct subsets. Diagnosis should begin with plain radiographs but may include a variety of imaging modalities. Cultures of the surface of ulcers or draining sinuses are often misleading, and bone cultures are necessary to determine the true pathogens of bone infections. The approach to treatment of osteomyelitis is complex, and often requires a multidisciplinary approach, with input from radiologists, vascular and orthopedic surgeons, infectious disease specialists, and wound care and rehabilitation specialists.

Methicillin-resistant Staphylococcus aureus outbreak in an intensive care nursery: potential for interinstitutional spread.

BACKGROUND: After surveillance surveys documented the absence of methicillin-resistant Staphylococcus aureus (MRSA) in our intensive care nursery, an outbreak of MRSA infection occurred there during a 7-month period in 2005. METHODS: Control measures included reinforcement of hand hygiene and contact precautions procedures. Active surveillance cultures were obtained on all neonates, including interinstitutional transfers. A cohort unit was dedicated exclusively for neonates with MRSA. Pulsed-field gel electrophoresis was performed on isolates to determine relatedness. We surveyed transferring hospitals to evaluate MRSA activity and surveillance practices in their nurseries. RESULTS: Twenty-five neonates were colonized with MRSA; 9 of these had clinical infections. Isolates from 18 of 21 neonates from this outbreak and 4 neonates from a previous cluster were identical, including 1 isolate obtained upon transfer from another institution. Admission and discharge logs from a 9-month period showed that 127 of 460 admissions (27.6%) were admitted from 34 hospitals, and 247 of 460 (53.7%) were discharged to 32 hospitals. Among 30 transferring hospitals responding to our survey, MRSA activity occurred in 2 of 28 (7%) level 1 nurseries, 4 of 11 (36%) level 2 nurseries and 6 of 10 (60%) level 3 nurseries. Nine of the 30 hospitals (30%) performed some active surveillance. CONCLUSIONS: Interinstitutional transfer can play a role in the initiation and propagation of MRSA outbreaks in neonatal nurseries. The burden of MRSA in area nurseries and the rate of transfers affect the potential for interhospital spread of MRSA and may justify changes in policy regarding surveillance for MRSA and communication between hospitals.

Prevalence of Clostridium difficile environmental contamination and strain variability in multiple health care facilities.

BACKGROUND: Clostridium difficile spores can contaminate the hospital environment. Little is known about the prevalence and strain variability of C. difficile environmental contamination in health care facilities. The objective of this study was to assess C. difficile environmental contamination at various health care facilities in a metropolitan area and determine if the North American pulsed field gel electrophoresis type 1 (NAP1) strain was present. METHODS: A cross-sectional pilot survey was conducted. Forty-eight environmental samples were collected from six health care facilities. Samples were cultured for the presence of C. difficile, and positive samples underwent pulsed field gel electrophoresis, toxinotyping, and detection of binary toxin and/or tcdC deletion. RESULTS: C. difficile was cultured from 13 of 48 (27%) samples. Rooms housing a patient with C. difficile-associated disease (CDAD) were more likely to be culture positive than non-CDAD patient rooms (100% vs. 33%; P < 0.01); C. difficile was not isolated outside of patient rooms (0 of 12 samples). The NAP1 epidemic strain was found in 5 out of 6 facilities. CONCLUSION: C. difficile spores frequently contaminated the hospital environment. Rooms with a CDAD patient were more likely to be contaminated than rooms without a CDAD patient. The NAP1 strain was prevalent throughout the metropolitan area.

Mycobacterium avium-intracellulare cellulitis occurring with septic arthritis after joint injection: a case report.

BACKGROUND: Cellulitis caused by Mycobacterium avium-intracellulare has rarely been described. Mycobacterium avium-intracellulare is a rare cause of septic arthritis after intra-articular injection, though the causative role of injection is difficult to ascertain in such cases. CASE PRESENTATION: A 57-year-old with rheumatoid arthritis treated with prednisone and azathioprine developed bilateral painful degenerative shoulder arthritis. After corticosteroid injections into both acromioclavicular joints, he developed bilateral cellulitis centered over the injection sites. Skin biopsy showed non-caseating granulomas, and culture grew Mycobacterium avium-intracellulare. Joint aspiration also revealed Mycobacterium avium-intracellulare infection. CONCLUSION: Although rare, skin and joint infections caused by Mycobacterium avium-intracellulare should be considered in any immunocompromised host, particularly after intra-articular injection. Stains for acid-fast bacilli may be negative in pathologic samples even in the presence of infection; cultures of tissue specimens should always be obtained.

Risk factors for ineffective therapy in patients with bloodstream infection.

BACKGROUND: Infections occurring among outpatients having recent contact with the health care system have been termed health care-associated infections. The objective of this study was to analyze the impact of health care-associated status on effectiveness of initial therapy in hospitalized patients with bloodstream infections. METHODS: Prospective cohort study of adults with bloodstream infections at 3 North Carolina hospitals. Bloodstream infection was defined as health care-associated if it occurred within the first 48 hours after hospitalization and if patients had 1 of the following characteristics: had received home health services, outpatient intravenous therapy, or outpatient renal dialysis in the 30 days prior to hospital admission; had been hospitalized within 90 days prior to admission; or lived in a long-term care facility. RESULTS: Of 466 bloodstream infections, 132 (28%) were community-acquired, 178 (38%) were health care-associated, and 156 (33%) were nosocomial. Multivariable logistic regression using community-acquired status as a reference identified health care-associated status (odds ratio, 3.1; 95% confidence interval, 1.6-6.1) and nosocomial status (odds ratio, 4.3; 95% confidence interval, 2.2-8.3) as independent predictors of ineffective initial antibiotic therapy. Among health care-associated characteristics, hospitalization in the 90 days prior to admission was independently associated with ineffective initial therapy (odds ratio, 2.4; 95% confidence interval, 1.4-4.2). CONCLUSIONS: Among patients treated in the hospital for bloodstream infection, health care-associated status was an independent predictor of ineffective initial antibiotic therapy. Hospitalization within 90 days prior to hospital admission was the component of health care-associated status most strongly associated with ineffective initial therapy.

Tumor Necrosis Factor Inhibition and Head and Neck Cancer Recurrence and Death in Rheumatoid Arthritis.

The objective of this retrospective cohort study was to determine the effect of tumor necrosis factor inhibitor (TNFi) therapy on the risk of head and neck cancer (HNC) recurrence or HNC-attributable death in patients with rheumatoid arthritis (RA). RA patients with HNC were assembled from the US national Veterans' Affairs (VA) administrative databases, and diagnoses confirmed and data collected by electronic medical record review. The cohort was divided into those treated with non-biologic disease-modifying anti-rheumatic drugs (nbDMARDs) versus TNF inhibitors (TNFi) after a diagnosis of HNC. Likelihood of a composite endpoint of recurrence or HNC-attributable death was determined by Cox proportional hazards regression. Of 180 patients with RA and HNC, 31 were treated with TNFi and 149 with nbDMARDs after the diagnosis of HNC. Recurrence or HNC-attributable death occurred in 5/31 (16.1%) patients in the TNFi group and 44/149 (29.5%) patients in the nbDMARD group (p = 0.17); it occurred in 2/16 (13%) patients who received TNFi in the year prior to HNC diagnosis but not after. Overall stage at diagnosis (p = 0.03) and stage 4 HNC (HR 2.49 [CI 1.06-5.89]; p = 0.04) were risk factors for recurrence or HNC-attributable death; treatment with radiation or surgery was associated with a lower risk (HR 0.35 [CI 0.17-0.74]; p = 0.01 and HR 0.39 [CI 0.20-0.76]; p = 0.01 respectively). Treatment with TNFi was not a risk factor for recurrence or HNC-attributable death (HR 0.75; CI 0.31-1.85; p = 0.54). We conclude that treatment with TNFi may be safe in patients with RA and HNC, especially as the time interval between HNC treatment and non-recurrence increases. In this study, TNF inhibition was not associated with an increase in recurrence or HNC-attributable death.