Economic and epidemiological impact of different intervention strategies for subclinical and clinical mastitis.

The objective of this study was to evaluate and compare different combinations of intervention strategies for contagious or opportunistic subclinical and clinical intramammary infections (IMI). We simulated two different Danish dairy cattle herds with ten different intervention strategies focusing on cow-specific treatment or culling, including three baseline strategies without subclinical interventions. In one herd, the main causative pathogen of IMI was Staphylococcus (S.) aureus. In the other herd, Streptococcus (St.) agalactiae was the main causative agent. For both herds, we investigated costs and effectiveness of all ten intervention strategies. Intervention strategies consisted of measures against clinical and subclinical IMI, with baselines given by purely clinical intervention strategies. Our results showed that strategies including subclinical interventions were more cost-effective than the respective baseline strategies. Increase in income and reduction of IMI cases came at the cost of increased antibiotic usage and an increased culling rate in relation to IMI. However, there were differences between the herds. In the St. agalactiae herd, the clinical intervention strategy did not seem to have a big impact on income and number of cases. However, intervention strategies which included cow-specific clinical interventions led to a higher income and lower number of cases in the S. aureus herd. The results show that intervention strategies including interventions against contagious or opportunistic clinical and subclinical IMI can be highly cost-effective, but should be herd-specific.

Evaluación infectológica inicial y seguimiento prospectivo de una cohorte de pacientes sometidos a inmunosupresión inducida / Initial assessment and prospective follow-up of a cohort of patients with immunosuppressive therapy by an infectious diseases physician

El uso de inmunosupresores generó una población creciente de pacientes con defectos en el sistema inmune. Creamos un consultorio especializado en la atención infectológica de dichos pacientes. Objetivos: Describir los antecedentes clínicos y la prevalencia de infecciones latentes, evaluar el estado de vacunación, determinar la necesidad de profilaxis antimicrobiana. Describir la frecuencia de aparición infecciones oportunistas (IO). Materiales y métodos: estudio descriptivo, prospectivo de pacientes atendidos en un consultorio que estuvieran bajo tratamiento inmunosupresor (noviembre 2015-enero 2017). Se recolectaron datos demográficos, clínicos y factores de riesgo para IO. Se realizó pesquisa de tuberculosis (TB), serologías para HIV, hepatitis A, B y C, sífilis, toxoplasmosis, Chagas, búsqueda de Strongyloides spp. Se indicaron vacunas de acuerdo con las recomendaciones actuales. Se realizó seguimiento para detección de IO. Resultados: n=197, media de edad 50,7 años (DE 14), mujeres 79,7%. Enfermedades de base: artritis reumatoidea 52%, lupus 12%. Drogas inmunosupresoras: metotrexato 45%, corticoides 16%, biológicos anti-TNF 15%, micofenolato 10%, ciclofosfamida 4%. Se diagnosticaron 49 (25%) infecciones: 15 Chagas, 15 anti-HBc positivo aislado, 7 sífilis, 4 HIV, 4 TB latentes, 2 HBV, 1 HCV, 1 estrongiloidiosis. Se indicó profilaxis antimicrobiana en 27 (14%) pacientes. En todos se intervino indicando o completando los esquemas de vacunación. Se detectaron 7 IO. Conclusiones: En el 39% de los pacientes, la evaluación sistematizada arrojó hallazgos que motivaron intervenciones, ya sea terapéuticas o de monitoreo. En el 100% fue necesaria la prescripción de vacunas. Esto pone en evidencia la importancia de evaluar sistemáticamente en consultorios especializados a estos pacientes

Introduction: The extensive use of immunosuppressive drugs resulted in a growing population of patients with defects in the immune system. We opened an infectious diseases practice focused on the attention of these patients. Our objectives were to describe the clinical history and prevalence of latent infections, evaluate the vaccination status, determine the need for antimicrobial prophylaxis and describe the frequency of opportunistic infections (OI). Methods: We performed a descriptive and prospective study of patients seen at a medical practice who were under immunosuppressive therapy (November 2015-January 2017). Demographic and clinical history, as well as risk factors for OI were collected. Tuberculosis (TB) screening, serologies for HIV, hepatitis A, B and C, syphilis, toxoplasmosis, Chagas and Strongyloides spp. screening were performed. Vaccines were indicated according to current recommendations. Follow-up was performed for IO detection. Results: n=197. Mean age: 50.7 years (SD 14). Female 79.7%. Underlying diseases: rheumatoid arthritis 52%, 12% lupus. Immunosuppressive drugs: methotrexate 45%, corticoids 16%, biological anti-TNF agents 15%, mycophenolate 10%, cyclophosphamide 4%. Forty-nine (25%) infections were diagnosed: 15 Chagas, 15 anti-HBc positive isolated, 7 syphilis, 4 HIV, 4 latent TB, 2 HBV, 1 HCV, 1 strongyloidiosis. Antimicrobial prophylaxis was indicated in 27 (14%) patients. In all cases, vaccination schemes were indicated or completed. Seven IO were detected. Conclusions: In 39% of the patients, the systematized evaluation revealed findings that motivated interventions, either therapeutic or monitoring. In 100% the prescription of vaccines was necessary. These findings highlight the importance of a systematically evaluation of these patients in specialized care centers.

A Markov Analysis of Screening for Late-Onset Cytomegalovirus Disease in Cytomegalovirus High-Risk Kidney Transplant Recipients.

BACKGROUND AND OBJECTIVES: Management strategies are unclear for late-onset cytomegalovirus infection occurring beyond 6 months of antiviral prophylaxis in cytomegalovirus high-risk (cytomegalovirus IgG positive to cytomegalovirus IgG negative) kidney transplant recipients. Hybrid strategies (prophylaxis followed by screening) have been investigated but with inconclusive results. There are clinical and potential cost benefits of preventing cytomegalovirus-related hospitalizations and associated increased risks of patient and graft failure. We used decision analysis to evaluate the utility of postprophylaxis screening for late-onset cytomegalovirus infection. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We used the Markov decision analysis model incorporating costs and utilities for various cytomegalovirus clinical states (asymptomatic cytomegalovirus, mild cytomegalovirus infection, and cytomegalovirus infection necessitating hospitalization) to estimate cost-effectiveness of postprophylaxis cytomegalovirus screening strategies. Five strategies were compared: no screening and screening at 1-, 2-, 3-, or 4-week intervals. Progression to severe cytomegalovirus infection was modeled on cytomegalovirus replication kinetics. Incremental cost-effectiveness ratios were calculated as a ratio of cost difference between two strategies to difference in quality-adjusted life-years starting with the low-cost strategy. One-way and probabilistic sensitivity analyses were performed to test model's robustness. RESULTS: There was an incremental gain in quality-adjusted life-years with increasing screening frequency. Incremental cost-effectiveness ratios were $783 per quality-adjusted life-year (every 4 weeks over no screening), $1861 per quality-adjusted life-year (every 3 weeks over every 4 weeks), $10,947 per quality-adjusted life-year (every 2 weeks over every 3 weeks), and $197,086 per quality-adjusted life-year (weekly over every 2 weeks). Findings were sensitive to screening cost, cost of hospitalization, postprophylaxis cytomegalovirus incidence, and graft loss after cytomegalovirus infection. No screening was favored when willingness to pay threshold was <$14,000 per quality-adjusted life-year, whereas screening weekly was favored when willingness to pay threshold was >$185,000 per quality-adjusted life-year. Screening every 2 weeks was the dominant strategy between willingness to pay range of $14,000-$185,000 per quality-adjusted life-year. CONCLUSIONS: In cytomegalovirus high-risk kidney transplant recipients, compared with no screening, screening for postprophylactic cytomegalovirus viremia is associated with gains in quality-adjusted life-years and seems to be cost effective. A strategy of screening every 2 weeks was the most cost-effective strategy across a wide range of willingness to pay thresholds.

Fluconazole versus mould-active triazoles for primary antifungal prophylaxis in adult patients with acute lymphoblastic leukemia: clinical outcome and cost-effectiveness analysis.

This study evaluated the clinical and cost-effectiveness of prophylactic use of fluconazole versus mould-active triazoles (voriconazole and posaconazole) in adult patients with acute lymphoblastic leukemia (ALL). A decision analytical model was developed with inputs from a 7-year retrospective study (2009-2016) of 103 consecutive adult patients with ALL who received antifungal prophylaxis. Information on the administration of antifungal agents, clinical outcomes, and costs were collected. One-way sensitivity analyses and probabilistic sensitivity analysis were performed. The mould-active triazoles group was associated with higher life-years (3.71 vs 3.59) and lower total costs (US$4886 vs US$5722) per patient compared with fluconazole. One-way sensitivity analyses revealed that varying all of the key variables in the model did not affect the robustness of the results. Probabilistic sensitivity analysis demonstrated that mould-active triazoles had a probability of 77.1 and 90.1% of providing a dominant and cost-effective option relative to fluconazole, respectively. Mould-active triazoles should be regarded as preferable to fluconazole as the first-line prophylactic for adult patients with ALL accompanied by uncommon severe vinca alkaloid-induced neurotoxicity. However, the results reported here should be interpreted with caution owing to the observational nature of the data.

Intravenous Antibiotic and Antifungal Agent Pharmacokinetic-Pharmacodynamic Dosing in Adults with Severe Burn Injury.

PURPOSE: Despite advances in the care of patients with severe burn injury, infection-related morbidity and mortality remain high and can potentially be reduced with antimicrobial dosing optimized for the infecting pathogen. However, anti-infective dose selection is difficult because of the highly abnormal physiologic features of burn patients, which can greatly affect the pharmacokinetic (PK) disposition of these agents. We review published PK data from burn patients and offer evidence-based dosing recommendations for antimicrobial agents in burn-injured patients. METHODS: Because most infections occur at least 48 hours after initial burn injury and anti-infective therapy often lasts ≥10 days, we reviewed published data informing PK-pharmacodynamic (PD) dosing of anti-infectives administered during the second, hypermetabolic stage of burn injury, in those with >20% total body surface area burns, and in those with normal or augmented renal clearance (estimated creatinine clearance ≥130 mL/min). Analyses were performed using 10,000-patient Monte Carlo simulations, which uses PK variability observed in burn patients and MIC data to determine the probability of reaching predefined PK-PD targets. The probability of target attainment, defined as the likelihood that an anti-infective dosing regimen would achieve a specific PK-PD target at the single highest susceptible MIC, and the cumulative fraction of response, defined as the population probability of target attainment given a specific dose and a distribution of MICs, were calculated for each recommended anti-infective dosing regimen. FINDINGS: Evidence-based doses were derived for burn-injured patients for 15 antibiotics and 2 antifungal agents. Published data were unavailable or insufficient for several agents important to the care of burn patients, including newer antifungal and antipseudomonal agents. Furthermore, available data suggest that antimicrobial PK properties in burned patients is highly variable. We recommend that, where possible, therapeutic drug monitoring be performed to optimize PK-PD parameter achievement in individual patients. IMPLICATIONS: Given the high variability in PK disposition observed in burn patients, doses recommended in the package insert may not achieve PK-PD parameters associated with optimal infectious outcomes. Our study is limited by the necessity for fixed assumptions in depicting this highly variable patient population. New rapid-turnaround analytical technology is needed to expand the menu of antimicrobial agents for which therapeutic drug monitoring is available to guide dose modification within a clinically actionable time frame.

Comparing guideline-based care quality for inflammatory bowel disease and rheumatoid arthritis patients within a medical home.

BACKGROUND: Rheumatoid arthritis (RA) and inflammatory bowel disease (IBD) patient populations face similar risks of chronic immunosuppression including corticosteroid use. We compared the receipt of preventive services between IBD and RA populations according to published quality metrics. METHODS: We defined a single-center cohort of patients with IBD or RA receiving specialty and primary care. Electronic health record abstraction assessed quality metrics, sociodemographics, comorbidity, and utilization. Comparisons used multivariate odds ratios and Student's t-tests. RESULTS: 218 RA and 190 IBD patients were included. In multivariate analysis, IBD patients were less likely to receive pneumococcal vaccination (OR=0.29, 95% CI: 0.11-0.85), while RA patients underwent glucocorticoid-induced osteoporosis screening more often (100% vs. 82.5%, p = 0.023). CONCLUSIONS: Gastroenterologists can improve care quality for IBD patients by assuming greater responsibility for preventive care in IBD patients and/or collaborating with primary care and health systems to improve preventive care delivery.

A Quasi-Experimental Study Analyzing the Effectiveness of Portable High-Efficiency Particulate Absorption Filters in Preventing Infections in Hematology Patients during Construction.

OBJECTIVE: The increased risk of infection for patients caused by construction and renovation near hematology inpatient clinics is a major concern. The use of high-efficiency particulate absorption (HEPA) filters can reduce the risk of infection. However, there is no standard protocol indicating the use of HEPA filters for patients with hematological malignancies, except for those who have undergone allogeneic hematopoietic stem cell transplantation. This quasi-experimental study was designed to measure the efficacy of HEPA filters in preventing infections during construction. MATERIALS AND METHODS: Portable HEPA filters were placed in the rooms of patients undergoing treatment for hematological malignancies because of large-scale construction taking place near the hematology clinic. The rates of infection during the 6 months before and after the installation of the portable HEPA filters were compared. A total of 413 patients were treated during this 1-year period. RESULTS: There were no significant differences in the antifungal prophylaxis and treatment regimens between the groups. The rates of infections, clinically documented infections, and invasive fungal infections decreased in all of the patients following the installation of the HEPA filters. When analyzed separately, the rates of invasive fungal infections were similar before and after the installation of HEPA filters in patients who had no neutropenia or long neutropenia duration. HEPA filters were significantly protective against infection when installed in the rooms of patients with acute lymphocytic leukemia, patients who were undergoing consolidation treatment, and patients who were neutropenic for 1-14 days. CONCLUSION: Despite the advent of construction and the summer season, during which environmental Aspergillus contamination is more prevalent, no patient or patient subgroup experienced an increase in fungal infections following the installation of HEPA filters. The protective effect of HEPA filters against infection was more pronounced in patients with acute lymphocytic leukemia, patients undergoing consolidation therapy, and patients with moderate neutropenia.

Meta-Analysis and Cost Comparison of Empirical versus Pre-Emptive Antifungal Strategies in Hematologic Malignancy Patients with High-Risk Febrile Neutropenia.

BACKGROUND: Invasive fungal disease (IFD) causes significant morbidity and mortality in hematologic malignancy patients with high-risk febrile neutropenia (FN). These patients therefore often receive empirical antifungal therapy. Diagnostic test-guided pre-emptive antifungal therapy has been evaluated as an alternative treatment strategy in these patients. METHODS: We conducted an electronic search for literature comparing empirical versus pre-emptive antifungal strategies in FN among adult hematologic malignancy patients. We systematically reviewed 9 studies, including randomized-controlled trials, cohort studies, and feasibility studies. Random and fixed-effect models were used to generate pooled relative risk estimates of IFD detection, IFD-related mortality, overall mortality, and rates and duration of antifungal therapy. Heterogeneity was measured via Cochran's Q test, I2 statistic, and between study τ2. Incorporating these parameters and direct costs of drugs and diagnostic testing, we constructed a comparative costing model for the two strategies. We conducted probabilistic sensitivity analysis on pooled estimates and one-way sensitivity analyses on other key parameters with uncertain estimates. RESULTS: Nine published studies met inclusion criteria. Compared to empirical antifungal therapy, pre-emptive strategies were associated with significantly lower antifungal exposure (RR 0.48, 95% CI 0.27-0.85) and duration without an increase in IFD-related mortality (RR 0.82, 95% CI 0.36-1.87) or overall mortality (RR 0.95, 95% CI 0.46-1.99). The pre-emptive strategy cost $324 less (95% credible interval -$291.88 to $418.65 pre-emptive compared to empirical) than the empirical approach per FN episode. However, the cost difference was influenced by relatively small changes in costs of antifungal therapy and diagnostic testing. CONCLUSIONS: Compared to empirical antifungal therapy, pre-emptive antifungal therapy in patients with high-risk FN may decrease antifungal use without increasing mortality. We demonstrate a state of economic equipoise between empirical and diagnostic-directed pre-emptive antifungal treatment strategies, influenced by small changes in cost of antifungal therapy and diagnostic testing, in the current literature. This work emphasizes the need for optimization of existing fungal diagnostic strategies, development of more efficient diagnostic strategies, and less toxic and more cost-effective antifungals.

A 'cocoon immunization strategy' among patients with inflammatory bowel disease.

BACKGROUND AND AIMS: A 'cocoon strategy' is defined as the strategy of protecting vulnerable patients from infectious diseases by vaccinating those in close contact with them. In our study, we evaluate the vaccination status among children living with patients with inflammatory bowel disease (IBD) to determine the realization of the cocoon strategy and to identify characteristics associated with pediatric vaccine refusal. PATIENTS AND METHODS: A self-completed survey was conducted on 136 hospitalized patients with IBD. The survey comprised questions about household child vaccination coverage, the reasons for vaccine refusal, and the history of infectious diseases among the patients. RESULTS: Fifty-six patients reported living with children. Forty percent of children were vaccinated with at least one of the recommended vaccines. Most frequently, children received pneumococcal (26%) and rotaviruses (22%) vaccines. The most common reason for nonimmunization was patients' opinion that immunizations are not necessary for them (52%). There was a statistically significant association between the nonreimbursed vaccines coverage and the educational level of the patients (P<0.0001). Despite the fact that 28% of the patients could not definitively recall varicella infection, none of them and none of the children in their household had been vaccinated against chickenpox. CONCLUSION: The use of nonmandatory vaccines recommended in family members of patients with IBD is insufficient. Further vaccine promotion and education of patients as well as their healthcare providers is required. A particular concern is associated with the pneumococcal, influenza, rotaviruses, and varicella infections. Nonimmunized and varicella-zoster virus-seronegative patients should be vaccinated, and in case of immunosuppression, vaccination of children in the household is required.

Risks of herpes zoster in patients with rheumatoid arthritis according to biologic disease-modifying therapy.

OBJECTIVE: To evaluate whether the risks of herpes zoster (HZ) differed by biologic agents with different mechanisms of action (MOAs) in older rheumatoid arthritis (RA) patients. METHODS: Using Medicare data from 2006-2011, among RA patients with prior biologic agent use and no history of cancer or other autoimmune diseases, this retrospective cohort study identified new treatment episodes of abatacept, adalimumab, certolizumab, etanercept, golimumab, infliximab, rituximab, and tocilizumab. Followup started on initiation of the new biologic agent and ended at any of the following: first incidence of HZ, a 30-day gap in current exposure, death, a diagnosis of other autoimmune disease or cancer, loss of insurance coverage, or December 31, 2011. We calculated the proportion of RA patients vaccinated for HZ in each calendar year prior to biologic agent initiation and HZ incidence rate for each biologic agent. We compared HZ risks among therapies using Cox regression adjusted for potential confounders. RESULTS: Of 29,129 new biologic treatment episodes, 28.7% used abatacept, 15.9% adalimumab, 14.8% rituximab, 12.4% infliximab, 12.2% etanercept, 6.1% tocilizumab, 5.8% certolizumab, and 4.4% golimumab. The proportion of RA patients vaccinated for HZ prior to biologic agent initiation ranged from 0.4% in 2007 to 4.1% in 2011. We identified 423 HZ diagnoses with the highest HZ incidence rate for certolizumab (2.45 per 100 person-years) and the lowest for golimumab (1.61 per 100 person-years). Neither the crude incidence rate nor the adjusted hazard ratio differed significantly among biologic agents. Glucocorticoid use had a significant association with HZ. CONCLUSION: Among older patients with RA, the HZ risk was similar across biologic agents, including those with different MOAs.

Consensus guidelines for antifungal prophylaxis in haematological malignancy and haemopoietic stem cell transplantation, 2014.

There is a strong argument for the use of antifungal prophylaxis in high-risk patients given the significant mortality associated with invasive fungal disease, the late identification of these infections, and the availability of safe and well-tolerated prophylactic medications. Clinical decisions about which patients should receive prophylaxis and choice of antifungal agent should be guided by risk stratification, knowledge of local fungal epidemiology, the efficacy and tolerability profile of available agents, and estimates such as number needed to treat and number needed to harm. There have been substantial changes in practice since the 2008 guidelines were published. These include the availability of new medications and/or formulations, and a focus on refining and simplifying patient risk stratification. Used in context, these guidelines aim to assist clinicians in providing optimal preventive care to this vulnerable patient demographic.

Preventing infections during cancer treatment: development of an interactive patient education website.

Despite advances in oncology care, infections from both community and healthcare settings remain a major cause of hospitalization and death among patients with cancer receiving chemotherapy. Neutropenia (low white blood cell count) is a common and potentially dangerous side effect in patients receiving chemotherapy treatments and may lead to higher risk of infection. Preventing infection during treatment can result in significant decreases in morbidity and mortality for patients with cancer. As part of the Centers for Disease Control and Prevention's (CDC's) Preventing Infections in Cancer Patients public health campaign, a public-private partnership was formed between the CDC Foundation and Amgen, Inc. The CDC's Division of Cancer Prevention and Control developed and launched an interactive website, www.PreventCancerInfections.org, designed for patients with cancer undergoing chemotherapy. The site encourages patients to complete a risk assessment for developing neutropenia during their treatment. After completing the assessment, patients receive information about how to lower the risk for infection and keep themselves healthy while receiving chemotherapy.

Challenges for lupus management in emerging countries.

In emerging countries, systemic lupus erythematosus (SLE) has been associated with several unfavorable outcomes including disease activity, damage accrual, work disability and mortality. Poor socioeconomic status (SES) and lack of access to healthcare, especially in medically underserved communities, may be responsible for many of the observed disparities. Diagnostic delay of SLE or for severe organ damages (renal involvement) have a negative impact on those adverse outcomes in lupus patients who either belong to minority groups or live in emerging countries. Longitudinal and observational prospective studies and registries may help to identify the factors that influence poor SLE outcomes in emerging countries. Infection is an important cause of mortality and morbidity in SLE, particularly in low SES patients and tuberculosis appears to be frequent in SLE patients living in endemic areas (mainly emerging countries). Thus, tuberculosis screening should be systematically performed and prophylaxis discussed for patients from these areas. SLE treatment in the developing world is restricted by the availability and cost of some immunosuppressive drugs. Moreover, poor adherence has been associated to bad outcomes in lupus patients with a higher risk of flares, morbidity, hospitalization, and poor renal prognosis. Low education and the lack of money are identified as the main barrier to improve lupus prognosis. Newer therapeutic agents and new protocols had contributed to improve survival in SLE. The use of corticoid-sparing agents (hydroxychloroquine, methotrexate, azathioprine and mycophenolate mofetif) is one of the most useful strategy; availability of inexpensive generics may help to optimize access to these medications.

Cost-effectiveness of the introduction of specialized oral care with laser therapy in hematopoietic stem cell transplantation.

Oral mucositis (OM) is one of the side effects of hematopoietic stem cell transplantation (HSCT), resulting in major morbidity. The aim of this study was to determine the cost-effectiveness of the introduction of a specialized oral care program including laser therapy in the care of patients receiving HSCT with regard to morbidity associated with OM. Clinical information was gathered on 167 patients undergoing HSCT and divided according to the presence (n = 91) or absence (n = 76) of laser therapy and oral care. Cost analysis included daily hospital fees, parenteral nutrition (PN) and prescription of opioids. It was observed that the group without laser therapy (group II) showed a higher frequency of severe degrees of OM (relative risk = 16.8, 95% confidence interval -5.8 to 48.9, p < 0.001), with a significant association between this severity and the use of PN (p = 0.001), prescription of opioids (p < 0.001), pain in the oral cavity (p = 0.003) and fever > 37.8°C (p = 0.005). Hospitalization costs in this group were up to 30% higher. The introduction of oral care by a multidisciplinary staff including laser therapy helps reduce morbidity resulting from OM and, consequently, helps minimize hospitalization costs associated with HSCT, even considering therapy costs.

Opportunities taken: the need for and effectiveness of secondary care opportunistic immunisation.

AIM: To evaluate the effectiveness of a formalised opportunistic immunisation (OI) system in a hospital setting. METHODS: Pre-post implementation audit of missed immunisation opportunities. RESULTS: Of 5583 children in the National Immunisation Register cohort seen in a hospital setting, 1641 (29.4%) were under-immunised, compared with the concurrent regional cohort of 15%. Maori children were less likely to be age-appropriately immunised (36.9% under-immunised, P < 0.0005, χ(2) = 41.4). Of the 1641 under-immunised children, 337 (20.5%) were deemed to have current medical reasons not to be immunised acutely, and of the remaining 1304, 244 (18.7%) declined immunisations. This left 1060 for whom immunisation was possible, and we immunised 880 (83.0%) of these. All children were re-engaged with primary care services. CONCLUSIONS: Children in contact with secondary care services have low immunisation rates with ethnic disparity. Appropriately resourced formalised OI is effective, with potential for further improvement. The system we have implemented enhances primary care involvement.

Vaccination in adult patients with auto-immune inflammatory rheumatic diseases: a systematic literature review for the European League Against Rheumatism evidence-based recommendations for vaccination in adult patients with auto-immune inflammatory rheumatic diseases.

OBJECTIVES: To present the systematic literature review (SLR), which formed the basis for the European League Against Rheumatism (EULAR) evidence-based recommendations for vaccination in adult patients with auto-immune inflammatory rheumatic diseases (AIIRD). METHODS: AIIRD, vaccines and immunomodulating drugs, as well as eight key questions were defined by the multidisciplinary expert committee commissioned by EULAR for developing the recommendations. A SLR was performed using MedLine through October 2009 and including data from meta-analyses, systematic reviews, randomized trials, and observational studies, excluding case series with ≤ 5 participants. Articles in English and regarding patients ≥ 16 years of age, were eligible. RESULTS: Several vaccine-preventable infections (VPI) occur more often in AIIRD-patients and most vaccines are efficacious in AIIRD-patients, even when treated with immunomodulating agents, except rituximab. There does not appear to be an increase in vaccination-related harms in vaccinated patients with AIIRD in comparison with unvaccinated patients with AIIRD. However, these studies are underpowered and therefore not conclusive. CONCLUSION: Based on the current evidence from the literature, recommendations for vaccination in patients with AIIRD were made. However, more research is needed in particular regarding incidence of VPI, harms of vaccination and the influence of (new and established) immunomodulating agents on vaccination efficacy.