Efficacy and cost-effectiveness of nurse-led care involving education and engagement of patients and a treat-to-target urate-lowering strategy versus usual care for gout: a randomised controlled trial.

BACKGROUND: In the UK, gout management is suboptimum, with only 40% of patients receiving urate-lowering therapy, usually without titration to achieve a target serum urate concentration. Nurses successfully manage many diseases in primary care. We compared nurse-led gout care to usual care led by general practitioners (GPs) for people in the community. METHODS: Research nurses were trained in best practice management of gout, including providing individualised information and engaging patients in shared decision making. Adults who had experienced a gout flare in the previous 12 months were randomly assigned 1:1 to receive nurse-led care or continue with GP-led usual care. We assessed patients at baseline and after 1 and 2 years. The primary outcome was the percentage of participants who achieved serum urate concentrations less than 360 µmol/L (6 mg/dL) at 2 years. Secondary outcomes were flare frequency in year 2, presence of tophi, quality of life, and cost per quality-adjusted life-year (QALY) gained. Risk ratios (RRs) and 95% CIs were calculated based on intention to treat with multiple imputation. This study is registered with www.ClinicalTrials.gov, number NCT01477346. FINDINGS: 517 patients were enrolled, of whom 255 were assigned nurse-led care and 262 usual care. Nurse-led care was associated with high uptake of and adherence to urate-lowering therapy. More patients receiving nurse-led care had serum urate concentrations less than 360 µmol/L at 2 years than those receiving usual care (95% vs 30%, RR 3·18, 95% CI 2·42-4·18, p<0·0001). At 2 years all secondary outcomes favoured the nurse-led group. The cost per QALY gained for the nurse-led intervention was £5066 at 2 years. INTERPRETATION: Nurse-led gout care is efficacious and cost-effective compared with usual care. Our findings illustrate the benefits of educating and engaging patients in gout management and reaffirm the importance of a treat-to-target urate-lowering treatment strategy to improve patient-centred outcomes. FUNDING: Arthritis Research UK.

Temporal relationships between systemic lupus erythematosus and comorbidities.

OBJECTIVE: To examine the burden of comorbidities prior to and after the diagnosis of SLE and its impact on mortality. METHODS: We identified 1605 incident cases of SLE and 6284 matched controls from the UK primary care. The risks of comorbidities before (prevalence; odds ratios) and after SLE diagnosis (incidence; hazard ratios) and the impact of comorbidities at diagnosis on all-cause mortality were estimated. RESULTS: At diagnosis, SLE was associated with adjusted odds ratios (95% CI) of 2.25 (1.97-2.56), 3.37 (2.49-4.57) and 3.54 (1.89-6.63) for a Charlson comorbidity index of 1-2, 3-4 and ≥5, respectively. Following diagnosis, SLE also associated with increased risk of developing any comorbidity with an adjusted hazard ratio (95% CI) of 1.30 (95% CI, 1.13-1.49). At diagnosis, SLE was associated with a greater risk of cancer, cardiovascular, renal, liver, rheumatological and neurological diseases as well as depression, anaemia and psoriasis. Risks of developing incident comorbidity in the categories of neoplasm, cardiovascular, genitourinary, metabolic/endocrine, gastrointestinal and hepatic diseases, chronic pulmonary diseases, musculoskeletal/connective tissue and neurological diseases were higher in SLE patients. People with SLE had higher mortality risk compared with controls, with adjusted hazard ratio of 1.91 (95% CI, 1.62-2.26); after further adjusting for comorbidities this reduced to 1.64 (1.37-1.97). Comorbidities at SLE diagnosis accounted for 27.6% of the apparent difference in mortality between SLE patients and matched controls. CONCLUSION: People with SLE have increased risks of multiple comorbidities both prior to and after diagnosis and this contributes significantly to all-cause mortality.

The worldwide incidence and prevalence of systemic lupus erythematosus: a systematic review of epidemiological studies.

Objectives: The aim was to review the worldwide incidence and prevalence of SLE and variation with age, sex, ethnicity and time. Methods: A systematic search of MEDLINE and EMBASE search engines was carried out using Medical Subject Headings and keyword search terms for Systemic Lupus Erythematosus combined with incidence, prevalence and epidemiology in August 2013 and updated in September 2016. Author, journal, year of publication, country, region, case-finding method, study period, number of incident or prevalent cases, incidence (per 100 000 person-years) or prevalence (per 100 000 persons) and age, sex or ethnic group-specific incidence or prevalence were collected. Results: The highest estimates of incidence and prevalence of SLE were in North America [23.2/100 000 person-years (95% CI: 23.4, 24.0) and 241/100 000 people (95% CI: 130, 352), respectively]. The lowest incidences of SLE were reported in Africa and Ukraine (0.3/100 000 person-years), and the lowest prevalence was in Northern Australia (0 cases in a sample of 847 people). Women were more frequently affected than men for every age and ethnic group. Incidence peaked in middle adulthood and occurred later for men. People of Black ethnicity had the highest incidence and prevalence of SLE, whereas those with White ethnicity had the lowest incidence and prevalence. There appeared to be an increasing trend of SLE prevalence with time. Conclusion: There are worldwide differences in the incidence and prevalence of SLE that vary with sex, age, ethnicity and time. Further study of genetic and environmental risk factors may explain the reasons for these differences. More epidemiological studies in Africa are warranted.

The incidence and prevalence of systemic lupus erythematosus in the UK, 1999-2012.

OBJECTIVES: To estimate the incidence and prevalence of systemic lupus erythematosus (SLE) in the UK over the period 1999-2012. METHODS: A retrospective cohort study using the Clinical Practice Research Datalink (CPRD). The incidence was calculated per 100 000 person-years and the prevalence was calculated per 100 000 people for the period 1999-2012 and stratified by year, age group, gender, region and ethnicity. Three definitions of SLE were explored: (1) systemic lupus, (2) a fully comprehensive definition of lupus including cutaneous only lupus and (3) requiring supporting evidence of SLE in the medical record. RESULTS: Using our primary definition of SLE, the incidence during the study period was 4.91/100 000 person-years (95% CI 4.73 to 5.09), with an annual 1.8% decline (p<0.001). In contrast, the prevalence increased from 64.99/100 000 in 1999 (95% CI 62.04 to 67.93) (0.065%) to 97.04/100 000 in 2012 (95% CI 94.18 to 99.90) (0.097%). SLE was six times more common in women. The peak age of incidence was 50-59 years. There was regional variation in both incidence and prevalence. People of Black Caribbean ethnicity had the highest incidence and prevalence. Alternative definitions of SLE increased (definition 2) or decreased (definition 3) estimates of incidence and prevalence, but similar trends were found. CONCLUSIONS: The incidence of SLE has been declining but the prevalence has been increasing in the UK in recent years. Age, gender, region and ethnicity are risk factors for SLE. This is the first study to report ethnic differences on the incidence and prevalence of SLE using the CPRD.

Mortality in systemic lupus erythematosus in the United Kingdom 1999-2012.

OBJECTIVES: To estimate the mortality associated with SLE during the period 1999-2012 by age, gender and region; and to ascertain the cause of death for people with SLE. METHODS: A retrospective cohort study using the UK Clinical Practice Research Datalink. Incident SLE cases diagnosed between 1999 and 2012 were matched by age, sex and practice to four controls. Age-, gender- and region-specific mortality rates were calculated per 1000 person-years and compared with control mortality rates using mortality rate ratios (MRRs). For individuals with linked Office of National Statistics data, cause of death was summarized by International Classification of Disease-10 chapter heading. RESULTS: Of 2740 incident cases, 227 died, giving a mortality rate of 15.84/1000 person-years (95% CI 13.91, 18.04). This was 67% higher than in controls (MRR 1.67, 95% CI 1.43, 1.94, P < 0.001). Men with SLE had higher rates of mortality than females with SLE. Compared with controls, the mortality rate for males with SLE was 1.80 times that of male controls (95% CI 1.32, 2.45, P < 0.001); for females the mortality rate was 1.64 times higher (95% CI 1.37, 1.96, P < 0.001). The age-specific mortality rates increased significantly with age; however, the MRR diminished from 3.81 (95% CI 1.43, 10.14) in those aged <40 years to 0.82 (95% CI 0.36, 1.83) in those ⩾90 years. There was no significant difference in mortality between regions. Circulatory system disease and malignancy were the most frequent causes of death in both cases and controls. CONCLUSION: There remains an increased mortality for people with SLE compared with matched controls, particularly at younger ages.

Patients with gout can be cured in primary care.

Gout affects 2.5% of the total UK population and is four times more common in men than women. The peak prevalence and incidence in the UK is in those aged 80-84 years. Gout is associated with comorbidities such as nephrolithiasis, chronic renal impairment, metabolic syndrome, depression and heart disease. It is also associated with increased mortality. Untreated gout can result in disabling irreversible peripheral joint damage and chronic usage-related pain. However, gout is curable. The pathogenic agents that cause gout i.e.urate crystals can be eliminated through a combination of effective patient education and evidence-based, targeted urate-lowering therapy. Gout is caused by the precipitation of monosodium urate crystals in and around a joint. The crystals preferentially form in peripheral, cooler joints and especially in those with osteoarthritis. It is thought that some of these preformed crystals within articular cartilage spill over into the joint space and trigger an acute attack of inflammation. Uric acid is predominantly renally excreted and the common heritable component of gout results from relative inefficiency of urate excretion. Chronic kidney disease, metabolic syndrome and drugs that reduce renal function (e.g. thiazide diuretics, beta-blockers and ACE inhibitors) will all lead to reduced elimination. Patients with chronic gout can present with monoarthritis but more commonly present with asymmetrical polyarthritis or tophi. Joints affected by osteoarthritis are preferentially targeted, the most common sites of involvement are feet, knees, hands and elbows. Diagnosis can be confirmed in primary care by taking a good history and clinical examination. An acute peripheral monoarthritis which reaches its peak within 24 hours and causes 'the worst pain ever experienced' is characteristic of an acute attack. A patient may have co-existing risk factors for gout such as osteoarthritis, obesity, hypertension, renal impairment, diuretic and antihypertensive drug use or increased beer or spirit consumption. A raised serum uric acid can confirm the diagnosis, however, this can be normal in the acute phase. Radiographs are rarely helpful but joint ultrasound may demonstrate deposits in cartilage, the synovium and peri-articular sites.

Patients with gout adhere to curative treatment if informed appropriately: proof-of-concept observational study.

INTRODUCTION: Many doctors believe that patients with gout are unwilling to receive urate-lowering therapy (ULT) and blame them for poor adherence to management. OBJECTIVE: To test the effectiveness of a complex intervention for gout that incorporates key elements of current guidelines, including full patient information, delivered in an optimal setting (specialist hospital clinic). METHOD: Observational study of patients reporting ongoing attacks of gout recruited from primary care lists. 106 participants (94 men, 12 women; mean age 61 years) were enrolled in the study. Patients received a predominantly nurse-delivered intervention that included education, individualised lifestyle advice and appropriate ULT. The predefined goal was to achieve serum uric acid (SUA) levels≤360 µmol/l after 1 year in at least 70% of participants. RESULTS: Of the 106 participants at baseline, 16% had tophi; mean (SD) baseline SUA was 456 (98) µmol/l. All participants agreed to joint aspiration to confirm gout and all wished to receive ULT. At 12 months, 92% of the 106 participants had achieved the therapeutic target (SUA≤360 µmol); 85% had SUA<300 µmol/l. Allopurinol was the most commonly used ULT, requiring a median dose of 400 mg daily to achieve the target. Improvements in Short Form-36 were observed (significant for pain) after 1 year. CONCLUSION: A predominantly nurse-led intervention including education, lifestyle advice and ULT can successfully achieve the recommended treatment target in more than 9 out of 10 patients. Full explanation and discussion about the nature of gout and its treatment options and individualisation of management probably account for this success.

Compliance with NICE guidance on the use of anti-TNFalpha agents in ankylosing spondylitis: an east and west Midlands regional audit.

Here we report on an audit performed to examine compliance with National Institute for Health and Clinical Excellence (NICE) guidelines for the use of anti-tumour necrosis factor alpha (anti-TNFalpha) in treating patients with ankylosing spondylitis (AS). Data from 17 rheumatology centres across the Midlands were collected prospectively from patients with AS attending outpatient clinics and retrospectively in patients receiving anti-TNFalpha but not attending outpatient clinics during the audit. In total, 80% of the 416 patients for whom data were collected were male. Of the 238 patients recruited prospectively, 41% were receiving anti-TNFalpha. Reviewing all patients on anti-TNFalpha (N=275), pre-treatment assessments 12 weeks apart were documented in 55% of patients. After anti-TNFalpha treatment had started, regular 12-weekly assessments occurred in 46% of patients. Therefore, compliance with NICE guidance was found to vary among centres. Based on our audit, clinical capacity, and clinical or patient choice might be influencing the suboptimal adherence seen in assessment timing suggested by NICE guidelines relating to the use of anti-TNFalpha in treating patients with AS.

Conformational isomerization kinetics of pent-1-en-4-yne with 3,330 cm-1 of internal energy measured by dynamic rotational spectroscopy.

We demonstrate the application of molecular rotational spectroscopy to measure the conformation isomerization rate of vibrationally excited pent-1-en-4-yne (pentenyne). The rotational spectra of single quantum states of pentenyne are acquired by using a combination of IR-Fourier transform microwave double-resonance spectroscopy and high-resolution, single-photon IR spectroscopy. The quantum states probed in these experiments have energy eigenvalues of approximately 3,330 cm(-1) and lie above the barrier to conformational isomerization. At this energy, the presence of intramolecular vibrational energy redistribution (IVR) is indicated through the extensive local perturbations found in the high-resolution rotation-vibration spectrum of the acetylenic C-H stretch normal-mode fundamental. The fact that the IVR process produces isomerization is deduced through a qualitatively different appearance of the excited-state rotational spectra compared with the pure rotational spectra of pentenyne. The rotational spectra of the vibrationally excited molecular eigenstates display coalescence between the characteristic rotational frequencies of the stable cis and skew conformations of the molecule. This coalescence is observed for quantum states prepared from laser excitation originating in the ground vibrational state of either of the two stable conformers. Experimental isomerization rates are extracted by using a three-state Bloch model of the dynamic rotational spectra that includes the effects of chemical exchange between the stable conformations. The time scale for the conformational isomerization rate of pentenyne at total energy of 3,330 cm(-1) is approximately 25 ps and is 50 times slower than the microcanonical isomerization rate predicted by the statistical Rice-Ramsperger-Kassel-Marcus theory.

Early Clinical Features in Systemic Lupus Erythematosus: Can They Be Used to Achieve Earlier Diagnosis? A Risk Prediction Model.

OBJECTIVE: To compare the primary care consulting behavior, prior to diagnosis, of people with systemic lupus erythematosus (SLE) with controls, and to develop and validate a risk prediction model to aid earlier SLE diagnosis. METHODS: We included a total of 1,739 incident SLE cases practice-matched to 6,956 controls from the UK Clinical Practice Research Datalink. Using logistic regression, odds ratios were calculated for age, sex, consultation rates, selected presenting clinical features, and previous diagnoses in the 5 years preceding diagnosis date. A risk prediction model was developed from pre-selected variables using backward stepwise logistic regression. Model discrimination and calibration were tested in an independent validation cohort of 1,831,747 patients. RESULTS: People with SLE had a significantly higher consultation rate than controls (median 9.2 versus 3.8 per year), which was in part attributable to clinical features that occur in SLE. The final risk prediction model included the variables age, sex, consultation rate, arthralgia or arthritis, rash, alopecia, sicca, Raynaud's phenomenon, serositis, and fatigue. The model discrimination and calibration in the validation sample was good (receiver operating characteristic curve 0.75, 95% confidence interval 0.73, 0.78). However, absolute risk predictions for SLE were typically less than 1% due to the rare nature of SLE. CONCLUSION: People with SLE consult their general practitioner more frequently and with clinical features attributable to SLE in the 5 years preceding diagnosis, suggesting that there are potential opportunities to reduce diagnostic delay in primary care. A risk prediction model was developed and validated that may be used to identify people at risk of SLE in future clinical practice.

Burden of Comorbidity in Systemic Lupus Erythematosus in the UK, 1999-2012.

OBJECTIVE: To estimate the comorbidity associated with systemic lupus erythematosus (SLE) in the UK during 1999-2012. METHODS: A retrospective cohort study using the UK Clinical Practice Research Datalink was conducted. Prevalent cases of SLE were matched by age, sex, and practice to 4 controls. The incidence of cardiovascular disease (CVD), stroke, end-stage renal failure (ESRF), cancer, osteoporosis, and infection were calculated per 1,000 person-years during the study period and compared to controls using Poisson regression to obtain incidence rate ratios (IRRs). IRRs were adjusted for baseline age, sex, body mass index, smoking status, alcohol intake, hypertension, hyperlipidemia, Charlson Index scores, and prednisolone use. Age- and sex-specific incidence rates were calculated. RESULTS: When comparing the 7,732 prevalent cases of SLE with 28,079 matched controls, the unadjusted IRR was 1.98 (95% confidence interval [95% CI] 1.69-2.31) for CVD, 1.81 (95% CI 1.49-2.19) for stroke, 7.81 (95% CI 4.68-13.05) for ESRF, 1.28 (95% CI 1.17-1.40) for cancer, 2.53 (95% CI 2.27-2.82) for osteoporosis, and 1.49 (95% CI 1.40-1.58) for infection. After adjustment, the rates remained significantly higher in cases. Men with SLE had higher rates of CVD, stroke, and cancer, whereas women had higher rates of infection and osteoporosis. Those at younger ages were at the greatest relative risk compared with controls. Cases had significantly higher Charlson Index scores at baseline. CONCLUSION: People with SLE in the UK have a greater burden of comorbidity and are more likely to develop CVD, stroke, ESRF, cancer, osteoporosis, and infection than people of the same age and sex.

Optimizing current treatment of gout.

Gout is the most common inflammatory arthritis worldwide. Although effective treatments exist to eliminate sodium urate crystals and to 'cure' the disease, the management of gout is often suboptimal. This article reviews available treatments, recommended best practice and barriers to effective care, and how these barriers might be overcome. To optimize the management of gout, health professionals need to know not only how to treat acute attacks but also how to up-titrate urate-lowering therapy against a specific target level of serum uric acid that is below the saturation point for crystal formation. Current perspectives are changing towards much earlier use of urate-lowering therapy, even at the time of first diagnosis of gout. Holistic assessment and patient education are essential to address patient-specific risk factors and ensuring adherence to individualized therapy. Shared decision-making between a fully informed patient and practitioner greatly increases the likelihood of curing gout.

Distribution of finger nodes and their association with underlying radiographic features of osteoarthritis.

OBJECTIVE: To determine the distribution of clinically palpable hand interphalangeal (IP) nodes at each finger and thumb joint in a population with nodes, the influence of left or right hand dominance and sex on the development of nodes, and the association between nodes and underlying radiographic features of osteoarthritis (OA). METHODS: We performed a cross-sectional analysis of participants in the Genetics of Osteoarthritis and Lifestyle (GOAL) study who had ≥1 Heberden's nodes or Bouchard's nodes on clinical examination. Frequencies (%) of nodes were described for each IP joint in the hand. Associations between nodes and underlying radiographic OA were shown with odds ratios (ORs) and 95% confidence intervals. A logistic regression model was used to adjust for the following confounding factors: age, sex, body mass index, left or right hand dominance, hand trauma, occupation with heavy manual activity, and participation in sports. RESULTS: Of the 3,170 GOAL participants, 1,939 had ≥1 nodes (mean age 68 years, 54% women). The distal IP joints of the index finger were the most frequently affected, followed by the thumb IP joint. Nodes were more common in dominant hands and women. There was a significant association between nodes and underlying radiographic OA (OR range 2.26-21.23). This association was stronger for joint space narrowing than for osteophytes. A dose-response relationship was found between clinical severity of Heberden's nodes and underlying radiographic change. CONCLUSION: Our study supports the positive association between nodes and radiographic OA, especially narrowing, and the influence of sex and left or right hand dominance on development of nodes. In this age group, presence of nodes may be taken as an indication of underlying small joint OA.

Long-term follow-up of different refractory systemic vasculitides treated with rituximab.

There is increasing interest in rituximab (RTX) as an alternative to cyclophosphamide (CYC) for remission induction in systemic vasculitis. Recent studies have reported high remission rates, but it is not clear how long the initial remission lasts [1, 2]. A retrospective study was undertaken of 15 cases of refractory systemic vasculitis (11 Wegener's granulomatosis, 1 Churg-Strauss syndrome, 1 cutaneous polyarteritis nodosa and 2 cryoglobulinaemic vasculitis) treated with RTX, with a mean follow-up of 34 months. All had previously received CYC, and 14, at least one other immunosuppressive drug. All had active disease when treated (median Birmingham Vasculitis Activity Score (BVAS) 2003, 13). All cases achieved remission (BVAS 2003, 0). Thirteen required re-treatment, nine due to relapse (mean, 9 months after initial treatment) and four because of repopulation or rising ANCA in the context of CYC intolerance or previous CYC refractory disease. Relapsing cases have been successfully re-treated up to five further cycles, either at B cell repopulation or at six monthly intervals. Infections were rare. Mean IgG levels fell significantly, and IgM levels became subnormal in six cases. There were three cases of neutropenia, one severe at 10 months post-treatment. These results provide further evidence that RTX is an effective induction agent in systemic vasculitis. The optimal and long-term outcome of re-treatment remains to be defined.