Vitamin D supplementation in systemic lupus erythematosus: relationship to disease activity, fatigue and the interferon signature gene expression.

BACKGROUND: In addition to the well-known role of vitamin D in calcium homeostasis and bone metabolism, vitamin D is important in the modulation of the immune system and inflammatory processes. Vitamin D deficiency is common in patients with systemic lupus erythematosus (SLE), possibly as a result of sun avoidance. The aim of this prospective open-label study was to assess the effect of the treatment of vitamin D deficiency and insufficiency in SLE patients, particularly with regards to disease activity, fatigue and interferon signature gene expression. METHODS: 31 SLE patients, 13 with vitamin D deficiency and 18 with vitamin D insufficiency were treated with vitamin D3. They were supplemented with vitamin D3 8000 IU daily for 8 weeks if they were vitamin D deficient, or 8000 IU daily for 4 weeks if they were insufficient. This was followed by 2000 IU daily maintenance. They were assessed at baseline, after 6 and 12 months by means of an interview, filling in questionnaires and blood tests. The expression of 12 interferon signature genes in RNA extracted from whole blood was measured by using QuantiGene Plex technology. RESULTS: An improvement in disease activity measured by systemic lupus erythematosus disease activity index-2K (SLEDAI-2K; p = 0.028) and fatigue measured by fatigue severity scale (FSS; p = 0.071) at 12 months were noted. A significant decrease in anti-double stranded deoxyribonucleic acid (dsDNA) titre (p = 0.045) was also noted. The mean interferon signature gene expression score decreased from baseline to 6 months, however statistical significance was not achieved (p = 0.165). CONCLUSIONS: Improved disease activity and fatigue have been noted when Vitamin D has been supplemented in vitamin D deficient/insufficient SLE patients. One possible mechanism could be the suppression of the interferon signature gene expression. TRIAL REGISTRATION: The study was registered with the ISRCTN registry on 12/04/2021 (Trial ID: ISRCTN59058825).

Diabetes mellitus and cardiovascular risk management in patients with rheumatoid arthritis: an international audit.

AIM: The objective was to examine the prevalence of atherosclerotic cardiovascular disease (ASCVD) and its risk factors among patients with RA with diabetes mellitus (RA-DM) and patients with RA without diabetes mellitus (RAwoDM), and to evaluate lipid and blood pressure (BP) goal attainment in RA-DM and RAwoDM in primary and secondary prevention. METHODS: The cohort was derived from the Survey of Cardiovascular Disease Risk Factors in Patients with Rheumatoid Arthritis from 53 centres/19 countries/3 continents during 2014-2019. We evaluated the prevalence of cardiovascular disease (CVD) among RA-DM and RAwoDM. The study population was divided into those with and without ASCVD, and within these groups we compared risk factors and CVD preventive treatment between RA-DM and RAwoDM. RESULTS: The study population comprised of 10 543 patients with RA, of whom 1381 (13%) had DM. ASCVD was present in 26.7% in RA-DM compared with 11.6% RAwoDM (p<0.001). The proportion of patients with a diagnosis of hypertension, hyperlipidaemia and use of lipid-lowering or antihypertensive agents was higher among RA-DM than RAwoDM (p<0.001 for all). The majority of patients with ASCVD did not reach the lipid goal of low-density lipoprotein cholesterol <1.8 mmol/L. The lipid goal attainment was statistically and clinically significantly higher in RA-DM compared with RAwoDM both for patients with and without ASCVD. The systolic BP target of <140 mm Hg was reached by the majority of patients, and there were no statistically nor clinically significant differences in attainment of BP targets between RA-DM and RAwoDM. CONCLUSION: CVD preventive medication use and prevalence of ASCVD were higher in RA-DM than in RAwoDM, and lipid goals were also more frequently obtained in RA-DM. Lessons may be learnt from CVD prevention programmes in DM to clinically benefit patients with RA .

The Epidemiology and Outcomes of Septic Arthritis in the Maltese Islands: A Hospital-Based Retrospective Cohort Study.

OBJECTIVE/AIM: Septic arthritis is an uncommon but important disease with significant morbidity and mortality, especially if inadequately managed. The aim of this epidemiological study was to identify the characteristics and outcomes of patients treated for septic arthritis at Mater Dei Hospital, Malta, over a 10-year period. METHODS: This was a retrospective observational study. Patients diagnosed with septic arthritis between 2008 and 2018 were recruited. Cases were identified by reviewing all inhospital episodes of patients diagnosed with septic arthritis according to Newman criteria. RESULTS: There were 124 cases of native joint septic arthritis and 138 of prosthetic joint infection. Cases were present amongst all age groups, with the highest incidence amongst those aged 61-70 years for both native and prosthetic infections. Fever was present in around 40% of cases. Raised white cell count was prevalent in 66.9% of native joint infections and 52.9% of prosthetic joints. Elevated C-reactive protein was overwhelmingly seen in most cases, present in 93.5% (median=159.5 mg/L; IQR=85.8-291) of native joints and 92.0% of prosthetic joint infections (median=68.7 mg/L; IQR=20.5-186). Over 55% of patients had one or more risk factors for joint sepsis, diabetes mellitus being the most prevalent clinical comorbidity (22.6% and 24.6% for native and prosthetic joint infections respectively). Synovial cultures were positive in 66% and 82% of native and prosthetic joint aspirates respectively. Staphylococcus aureus was the most commonly isolated organism from both native and prosthetic joint infection, followed by streptococcal infections in native joints and coagulase negative staphylococci and gram-negative infections in prosthetic joints. Fifteen deaths were directly attributed to joint sepsis. CONCLUSION: Absence of fever and elevated white cell count does not exclude the diagnosis. The mortality rate due to septic arthritis in this cohort of patients was found to be 5.7%. All deaths occurred in elderly patients with clinical comorbidities suggesting that this group is at highest risk.

Characterisation of Patients with Systemic Lupus Erythematosus in Malta: A Population Based Cohort Cross-Sectional Study.

Systemic Lupus Erythematosus (SLE) is a multisystemic autoimmune disorder. The aim of this study was to characterise the SLE patients living in Malta in order to estimate the prevalence and incidence of SLE and characterise the clinical presentation as well as identify any unmet needs. 107 SLE patients who fulfilled SLICC classification criteria were identified. These were invited to participate in the study by means of an interview, blood and urine tests, and filling of the following questionnaires: Fatigue Severity Scale (FSS), visual analogue scale (VAS) for fatigue, Hospital Anxiety and Depression Scale (HADS), VAS for pain, Pittsburgh Sleep Quality Index (PSQI), and modified Health Assessment Questionnaire (mHAQ). The estimated prevalence of SLE in Malta is 29.3 patients per 100,000 and the estimated incidence is 1.48 per 100,000 per year. 93.5% of SLE patients were female, and the mean age at diagnosis was 33.1 years. 60.8% were overweight or obese and body mass index (BMI) had a significant positive correlation with daily dose of prednisolone (R=0.177, p=0.046). 20.7% and 3.3% had a moderate and high disease activity, respectively, as measured by SLEDAI-2K. Disease activity had a significant positive correlation with functional disability measured by mHAQ (R=0.417, p<0.001). 56.5% had an abnormal level of fatigue (FSS >3.7) and 57.6% had a high level of anxiety (HADS ≥8). This study has identified a number of unmet needs of SLE patients, including obesity, uncontrolled disease activity, fatigue, and anxiety.

Opinions of Maltese doctors and pharmacists on medication errors.

BACKGROUND: Pharmacovigilance directive 2010/84/EU focused attention on medication errors and encouraged regulators to identify causing and contributing factors. OBJECTIVES: (1) To study opinions of doctors/pharmacists on factors bearing a causal link to MEs as well as ways to minimise MEs (2) to test whether differences in opinion exist between subgroups of doctors and pharmacists working in community, hospital or office settings. METHODS: Different questionnaires were circulated to doctors and pharmacists. Respondents were subdivided according to their primary practice. RESULTS: 320 responses were received (204 doctors/116 pharmacists). Differences in opinion reaching statistical significance were observed on distractions from staff, overwork and fatigue, availability of technical resources and having more than 1 doctor on duty. For pharmacists', differences on issues of generic medicine availability and interruptions were found. CONCLUSION: Distractions and interruptions while executing tasks was flagged as an area requiring attention. Issues of overwork and fatigue affect especially doctors in hospital the majority of which are of the opinion that regulatory control on patient numbers could minimize errors. Increasing technical resources and keeping knowledge up-to-date, addressing overwork and high patient workloads have been identified as important areas when looking to reduce MEs.

Determining the presence of Peripheral Arterial Disease in patients with Rheumatoid Arthritis.

OBJECTIVES: The aim of the study was to determine the manifestations of PAD in a population of RA participants with no history of cardiovascular events. METHODS: A prospective observational non-experimental study was conducted on 100 participants presenting with RA and no history of significant cardiovascular events. Vascular assessment including Doppler spectral waveform analysis and Ankle Brachial Pressure Index was conducted. RESULTS: Triphasic waveforms was found in the Posterior Tibial Artery (PT) in 70% right foot, 66% left foot and Dorsalis Pedis Artery (DP) in both feet in the64% of the patients. Twenty-nine per cent of the participants had biphasic PT right foot and 33% had biphasic PT left foot. Thirty-six per cent had biphasic DP both feet whilst only one participant (1%) had a discontinuous monophasic PT of both feet. The ABPI readings were found to be normal in 96% of participants and mild PAD was found in only 4% of the study population. CONCLUSIONS: Results indicate that whilst the ABPI index was normal in the majority of participants, waveform analysis was suboptimal (biphasic) in approximately one-third of the study sample. These findings highlight that the assessment of peripheral arterial perfusion should utilize both modalities to identify patients with early PAD.

The effect of vitamin D on disease activity, fatigue and interferon signature gene expression in systemic lupus erythematosus.

Systemic Lupus Erythematosus (SLE) is multi-system autoimmune disorder, whose pathogenesis involves several cascades that lead to the production of interferon alpha, which then mediates the manifestations of the disease. In SLE, the overexpression of interferon regulated genes, produce a unique interferon signature. This has a positive correlation with disease activity. Vitamin D deficiency is highly prevalent in SLE; the role of vitamin D in the course and prognosis of SLE is unknown. Vitamin D deficiency has been associated with a higher disease activity in SLE. Fatigue is also highly prevalent in SLE; its aetiology is multi-factorial. There is limited evidence on the relationship between vitamin D, fatigue and interferon signature gene expression. Further studies on this will establish whether treatment of vitamin D deficiency in SLE, has any significant effect on the level of fatigue and disease activity, and whether this could be due to the suppression of interferon signature gene expression.

Can rheumatologists diagnose and manage Giant Cell Arteritis better than non-rheumatologists? The Maltese Experience.

OBJECTIVES: Giant Cell Arteritis (GCA) remains a challenge both in terms of diagnosis and management as patients may present to several different specialists. The objectives were to determine incidence of biopsy-proven GCA in Malta and to compare the management between rheumatologists and non-rheumatologists. METHODS: This was a retrospective observational population study of patients with suspected GCA who underwent a temporal artery biopsy (TAB) between 2012 and 2015. Data collected consisted of demographics, presenting symptoms, TAB histology reports, treatment and outcome. The British Society for Rheumatology (BSR) 2010 guidelines were used as standard of care. RESULTS: 136 patients underwent a TAB for suspected GCA of which 26 were positive. The incidence of biopsy-proven GCA in Malta was 3.82 per 100,000 patient years in the over 50 population. There were 63 patients who were treated as GCA. Only 43.3% of confirmed cases had rheumatology input. TABs requested by rheumatologists were twice more likely to be positive compared to requests by non-rheumatologists (30.5% vs. 14.1%).The majority of patients were started on a Prednisolone dose between 40-60mg. Rheumatologists maintained patients on high doses for at least 1 month in 54% of cases as opposed to 20% under non-rheumatologists. Monitoring was more regular for cases followed up by rheumatologists (40% vs. 21%). CONCLUSIONS: Malta has a low incidence of biopsy proven GCA. Although rheumatologists are more likely to adhere to the recommended guidelines, improvement is needed. Rheumatologists should take the lead to minimise variation and optimise management of GCA.

Translation and validation of the Fatigue Severity Scale, Pittsburgh Sleep Quality Index and Modified Health Assessment Questionnaire into the Maltese Language, in a cohort of Maltese Systemic Lupus Erythematosus patients.

PURPOSE: The assessment of fatigue, sleep quality and functional disability requires the use of validated instruments such as the Fatigue Severity Scale (FSS), the Pittsburgh Sleep Quality Index (PSQI) and the Modified Health Assessment Questionnaire (mHAQ) respectively. The aim of this study was to translate and validate these instruments into the Maltese Language. METHOD: Forward translation from the original English version into Maltese was carried out by two translators. The two versions were compiled to produce a preliminary initial Maltese translation. This was translated back into English by two other translators. This led to the development of the pre-final version of the Maltese translation, which was pilot-tested in 20 bilingual patients with systemic lupus erythematosus. RESULTS: Psychometric testing revealed good reliability of the Maltese translation of the three questionnaires. Cronbach's alpha of the Maltese versions of the FSS, PSQI and mHAQ were 0.877, 0.859 and 0.897 respectively, showing good internal consistency. Validity of the Maltese version of the FSS was shown, since it had a significant positive correlation with visual analogue scale for fatigue (r=0.809, p<0.001). CONCLUSION: The Maltese translations were thus finalised, and could be used for clinical assessment or research purposes.

Pulmonary, renal and neurological comorbidities in patients with ankylosing spondylitis; implications for clinical practice.

Ankylosing spondylitis (AS) is associated with several comorbidities which contribute significantly to morbidity and mortality and add to the complexity of management. In addition to the well known extra-articular manifestations and increased cardiovascular risk, several pulmonary, renal, and neurological complications which have been associated with AS deserve equal attention. Whereas a clear link has been established for some manifestations, the evidence for other associations is less clear. Interstitial lung disease, apical fibrosis, secondary infection, and ventilatory restriction from reduced chest wall movement are well known pulmonary complications; more recently an association with sleep apnoea has been suggested. Renal amyloidosis and IgA nephropathy remain a treatment challenge which may respond to anti-TNF therapy. Atlanto axial subluxation and vertebral fractures can result in serious neurological complications and are notoriously difficult to diagnose unless a high level of suspicion is maintained. Despite several reports linking AS with demyelination a true link remains to be proved. This review discusses the prevalence, pathophysiology, and management of pulmonary, renal, and neurological complications, and implications for clinical practice.

Listening to patients: improving the outpatient service.

PURPOSE: This paper assesses the patients' healthcare information needs and expectations when they attend a rheumatology outpatient clinic. It proposes that obtaining the patients' perspectives about the services they use is an essential service-development tool. The aim of this paper is to expand the current domains used to evaluate these perspectives. DESIGN/METHODOLOGY/APPROACH: This paper is an exploratory study, looking at quality assessment and improvement based on Donabedian's quality model in a rheumatology outpatient setting. A structured interview schedule addressing care pathways was used and 70 consecutive patients were recruited. FINDINGS: The article provides insights about how relevant change can be brought about when service development is contemplated. It suggests that patients are important stakeholders in the ongoing service development process. RESEARCH LIMITATIONS/IMPLICATIONS: Because rheumatological conditions tend to be chronic and require long-term follow-up, the results may lack generalisability. Therefore, researchers are encouraged to test propositions in different clinical settings. PRACTICAL IMPLICATIONS: The article highlights healthcare delivery areas that are not meeting patient expectations. Some recommendations (such as informing waiting patients regularly about any delays) require minimal additional resources for successful implementation. Service providers need to obtain the patients' healthcare perspectives to ensure that services are built around their needs. ORIGINALITY/VALUE: This article fulfils an identified need to study how patients perceive service quality.

Freedom of movement across the EU: legal and ethical issues for children with chronic disease.

While freedom of movement has been one of the most highly respected human right across the EU, there are various aspects which come into play which still need to be resolved for this to be achieved in practice. One of these key issues is cross border health care. Indeed, there is an increasing awareness of standardisation of health service provision and cross border collaboration in the EU. However, certain groups particularly children may be at risk of suboptimal treatment as a result. We present the case of a child patient which highlights the complexity of this matter spanning family law, health law, social security law as well as ethical issues. EU legislation needs to ensure that children patients have access to high quality care across the EU borders.

Demyelination during anti-TNFα therapy for ankylosing spondylitis.

A 34-year-old ankylosing spondylitis (AS) patient on etanercept for 30 months presented to neurologists with paresthesia of his hands and feet. Magnetic resonance imaging (MRI) scans showed multifocal hyperintense lesions. Symptoms did not improve on stopping the anti-tumor necrosis factor (TNF) agent. Few cases of demyelinating disease occurring after more than 2 years of treatment with anti-TNF agents have been reported in patients with AS. Opthalmologists, internists, neurologists, and rheumatologists need to be aware of these adverse events, as patients may present to any of these specialties many years after treatment.