Maternal and neonatal complications in pregnancies with and without pre-gestational diabetes mellitus.

OBJECTIVES: To compare pregnancy complications in pregnancies with and without pre-gestational diabetes mellitus (DM) managed in a multidisciplinary high-risk diabetes antenatal clinic. METHODS: This screening cohort study was undertaken at a large maternity unit in the United Kingdom between January 2010 and December 2022. We included singleton pregnancies that booked at our unit at 11-13 weeks' gestation. Univariate and multivariate logistic regression analysis was carried out to determine risks of complications in pregnancies with type 1 and type 2 DM after adjusting for maternal and pregnancy characteristics. Effect sizes were expressed as absolute risks (AR) and odds ratio (OR) (95 % confidence intervals [CI]). RESULTS: The study population included 53,649 singleton pregnancies, including 509 (1.0 %) with pre-existing DM and 49,122 (99.0 %) without diabetes. Multivariate logistic regression analysis demonstrated that there was a significant contribution from pre-existing DM in prediction of adverse outcomes, including antenatal complications such as fetal defects, stillbirth, preterm delivery, polyhydramnios, preeclampsia and delivery of large for gestational age (LGA) neonates; intrapartum complications such as caesarean delivery (CS) and post-partum haemorrhage; and neonatal complications including admission to neonatal intensive care unit, hypoglycaemia, jaundice and hypoxic ischaemic encephalopathy (HIE). In particular, there was a 5-fold increased risk of stillbirth and HIE. CONCLUSIONS: The maternal and neonatal complications in pregnancies with pre-existing DM are significantly increased compared to those without DM despite a decade of intensive multidisciplinary antenatal care. Further research is required to investigate strategies and interventions to prevent morbidity and mortality in pregnancies with pre-gestational DM.

Gestational Diabetes Mellitus: Association with Maternal and Neonatal Complications.

Background and objectives: Gestational diabetes mellitus (GDM) is known to be associated with pregnancy complications but there is limited evidence about the strength of these associations in recent clinical practice, especially after the introduction of strict guidelines for the management of pregnancies with GDM in a multidisciplinary team setting. The objectives of our study were to first compare the rates of complications in pregnancies with GDM with those that had pre-existing diabetes mellitus and those without diabetes; and second, to derive measures of effect size expressed as odds ratios after adjustment for confounding factors to assess the independent association of GDM in prediction of these pregnancy complications. Materials and Methods: This was a prospective cohort study undertaken at a large maternity unit in the United Kingdom between January 2010 and June 2022. We included singleton pregnancies that were booked at our unit at 11-13 weeks' gestation. Multivariate regression analysis was carried out to determine the risks of complications in pregnancies with GDM after adjusting for pregnancy characteristics. Risks were expressed as odds ratio (OR) (95% confidence intervals [CI]) and expressed graphically in forest plots. Results: The study population included 53,649 singleton pregnancies including 509 (1%) with pre-existing DM, 2089 (4%) with GDM and 49,122 (95%) pregnancies without diabetes. Multivariate regression analysis demonstrated that there was a significant independent contribution from GDM in the prediction of adverse outcomes, including maternal complications such as preterm delivery, polyhydramnios, preeclampsia and delivery of large for gestational age neonates and elective caesarean section (CS); and neonatal complications including admission to neonatal intensive care unit, hypoglycaemia, jaundice and respiratory distress syndrome. Conclusions: GDM is associated with an increased rate of pregnancy complications compared to those without diabetes, even after adjustment for maternal and pregnancy characteristics. GDM does not increase the risk of stillbirth, hypoxic ischaemic encephalopathy or neonatal death.

Infective endocarditis in the military patient.

Infective endocarditis (IE) is a potentially fatal cardiac infection associated with an inhospital mortality rate of up to 22%. Fifty per cent of IE cases develop in patients with no known history of valve disease. It is therefore important to remain vigilant to the possibility of the diagnosis in patients with a febrile illness and unknown source. From a military perspective, our patients are unique due to the breadth of pathogens they are exposed to, and blood-culture-negative IE is a risk. In particular, there should be awareness of Coxiella burnetii as a possible causative pathogen. In this review we incorporate the latest consensus from systematic reviews and publications identified by a literature search through Medline. We describe the diagnosis and management of IE with particular reference to the military population.

Sustained clinical remission in rheumatoid arthritis: prevalence and prognostic factors in an inception cohort of patients treated with conventional DMARDS.

OBJECTIVE: Clinical remission is now a realistic goal in managing RA following the introduction of biologic agents. As there are limited data on sustained remission in conventionally treated RA, this study examines prevalence and predictive factors of sustained remission in a pre-biologic inception cohort of RA. METHODS: Patients with recent onset RA and before use of DMARDs were recruited from nine centres. Standard clinical and radiological assessments were recorded at baseline and yearly. Point remission was defined by DAS of <1.6, and sustained remission if DAS was <1.6 at all 3-, 4- and 5-year follow-ups. Sustained remission was compared with baseline features, with mortality and with radiological and functional progression in 704 patients. RESULTS: Point remission at 3, 4 and 5 years was 25, 26 and 22%, respectively. Eleven per cent (n = 78) had sustained remission. Male sex, short duration of symptoms and less tender joints at baseline were independent predictors of sustained remission. These patients had fewer DMARD therapies and less radiographic progression by 5 years. Mean HAQ decreased from 0.79 to 0.13 (P < 0.001) in sustained remission, compared with an increase from 0.92 to 1.1 (P < 0.001) in the non-remission group. CONCLUSION: Sustained clinical remission by 5 years with conventional DMARDs was 11%, half as likely as point remission. Prognostic factors were similar to comparable studies and simple to measure. Patients in sustained clinical remission showed less structural damage and better functional outcomes.

Use of conservative and surgical foot care in an inception cohort of patients with rheumatoid arthritis.

OBJECTIVES: To describe conservative and surgical foot care in patients with RA in England and explore factors that predict the type of foot care received. METHODS: Use of podiatry and type of foot surgery were outcomes recorded in an inception cohort involving nine rheumatology centres that recruited patients with RA between 1986 and 1998 across England. Associations between patient-specific factors and service use were identified using univariate logistic regression analyses. The independence of these associations was then verified through multiple binary logistic regression modelling. RESULTS: Data were collected on 1237 patients with RA [66.9% females, mean (s.d.) age at disease onset = 54.36 (14.18) years, median DAS = 4.09 (1st quartile = 3.04, 3rd quartile = 5.26), median HAQ = 1 (0.50, 1.63)]. Interventions involving the feet in the cohort were low with only 364 (30%) out of 1218 receiving podiatry and 47 (4%) out of 1237 patients having surgery. At baseline, female gender, increasing age at onset, being RF positive and higher DAS scores were each independently associated with increased odds of seeing a podiatrist. Gender, age of onset and baseline DAS were independently associated with the odds of having foot surgery. CONCLUSIONS: Despite the known high prevalence of foot pathologies in RA, only one-third of this cohort accessed podiatry. While older females were more likely to access podiatry care and younger patients surgery, the majority of the RA population did not access any foot care.

Ischaemic manifestations in giant cell arteritis are associated with area level socio-economic deprivation, but not cardiovascular risk factors.

OBJECTIVES: To determine whether ischaemic manifestations of GCA are associated with pre-existing hypertension, atherosclerosis or area-level socio-economic deprivation. METHODS: We conducted an observational study of rheumatologist/ophthalmologist-diagnosed GCA in eight UK centres. The main outcome measure was ischaemic manifestations observed during active GCA: visual loss/blurring, aura, diplopia, jaw/tongue/limb claudication, cerebral/myocardial ischaemia or scalp necrosis. RESULTS: Out of 271 patients, 222 had ischaemic manifestations. Adjusted odds ratios (ORs) for the influence of hypertension and atherosclerosis were 1.6 (95% CI 0.8, 3.1) and 1.5 (0.6, 3.5). The most striking finding was an association of ischaemic manifestations with increasing Index of Deprivation 2007 score: OR 4.2 (95% CI 1.3, 13.6) for the most-deprived quartile compared with the least-deprived quartile. Similar effect sizes were seen within each recruitment centre. Deprivation was associated with smoking and negatively associated with previous polymyalgia. However, neither of these variables, nor hypertension or atherosclerosis, appeared responsible for mediating the effect of deprivation on ischaemic complications. Smoking was not associated with ischaemic manifestations. Median symptom duration before treatment was 30 days; after adjusting for symptom duration, the OR for ischaemic complications was 3.2 (95% CI 1.0, 10.8) for the most-deprived quartile compared with the least-deprived quartile. CONCLUSIONS: In GCA, area-level socio-economic deprivation was associated with ischaemic manifestations: this was not mediated by traditional cardiovascular risk factors. These findings are novel and require replication. Delay between first symptoms and treatment may play a role. Public awareness campaigns about GCA should aim especially to engage individuals living in more deprived areas to encourage early presentation and prompt treatment.

Interstitial lung disease has a poor prognosis in rheumatoid arthritis: results from an inception cohort.

OBJECTIVES: Pulmonary complications of RA are well described. Although some are benign, interstitial lung disease (ILD) has a poor prognosis. Few RA inception cohorts have reported the natural history of ILD related to RA (RA-ILD). We examine its incidence, outcome and prognostic indicators. METHODS: Extra-articular features and comorbidity have been recorded yearly in a well-established inception cohort of RA with a 20-year follow-up. Standard clinical, laboratory and radiological measures of RA were recorded at baseline and yearly. Details of deaths were provided by a national central register. RESULTS: Out of 1460 patients, 52 developed RA-ILD, half either at baseline or within 3 years of onset. The annualized incidence was 4.1/1000 (95% CI 3.0, 5.4) and the 15-year cumulative incidence 62.9/1000 (95% CI 43.0, 91.7). Incidence of RA-ILD was associated with older age, raised baseline ESR and HAQ. Evidence to implicate any drug effect (e.g. MTX) was lacking. Of these patients, 39 died, attributed to RA-ILD in 28. Median survival following diagnosis of RA-ILD was 3 years. CONCLUSIONS: RA-ILD is an important and early feature of RA. It is related to disease activity and has a poor prognosis. Further studies are required to determine whether screening for pulmonary disease would identify these patients at an earlier stage.

Mixed results with baricitinib in biological-resistant adult-onset Still's disease and undifferentiated systemic autoinflammatory disease.

This clinical case series describes our experience with the use of Janus kinase 1/2 inhibitor baricitinib in two patients suffering from refractory adult-onset Still's disease (AOSD) as well as in one case suffering from AOSD-like autoinflammatory disease in the context of myelodysplastic syndrome. All patients suffered from disease non-responsive to conventional Disease-modifying antirheumatic drugs (DMARDs) as well as biological therapies including interleukin (IL)-1 and IL-6 blockade, relying instead on high daily doses of prednisolone. We also report the first case of Pneumocystis jirovecii infection following baricitinib use.

Liver fibrosis in patients with psoriasis and psoriatic arthritis on long-term, high cumulative dose methotrexate therapy.

OBJECTIVES: Dermatologists and rheumatologists have differed in their use of serial liver biopsy and liver function tests (LFT) to monitor the risk of hepatic fibrosis in long-term MTX therapy. It is judged safe to monitor LFT only in RA. Whilst there are few studies in PsA to justify this approach, it is widely used in rheumatology practice. The study aimed to assess prevalence of hepatic fibrosis in both psoriasis and PsA patients on long-term MTX therapy. METHODS: A prospective study of 54 patients with psoriatic disease had a liver biopsy according to dermatology guidelines on long-term MTX treatment with full assessment of risk factors. Previously, monitoring these patients was in accordance with ACR guidelines with 3-monthly LFT. RESULTS: MTX treatment duration was a mean of 6.9 years, with a mean cumulative dose of 4396 mg. There were no cases of advanced fibrosis or of cirrhosis and mild early fibrosis in 11 (22%) patients. The presence of early mild changes was related to the number of risk factors that the patient had for hepatic fibrosis [also the risk factors for non-alcoholic steatohepatitis (NASH)]. Pro-collagen 3 N-terminal peptide (PIIINP) was unhelpful in PsA and frequently elevated despite normal liver biopsy. CONCLUSIONS: Despite other risk factors for NASH, monitoring for hepatic fibrosis using serial liver function and ACR guidelines tests alone as in RA appears safe in psoriasis and PsA. Liver biopsy ought to be considered to assess the liver if LFT are persistently elevated. PIIINP is misleading in active PsA.

18F-FDG PET/CT Imaging of Necrotizing Crescentic Glomerulonephritis With Anti-Glomerular Basement Membrane Disease.

A 30-year-old woman presented with lethargy, night sweats, and fever with raised inflammatory markers. Anti-neutrophil cytoplasmic antibody was negative. Abdominopelvic CT was unremarkable. Subsequently, she underwent FDG PET/CT showing globally enlarged kidneys with diffuse hypermetabolic activity within the renal parenchyma bilaterally. Renal biopsies showed morphologic features of an active necrotizing crescentic glomerulonephritis, which was confirmed clinically and treated. This case demonstrates the role that FDG PET/CT can play in inflammatory conditions, such as glomerulonephritis, where it may be clinically useful when the presentation is atypical.

Long-term effectiveness of tumour necrosis factor-α inhibitor treatment for psoriatic arthritis in the UK: a multicentre retrospective study.

OBJECTIVE: Real-world evidence of the long-term effectiveness of TNF-α inhibitor (TNFi) therapy in patients with PsA is limited. This study was conducted to describe patterns of TNFi therapy and treatment responses in patients with PsA treated in UK clinical practice. METHODS: A multicentre, retrospective, observational cohort study of consenting patients treated with TNFi for PsA with ≥3 years follow-up from first TNFi initiation (observation period) was carried out in 11 UK National Health Service hospitals. Data were collected concerning baseline patient characteristics, PsA-related treatment pathways and TNFi treatment responses (PsA response criteria components: swollen/tender joint counts, physician and patient global assessments). RESULTS: The mean age of patients (n = 141) was 50.3 (s.d.: 12.1) years (50% male). During a median observation period of 4.5 (range: 3.4-5.5) years, patients received a median of one (range: one to five) TNFi. Twelve-week response rates for first TNFi (where available) were as follows: 80% (n = 64/80) for swollen joint counts, 79% (n = 63/79) for tender joint counts, 79% (n = 37/47) for physician global assessments, 69% (n = 41/59) for patient global assessments and 79% (n = 37/47) for PsA response criteria. At the end of the observation period, the proportions of patients remaining on first, second, third and fourth/fifth TNFi were 56, 15, 5 and 3%, respectively; 21% of patients permanently discontinued TNFi therapy. CONCLUSION: Long-term TNFi therapy is generally well tolerated and may be effective; however, after initial TNFi failure, there appears to be progressively less benefit and more adverse effects with successive TNFi switches. Strategies are needed for effective therapy for PsA beyond the first TNFi failure.

The effectiveness of ultrasound guided hydrodistension and physiotherapy in the treatment of frozen shoulder/adhesive capsulitis in primary care: a single centre service evaluation.

BACKGROUND: Evidence for optimal non-operative treatment of frozen shoulder is lacking. The present study aimed to evaluate a treatment strategy for stage II to III frozen shoulder provided by the current primary care musculoskeletal service. METHODS: General practioner referrals of shoulder pain to the musculoskeletal service diagnosed with stage II to III frozen shoulder and who opted for a treatment strategy of hydrodistension and guided physiotherapy exercise programme over a 12-month period were evaluated for 6 months. Thirty-three patients were diagnosed with stage II to III frozen shoulder by specialist physiotherapists and opted for the treatment strategy. Outcome measures included Shoulder Pain Disability Index (SPADI) and Shortened Disabilities of the Arm, Shoulder and Hand (QuickDASH), pain score and range of movement. Data were collected at baseline, as well as at 6 weeks, 12 weeks and 6 months. RESULTS: All patients significantly improved in shoulder symptoms on the SPADI and QuickDASH scores (p < 0.001). Pain scores and range of shoulder movement flexion, abduction, external rotation showed significant improvement at all time points (p < 0.001). CONCLUSIONS: This service evaluation demonstrates that management of frozen shoulder stage II to III, as conducted by physiotherapists in a primary care setting utilizing hydrodistension and a guided exercise programme, represents an effective non-operative treatment strategy.

Therapeutic effect of the combination of etanercept and methotrexate compared with each treatment alone in patients with rheumatoid arthritis: double-blind randomised controlled trial.

BACKGROUND: Etanercept and methotrexate are effective in the treatment of rheumatoid arthritis but no data exist on concurrent initiation or use of the combination compared with either drug alone. We aimed to assess combination treatment with etanercept and methotrexate versus the monotherapies in patients with rheumatoid arthritis. METHODS: In a double-blind, randomised, clinical efficacy, safety, and radiographic study, 686 patients with active rheumatoid arthritis were randomly allocated to treatment with etanercept 25 mg (subcutaneously twice a week), oral methotrexate (up to 20 mg every week), or the combination. Clinical response was assessed by criteria of the American College of Rheumatology (ACR). The primary efficacy endpoint was the numeric index of the ACR response (ACR-N) area under the curve (AUC) over the first 24 weeks. The primary radiographic endpoint was change from baseline to week 52 in total joint damage and was assessed with the modified Sharp score. Analysis was by intention to treat. FINDINGS: Four patients did not receive any drug; thus 682 were studied. ACR-N AUC at 24 weeks was greater for the combination group compared with etanercept alone and methotrexate alone (18.3%-years [95% CI 17.1-19.6] vs 14.7%-years [13.5-16.0], p<0.0001, and 12.2%-years [11.0-13.4], p<0.0001; respectively). The mean difference in ACR-N AUC between combination and methotrexate alone was 6.1 (95% CI 4.5-7.8, p<0.0001) and between etanercept and methotrexate was 2.5 (0.8-4.2, p=0.0034). The combination was more efficacious than methotrexate or etanercept alone in retardation of joint damage (mean total Sharp score -0.54 [95% CI -1.00 to -0.07] vs 2.80 [1.08 to 4.51], p<0.0001, and 0.52 [-0.10 to 1.15], p=0.0006; respectively). The mean difference in total Sharp score between combination and methotrexate alone was -3.34 (95% CI -4.86 to -1.81, p<0.0001) and between etanercept and methotrexate was -27 (-3.81 to -0.74, p=0.0469). The number of patients reporting infections or adverse events was similar in all groups. INTERPRETATION: The combination of etanercept and methotrexate was significantly better in reduction of disease activity, improvement of functional disability, and retardation of radiographic progression compared with methotrexate or etanercept alone. These findings bring us closer to achievement of remission and repair of structural damage in rheumatoid arthritis.

Curry-assisted diagnosis in the rheumatology clinic.

We report five cases of glucocorticoid-responsive mouth symptoms in polymyalgia rheumatica/giant cell arteritis (GCA); three cases of tongue pain exacerbated by hot/spicy food, a case of scalp pain made worse by eating hot/spicy food and a case of sore tongue as a presenting feature of GCA. These cases emphasize the importance of asking about mouth symptoms and changes in taste when evaluating patients with suspected GCA.

Persistently raised aspartate aminotransferase (AST) due to macro-AST in a rheumatology clinic.

Macrocomplexes between immunoglobins and aspartate aminotransferase (macro-AST) may result in persistently increased AST concentration. The presence of macro-AST in patients has been implicated in unnecessary investigations of abnormal liver function tests. We report the case of a 44-year-old female who presented to the rheumatology clinic with a 12-months' history of constant widespread pain affecting her limbs and was found to have an elevated AST concentration. Further information from her GP revealed a 14-years' history of elevated AST with otherwise normal liver function. Previous abdominal ultrasound and two liver biopsies carried out 2 years apart were normal. This prompted further analytical investigation by the biochemistry department which identified macro-AST as the cause. This case illustrates that persistently raised isolated AST concentration with no other abnormal indices may warrant macroenzyme analysis potentially avoiding unnecessary invasive investigations.