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.

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.

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.

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.

Association of HLA-DRB1 amino acid residues with giant cell arteritis: genetic association study, meta-analysis and geo-epidemiological investigation.

INTRODUCTION: Giant cell arteritis (GCA) is an autoimmune disease commonest in Northern Europe and Scandinavia. Previous studies report various associations with HLA-DRB1*04 and HLA-DRB1*01; HLA-DRB1 alleles show a gradient in population prevalence within Europe. Our aims were (1) to determine which amino acid residues within HLA-DRB1 best explained HLA-DRB1 allele susceptibility and protective effects in GCA, seen in UK data combined in meta-analysis with previously published data, and (2) to determine whether the incidence of GCA in different countries is associated with the population prevalence of the HLA-DRB1 alleles that we identified in our meta-analysis. METHODS: GCA patients from the UK GCA Consortium were genotyped by using single-strand oligonucleotide polymerization, allele-specific polymerase chain reaction, and direct sequencing. Meta-analysis was used to compare and combine our results with published data, and public databases were used to identify amino acid residues that may explain observed susceptibility/protective effects. Finally, we determined the relationship of HLA-DRB1*04 population carrier frequency and latitude to GCA incidence reported in different countries. RESULTS: In our UK data (225 cases and 1378 controls), HLA-DRB1*04 carriage was associated with GCA susceptibility (odds ratio (OR) = 2.69, P = 1.5×10(-11)), but HLA-DRB1*01 was protective (adjusted OR = 0.55, P = 0.0046). In meta-analysis combined with 14 published studies (an additional 691 cases and 4038 controls), protective effects were seen from HLA-DR2, which comprises HLA-DRB1*15 and HLA-DRB1*16 (OR = 0.65, P = 8.2×10(-6)) and possibly from HLA-DRB1*01 (OR = 0.73, P = 0.037). GCA incidence (n = 17 countries) was associated with population HLA-DRB1*04 allele frequency (P = 0.008; adjusted R(2) = 0.51 on univariable analysis, adjusted R(2) = 0.62 after also including latitude); latitude also made an independent contribution. CONCLUSIONS: We confirm that HLA-DRB1*04 is a GCA susceptibility allele. The susceptibility data are best explained by amino acid risk residues V, H, and H at positions 11, 13, and 33, contrary to previous suggestions of amino acids in the second hypervariable region. Worldwide, GCA incidence was independently associated both with population frequency of HLA-DRB1*04 and with latitude itself. We conclude that variation in population HLA-DRB1*04 frequency may partly explain variations in GCA incidence and that HLA-DRB1*04 may warrant investigation as a potential prognostic or predictive biomarker.

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.

A case of Parry-Romberg syndrome and alien hand.

Parry-Romberg syndrome (PRS) is a rare condition characterised by progressive hemi-facial atrophy. Here we present a PRS case with alien-hand syndrome, which has not previously been described in adult onset disease. On the basis of the presumed auto-immune pathology of PRS we justify the treatment strategy we successfully used in this patient. A review of the literature was extensively done for understanding the history of alien hand sign over the years.

Specificity of quantitative latex agglutination assay for D-dimer in exclusion of pulmonary embolism in the emergency department.

We assessed the prevalence of elevated quantitative latex agglutination assay for D-dimer in patients in the emergency department in whom pulmonary embolism (PE) was excluded. D-dimer was normal (<230 ng/mL) in 435 (83%) of the 522 patients. D-dimer was normal in 88% of the patients with musculoskeletal or related chest pain, 74% with pleurisy or pleuritic chest pain, and 85% with upper respiratory tract infection. D-dimer was 230 to 500 ng/mL in 65 (75%) of the 87 in whom D-dimer was elevated. Clinical probability was low in 31 (48%) of the 65 patients with D-dimer levels of 230 to 500 ng/mL. D-dimer was 230 to 500 ng/mL and clinical probability was low in 31 (36%) of the 87 patients who had computed tomographic (CT) angiograms because of elevated D-dimer. Negative likelihood ratio for PE is sufficiently low that PE can be excluded with reasonable certainty in such patients. Tailoring cutoff value to 500 ng/mL in patients with low clinical probability would have reduced CT angiograms by 36%.

An unusual cause of diarrhoea and arthritis.

A 41-year-old lady was investigated by several hospital teams over a 5-year period. She initially presented with arthralgia but over time developed a myriad of signs and symptoms. Later, she was admitted for investigation of profound weight loss, anaemia and a rising C-reactive protein. Extensive gastrointestinal investigations were performed. Duodenal biopsy revealed microscopic evidence of villous blunting with prominent collections of macrophages within the lamina propria and submucosa. These changes were consistent with Whipple's disease and confirmed by polymerase chain reaction on the biopsy sample. Initiation of antibiotic therapy led to normalisation of inflammatory markers and marked clinical improvement. Even in younger female patients, this disease should always be considered.

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.