Tracking cryptococcal meningitis to monitor HIV program success during the Treat-All era: an analysis of national data in Botswana.

BACKGROUND: Cryptococcal meningitis causes substantial mortality in high-HIV prevalence African countries despite advances in disease management and increasing antiretroviral therapy coverage. Reliable diagnosis of cryptococcal meningitis is cheap and more accessible than other indicators of AHD burden such as CD4 testing or investigation for disseminated tuberculosis; therefore, monitoring cryptococcal meningitis incidence has the potential to serve as a valuable metric of HIV programmatic success. METHODS: Botswana national meningitis surveillance data from 2015 to 2022 were obtained from electronic health records. All electronic laboratory records from cerebrospinal fluid samples analysed within government healthcare facilities in Botswana were extracted from a central online repository. Adjustments for missing data were made through triangulation with prospective cohort study datasets. Cryptococcal meningitis case frequency was enumerated using a case definition and incidence calculated using national census data. RESULTS: A total of 1,744 episodes of cryptococcal meningitis were identified; incidence declined from 15.0 (95% CI 13.4-16.7) cases/100,000 person-years in 2015 to 7.4 (95% CI 6.4-8.6) cases/100,000 person-years in 2022. However, the rate of decline slowed following the introduction of universal treatment in 2016. The highest incidence was observed in men and individuals aged 40-44. The proportion of cases diagnosed through cryptococcal antigen testing increased from 35.5% to 86.3%. CONCLUSION: Cryptococcal meningitis incidence has decreased in Botswana following expansion of ART coverage but persists at a stubbornly high incidence. Most cases are now diagnosed through the cheap and easy-to-use cryptococcal antigen test highlighting the potential of using cryptococcal meningitis as key metric of programme success in the Treat All era.

Ultrasound for suspected Baker's cyst: A test of limited clinical value?

Introduction: Patients with posterior knee swellings are commonly encountered in clinical practice with the vast majority referred for an ultrasound scan to assess for a clinically suspected Baker's cyst. Aims: Our aim was to determine the incidence of different pathologies in patients investigated for a posterior knee swelling of a clinically suspected Baker's cyst using ultrasound. We also wanted to investigate the incidence of significant pathologies in the popliteal fossa to assess whether the ultrasound scan findings influenced patient management. Methodology: Retrospective analysis was performed on all patients who underwent an ultrasound scan for a suspected Baker's cyst or posterior knee swelling at our institution, between January 2017 and December 2018. Patient demographics, ultrasound findings, further imaging investigations and histopathology were recorded. Patient records were followed up for a minimum period of 3 years after ultrasound. Results: A total of 680 patients had a posterior knee ultrasound scan. Of that, 51% (347/680) had a Baker's cyst and 40% (273/680) had a normal ultrasound scan. Sixty (9%) patients had other abnormalities identified within the popliteal fossa. Four patients had significant findings on ultrasound that required a change of management. No malignancies identified. Conclusion: This study confirms the high incidence of Baker's cysts in patients presenting with a posterior knee swelling. In the absence of red flag symptoms, ultrasound of the posterior knee for a clinically suspected Baker's cyst is of limited clinical value.

Treatment of Open-Angle Glaucoma and Ocular Hypertension with Preservative-Free Tafluprost/Timolol Fixed-Dose Combination Therapy: UK and Ireland Results from the VISIONARY Study.

INTRODUCTION: Reducing intraocular pressure (IOP), the only modifiable risk factor for open-angle glaucoma (OAG), is important for the preservation of vision and slowing of disease progression. Preservative-free tafluprost (0.0015%)/timolol (0.5%) fixed combination (PF Taf-T FC) is an approved combination therapy for OAG treatment. The VISIONARY study aimed to evaluate the effectiveness and tolerability of PF Taf-T FC in real-world clinical settings. Here, we present the results from the United Kingdom (UK) and Ireland. METHODS: This observational, multicentre, European, prospective study recorded data during routine clinic appointments on the use of PF Taf-T FC for the treatment of OAG and ocular hypertension (OHT) in patients whose disease was insufficiently controlled on a prostaglandin analogue (PGA) or beta blocker monotherapy or who did not tolerate these medications. Mean change in IOP, symptom severity, changes in clinical signs, and tolerability were investigated over 6 months. RESULTS: Eighty-two patients were recruited in the UK and Ireland. After 6 months of PF Taf-T FC treatment, mean IOP was significantly reduced from 22.0 to 16.2 mmHg in the UK group and from 18.6 to 14.1 mmHg in the Ireland group. In the UK (65 patients), 49 adverse events (AEs) were reported, of which 3 were serious. No AEs were reported in the Ireland group (17 patients). Overall, 91.9% of UK physicians reported PF Taf-T FC treatment to be the same or better than prior medication for improving clinical signs; 90.0% of UK patients reported PF Taf-T FC treatment to have good or very good tolerability. CONCLUSIONS: Treatment with PF Taf-T FC resulted in significant reductions in mean IOP over 6 months. Patients and physicians reported that treatment was well tolerated. These data demonstrate real-world efficacy of PF Taf-T FC for the treatment of OAG and OHT in routine clinical practice in the UK and Ireland. TRIAL REGISTRATION: European Union electronic Register of Post-Authorisation Studies (EU PAS) register number, EUPAS22204.

A systematic review exploring the bidirectional relationship between puberty and autoimmune rheumatic diseases.

BACKGROUND: Autoimmune rheumatic diseases (ARDs) are associated with a significant sex-bias, which becomes more evident post-puberty. This systematic review aims to elucidate the bidirectional relationship between puberty and ARD-related outcomes. METHODS: Studies published in English until October 2019 were identified using a systematic search of endocrinology and rheumatology literature. Information was extracted on study design, sample size, demographics, puberty outcome measures, disease outcome measures, and main findings. The methodological quality of the studies included was analysed using the Newcastle-Ottawa Scale (NOS). RESULTS: Sixteen non-randomised studies reporting on the impact of puberty on ARD outcomes (n = 7), ARD impact on puberty-related outcomes (n = 8), or both (n = 1) have been identified. The impact of puberty on ARD outcomes were investigated in patients with juvenile idiopathic arthritis (JIA)-associated uveitis (n = 1), juvenile systemic lupus erythematosus (JSLE) (n = 5) or in healthy controls who developed adult-onset SLE (n = 1) or had non-specific symptoms (n = 1). The impact of ARD on puberty outcomes was explored in JIA (n = 4) and JSLE (n = 3). Quality assessment of studies showed a small to moderate risk of bias overall (NOS 4-9/9). Due to large heterogeneity of the studies it was not possible to perform a meta-analysis. Multiple studies reported on delayed puberty in patients with JIA/JSLE, menstrual and hormonal abnormalities, and lower height and weight than controls. Earlier (pre-pubertal) onset of JSLE was correlated with more severe disease and more need for systemic treatment. CONCLUSION: A bidirectional relationship exists between puberty and ARDs; however, more and better research is required to elucidate the complexity of this relationship. We propose puberty-related clinical assessments in patients with ARDs, which can improve patient outcomes and facilitate future research.

Seroprevalence of SARS-CoV-2 antibodies in healthcare workers at a London NHS Trust.

Healthcare workers (HCWs) have a theoretically increased risk of contracting severe acute respiratory coronavirus virus 2 (SARS-CoV-2) given their occupational exposure. We tested 2,167 HCWs in a London Acute Integrated Care Organisation for antibodies to SARS-CoV-2 in May and June 2020 to evaluate seroprevalence. We found a seropositivity rate of 31.6% among HCWs.

Giant cell tumour of soft tissue-a rare presentation of a common pathology.

We present the case of a giant cell tumour of soft tissue (GCT-ST) presenting as a slow-growing paraspinal mass. Imaging investigations revealed a well-circumscribed subcutaneous lesion containing fluid-fluid levels and an internal solid nodule. The imaging findings resulted in only a tentative differential which included haematoma or complex epidermoid cyst but failed to provide a definitive diagnosis. The patient underwent an image-guided biopsy from which a histopathological diagnosis of a GCT-ST was made. GCT-ST is a primary soft tissue neoplasm that is clinically and histologically similar to giant cell tumour of bone. Given its rare occurrence, there is very little published literature on the characteristic imaging findings of GCT-ST to help with its diagnosis which is usually only made histologically. The aim of this case report is to highlight our specific imaging findings and add to the limited pre-existing imaging data on GCT-ST.

Correction to: Improvements in Skeletal Muscle Can Be Detected Using Broadband NIRS in First-Time Marathon Runners.

This chapter was inadvertently published as an open access chapter. However, the open access for this chapter has now been reverted.

Improvements in Skeletal Muscle Can Be Detected Using Broadband NIRS in First-Time Marathon Runners.

Skeletal muscle metabolic function is known to respond positively to endurance exercise interventions, such as marathon training. Studies investigating skeletal muscle have typically used muscle biopsy samples or magnetic resonance spectroscopy (MRS) to interrogate metabolic function. We aimed to non-invasively detect exercise-training-induced improvements in muscle function using broadband near-infrared spectroscopy (NIRS). We used NIRS to determine concentration changes in oxygenated haemoglobin (HbO2) and the oxidation state of cytochrome-c-oxidase (oxCCO) in gastrocnemius during arterial occlusion in 14 volunteers. We also used a cardio-pulmonary exercise test (CPET) to assess peak total body oxygen uptake (peakVO2; a measure of fitness). Measurements were made at baseline (BL) which was prior to a period of at least 16 weeks of training for the 2017 London Marathon, and then within 3 weeks after completion of the marathon, follow-up (FU). We observed an increase in locally measured muscle oxygen consumption and rate of oxCCO concentration change, but not in cardio-respiratory fitness measured as whole-body peak oxygen consumption (peakVO2).

VITRECTOMY FOR PHACOANAPHYLACTIC GLAUCOMA SECONDARY TO POSTERIOR CAPSULAR RUPTURE IN AN ADULT WITH PERSISTENT HYPERPLASTIC PRIMARY VITREOUS.

PURPOSE: Persistent hyperplastic primary vitreous (PHPV) is a developmental anomaly in which the normal regression of the primary vitreous and hyaloid vasculature does not occur. In the literature, there are a few cases of PHPV in adulthood. We report the novel presentation of phacoanaphylactic glaucoma secondary to posterior capsular rupture in an adult with PHPV. We discuss the best management of this condition with a review of the literature on this topic. METHODS: Case report and literature review. RESULTS: Medical management was unsuccessful in this case and vitrectomy and fragmatome lensectomy improved vision from PL to counting fingers. CONCLUSION: This case is unusual in the age of the patient in question as PHPV usually presents in childhood, as such there are few accounts in the literature to guide optimum management of adult PHPV. We suggest that surgical management of late-presenting PHPV should be considered to improve functional outcome.

Study of fluid ingress through clear corneal incisions following phacoemulsification with or without the use of a hydrogel ocular bandage: a prospective comparative randomised study.

PURPOSE: To assess the use of a hydrogel ocular bandage (HOB) on clear corneal incisions in phacoemulsification cataract surgery and determine whether HOB reduces ocular surface contaminants ingress after routine surgery. METHODS: In this prospective randomized controlled study, thirty eyes of patients undergoing uneventful phacoemulsification were recruited consecutively and randomly assigned to have a HOB applied to the corneal incision at the end of the surgery or not. At the end of the surgery, trypan blue (TRB) was instilled on the ocular surface, aqueous fluid was aspirated from the anterior chamber (AC) and its optical density was measured using ultraviolet spectrophotometry. The corneal incisions were examined postoperatively using anterior segment optical coherence tomography. Main outcome measures were concentration of TRB in the AC, corneal incision architecture, intraocular pressure (IOP) and Seidel test. RESULTS: All incisions were Seidel negative. The mean IOP in the immediate postoperative period was 18.1 ± 5.48 mmHg for the intervention group and 16.9 ± 5.7 mmHg for the control group (p > 0.05). No architectural differences of the incisions between the two groups were noted. The total mean length of the three-step corneal incisions in the two groups was 2261.2 ± 96.92 µm and 2263 ± 119.75 µm, respectively (p > 0.05). No trace of TRB was detected in any of the samples. CONCLUSION: Proper surgical wound construction without the use of a HOB is efficient in preventing the ingress of fluid through the main corneal incision postoperatively.

A retrospective audit of the management and complications of pelvic inflammatory disease.

Our objective was to examine the management of pelvic inflammatory disease (PID) in Southend Hospital against the British Association for Sexual Health and HIV guidelines. In addition, we reviewed the Genito-Urinary (GU) Medicine and Gynaecology notes for patients who failed treatment for PID in GU medicine. This was to reveal their complications and subsequent management. Thirty of 249 patients diagnosed with PID failed treatment. Chlamydia was found in 30% of these patients, gonorrhoea in 10%, with the rest being categorized into presumed anaerobic/other aetiology. Appropriate antibiotic regimens were used in 96.6% of patients and the 66.7% of contacts who were traced and treated. Eighteen of the 30 patients had a laparoscopy. Findings were: confirmed PID in 5.6%; endometriosis in 27.8%, adhesions with no evidence of PID in 27.8%; and 38% had no abnormalities found. Laparoscopy has an important role in excluding other pathology in patients who have failed to respond to appropriate conservative management.

Regulation of the myelin gene periaxin provides evidence for Krox-20-independent myelin-related signalling in Schwann cells.

We investigated the role of Krox-20 (Egr2), a transcription factor that regulates myelination, in controlling the myelin-associated protein periaxin. In developing Schwann cells, periaxin immunoreactivity appeared at least 2 days before Krox-20-immunopositive nuclei. Consistent with this, in Krox-20 null mice periaxin was upregulated on schedule, albeit to a lower level. In culture Krox-20 and periaxin were upregulated by cAMP as expected for myelin genes. Only those cells with the highest periaxin levels also expressed Krox-20, while other periaxin-positive cells remained Krox-20-negative. Furthermore, cAMP elevated periaxin even in Krox-20 null cells. We also found that in culture enforced Krox-20 expression induced expression of periaxin mRNA and protein in the absence of cAMP elevating agents, and that this induction was inhibited by the co-repressor NAB2. These findings reveal a dual mechanism for periaxin regulation and suggest that the role of Krox-20 is to amplify an earlier Krox-20-independent activation of the periaxin gene. Thus the axonal signals responsible for myelination are only partially transduced in Schwann cells by mechanisms that depend on Krox-20.