The molecular epidemiology of human immunodeficiency virus type 1 in six cities in Britain and Ireland

The authors sequenced the p17 coding regions of the gag gene from 211 patients infected either through injecting drug use (IDU) or by sexual intercourse between men from six cities in Scotland, N. England, N. Ireland, and the Republic of Ireland. All sequences were of subtype 5. Phylogenetic analysis revealed substantial heterogeneity in the sequences from homosexual men. In contrast, sequence from over 80% of IDUs formed a relatively tight cluster, distinct both from those of published isolates and of the gay men. There was no large-scale clustering of sequences by city in either risk group, although a number of close associations between pairs of individuals were observed. From the known date of the HIV-1 epidemic among IDUs in Edinburgh, the rate of sequence divergence at synonymous sites is estimated to be about 0.8%. On this basis it has been estimated that the date of divergence of the sequences among homosexual men to be about 1975, which may correspond to the origin of the B subtype epidemic

OCT retinal nerve fiber layer thickness differentiates acute optic neuritis from MOG antibody-associated disease and Multiple Sclerosis: RNFL thickening in acute optic neuritis from MOGAD vs MS

BACKGROUND: Optic neuritis (ON) is the most common manifestation of myelin oligodendrocyte glycoprotein antibody associated disorder (MOGAD) and multiple sclerosis (MS). Acute ON in MOGAD is thought to be associated with more severe optic disk edema than in other demyelinating diseases, but this has not been quantitatively confirmed. The goal of this study was to determine whether optical coherence tomography (OCT) can distinguish acute ON in MOGAD from MS, and establish the sensitivity of OCT as a confirmatory biomarker of ON in these entities. METHODS: This was a multicenter cross-sectional study of MOGAD and MS patients with peripapillary retinal nerve fiber layer (pRNFL) thickness measured with OCT within two weeks of acute ON symptom. Cirrus HD-OCT (Carl Zeiss Meditec, Inc. Dublin, CA, USA) was used to measure the pRNFL during acute ON. Eyes with prior ON or disk pallor were excluded. A receiver operating characteristic (ROC) curve analysis was performed to assess the ability of pRNFL thickness to distinguish MOGAD from MS. RESULTS: Sixty-four MOGAD and 50 MS patients met study inclusion criteria. Median age was 46.5 years (interquartile range [IQR]: 34.3-57.0) for the MOGAD group and 30.4 years (IQR: 25.7-38.4) for the MS group (p<0.001). Thirty-nine (61%) of MOGAD patients were female compared to 42 (84%) for MS (p = 0.007). The median pRNFL thickness was 164 µm (IQR: 116-212) in 96 acute MOGAD ON eyes compared to 103 µm (IQR: 93-113) in 51 acute MS ON eyes (p<0.001). The ROC area under the curve for pRNFL thickness was 0.81 (95% confidence interval 0.74-0.88) to discriminate MOGAD from MS. The pRNFL cutoff that maximized Youden's index was 118 µm, which provided a sensitivity of 74% and specificity of 82% for MOGAD. Among 31 MOGAD and 48 MS eyes with an unaffected contralateral eye or a prior baseline, the symptomatic eye had a median estimated pRNFL thickening of 45 µm (IQR: 17-105) and 7.5 µm (IQR: 1-18), respectively (p<0.001). All MOGAD affected eyes had a ≥ 5 µm pRNFL thickening, whereas 26 (54%) MS affected eyes had a ≥ 5 µm thickening. CONCLUSION: OCT-derived pRNFL thickness in acute ON can help differentiate MOGAD from MS. This can aid with early diagnosis and guide disease-specific therapy in the acute setting before antibody testing returns, and help differentiate borderline cases. In addition, pRNFL thickening is a sensitive biomarker for confirming acute ON in MOGAD, which is clinically helpful and could be used for adjudication of attacks in future MOGAD clinical trials

Randomized controlled trials

This chapter covers the current gold standard for evaluating the effectiveness of therapeutic interventions, the randomized controlled trial (RCT). Key features of the RCT, regardless of sub-type, are randomization, allocation concealment, and blinding. These key features help reduce bias and the influence of confounding variables, making the randomized controlled trial eminently suitable to determine cause and effect relationships. Protocol design and registration prior to trial onset are important factors in determining the quality of the trial, and various trial design sub-types, including parallel, factorial, crossover, and cluster, are outlined and the strengths and weakness of each examined. Various checklists such as SPIRIT and CONSORT can be used to ensure proper reporting of both trial protocols and trial findings, to ensure clear, concise reporting. Finally, the shortcomings of RCTs and newer trial designs, such as comparative effectiveness research and pragmatic studies, designed to overcome some of these issues are examined, and ways to make clinical trial results more clinically applicable are discussed

OCT retinal nerve fiber layer thickness differentiates acute optic neuritis from MOG antibody-associated disease and Multiple Sclerosis RNFL thickening in acute optic neuritis from MOGAD vs MS

BackgroundOptic neuritis (ON) is the most common manifestation of myelin oligodendrocyte glycoprotein antibody associated disorder (MOGAD) and multiple sclerosis (MS). Acute ON in MOGAD is thought to be associated with more severe optic disk edema than in other demyelinating diseases, but this has not been quantitatively confirmed. The goal of this study was to determine whether optical coherence tomography (OCT) can distinguish acute ON in MOGAD from MS, and establish the sensitivity of OCT as a confirmatory biomarker of ON in these entities.MethodsThis was a multicenter cross-sectional study of MOGAD and MS patients with peripapillary retinal nerve fiber layer (pRNFL) thickness measured with OCT within two weeks of acute ON symptom. Cirrus HD-OCT (Carl Zeiss Meditec, Inc. Dublin, CA, USA) was used to measure the pRNFL during acute ON. Eyes with prior ON or disk pallor were excluded. A receiver operating characteristic (ROC) curve analysis was performed to assess the ability of pRNFL thickness to distinguish MOGAD from MS.ResultsSixty-four MOGAD and 50 MS patients met study inclusion criteria. Median age was 46.5 years (interquartile range [IQR]: 34.3-57.0) for the MOGAD group and 30.4 years (IQR: 25.7-38.4) for the MS group (p&lt;0.001). Thirty-nine (61%) of MOGAD patients were female compared to 42 (84%) for MS (p&nbsp;=&nbsp;0.007). The median pRNFL thickness was 164&nbsp;µm (IQR: 116-212) in 96 acute MOGAD ON eyes compared to 103&nbsp;µm (IQR: 93-113) in 51 acute MS ON eyes (p&lt;0.001). The ROC area under the curve for pRNFL thickness was 0.81 (95% confidence interval 0.74-0.88) to discriminate MOGAD from MS. The pRNFL cutoff that maximized Youden's index was 118&nbsp;µm, which provided a sensitivity of 74% and specificity of 82% for MOGAD. Among 31 MOGAD and 48 MS eyes with an unaffected contralateral eye or a prior baseline, the symptomatic eye had a median estimated pRNFL thickening of 45&nbsp;µm (IQR: 17-105) and 7.5&nbsp;µm (IQR: 1-18), respectively (p&lt;0.001). All MOGAD affected eyes had a&nbsp;≥&nbsp;5&nbsp;µm pRNFL thickening, whereas 26 (54%) MS affected eyes had a&nbsp;≥&nbsp;5&nbsp;µm thickening.ConclusionOCT-derived pRNFL thickness in acute ON can help differentiate MOGAD from MS. This can aid with early diagnosis and guide disease-specific therapy in the acute setting before antibody testing returns, and help differentiate borderline cases. In addition, pRNFL thickening is a sensitive biomarker for confirming acute ON in MOGAD, which is clinically helpful and could be used for adjudication of attacks in future MOGAD clinical trials