In-person versus virtual administration of the American College of Rheumatology gold standard cognitive battery in systemic lupus erythematosus: Are they interchangeable?

OBJECTIVE: During the COVID-19 pandemic, many research studies were adapted, including our longitudinal study examining cognitive impairment (CI) in systemic lupus erythematosus (SLE). Cognitive testing was switched from in-person to virtual. This analysis aimed to determine if the administration method (in-person vs. virtual) of the ACR-neuropsychological battery (ACR-NB) affected participant cognitive performance and classification. METHODS: Data from our multi-visit, SLE CI study included demographic, clinical, and psychiatric characteristics, and the modified ACR-NB. Three analyses were undertaken for cognitive performance: (1) all visits, (2) non-CI group visits only and (3) intra-individual comparisons. A retrospective preferences questionnaire was given to participants who completed the ACR-NB both in-person and virtually. RESULTS: We analysed 328 SLE participants who had 801 visits (696 in-person and 105 virtual). Demographic, clinical, and psychiatric characteristics were comparable except for ethnicity, anxiety and disease-related damage. Across all three comparisons, six tests were consistently statistically significantly different. CI classification changed in 11/71 (15%) participants. 45% of participants preferred the virtual administration method and 33% preferred in-person. CONCLUSIONS: Of the 19 tests in the ACR-NB, we identified one or more problems with eight (42%) tests when moving from in-person to virtual administration. As the use of virtual cognitive testing will likely increase, these issues need to be addressed - potentially by validating a virtual version of the ACR-NB. Until then, caution must be taken when directly comparing virtual to in-person test results. If future studies use a mixed administration approach, this should be accounted for during analysis.

Cognitive dysfunction and functional magnetic resonance imaging in systemic lupus erythematosus.

Cognitive dysfunction is a common aspect of systemic lupus erythematosus (SLE) and is increasingly reported as a problem by patients. In many cases the exact cause is unclear. Limited correlations between specific autoantibodies or structural brain abnormalities and cognitive dysfunction in SLE have been reported. It may be that the most appropriate biomarkers have yet to be found. Functional magnetic resonance imaging (fMRI) is a technique used in many other conditions and provides sensitive measures of brain functionality during cognitive tasks. It is now beginning to be employed in SLE studies. These studies have shown that patients with SLE often perform similarly to healthy controls in terms of behavioural measures on cognitive tasks. However, SLE patients appear to employ compensatory brain mechanisms, such as increased response in fronto-parietal regions, to maintain adequate cognitive performance. As there have been only a few studies using fMRI in SLE to investigate cognitive dysfunction, many questions remain unanswered. Further research could, however, help to identify biomarkers for cognitive dysfunction in SLE.

Profiles of objective and subjective cognitive function in Post-COVID Syndrome, COVID-19 recovered, and COVID-19 naïve individuals.

Post-COVID Syndrome has emerged as a significant public health concern worldwide with increasing evidence to suggest that individuals who have had an acute COVID-19 infection report lingering memory and attention difficulties, even in individuals who have fully recovered and no longer experiencing symptoms of COVID-19. The present study sought to investigate the profile of objective and subjective cognitive difficulties in people who have Post-COVID Syndrome, people who have fully recovered from an acute COVID infection and people who have never had COVID-19. We further sought to explore the extent to which self-reported fatigue and stress are related to subjective and objective cognitive difficulties. 162 participants including 50 people living with Post-COVID Syndrome, 59 people who have had COVID-19 but have fully recovered and 53 people who have never experienced symptoms of COVID-19 and had never tested positive for COVID-19 were recruited from Academic Prolific to complete a series of online questionnaires and neurocognitive tasks. Subjective cognitive function was measured using the Cognitive Failures Questionnaire and objective cognitive function was measured using the Cognitron cognitive test battery. We found that objective and subjective measures of cognitive function were not significantly related, suggesting that self-reports of "brain fog" are not reflecting objectively measured cognitive dysfunction. A MANOVA revealed that subjective cognitive deficits were driven by heightened perceived stress and fatigue and not significantly related to COVID-19 status. Objective cognitive function, however, was significantly related to perceived stress and COVID status whereby we observed significant objective cognitive deficits in people who have been exposed to an acute COVID-19 infection regardless of whether they had Post-COVID Syndrome or had fully recovered, as compared to people who had never had COVID-19. This suggests that an acute infection can have long term effects on cognitive function, even without persistent COVID-19 symptoms. Encouragingly, objective cognitive function was significantly associated with time since initial infection showing that cognitive deficits improved over time for people who had recovered from COVID-19. However, we did not observe the same improvement in individuals with Post-COVID Syndrome and observed that cognitive dysfunction was significantly related to the number of neurological symptoms presently experienced. These results add to the accumulating literature that COVID-19 is associated with significant cognitive difficulties following a COVID-19 infection, which appear to improve over time for those who have recovered from COVID-19 yet persist in people living with Post-COVID Syndrome.

Vipoma of the pancreas: observations on the diarhrhea and circulatory disturbances.

A patient with a vipoma of the pancreas and persistently elevated blood levels of vasoactive intestinal polypeptide (VIP) had watery diarrhea, hypokalemia, and achlorhydria (WDHA syndrome). In the untreated state, the diarrhea was never profuse. Fecal volumes ranged from 0.16 to 1.24 L/day. Attempts to correct the dehydration by fluid and electrolyte loading resulted in a massive increase in fecal water and electrolyte loss. Prednisone cured the diarrhea and was associated with a decrease in plasma VIP levels. The patient had a marked circulatory disturbance with systemic arterial hypotension and cutaneous vasodilation that caused a subnormal body temperature. Removal of the tumor led to a dramatic change in the patient's circulation. Generalized vasodilation with systemic venous and arterial hypotension gave away to vasoconstriction with severe venous and arterial hypertension. Central venous pressure rose from -4.4 to +4.0 cm H2O and arterial pressure rose from 80/55 to 195/110 mm Hg. These changes might explain the unexpected and sometimes fatal heart failure that has complicated the removal of these tumors from some patients.

Effects of adenosine 3',5'-monophosphate on renal function in the rabbit.

1. Intravenous injections of adenosine 3',5'-monophosphate (cyclic-AMP) were given to five conscious, diuretic rabbits, and the effects on urinary flow and composition were compared with those of intravenous injections of vasopressin given to the same animals.2. Cyclic-AMP produced antidiuresis with increases in urinary osmolality and in the urinary concentrations of creatinine, urea and usually of sodium.3. The fractional reabsorption of urea from renal tubular fluid increased during cyclic-AMP induced antidiuresis.4. The effects of cyclic-AMP thus closely resembled those of vasopressin and are consistent with the view that cyclic-AMP mediates the action of this hormone.

Effects of caffeine on functional asymmetry in a Posner letter-recognition task.

A Posner task was used to investigate whether caffeine, in common with other drugs, has an asymmetric effect on cerebral functioning. Subjects consumed decaffeinated coffee either with or without added caffeine at 2 mg/kg body weight. They were then required to identify letter-pairs as the same or different. Same was defined as two identical letters irrespective of case (AA, Aa); different was defined as two different letters irrespective of case (AB, Ab). Main effects of stimulus type were found for both accuracy and speed of response. In the noncaffeine condition pattern-matching was faster by the right hemisphere and phonologic matching was faster by the left hemisphere. These results replicate much previous work, but under caffeine, a previously unreported reversal in the balance of hemispheric processing efficiency was found. An explanation is offered in terms of the disruption of the normal, optimum, rate of cerebral processing for each hemisphere.

Potassium depletion induced by vasopressin and overhydration in the rabbit.

1. In order to study the effect of overhydration on body potassium, experiments were performed on pair-fed rabbits, one of which was maintained continuously on vasopressin and given extra water (60-90 ml day-1 kg-1) for 6-8 days, while the other served as control. 2. Overhydrated rabbits excreted significantly more potassium (53%) in their urine than control rabbits and accumulated a mean potassium deficit of 65-0 mmol, significantly higher than the mean value of 37-1 mmol in the control rabbits. 3. In the overhydrated rabbits, potassium fell significantly in both erythrocytes, from 266 to 173 mmol/kg of dry cells, and also in muscle, from 435 to 341 mmol/kg of fat-free dry solids. Neither changed significantly in the control animals. 4. Overhydration in the presence of vasopressin leads to potassium depletion in the rabbit and a similar phenomenon might be expected in man. Potassium depletion due to overhydration might account for the hypokalaemia and reduction in exchangeable potassium observed in some patients with the syndrome of inappropriate secretion of antidiuretic hormone.

Twenty-four hour ambulatory gastric and duodenal pH profiles in cystic fibrosis: effect of duodenal hyperacidity on pancreatic enzyme function and fat absorption.

Overt steatorrhoea remains a problem for some patients with cystic fibrosis (CF) despite supraphysiological dosages of pancreatic enzymes. As pancreatin release and enzyme function is influenced by duodenal pH, we have used 24-h ambulatory pH measurements to assess the extent and duration of postprandial hyperacidity. Readings were obtained from the stomach and proximal duodenum in 16 CF patients (aged 6 months to 12 years) using a dual-channel antimony electrode. The fasting gastric and duodenal pH values were normal in all patients (mean pH values of 1.3, and 6.8, respectively). There was, however, a marked drop in duodenal pH in the first postprandial hour, which became more pronounced with successive meals. The total time that duodenal pH was < 5 varied from 15 to 90% of the recording (mean 57%). Overnight the duodenal pH returned to normal levels. A subgroup of five patients were studied before and after treatment with omeprazole, a potent inhibitor of gastric acid secretion. There were significant improvements in both weight gain and fat absorption. This study supports the hypothesis that the postprandial duodenal pH is excessively acid in patients with CF and may be an important element in the continuing fat malabsorption experienced by some patients. This malabsorption may limit the efficacy of the newer high-lipase pancreatic enzyme supplements and lead to delayed enzyme release, a possible factor in the recent reports of proximal colonic strictures.

Urine concentration during solute diuresis in potassium-depleted rabbits. Evidence for a defect in tubular sodium transport.

1. The relationship between osmolal clearance (C(osm)) and the reabsorption of solute-free water by the kidney (T(H2O) (c)) was examined during 10% mannitol and 2.3% saline diuresis in normal and potassium-depleted rabbits.2. In normal rabbits at osmolal clearances close to 3.0 ml./min, T(H2O) (c) during mannitol diuresis was 0.87 +/- 0.06 ml./min and during saline diuresis 1.19 +/- 0.07 ml./min. The mean difference in T(H2O) (c) of 0.32 +/- 0.05 ml./min was highly significant (P < 0.001).3. In one group of potassium-depleted rabbits with a reduction in maximal urinary concentration, T(H2O) (c) during both mannitol and saline diureses was reduced significantly below normal and the increment in T(H2O) (c) normally seen during saline diuresis was abolished.4. In a second group of potassium-depleted rabbits maximal urinary concentration (1253 +/- 88 m-osmole/kg H(2)O) was not significantly different from that in normal rabbits (1272 +/- 116 m-osmole/kg H(2)O). In these animals, T(H2O) (c) at osmolal clearances close to 3.0 ml./min was not significantly different during mannitol diuresis (0.83 +/- 0.07 ml./min) from that in normal animals, whereas it was reduced significantly during saline diuresis (0.89 +/- 0.07 ml./min, P < 0.001) and the difference in T(H2O) (c) normally seen between mannitol and saline diuresis was abolished.5. The inability to increase T(H2O) (c) during saline diuresis above that achieved during mannitol appears to be the earliest manifestation of the concentrating defect associated with potassium depletion. It probably results from an impairment of sodium transport by the ascending limb of the loop of Henle. This is supported by the fact that potassium-depleted rabbits excreted a greater percentage of the filtered load of sodium than did normal controls.

Ureteric stricture with analgesic nephropathy.

Three patients with analgesic nephropathy are reported who, in addition to the accepted features of this syndrome, had dilatation of one or both upper urinary tracts due to ureteric or periureteric fibrosis without intraluminal obstruction. We attribute this lesion to analgesic abuse and suggest that any patient with unexplained ureteric fibrosis should be questioned about analgesic consumption. This association also suggests a possible role for analgesic abuse in the pathogenesis of retroperitoneal fibrosis.