Low-dose hydrocortisone in patients with COVID-19 and severe hypoxia (COVID STEROID) trial—Protocol and statistical analysis plan

Introduction

Severe acute respiratory syndrome coronavirus-2 has caused a pandemic of coronavirus disease (COVID-19) with many patients developing hypoxic respiratory failure. Corticosteroids reduce the time on mechanical ventilation, length of stay in the intensive care unit and potentially also mortality in similar patient populations. However, corticosteroids have undesirable effects, including longer time to viral clearance. Clinical equipoise on the use of corticosteroids for COVID-19 exists.

Methods

The COVID STEROID trial is an international, randomised, stratified, blinded clinical trial. We will allocate 1000 adult patients with COVID-19 receiving ≥10 L/min of oxygen or on mechanical ventilation to intravenous hydrocortisone 200 mg daily vs placebo (0.9% saline) for 7 days. The primary outcome is days alive without life support (ie mechanical ventilation, circulatory support, and renal replacement therapy) at day 28. Secondary outcomes are serious adverse reactions at day 14; days alive without life support at day 90; days alive and out of hospital at day 90; all-cause mortality at day 28, day 90, and 1 year; and health-related quality of life at 1 year. We will conduct the statistical analyses according to this protocol, including interim analyses for every 250 patients followed for 28 days. The primary outcome will be compared using the Kryger Jensen and Lange test in the intention to treat population and reported as differences in means and medians with 95% confidence intervals.

Discussion

The COVID STEROID trial will provide important evidence to guide the use of corticosteroids in COVID-19 and severe hypoxia.

     

Critical study of hair growth analysis with computer-assisted methods

BACKGROUND: Computer-assisted image analysis has been proposed for human hair growth studies. METHODS: The performances of Trichoscan, a commercially available automated system combining epiluminiscence microscopy with digital image analysis, developed for office-based hair growth measurements, have been evaluated comparatively on the same skin sites using standardized photographic equipment and calibrated processing for contrast-enhanced phototrichogram (CE-PTG) analysis. This reference method has been validated with scalp biopsies and histological examination of serial sectioning. RESULTS: Besides edge effects, hair fibres escaped the Trichoscan analysis for various reasons including, but not limited to, thickness, pigmentation, closeness and crossing. CONCLUSION: Most of these problems have been identified in the late 1980s and remain largely unsolved by the processing software that was evaluated in 2004. Therefore claims promoting the Trichoscan method for accurate hair measurements in clinical trials on scalp and body hair are not supported by the present investigation. The speed at which the analysis is performed is outweighed by the errors in signal detection. Therefore we suggest that improvements must be clearly documented before Trichoscan is established for quantified diagnostic purposes and detailed hair cycle monitoring during hair trials.     

Making the transition from information systems of the 1970s to medical information systems of the 1990s: The role of the Physician's Workstation

Many hospitals today have implemented widely disparate information systems on mainframe and mini-computer hardware. The advent of network technology in hospitals has made it possible to access information in these systems. Unfortunately, the user interfaces to applications on these systems are unique and difficult to learn, which makes them unsuitable for use by clinical services. In this paper we describe the development of a Physician's Workstation which integrates information from multiple existing information systems and discuss how the workstation makes it possible to move from the departmental systems of the present to the computer-based medical record system of the future.     

Compensation for light loss resulting from filtering by macular pigment: relation to the S-cone pathway.

PURPOSE: Macular pigment (MP) filters short-wavelength light before it reaches the visual pigments. At peak absorbance (460 nm), transmission of light through MP can range from almost 100% transmission to as little as 3%. As a result of the uneven topographic distribution of MP, spatial nonuniformities in visual perception would result if the visual system did not compensate for filtering differences across the central retina. This study characterizes compensation for different densities of MP. METHODS: Sixteen young subjects (aged 24-40 years) with a wide range of MP density were studied. Increment thresholds were measured at 440 and 500 nm in the center of the fovea and at 6 degrees to 7 degrees eccentricity using conditions chosen to isolate the pi-1 mechanism. For six of the subjects, increment thresholds were also obtained for eccentricities of 1 degrees , 1.75 degrees , and 3 degrees . MP density was measured using heterochromatic flicker photometry at the same locations as the increment thresholds. RESULTS: Peak sensitivity of the short-wavelength pathway across the central retina was constant despite MP density differences as large as 1.0 log unit. CONCLUSIONS: These results suggest that the visual system increases gain of the S-cone pathway to offset light absorption by MP.     

Factors relating to the sensory acuity of limbs with peripheral vascular insufficiency

We examined several possible causes for the high incidence of poor sensory acuity in the limbs of 176 patients with moderate to severe peripheral vascular insufficiency. We investigated the relationships of diabetes, alcoholism, and smoking, as well as the severity of peripheral vascular disease, to the integrity of basic sensory modalities such as two-point discrimination and perception of light touch. The presence or absence of diabetes exerted the strongest effect on peripheral sensation. In patients who did not have diabetes, sensation in the limbs was most strongly affected by whether the patient was an alcoholic. Smoking did not have a significant effect on limb sensation. Among nondiabetic, nonalcoholic patients, there was a weak residual effect related to the severity of the peripheral vascular insufficiency. Even among these patients, however, systemic factors predominated in determining the loss of sensation. We also examined the extent to which loss of sensation might be related to the development of ulcers. Among patients who were not diabetic, there was a highly significant relationship between loss of sensation and the presence of limb ulceration. Surprisingly, however, there was no discernable relationship between the presence of ulcers in diabetic patients and the degree of loss of peripheral sensation. This result suggests that a large percentage of ulcers seen in diabetic patients are not of neurogenic origin.     

Coronary artery vasospasm causing acute myocardial infarction in a heart transplant recipient.

The etiology of cardiac allograft vasculopathy is not known, but may be preceded by both endothelial cell and smooth muscle dysfunction of the epicardial coronary arteries. We here report a case of acute, reversible coronary artery vasospasm which caused a myocardial infarction in a cardiac transplant recipient. The patient had a complex post-transplant course, including an episode of severe vascular rejection several months before this presentation. Interestingly, the event was captured in its early stages because the patient presented with chest pain: a rare event because of the denervation of the transplanted heart. Our ability to document the etiology of this patient's myocardial infarction supports the concept that cardiac allograft vasculopathy is a progressive disease that, in its early stages, may include a reversible component of abnormal vasoreactivity.     

Cognitive evoked potentials and disorders of recent memory

P3 potentials evoked by spoken words were recorded from seven patients with disorders of recent memory and seven age-matched controls. Inclusion criteria included a clearly identifiable P3 to pure tone stimuli. Absence or marked decrement of P3 to word stimuli was seen in the patients even though they could perform the word task. The results are consistent with an encoding disorder and failure in elaboration of information processing.     

Disappointing results and low tolerability of photodynamic therapy with topical 5-aminolaevulinic acid in psoriasis. A randomized, double-blind phase I/II study

BACKGROUND: Based on good results in the treatment of superficial skin tumours, since the early 1990s topical photodynamic therapy with aminolaevulinic acid (ALA PDT) has been used for disseminated, inflammatory dermatoses including psoriasis. However, there is still a lack of well-documented trials. OBJECTIVE: A prospective randomized, double-blind phase I/II intrapatient comparison study was conducted in 12 patients to investigate whether topical ALA PDT is an effective treatment for chronic plaque-type psoriasis. METHODS: In each patient three psoriatic plaques were randomly treated with a light dose of 20 J/cm(2) and 0.1%, 1% and 5% ALA, respectively. Treatment was conducted twice a week until complete clearance or for a maximum of 12 irradiations. Therapeutic efficacy was assessed by weekly determination of the psoriasis severity index (PSI). RESULTS: The mean percentage improvement was 37.5%, 45.6% and 51.2% in the 0.1%, 1% and 5% ALA-treated groups, respectively. Irradiation had to be interrupted several times because of severe burning and pain sensation. CONCLUSION: Topical ALA PDT did not prove to be an appropriate treatment option for plaque-type psoriasis due to disappointing clinical efficacy, the time-consuming treatment procedure and its unfavourable adverse event profile.