BACKGROUNDCryptococcal meningitis accounts for more than 100,000 human immunodeficiency virus (HIV)-related deaths per year. We tested two treatment strategies that could be more sustainable in Africa than the standard of 2 weeks of amphotericin B plus flucytosine and more effective than the widely used fluconazole monotherapy. METHODSWe randomly assigned HIV-infected adults with cryptococcal meningitis to receive an oral regimen (fluconazole [1200 mg per day] plus flucytosine [100 mg per kilogram of body weight per day] for 2 weeks), 1 week of amphotericin B (1 mg per kilogram per day), or 2 weeks of amphotericin B (1 mg per kilogram per day). Each patient assigned to receive amphotericin B was also randomly assigned to receive fluconazole or flucytosine as a partner drug. After induction treatment, all the patients received fluconazole consolidation therapy and were followed to 10 weeks. RESULTSA total of 721 patients underwent randomization. Mortality in the oral-regimen, 1-week amphotericin B, and 2-week amphotericin B groups was 18.2% (41 of 225), 21.9% (49 of 224), and 21.4% (49 of 229), respectively, at 2 weeks and was 35.1% (79 of 225), 36.2% (81 of 224), and 39.7% (91 of 229), respectively, at 10 weeks. The upper limit of the one-sided 97.5% confidence interval for the difference in 2-week mortality was 4.2 percentage points for the oral-regimen group versus the 2-week amphotericin B groups and 8.1 percentage points for the 1-week amphotericin B groups versus the 2-week amphotericin B groups, both of which were below the predefined 10-percentage-point noninferiority margin. As a partner drug with amphotericin B, flucytosine was superior to fluconazole (71 deaths [31.1%] vs. 101 deaths [45.0%]; hazard ratio for death at 10 weeks, 0.62; 95% confidence interval [CI], 0.45 to 0.84; P = 0.002). One week of amphotericin B plus flucytosine was associated with the lowest 10-week mortality (24.2%; 95% CI, 16.2 to 32.1). Side effects, such as severe anemia, were more frequent with 2 weeks than with 1 week of amphotericin B or with the oral regimen.

Background As of November 2020, SARS-CoV-2 has resulted in 55 million infections worldwide and over 1.3 million deaths from COVID-19. Outcomes following SARS-CoV-2 infection in individuals with primary immunodeficiency or symptomatic secondary immunodeficiency remain uncertain. Objectives To document the outcomes of individuals with primary or symptomatic secondary immunodeficiency following COVID-19 in the United Kingdom. Methods At the start of the COVID-19 pandemic, the United Kingdom Primary Immunodeficiency Network (UK PIN) established a registry of cases to collate the nationwide outcomes of COVID-19 in individuals with PID or symptomatic SID and determine risk factors associated with morbidity and mortality from COVID-19 in these patient groups. Results 100 patients had been enrolled by 1st July 2020, 60 with primary immunodeficiency (PID), 7 with other inborn errors of immunity including autoinflammatory diseases and C1 inhibitor deficiency and 33 with symptomatic secondary immunodeficiency (SID). In individuals with PID, 53.3% (n=32/60) were hospitalized, the infection fatality rate (IFR) was 20.0% (n=12/60), the case fatality rate (CFR) was 31.6% (n=12/38) and the inpatient mortality 37.5% (n=12/32). Individuals with SID had worse outcomes than those with PID. 75.8% (n=25/33) were hospitalized, the IFR was 33.3% (n=11/33), the CFR was 39.2% (n=11/28), and inpatient mortality 44.0% (n=11/25). Conclusions In comparison to the general population, adult patients with PID and symptomatic SID display greater morbidity and mortality from COVID-19. This increased risk must be reflected in public health guidelines to adequately protect vulnerable patients from exposure to the virus.

Background -Glutaraldehyde is the best disinfectant for fibreoptic endoscopes. It is also used in the processing ofx ray films. A number of studies have reported eye, nose, and respiratory symptoms in exposed workers. Three individual case reports ofoccupational asthma in endoscopy workers and a radiographer have also been published. We describe a further seven cases ofoccupational asthma due to glutaraldehyde in endoscopy and x ray departments, together with exposure levels measured during the challenge tests and in 19 endoscopy and x ray departments in the region. Methods -Eight workers were referred for investigation ofsuspected occupational asthma following direct or indirect exposure to glutaraldehyde at work. They were investigated by serial measurements of peak expiratory flow (PEF) and specific bronchial provocation tests. Glutaraldehyde levels were measured using personal and static short and longer term air samples during the challenge tests and in 13 endoscopy units and six x ray darkrooms in the region where concern about glutaraldehyde exposure had been expressed. Three of the workers investigated with occupational asthma came from departments where glutaraldehyde air measurements had been made; the others came from other hospitals or departments. Results -The diagnosis of occupational asthma was confirmed in seven workers, all ofwhom had PEF records suggestive of occupational asthma and positive specific bronchial challenge tests to glutaraldehyde. Bronchial provocation testing was negative in one worker who was no longer exposed and who had a less clearcut history of occupational asthma. Three workers also had a positive specific bronchial challenge to formaldehyde. The mean level of glutaraldehyde in air during the challenge tests was 0-068 mg/m3, about one tenth of the short term occupational exposure standard of0 7 mg/m3. The levels obtained in the challenge chamber were similar to those measured in 13 endoscopy suites and six x ray darkrooms where median short term levels were 0-16 mg/m3 during decantation in endoscopy suites and <0_009 mg/m3 in darkrooms. Conclusions -Glutaraldehyde can cause occupational asthma. The exposure levels measured in the workplace suggest that sensitisation may occur at levels below the current occupational exposure standard. (Thorax 1995;50:156-159)

Abstractchromate solution is helpful in making the specific diagnosis where doubt exists. Background -Exposure to chromium dur- (Thorax 1997;52:28-32) ing electroplating is a recognised though poorly characterised cause of occupational Keywords: occupational asthma, electroplating, asthma. The first series of such patients chrome, nickel, bronchial provocation testing. referred to a specialist occupational lung disease clinic is reported. Methods -The diagnosis of occupationalChromium is the major industrial contact allerasthma was made from a history of asthma gen that causes dermatitis 1 and is widely used with rest day improvement and confirmed in electroplating, dyes, leather tanning, and by specific bronchial provocation testing cement works. Single cases of asthma caused with potassium dichromate and nickel by chrome have been described since the ninechloride.teenth century and in the 1930s both Smith 2 Results -Seven workers had been exposed and Joules 3 reported chromium induced to chrome and nickel fumes from electro-asthma due to exposure at work. Since then plating for eight months to six years before there have been very few reports of respiratory asthma developed. One subject, although symptoms in workers associated with electroexposed for 11 years without symptoms, plating. developed asthma after a single severeElectroplating is the application of a metallic exposure during a ventilation failure. coating to articles using inorganic salts of metals This was the only subject who had never such as chromium or nickel. In the electrosmoked. The diagnosis was confirmed by plating process the gases released at the elecspecific bronchial challenges. Two workers trodes rise to the surface of the bath and genhad isolated immediate reactions, one a erate a fine aerosol. Nickel electroplating is late asthmatic reaction, and four a dual 95% efficient and gas generation is minimal response following exposure to nebulised whereas chromium electroplating is inefficient potassium dichromate at 1-10 mg/ml. Two and 80-90% of the total energy used may of the four subjects were also challenged be directed to the generation of potentially with nebulised nickel chloride at respirable aerosols of chromic acid. Epi-0.1-10 mg/ml. Two showed isolated late demiological studies have suggested increased asthmatic reactions, in one at 0.1 mg/ml, respiratory morbidity in electroplaters comwhere nickel was probably the primary pared with galvanisers that is related to exsensitising agent. Four workers carried out posure to chromium. 4 We report here our two hourly measurements of peak ex-experience with chromium induced asthma in piratory flow over days at and away workers referred to a specialist occupational from work. All were scored as having lung disease clinic over 10 years. occupational asthma using OASYS-2. Breathing zone air monitoring was carried out in 60 workers from four decorative Methods The Occupational Lung Disease Unit, and two hard chrome plating shops from Subjects were identified at a specialist oc-