Study:Pietrobon 2004. Outcome: mortality
Confounding domains	Measured variable(s)	Is there evidence that controlling for this variable was unnecessary?	Is the confounding domain measured validly and reliably?	OPTIONAL Is failure to adjust for this variable expected to favour intervention or comparator
Severity of PDH	Not defined or reported.	No	No	—
Severity of HIV	Authors reported 11/16 participants with histoplasmosis had CD4 count < 50 cells/μL	No	Yes	—
Comorbidities and comedications	Authors reported none of participants were receiving ART. Study population was 16. Comorbidities mentioned but not systemically.	No	No	—
Cointerventions	Is there evidence that controlling for this cointervention was unnecessary?		Is presence of this cointervention likely to favour outcomes in the intervention or comparator?
ART at time of PDH diagnosis	No		—
Supportive therapy	No		—
Bias domain	Signalling questions	Comments		Risk of bias judgement
Bias due to confounding	1.1–1.8	No use of ART during treatment period. Comorbidities mentioned but unclear whether all relevant comorbidities studied. Severity of PDH not reported. No report of statistical methods to control for confounders. ≥ 1 known important domain was not appropriately measured or controlled for.		Serious
Bias in participant selection	2.1–2.5	Drug treatment for the initial phase provided for all participants – all received AmB. Time to commencement of treatment not reported. Data reported were retrospective analyses of medical records of patients with HIV and opportunistic infections.		No information
Bias in classification of intervention	3.1–3.3	Intervention for management of acute phase was well defined.		Low
Bias due to deviations from intended intervention	4.1–4.6	Deviations not reported.		No information
Bias due to missing data	5.1–5.5	Data were reasonably complete.		Low
Bias in measurement of outcomes	6.1–6.4	Measurement of mortality outcome unlikely to be influenced by knowledge of intervention received.		Low
Bias in selection of reported result	7.1–7.3	Descriptive retrospective study. No protocol; however, there was no indication of selection of the cohort for analysis and reporting on the basis of the result.		Moderate
Overall bias				Serious