Clofazimine for Treatment of Cryptosporidiosis in Human Immunodeficiency Virus Infected Adults: An Experimental Medicine, Randomized, Double-blind, Placebo-controlled Phase 2a Trial.

BACKGROUND: We evaluated the efficacy, pharmacokinetics (PK), and safety of clofazimine (CFZ) in patients living with human immunodeficiency virus (HIV) with cryptosporidiosis. METHODS: We performed a randomized, double-blind, placebo-controlled study. Primary outcomes in part A were reduction in Cryptosporidium shedding, safety, and PK. Primary analysis was according to protocol (ATP). Part B of the study compared CFZ PK in matched individuals living with HIV without cryptosporidiosis. RESULTS: Twenty part A and 10 part B participants completed the study ATP. Almost all part A participants had high viral loads and low CD4 counts, consistent with failure of antiretroviral (ARV) therapy. At study entry, the part A CFZ group had higher Cryptosporidium shedding, total stool weight, and more diarrheal episodes compared with the placebo group. Over the inpatient period, compared with those who received placebo, the CFZ group Cryptosporidium shedding increased by 2.17 log2 Cryptosporidium per gram stool (95% upper confidence limit, 3.82), total stool weight decreased by 45.3 g (P = .37), and number of diarrheal episodes increased by 2.32 (P = .87). The most frequent solicited adverse effects were diarrhea, abdominal pain, and malaise. One placebo and 3 CFZ participants died during the study. Plasma levels of CFZ in participants with cryptosporidiosis were 2-fold lower than in part B controls. CONCLUSIONS: Our findings do not support the efficacy of CFZ for the treatment of cryptosporidiosis in a severely immunocompromised HIV population. However, this trial demonstrates a pathway to assess the therapeutic potential of drugs for cryptosporidiosis treatment. Screening persons living with HIV for diarrhea, and especially Cryptosporidium infection, may identify those failing ARV therapy. CLINICAL TRIALS REGISTRATION: NCT03341767.

Children with cognitive impairment: parent report of pain and coping.

Information about pain in children with cognitive impairment is lacking. To gather pain-relevant information in this population, parents of 145 children with borderline to profound cognitive impairment were interviewed regarding their children's pain expression, experience, treatment, and coping behavior. Descriptions of pain expression and coping behavior were associated with the level of cognitive impairment. Children with mild to moderate cognitive impairment were more likely to be described as directly communicating their pain and exhibiting procedural coping strategies similar to those observed in children without cognitive impairments. More than half of the parents reported that their children experienced pain differently than did children without cognitive impairment, with the majority perceiving decreased pain sensitivity and greater pain tolerance. Finally, one third of parents felt that their children's pain was treated differently than that of other children. Half of these parents believed that health care providers had difficulties assessing and treating their children's pain. Results contribute to the developing foundation of information about pain in this special pediatric population.

Pain assessment in children with cognitive impairment. An exploration of self-report skills.

Prior to surgery, 47 children (ages 8 to 17) with borderline to profound cognitive impairment were administered tasks to evaluate their understanding of the concepts of magnitude and ordinal position and their abilities to use a 0 to 5 numerical scale to rate pain levels in schematic faces. Of the 111 children (ages 4 to 14) without cognitive impairment, were administered the same tasks. Nurses conducting preoperative evaluations predicted whether children would understand the numerical scale. Fifty percent (n = 3) of children with borderline and 35% (n = 7) of children with mild cognitive impairment (and all children 8 years and older nonimpaired) correctly used the scale. Half of the children with cognitive impairment demonstrated skills (magnitude and ordinal position) that may allow them to use simpler pain rating methods. Nurses overestimated the abilities of cognitively impaired children (and younger children without cognitive impairment) to use the rating scale.