How is cognitive behavioural therapy for insomnia delivered to adults with comorbid persistent musculoskeletal pain and disordered sleep? A scoping review.

BACKGROUND: Disordered sleep and persistent musculoskeletal pain are highly comorbid. Behavioural interventions such as Cognitive Behavioural Therapy for Insomnia (CBT-I) have shown promise in the management of both disordered sleep and persistent musculoskeletal pain. The aim of this review was to examine how CBT-I is delivered in randomised controlled trials involving people with comorbid disordered sleep and persistent musculoskeletal pain. METHODS: The protocol for this scoping review was registered with the Open Science Framework. Electronic searches of ten database and three clinical trials registries were performed up to 25 October 2023. The methodological quality of each study was evaluated by two independent reviewers using the PEDro tool. The reporting of CBT-I interventions was evaluated using the Template for Intervention Description and Replication (TIDieR) checklist. RESULTS: Twelve studies met the eligibility criteria. TIDieR scores ranged from 7-11/12, with a mean score of 8.8/12. CBT-I always involved two core components-sleep restriction and stimulus control. Furthermore, an additional five components were usually involved-a cognitive component, sleep hygiene, sleep education, relaxation/deactivation procedures and relapse planning. There was also considerable consistency in the frequency (weekly) and duration (5-9 weeks) of CBT-I programmes. Aspects inconsistently reported included who delivered the intervention; what modifications were made, if any; and the session content and duration. PEDro scores ranged from 5-8/10, with a mean score of 6.7/10. CONCLUSIONS: These findings demonstrate considerable consistency in the components of CBT-I delivered in clinical trials along with the number of sessions. The frequency of sessions was also consistent where almost all studies held weekly session. However, some aspects were either not reported (e.g., precise content of components) or inconsistent (e.g., use of terminology). CBT-I was delivered both individually and in groups. Greater consistency, and more detailed reporting regarding who delivered the intervention, the training provided, and the specific content of CBT-I components would add clarity, and may enhance CBT-I efficacy and allow better replication.

Oral bioavailability and in vivo efficacy of the helicase-primase inhibitor BILS 45 BS against acyclovir-resistant herpes simplex virus type 1.

This study investigated the oral bioavailability and efficacy of BILS 45 BS, a selective herpes simplex virus (HSV) helicase-primase inhibitor, against acyclovir (ACV)-resistant (ACV(r)) infections mediated by the HSV type 1 (HSV-1) dlsptk and PAA(r)5 mutant strains. In vitro, the compound was more potent than ACV against wild-type clinical and laboratory HSV-1 strains and ACV(r) HSV isolates, as determined by a standard plaque reduction assay, with a mean 50% effective concentration of about 0.15 microM. The oral bioavailability of BILS 45 BS in hairless mice was 49%, with a peak concentration in plasma of 31.5 microM after administration of a single dose of 25 mg/kg. Following cutaneous infection of nude mice, both the HSV-1 dlsptk and PAA(r)5 mutant strains induced significant, reproducible, and persistent cutaneous lesions that lasted for more than 2 weeks. Oral treatment with ACV (100 or 125 mg/kg/day, three times a day by gavage) did not affect either mutant-induced infection. In contrast, BILS 45 BS at an oral dose of 100 mg/kg/day almost completely abolished cutaneous lesions mediated by both ACV(r) HSV-1 mutants. The 50% effective doses of BILS 45 BS were 56.7 and 61 mg/kg/day against dlsptk- and PAA(r)5-induced infections, respectively. Taken together, our results demonstrate very effective oral therapy of experimental ACV(r) HSV-1 infections in nude mice and support the potential use of HSV helicase-primase inhibitors for the treatment of nucleoside-resistant HSV disease in humans.