Trazodone is widely prescribed off label for insomnia symptoms, but the dose range that best balances efficacy with acceptability and tolerability remains uncertain. This systematic review and dose–response meta-analysis evaluated trazodone for insomnia symptoms, with emphasis on clinically relevant dose selection. We searched Embase, PubMed, Web of Science, and the Cochrane Library from inception to 17 November 2025, for randomized controlled trials comparing trazodone with placebo or different trazodone doses in patients with insomnia symptoms. Dose–response relationships were evaluated using a one-stage random-effects model with restricted cubic splines. The primary outcome was subjective sleep quality; secondary outcomes were all-cause dropout rate and dropout due to adverse events. Thirteen randomized controlled trials involving 1366 participants were included. Compared with placebo, trazodone moderately improved subjective sleep quality (Cohen’s d = 0.67, 95
Idiopathic pulmonary fibrosis (IPF) and progressive pulmonary fibrosis (PPF) are chronic, progressive interstitial lung diseases associated with poor prognosis and few effective treatment options. Nintedanib and pirfenidone remain the cornerstones of antifibrotic therapy, yet both are limited by their tolerability issues and fail to stop the disease progression in many patients. Nerandomilast (Jascayd®; BI 1015550) is an oral, preferential PDE4B inhibitor designed to suppress pro-fibrotic inflammation, with an acceptable and generally manageable safety profile. This structured narrative review examines its mechanism of action, clinical evidence, and place in the management of fibrotic lung diseases. Preclinical work demonstrated consistent anti-inflammatory and antifibrotic activity across several experimental models. In a 12-week Phase 2 IPF trial, nerandomilast stabilized forced vital capacity (FVC) regardless of background antifibrotic use. Both Phase 3 trials, FIBRONEER-IPF and FIBRONEER-ILD, met their primary endpoint, with nerandomilast 9 mg and 18 mg twice daily significantly reducing FVC decline at 52 weeks versus placebo. In IPF, the 18 mg and 9 mg doses reduced FVC decline by 68.8 mL (p < 0.001) and 44.9 mL (p = 0.02); in PPF, reductions reached 67.2 mL (18 mg) and 81.1 mL (9 mg) (both p < 0.001). The key secondary composite endpoint was not met in IPF and did not reach significance in PPF, and patient-reported outcomes were similar between groups. Diarrhea was the most frequent adverse event, causing discontinuation in up to 6.1
Generalised anxiety disorder (GAD) is a prevalent condition that significantly impairs quality of life and is associated with substantial economic costs and increased use of healthcare resources. GAD is associated with numerous comorbidities, particularly psychiatric ones, which complicate therapeutic management and increase the severity and burden of the condition. Serotonin and norepinephrine reuptake inhibitors (SNRIs) are among the first-line pharmacological options for managing GAD. Their use is supported by efficacy and a favourable safety profile demonstrated in randomised clinical trials and meta-analyses. Furthermore, their dual mechanism of action has shown therapeutic benefit in a subset of patients with treatment-resistant disease. Our paper reviews the mechanism of action of these drugs, their efficacy and their safety. A non-systematic literature search was conducted in PubMed/MEDLINE, Embase and the Cochrane Central Register of Controlled Trials, prioritising randomised controlled trials, meta-analyses, systematic reviews and international clinical guidelines. Both venlafaxine and duloxetine are well tolerated and effective for the treatment of GAD, and their use is recommended in current clinical practice guidelines. Furthermore, this work summarises the available evidence on their use in patients with comorbidities and complex clinical profiles, such as those with other psychiatric conditions or older adults.
Tebipenem pivoxil is an orally available carbapenem prodrug with antibacterial activity against a range of Gram-negative and some Gram-positive bacterial pathogens. A fine granule formulation of tebipenem pivoxil (Orapenem®) was approved in Japan in 2009 and is indicated for use in the treatment of pneumonia, otitis media and sinusitis in paediatric patients. More recently, Spero Therapeutics in collaboration with GSK has developed a high-drug-content tebipenem pivoxil tablet formulation (UTEBZI), containing the hydrobromide salt of tebipenem pivoxil, for oral administration. In June 2026, the tebipenem pivoxil tablet formulation received its first approval, in the USA, where it is indicated for the treatment of complicated urinary tract infections (cUTIs), including pyelonephritis, caused by certain specified susceptible pathogens in adult patients who have limited or no alternative oral treatment options. This article summarises the milestones in the development of the tebipenem pivoxil tablet formulation leading to this first approval for the treatment of cUTIs, including pyelonephritis, in adults.
Influenza remains a major global health challenge, with seasonal epidemics causing 3–5 million severe cases and 290,000–650,000 deaths annually. Existing antiviral agents, while clinically useful, face limitations including narrow spectrum, drug resistance, and multi-dose regimens that compromise patient adherence. Single-dose anti-influenza therapy has emerged as a promising strategy to address these challenges by simplifying treatment and improving compliance. This review systematically summarizes recent advances in three classes of single-dose agents: polymerase acidic (PA) endonuclease inhibitors (baloxavir marboxil, suraxavir marboxil, sebaloxavir marboxil, pixavir marboxil, ADC189), neuraminidase inhibitors (e.g., the long-acting Fc conjugate CD388), and polyclonal antibodies (SAB-176). We discuss their mechanisms of action, clinical trial outcomes, and resistance profiles. The comparative analysis reveals that these three classes are not competitive alternatives but rather address distinct clinical needs: PA inhibitors provide convenient acute-phase oral therapy with rapid symptom relief but face I38T/M resistance mutations; CD388 offers extended protection suitable for seasonal prophylaxis in high-risk populations; and SAB-176 represents a passive immunization strategy for immunocompromised patients. Key challenges remain, particularly the I38T/M resistance shared across PA inhibitors and the need for head-to-head clinical comparisons. Together, these developments mark significant progress toward effective, convenient, and resistance-aware influenza management.
