Synovial sarcoma (SS) is an aggressive malignancy which accounts for approximately 5–10% of all soft-tissue sarcomas. SS has pathologic and genomic characteristics that define it as a distinct subtype of soft tissue sarcoma (STS). STS subtypes continue to be recognized as distinct entities with specific characteristics, including differential chemo-sensitivity. The objective of this study was to conduct a descriptive review of current data on survival outcomes of systemic anti-cancer therapy specific to SS. A systematic literature review was conducted, using a custom search strategy to search EMBASE, Medline and CENTRAL for clinical trials and observational studies reporting overall survival (OS), progression-free survival (PFS) and/or response for cohorts of at least 50 SS patients. We identified 28 studies meeting these criteria, 25 of which were retrospective studies. Only three prospective studies were identified. Survival reports varied widely between studies based on the population, in particular on the disease stage, and reporting was heterogeneous in terms of the time points reported on. For patients with localized disease, reports of five-year PFS ranged from 26% to 80.7% and five-year OS from 40% to 90.7%, whereas five-year OS for patients with metastatic disease was very low at around 10%; and in one case, 0% was reported. Only four of the included publications reported outcomes by type of systemic anti-cancer therapy received. Our study draws attention to the fact that additional prospective studies to better define the most appropriate treatment for SS in all stages and lines of therapy are still needed.

Introduction Cerebral vasospasm (VSP) is the leading risk factor of neurological deterioration (i.e., delayed cerebral ischemia [DCI] and cerebral infarction) after aneurysmal subarachnoid hemorrhage (aSAH) and a cause of morbidity and mortality. The objective of this systematic literature review is to summarize the economic and humanistic burden of VSP and its related complications after aSAH. Methods A predefined protocol was designed, and Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed. Systematic searches were conducted in MEDLINE, Embase, and Cochrane (in January 2021) to identify studies reporting economic and/or humanistic (i.e., health-related quality of life [HRQoL]) outcomes for patients with asymptomatic and symptomatic VSP after aSAH. Related conferences and additional sources were searched manually. Dual screening, data extraction, and qualitative analysis were conducted. Results Of 3818 abstracts identified for review, 43 full-text articles representing 42 single studies met the inclusion criteria and were included. Most studies (33) were observational; nine were randomized clinical trials (RCTs). Economic outcomes were reported in 31 studies, and alongside HRQoL outcomes in 4 studies; 7 studies reported HRQoL outcomes only. Forty studies were conducted in single countries, while only 2 RCTs were conducted in multiple countries. Patients diagnosed with VSP or DCI spent between 2.1 and 7.4 days longer in intensive care and between 4.7 and 17 days longer in hospital (total) compared with patients without VSP or DCI. A significantly higher cost burden of US$33,945 (2021 £26,712) was identified for patients with VSP and £9370 (2021 £13,733) for patients with DCI compared with patients without. Patients with DCI were also disadvantaged by being employed for 62 fewer days (during 24-month follow-up), with an estimated mean cost of £3821 (2021 £5600) for days off work. Poor HRQoL was associated with ≥ 1 days with VSP symptoms (odds ratio [OR]: 2.8, 95% confidence interval [CI]: 1.4–5.3), symptomatic VSP (OR: 1.9, 95% CI: 1.0–3.6), and DCI (OR: 2.3, 95% CI: 1.3–4.2), although this was not consistent across all studies. Symptomatic VSP and DCI were identified as significant risk factors for depressed mood (OR: 2.2, 95% CI: 1.0–4.9) and global cognitive impairment (OR: 2.3) at 12 months, respectively. The severity of VSP was a critical predictor of post-aSAH economic and humanistic burden. Similar trends in economic and humanistic burden were identified in the general aSAH patient population. Study design and patient heterogeneity precluded direct metaanalysis of the results. Conclusion A substantial direct and indirect economic burden is linked to VSP and its related complications after aSAH. Although limited evidence was identified for humanistic burden, these patients seem to suffer from poor HRQoL with long-lasting burden. Overall, there is an urgent need to understand better the concept of “burden of illness” of VSP and its related complications after aSAH.

Introduction Angiographic vasospasm (VSP), the narrowing of intracranial arteries, is a complication of aneurysmal subarachnoid hemorrhage (aSAH) and often results in delayed cerebral ischemia (DCI) and cerebral infarction. The objective of this systematic review was to summarize the clinical burden of angiographic VSP and its related complications (DCI and cerebral infarction) after aSAH. Methods Systematic searches of MEDLINE, Embase, and the Cochrane Library were conducted (in January 2021) in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines to identify studies reporting clinical outcomes of angiographic VSP and its related complications after aSAH. Study outcomes included measures of functional status (modified Rankin Scale [mRS], Glasgow Outcome Scale [GOS], extended Glasgow Outcome Scale [GOS-E], modified Barthel Index, or the modified National Institutes of Health Stroke Scale), cognitive status (Montreal Cognitive Assessment or the Mini Mental State Exam), clinical events (rebleeding), and mortality. Study selection, data extraction, and qualitative analyses were conducted. Results Of 5704 abstracts reviewed, 110 studies were selected: 20 comparative and 39 regression-based studies were included in the qualitative synthesis, 51 descriptive studies were excluded. Most studies (51) were observational and conducted in a single country (53). The occurrence of angiographic VSP and its related complications after aSAH resulted in significantly poorer functional outcomes in three of nine comparative and 11 of 13 regression-based studies, measured by the mRS, and in five of six comparative and eight of nine regression-based studies, measured by the GOS and GOS-E. Angiographic VSP and its related complications were significantly associated with poor cognitive status in all five regression-based studies. Numerically or significantly higher mortality rates in patients with versus those without angiographic VSP and its related complications were reported in five of ten comparative studies and in eight of nine regression-based studies. Six studies looked at specific VSP populations (e.g., by severity or timing of VSP). Conclusion Patients with angiographic VSP and its related complications often had poor functional, neurological, and cognitive outcomes and reduced odds of survival both in hospital and at follow-up. We estimate that angiographic VSP and its related complications, DCI and cerebral infarction, lead to an approximately threefold higher odds of poor functional and cognitive outcomes, and about a twofold increase in the odds of death.

Increasing evidence suggests pharmacological treatments may impact on overall survival in Chronic Obstructive Pulmonary Disease (COPD) patients. Individual clinical trials are rarely powered to detect mortality differences between treatments and may not include all treatment options relevant to healthcare decision makers. A systematic review was conducted to identify RCTs of COPD treatments reporting mortality; evidence was synthesised using network meta-analysis (NMA). The analysis included 40 RCTs; a quantitative indirect comparison between 14 treatments using data from 55,220 patients was conducted. The analysis reported two treatments reducing all-cause mortality; salmeterol/fluticasone propionate combination (SFC) was associated with a reduction in mortality versus placebo in the fixed effects (HR 0.79; 95 % Crl 0.67, 0.94) but not the random effects model (0.79; 0.56, 1.09). Indacaterol was associated with a reduction in mortality versus placebo in fixed (0.28; 0.08 to 0.85) and random effects (0.29; 0.08, 0.89) models. Mean estimates and credible intervals for hazard ratios for indacaterol versus placebo are based on a small number of events; estimates may change when the results of future studies are included. These results were maintained across a variety of assumptions and provide evidence that SFC and indacaterol may lead to improved survival in COPD patients. Results of an NMA of COPD treatments suggest that SFC and indacaterol may reduce mortality. Further research is warranted to strengthen this conclusion.

Introduction The efficacy of long-acting injectable cabotegravir (hereafter referred to as cabotegravir) versus daily oral tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) for pre-exposure prophylaxis (PrEP) was demonstrated in two phase 3 randomized controlled trials (RCTs), HPTN 083 and HPTN 084. As these trials did not have a no-PrEP group, this analysis aimed to perform an indirect treatment comparison (ITC) of cabotegravir versus no PrEP via the common comparator of oral TDF/FTC. Methods A systematic literature review identifying trials of oral or both oral and injectable PrEP reporting HIV acquisition and oral PrEP adherence, measured by detectable TDF/FTC plasma levels, was conducted (November 1, 2023). Heterogeneity in oral TDF/FTC adherence level between trials was expected to confound ITC estimates; therefore, a meta-regression of adherence and resulting oral PrEP effectiveness, or reduction in HIV acquisition, was incorporated into an ITC using a joint Bayesian model framework. Results The analysis included ten RCTs. The meta-regression showed a strong relationship between oral TDF/FTC adherence and effectiveness. The predicted effectiveness of oral TDF/FTC versus no PrEP was greater for HPTN 083 (77%) compared with HPTN 084 (47%), reflecting the higher level of adherence observed in HTPN 083 (86%) compared with HPTN 084 (56%). Based on the ITC, the predicted effectiveness of cabotegravir versus no PrEP was similar for both populations investigated in HPTN 083 (92%) and HPTN 084 (93%). Conclusions The ITC of cabotegravir versus no PrEP predicted similar estimates of cabotegravir effectiveness in the HPTN 083 and 084 trials, suggesting a very high level of efficacy despite differences in population, setting, underlying rate of HIV acquisition, and oral TDF/FTC adherence. These estimates support the generalizability of the cabotegravir results from both HPTN trials to other populations and regions than those in which these trials were conducted. Graphical abstract available for this article. Graphical abstract

Long-acting injectable cabotegravir (hereafter referred to as cabotegravir) is the first long-acting injectable approved for pre-exposure prophylaxis (PrEP) based on the HPTN 083 and 084 trials. Long-acting injectable lenacapavir (hereafter referred to as lenacapavir) was approved for PrEP based on the PURPOSE 1 and 2 trials. In the absence of a head-to-head trial, we conducted an indirect treatment comparison (ITC) to assess efficacy of lenacapavir versus cabotegravir in reducing the risk of HIV acquisition. A systematic literature review identified all relevant trials. Efficacy inputs for this ITC were derived from re-adjudicated data from the injection phase of the HPTN trials or published data from the PURPOSE trials. The ITC was performed using 2 network approaches: (1) using no PrEP and (2) using daily oral tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) as common comparators, with adjustments accounting for differing levels of adherence to TDF/FTC across trials. Sensitivity analyses were also performed using data from both the oral lead-in and injection phases of the HPTN trials. Both network approaches estimated high and comparable efficacy of cabotegravir and lenacapavir. Using no PrEP (network approach 1), the base case estimated hazard ratio (95% CrI) of lenacapavir versus cabotegravir was 1.04 (0.19, 5.69) in men who have sex with men and transgender women and 0.00 (0.00, 3.21) in cisgender women. Predicted efficacy (95% CrI) rates of cabotegravir versus no PrEP were high in men who have sex with men and transgender women 96% (90%, 98%)] and cisgender women [98% (89%, 100%)] in the HPTN trials, which were comparable to the PURPOSE trials [men and gender-diverse people, 96% (82%, 99%); cisgender women, 100%(96%,100%)]. Sensitivity analyses confirmed these findings. Based on this ITC, cabotegravir and lenacapavir offer similar and high efficacy in preventing HIV acquisitions compared with no PrEP or TDF/FTC. Graphical abstract and video abstract available for this article.