Methodological and Reporting Quality of Noninferiority Randomized Controlled Trials Comparing Antiretroviral Therapies: A Systematic Review.

BACKGROUND: It is unclear whether the reporting quality of antiretroviral (ARV) noninferiority (NI) randomized controlled trials (RCTs) has improved since the CONSORT guideline release in 2006. The primary objective of this systematic review was assessing the methodological and reporting quality of ARV NI-RCTs. We also assessed reporting quality by funding source and publication year. METHODS: We searched Medline, Embase, and Cochrane Central from inception to 14 November 2022. We included NI-RCTs comparing ≥2 ARV regimens used for human immunodeficiency virus treatment or prophylaxis. We used the Cochrane Risk of Bias 2.0 tool to assess risk of bias. Screening and data extraction were performed blinded and in duplicate. Descriptive statistics were used to summarize data; statistical tests were 2 sided, with significance defined as P < .05. The systematic review was prospectively registered (PROSPERO CRD42022328586), and not funded. RESULTS: We included 160 articles reporting 171 trials. Of these articles, 101 (63.1%) did not justify the NI margin used, and 28 (17.5%) did not provide sufficient information for sample size calculation. Eighty-nine of 160 (55.6%) reported both intention-to-treat and per-protocol analyses, while 118 (73.8%) described missing data handling. Ten of 171 trials (5.9%) reported potentially misleading results. Pharmaceutical industry-funded trials were more likely to be double-blinded (28.1% vs 10.3%; P = .03) and to describe missing data handling (78.5% vs 59.0%; P = .02). The overall risk of bias was low in 96 of 160 studies (60.0%). CONCLUSIONS: ARV NI-RCTs should improve NI margin justification, reporting of intention-to-treat and per-protocol analyses, and missing data handling to increase CONSORT adherence.

Gallium arsenide whispering gallery mode resonators for terahertz photonics.

As the field of terahertz (THz) photonics advances, we present a monolithic gallium arsenide (GaAs) disk-shaped whispering gallery mode resonator that has potential as a component in THz nonlinear optics. GaAs is a material with significant optical nonlinearity which can be enhanced when the crystal is shaped into a microdisk resonator. A 4-mm-disk-resonator was fabricated using single-point diamond turning and was characterized to obtain a quality (Q) factor of 2.21k at ∼150 GHz and 1.41k at ∼300 GHz. We also demonstrated the blue-shifting of up to ∼0.3 GHz of the THz modes using a block of metal. This post-fabrication degree of freedom could be useful for phase-matching requirements for nonlinear optical processes, such as detection based on optical up-conversion of THz radiation. This proof-of-concept demonstration can pave the way for the implementation of a compact, tunable and efficient device which could be integrated into nonlinear photonic platforms for THz generation, manipulation and detection.

How Generalizable Are Randomized Controlled Trials (RCTs) in Staphylococcus aureus Bacteremia? A Description of the Mortality Gap Between RCTs and Observational Studies.

In Staphylococcus aureus bacteremia, mortality rates in randomized controlled trials (RCTs) are consistently lower than observational studies. Stringent eligibility criteria and omission of early deaths in RCTs contribute to this mortality gap. Clinicians should acknowledge the possibility of a lower treatment effect when applying RCT results to bedside care.

An Integrated Millimeter-Wave Satellite Radiometer Working at Room-Temperature with High Photon Conversion Efficiency.

In this work, the design of an integrated 183GHz radiometer frontend for earth observation applications on satellites is presented. By means of the efficient electro-optic modulation of a laser pump with the observed millimeter-wave signal followed by the detection of the generated optical sideband, a room-temperature low-noise receiver frontend alternative to conventional Low Noise Amplifiers (LNAs) or Schottky mixers is proposed. Efficient millimeter-wave to 1550 nm upconversion is realized via a nonlinear optical process in a triply resonant high-Q Lithium Niobate (LN) Whispering Gallery Mode (WGM) resonator. By engineering a micromachined millimeter-wave cavity that maximizes the overlap with the optical modes while guaranteeing phase matching, the system has a predicted normalized photon-conversion efficiency ≈10-1 per mW pump power, surpassing the state-of-the-art by around three orders of magnitude at millimeter-wave frequencies. A piezo-driven millimeter-wave tuning mechanism is designed to compensate for the fabrication and assembly tolerances and reduces the complexity of the manufacturing process.

Deep-UV-enhanced supercontinuum generated in a tapered gas-filled photonic crystal fiber.

We present the use of a linearly down-tapered gas-filled hollow-core photonic crystal fiber in a single stage, pumped with pulses from a compact infrared (IR) laser source, to generate a supercontinuum (SC) carrying significant spectral power in the deep ultraviolet (UV) [200-300 nm]. The generated SC extends from the near IR down to ∼213nm with 0.58 mW/nm and down to ∼220nm with 0.83 mW/nm in the deep UV.

Covariance spectroscopy of molecular gases using fs pulse bursts created by modulational instability in gas-filled hollow-core fiber.

We present a technique that uses noisy broadband pulse bursts generated by modulational instability to probe nonlinear processes, including infrared-inactive Raman transitions, in molecular gases. These processes imprint correlations between different regions of the noisy spectrum, which can be detected by acquiring single shot spectra and calculating the Pearson correlation coefficient between the different frequency components. Numerical simulations verify the experimental measurements and are used to further understand the system and discuss methods to improve the signal strength and the spectral resolution of the technique.

Staphylococcus aureus bacteremia mortality across country income groups: A secondary analysis of a systematic review.

OBJECTIVES: Staphylococcus aureus bacteremia (SAB) is a common infection worldwide. We compared SAB mortality in low- and middle-income countries (LMIC) versus high-income countries (HIC) in a meta-analysis. METHODS: We searched MEDLINE, Embase, and Cochrane Database of Systematic Reviews from 1991-2021 and included observational, single-country studies on patients with positive blood cultures for S. aureus. The main outcome was the proportion of patients with SAB who died in the hospital. A generalized linear mixed random-effects model was used to pool estimates, and a meta-regression was used to adjust for study-level characteristics. RESULTS: A total of 332 studies involving 517,671 patients in 39 countries were included. No study was conducted in a low-income country. Only 33 (10%) studies were performed in middle-income countries (MIC), which described 6,216 patients. The pooled in-hospital mortality was 32.4% (95% confidence interval [CI] 27.2%-38.2%, T2 = 0.3063) in MIC and 22.3% (95% CI 20.1%-24.6%, T2 = 0.3257) in HIC. In a meta-regression model, MIC had higher in-hospital mortality (adjusted odds ratio 1.37, 95% CI 1.11-1.71; P = 0.0042) than HIC. CONCLUSION: In SAB studies, LMIC are poorly represented. In-hospital mortality was significantly higher in MIC than in HIC. Research should be conducted in LMIC to characterize differences in care processes driving the mortality gap.

Staphylococcus aureus bacteraemia mortality: a systematic review and meta-analysis.

BACKGROUND: Precise estimates of mortality in Staphylococcus aureus bacteraemia (SAB) are important to convey prognosis and guide the design of interventional studies. OBJECTIVES: We performed a systematic review and meta-analysis to estimate all-cause mortality in SAB and explore mortality change over time. DATA SOURCES: The MEDLINE and Embase databases, as well as the Cochrane Database of Systematic Reviews, were searched from January 1, 1991 to May 7, 2021. STUDY ELIGIBILITY CRITERIA: Human observational studies on patients with S. aureus bloodstream infection were included. PARTICIPANTS: The study analyzed data of patients with a positive blood culture for S. aureus. METHODS: Two independent reviewers extracted study data and assessed risk of bias using the Newcastle-Ottawa Scale. A generalized, linear, mixed random effects model was used to pool estimates. RESULTS: A total of 341 studies were included, describing a total of 536,791 patients. From 2011 onward, the estimated mortality was 10.4% (95% CI, 9.0%-12.1%) at 7 days, 13.3% (95% CI, 11.1%-15.8%) at 2 weeks, 18.1% (95% CI, 16.3%-20.0%) at 1 month, 27.0% (95% CI, 21.5%-33.3%) at 3 months, and 30.2% (95% CI, 22.4%-39.3%) at 1 year. In a meta-regression model of 1-month mortality, methicillin-resistant S. aureus had a higher mortality rate (adjusted OR (aOR): 1.04; 95% CI, 1.02-1.06 per 10% increase in methicillin-resistant S. aureus proportion). Compared with prior to 2001, more recent time periods had a lower mortality rate (aOR: 0.88; 95% CI, 0.75-1.03 for 2001-2010; aOR: 0.82; 95% CI, 0.69-0.97 for 2011 onward). CONCLUSIONS: SAB mortality has decreased over the last 3 decades. However, more than one in four patients will die within 3 months, and continuous improvement in care remains necessary.

What Is the Optimal Follow-up Length for Mortality in Staphylococcus aureus Bacteremia? Observations From a Systematic Review of Attributable Mortality.

Background: Deaths following Staphylococcus aureus bacteremia (SAB) may be related or unrelated to the infection. In SAB therapeutics research, the length of follow-up should be optimized to capture most attributable deaths and minimize nonattributable deaths. We performed a secondary analysis of a systematic review to describe attributable mortality in SAB over time. Methods: We systematically searched Medline, Embase, and Cochrane Database of Systematic Reviews from 1 January 1991 to 7 May 2021 for human observational studies of SAB. To be included in this secondary analysis, the study must have reported attributable mortality. Two reviewers extracted study data and assessed risk of bias independently. Pooling of study estimates was not performed due to heterogeneity in the definition of attributable deaths. Results: Twenty-four observational cohort studies were included. The median proportion of all-cause deaths that were attributable to SAB was 77% (interquartile range [IQR], 72%-89%) at 1 month and 62% (IQR, 58%-75%) at 3 months. At 1 year, this proportion was 57% in 1 study. In 2 studies that described the rate of increase in mortality over time, 2-week follow-up captured 68 of 79 (86%) and 48 of 57 (84%) attributable deaths that occurred by 3 months. By comparison, 1-month follow-up captured 54 of 57 (95%) and 56 of 60 (93%) attributable deaths that occurred by 3 months in 2 studies. Conclusions: The proportion of deaths that are attributable to SAB decreases as follow-up lengthens. Follow-up duration between 1 and 3 months seems optimal if evaluating processes of care that impact SAB mortality. Clinical Trials Registration: PROSPERO CRD42021253891.