The regulatory ancestral network of surgical meshes - Fig 1

<p>a) The number of ancestral predicates underlying surgical meshes cleared by the FDA between 2013–2015. Each surgical mesh has on average 33 ancestral predicates, but the number of ancestors differs widely between meshes b) the number of devices in our dataset (n = 477) cleared by the FDA each year from prior to the 1976 Medical Device Amendment Act 2015 (i.e. < 1976) to 2015.</p

Public availability of clinical and scientific evidence for the meshes that have led to over 100 off-spring devices.

<p>Public availability of clinical and scientific evidence for the meshes that have led to over 100 off-spring devices.</p

The ancestral device network of the recalled devices Composix Kugel Mesh (K003323) and PROCEED Trilaminate SurgicalMesh (K031925).

<p><b>+</b> Shows devices with more than 2 recalled predicates.</p

The total number of descendent devices connected to each ancestral predicate (n = 400) by chains of substantial equivalency.

<p>Ancestral predicates are grouped according to the time period in which they entered the market (bar color) to highlight that the skewed distribution in the number of descendent devices is not an artefact of the time available for ancestral predicates to accumulate descendants. Mersilene Surgical Mesh had the largest number of descendent devices and is highlighted (see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0197883#pone.0197883.g003" target="_blank">Fig 3</a> for the ancestral history of this device).</p

The ancestral device network of Mersilene Surgical Mesh manufactured by Ethicon Inc.

<p>Mersilene Mesh has led to 183 descendent devices. Devices in the ancestral network that have since been recalled for ‘design and material related flaws’ (n = 2) are highlighted in red. Devices that are descended from recalled devices by substantial equivalency chains (n = 12) are highlighted in yellow (see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0197883#pone.0197883.s002" target="_blank">S2 Data</a> for devices).</p

Switching and simplifying antiretroviral therapy in a patient with controlled HIV replication.

<p>Switching and simplifying antiretroviral therapy in a patient with controlled HIV replication.</p

Additional file 1: of A survey on beliefs and attitudes of trainee surgeons towards placebo

The survey document. (PDF 285 kb

Efficacy and categories of premature treatment cessation.

<p>*According to United States Department of Health and Human Services February 2013 Adult and Adolescent Guidelines.</p>†<p>Data for premature cessation stratified by pre-treatment viral load not available.</p><p>SD, standard deviation.</p

Efficacy by year of study commencement.

<p>Summary bubble plot displaying the change in weighted intention-to-treat antiviral efficacy of initial antiretroviral therapy by the year included studies were commenced. Each bubble represents an individual treatment group, proportional to size. SD, standard deviation.</p

Efficacy of Initial Antiretroviral Therapy for HIV-1 Infection in Adults: A Systematic Review and Meta-Analysis of 114 Studies with up to 144 Weeks' Follow-Up

<div><p>Background</p><p>A comprehensive assessment of initial HIV-1 treatment success may inform study design and treatment guidelines.</p><p>Methods</p><p>Group-based, systematic review and meta-analysis of initial antiretroviral therapy studies, in adults, of ≥48 weeks duration, reported through December 31, 2012. Size-weighted, intention-to-treat efficacy was calculated. Parameters of study design/eligibility, participant and treatment characteristics were abstracted. Multivariable, random effects, linear regression models with backwards, stepwise selection were then used to identify variables associated with efficacy.</p><p>Outcome Measures</p><p>Antiviral efficacy (undetectable plasma viral load) and premature cessation of therapy.</p><p>Results</p><p>114 studies were included (216 treatment groups; 40,124 participants; mean CD4 count 248 cells/µL [SD 81]; mean HIV-1 plasma viral load log₁₀ 4.9 [SD 0.2]). Mean efficacy across all groups was 60% (SD 16) over a mean 82 weeks' follow-up (SD 38). Efficacy declined over time: 66% (SD 16) at 48 weeks, 60% (SD 16) at 96 weeks, 52% (SD 18) at 144 weeks. The most common reason for treatment cessation was participant decision (11%, SD 6.6). Efficacy was higher with ‘Preferred’ than ‘Alternative’ regimens (as defined by 2013 United States antiretroviral guidelines): 75% vs. 65%, respectively, difference 10%; 95%CI 7.6 to 15.4; <i>p</i><0.001. In 98 groups (45%) reporting efficacy stratified by pre-treatment viral load (< or ≥100,000 copies/mL), efficacy was greater for the lower stratum (70% vs. 62%, respectively, difference 8.4%; 95%CI 6.0 to 10.9; <i>p</i><0.001). This difference persisted within ‘Preferred’ regimens. Greatest efficacy was associated with use of tenofovir-emtricitabine (vs. other nucleoside analogue backbones) and integrase strand transfer inhibitors (vs. other third drug classes).</p><p>Conclusion</p><p>Initial antiretroviral treatments for HIV-1 to date appear to have suboptimal long-term efficacy, but are more effective when commenced at plasma viral loads <100,000 copies/mL. Rising viral load should be considered an indication for starting treatment. Integrase inhibitors offer a treatment advantage (vs. other third drug classes).</p></div