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Background: Network meta-analysis (NMA) requires a connected network of randomized controlled trials (RCTs) and cannot include single-arm studies. Regulators or academics often have only aggregate data. Two aggregate data methods for analyzing disconnected networks are random effects on baseline and aggregate-level matching (ALM). ALM has been used only for single-arm studies, and both methods may bias effect estimates.


Methods: We modified random effects on baseline to separate RCTs connected to and disconnected from the reference and any single-arm studies, minimizing the introduction of bias. We term our modified method reference prediction. We similarly modified ALM and extended it to include RCTs disconnected from the reference. We tested these methods using constructed data and a simulation study.

Results: In simulations, bias for connected treatments for ALM ranged from -0.0158 to 0.051 and for reference prediction from -0.0107 to 0.083. These were low compared with the true mean effect of 0.5. Coverage ranged from 0.92 to 1.00. In disconnected treatments, bias of ALM ranged from -0.16 to 0.392 and of reference prediction from -0.102 to 0.40, whereas coverage of ALM ranged from 0.30 to 0.82 and of reference prediction from 0.64 to 0.94. Under fixed study effects for disconnected evidence, bias was similar, but coverage was 0.81 to 1.00 for reference prediction and 0.18 to 0.76 for ALM. Trends of similar bias but greater coverage for reference prediction with random study effects were repeated in constructed data.

Conclusions: Both methods with random study effects seem to minimize bias in treatment connected to the reference. They can estimate treatment effects for disconnected treatments but may be biased. Reference prediction has greater coverage and may be recommended overall.

Highlights: Two methods were modified for network meta-analysis on disconnected networks and for including single-arm observational or interventional studies in network meta-analysis using only aggregate data and for minimizing the bias of effect estimates for treatments only in trials connected to the reference.Reference prediction was developed as a modification of random effects on baseline that keeps analyses of trials connected to the reference separately from those disconnected from the reference and from single-arm studies. The method was further modified to account for correlation in trials with more than 2 arms and, under random study effects, to estimate variance in heterogeneity separately in connected and disconnected evidence.Aggregate-level matching was extended to include trials disconnected from the reference, rather than only single-arm studies. The method was further modified to separately estimate treatment effects and heterogeneity variance in the connected and disconnected evidence and to account for the correlation between arms in trials with more than 2 arms.Performance was assessed using a constructed data example and simulation study.The methods were found to have similar, and sometimes low, bias when estimating the relative effects for disconnected treatments, but reference prediction with random study effects had the greatest coverage.The use of reference prediction with random study effects for disconnected networks is recommended if no individual patient data or alternative real-world evidence is available.

This scenario can be used to assess a disconnected environment. Disconnected means there's zero network connectivity from the assessed environment to the Internet or to any other machine that has Internet access. This scenario requires extra configuration and steps that are outlined in the following sections.

However, sometimes entities are queried using one context instance and then saved using a different instance. This often happens in "disconnected" scenarios such as a web application where the entities are queried, sent to the client, modified, sent back to the server in a request, and then saved. In this case, the second context instance needs to know whether the entities are new (should be inserted) or existing (should be updated).

Here are some scenarios to consider when deploying Defender for Endpoint in a disconnected environment. These scenarios will help you prepare and understand how Defender for Endpoint will behave depending on the proxy configuration used in your environment.

These scenarios should provide you an overview of the different configurations required when you are deploying Microsoft Defender for Endpoint in a disconnected environment using a proxy to access the internet.

To install OpenShift Data Foundation in a disconnected environment, refer to the steps in the Using Operator Lifecycle Manager on restricted networks chapter of Operators guide in OpenShift Container Platform documentation.

First, bring your Apple Watch and paired iPhone close together. If you still see that the devices are disconnected and need help, try the steps below. After each step, see if your devices can connect.

Youth disconnection portrays a dynamic between individuals and the society they live in. Disconnected youth are at an increased risk of violence, smoking, alcohol consumption and marijuana use, and may have emotional deficits and less cognitive and academic skills than their peers who are working and/or in school.1-5 Approximately 1 in 9 teenagers and young adults in the U.S. is currently referred to as disconnected; not in education, employment, or training.1 Several studies have shown that disconnected youth have a disproportionate share of related health problems including chronic unemployment, poverty, mental health disorders, criminal behaviors, incarceration, poor health, and early mortality.6-9

This measure does not account for the varying levels of risk assumed among disconnected youth. For instance, someone that drops out of high school and is incarcerated is considered just as disconnected as someone that graduated and is taking time off before beginning college.

1 Mendelson T, Mmari K, Blum RW, Catalano RF, Brindis CD. Opportunity youth: insights and opportunities for a public health approach to reengage disconnected teenagers and young adults. Public Health Reports. 2018; 133, 54S-64S.

7 Hair EC, Moore KA, Ling TJ, McPhee-Baker C, Brown BV. Youth who are disconnected and those who then reconnect: assessing the influence of family, programs, peers and communities. Child Trends Research Brief. 2009.

Endoscopic retrograde cholangiopancreatography with fluoroscopy. (A) The stent is advanced in the early part of the pancreatic duct (arrow). (B) Endoscopic retrograde cholangiopancreatography wire is incapable of passing distal to the disconnected segment and near the drainage catheter (arrow). (C) Disrupted continuity of the duct and disconnected pancreatic duct syndrome as the contrast did not fill the distal part of the pancreatic duct (arrow).

With the limited success of conservative management for the resolution of DPDS, CT-guided percutaneous drainage of fluid surrounding the disconnected segment has classically been the first-line treatment. Unfortunately, those drainage procedures are amenable to be complicated by fistula formation and often require endoscopic repair procedures.57

ERCP insertion of an indwelling stent between the two disconnected ends of the main pancreatic duct appears to be a useful option for this group of patients. Some studies have shown that this procedure reduces the recurrence of pancreatic fluid collection in DPDS patients; however, the rate of stent migration is high.78 Another challenge with ERCP stenting in DPDS is difficulty of passing the stent between the two disconnected ends of the pancreatic duct, which is similar to our experience. Those two factors make surgery the last resort for those in whom ERCP stenting was unsuccessful.

Roux-en-Y internal drainage (by pancreaticogastrostomy, pancreaticojejunostomy or fistulotomy) and distal pancreaticosplenectomy are the two main types of surgery that are generally recommended for patients with DPDS and pancreatic necrosis for whom other non-surgical measures have failed.9 Many of those surgical procedures are associated with a high level of mortality and morbidity represented by infection, chronic pancreatic insufficiency, necrosis, multiorgan failure and death.1011 Our patient underwent Roux-en-Y internal drainage pancreaticogastrostomy and not distal pancreaticosplenectomy for two main reasons. First, the involved segment of the duct was near the head of the pancreas, mandating a complete resection of the head of the pancreas proximal to the disconnected segment and an immediate drainage to the stomach. Second, the distal portion of the pancreas was completely intact, making its removal along with the spleen an excessively invasive procedure to a functional part of the pancreas which may carry procedural complications and ultimately, poor outcome.1011 Splenectomy is usually performed when the distal pancreatic segments (body and tail) are surgically removed, which was not the case in our patient.910 Limited therapeutic options seem to be the main driver for the surgical intervention in this group of patients.

This paper was commissioned by the Youth Transition Funders Group in 2015. The purpose was to conduct a scan of the current state of the evidence regarding what works in helping disconnected young people, defined as the population of young people ages 16 to 24 who are not connected to work or school. To prepare the paper, MDRC conducted a literature review of relevant policies and programs. The literature reviewed included writing on impact, quasi-experimental, and implementation studies. MDRC also conducted reviews of numerous websites to learn about current policy trends and evaluations in process. To supplement what was learned from written materials, MDRC interviewed a number of practitioners in the field, including representatives from foundations, coalitions, and research organizations. 041b061a72


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