Statutory Thickets and Drug Shortages: Accumulating Legislation as an Underlying Cause.

Prescription drug shortages have become increasingly common and more severe over the past decade. In addition, reported shortages are longer in duration and have had a greater effect on patient care. Some of the causes of current drug shortages are multifactorial, including the consolidation of drug manufacturers, quality problems at production plants that restrict the supply of drugs, and a lack of financial incentives for manufacturers to produce certain products, particularly generic medications. Generic injectable medications are most commonly affected by shortages because the production process is complex and costly for these drugs, and profit margins are often smaller than for branded medications. Many commonly used emergency department (ED) generic injectables have been affected by shortages, including multiple resuscitation and critical care drugs. Several reports have shown that shortages can potentially have major effects on the quality of medical care, including medication errors, treatment delays, adverse outcomes, and increased health care costs. Currently, no published data exist outside of case reports that directly link ED-based drug shortages to overall patient safety events; however, there are several examples in the ED where first-line therapies for life-saving medications have been in short supply, and alternatives have higher rates of adverse events, narrower therapeutic indexes, or both. Aside from increasing notification about shortages, the U.S. Food and Drug Administration has little power to coerce manufacturers to produce medications during a shortage. Therefore, ED providers must learn to mitigate the effects of shortages locally, through active communication with pharmacy staff to identify safe and effective alternatives for commonly used medications when possible. Particularly given the effect on critical care medications, therapeutic alternatives should be clearly communicated to all staff so that providers have easy access to this information during resuscitations. This review focuses on the etiology of drug shortages, their effect on the ED, and potential solutions and mitigation strategies.

US drug shortages could continue for years

Root cause analysis was performed to determine the cause of failure of numerous cast aluminum pistons used in high speed diesel engines over ~7 months. The analysis consisted of metallurgical and engine systems evaluations. The metallurgical evaluation of two of the initial failed pistons showed failure by exposure to incompletely atomized and combusted fuel droplets that melted and eroded the piston crown outer diameters. The initial suspected root cause of the uncombusted fuel droplets was the presence of fuel-tank biological growth. The tanks were cleaned and the engines restored to service, but there were additional piston failures after only a short time back on-line, including piston seizures that fractured the pistons and cylinder liners. A subsequent, much more detailed engine system evaluation showed that the true root cause explaining all the failures was incorrect fuel injection timing. Two key points to be taken from this analysis are: (1) determination of the true root cause in this case required continuous and close interaction among metallurgical and engine systems personnel throughout an extended analysis process; (2) getting to the true root cause may require tenacious ‘detective’ work to track down and eliminate all other potential causes.

Overlap has been identified in previous works as a significant obstacle to automated diagnosis using data mining algorithms, since it makes it impossible to discern how each machine influences product quality. Several solutions that handle overlap have been proposed, but the final result is a list of potential overlapped root causes. The goal of this paper is to develop a solution resilient to overlap that can determine the true root cause from a list of possible root causes, when possible, and determine the conditions in which it is possible to identify the root causes. This allows for a better understanding of overlap, and enables the development of a fully automatic root cause analysis for manufacturing. To do so, we propose an automatic root cause analysis approach that uses causal inference and <i>do</i> calculus to determine the true root cause. The proposed approach was validated on simulated and real case-study data, and allowed for an estimation of the effect of a product passing through a certain machine while disregarding the effect of overlap, in certain conditions. The results were on par with the state-of-the-art solutions capable of handling overlap. The contributions of this paper are a graphical definition of overlap, the identification of the conditions in which is possible to overcome the effect of overlap, and a solution that can present a single true root cause when such conditions are met.

Aluminum bondpad peeling was observed in a newly developed thermosonic wirebonding process for chip-on-board assembly. Through detailed failure analysis and with the help of finite element analysis on stress simulation, the true root cause of the peeling is identified. It is found that the true root cause is the effect of skidding force as a result of the constrained movement of the bonding tool as bonding is done on a chip assembled in a plastic casing. With a change in the bonding tool movement, the peeling phenomenon is completely eliminated.

Editorial: Re-examining How We Study Race and Ethnicity.

Aggregated results from twenty years of community-engaged assiduous restoration of severely degraded coastal littoral systems in New Zealand (NZ) reveal numerous fundamental and substantive natural improvements to dune form, function, and storm resilience. This is accomplished by simple, low-cost exclusive utilisation of the variably threatened local indigenous dune plant species. These valuable and innovative enhancements succeed countless decades of cascading consequences from numerous impacts instigated by historic (and frequently continuing) damaging effects on those previously natural coastal dune ecosystems – impacts that subsequently induced problematic littoral retreat – the true root cause of prevailing coastal erosion. The durable reversals were often generated in less than two decades, contemporaneously with adverse storm surge and sea level rise conditions. Research reveals many global dune ecosystems are afflicted with analogous normalised degradation and erosion difficulties, with the earliest active circumvention recorded in sixteenth century Denmark (McKelvey 1999). Historic plus current pressures such as coastal settlement impacts and continuing agricultural use of dunelands similarly threaten numerous global littoral margins, alongside recent concerns regarding the compounding effects of climate change. Successful, affordable, diligent dune restoration work pioneered in NZ has extensive benefits for other nations experiencing similarly challenging attrition on degraded coastal zones. Persuasive data is presented to validate the numerous persistently accrued benefits of this cost-effective and enduring coastal adaptation response.

Access to medications is a fundamental aspect of healthcare and vital for human well-being. Medicine shortages are widespread and impact countries across all income levels. This research aimed to monitor the characteristics of drug shortages in Syria through a distributed survey. 76% of the sample were females. 88.9% of the sample were 20-29 years old. A high percentage of the participants were single (86.6%). 62% were students. Pharmacy is the profession or field of study for most participants (83.4%). Half of the participants live in the city (51%). Most participants work at a local pharmacy. The majority (79.5%) have fewer than 5 years of experience. Most participants were well-informed about medication shortages and personally experienced the impact of this issue in their professional or personal lives. A shortage of baby supplies, specifically baby milk, was reported by 70.33% of the surveyed parents. Tablets and capsules are the pharmaceutical formulations that experience shortages most commonly. Shortages were reported in all categories of medications. Participants identified the shortage of raw materials and low profit margins as significant factors contributing to drug shortages. Further research into drug shortages in Syria is warranted to address this issue.

Memory‐related program failures in multithreaded programs can be caused by a variety of bugs. Concurrency bugs can occur due to unexpected or incorrect thread interleavings during execution. Other kinds of memory bugs, such as buffer overflows and uninitialized reads, may also occur in multithreaded as well as single‐threaded programs. Most prior techniques for isolating these bugs are specialized, addressing only one type of concurrency bug or certain types of other memory bugs. The memory corruption caused by these bugs can also undergo significant propagation during program execution. When a program failure finally occurs due to memory corruption, the true root cause of the failure may be effectively concealed as significant portions of memory may have become corrupted. We propose a general framework that can isolate the root cause of any failure in a multithreaded program that involves memory corruption and reveals at least a subset of this memory corruption. This includes three important types of concurrency bugs—data races, atomicity violations, and order violations—as well as other kinds of memory bugs. To account for propagation of memory corruption, our approach uses a dynamic technique called ‘execution suppression’ that iteratively reveals memory corruption in a failing execution to isolate the true root cause of the failure. Copyright © 2011 John Wiley &amp; Sons, Ltd.

The shift in power conversion and power management applications to thick copper clip technologies and thinner silicon dies enable high-current connections (overcoming limitations of common wire bond) and enhance the heat dissipation properties of System-in-Package solutions. Powerstage innovation integrates enhanced gate drivers with two MOSFETs combining vertical current flow with a lateral power MOSFET. It provides a low on-resistance and requires an extremely low gate charge with industry-standard package outlines - a combination not previously possible with existing silicon platforms. These advancements in both silicon and 3D Multi-Chip- Module packaging complexity present multifaceted challenges to the failure analyst. The various height levels and assembly interfaces can be difficult to deprocess while maintaining all the critical evidence. Further complicating failure isolation within the system is the integration of multiple chips, which can lead to false positives. Most importantly, the discrete MOSFET all too often gets overlooked as just a simple threeterminal device leading to incorrect deductions in determining true root cause. This paper presents the discrete power MOSFET perspective amidst the competing forces of the system-to-board-level failure analysis. It underlines the requirement for diligent analysis at every step and the importance as an analyst to contest the conflicting assumptions of challenging customers. Automatic Test Equipment (ATE) data-logs reported elevated power MOSFET leakage. Initial assumptions believed a MOSFET silicon process issue existed. Through methodical anamnesis and systematic analysis, the true failure was correctly isolated and the power MOSFET vindicated. The authors emphasize the importance of investigating all available evidence, from a macro to micro 3D package perspective, to achieve the bona fide path forward and true root cause.

9 - Step 6: part I—root cause analysis

Organizations often experience safety problems which are chronic in nature, reoccurring problems that have been tackled many times through an array of solutions, but remain embedded in everyday working life and become a tolerated norm. Our brains are biased toward solving problems using conventional logical processes, thinking in very linear selective pathways, where each step is precise, requiring exact and logical reasoning that must be correct before moving on. Although very effective, this ‘vertical thinking’ can lead us to overlook the REAL root cause of a problem, that, if not truly identified, creates the risk of providing misguided solutions, whose results are never potent enough. Saipem's aim was to break from the limitation of traditional vertical thinking and to generate largescale lateral thinking ideas, solving problems through an indirect and creative approach. This was done by utilizing the power of provocation. Individuals began challenging normal assumptions that arise from a vertical thinking process, while applying these techniques to ‘identify the problem behind the problem’, uncovering the true root cause before moving onto solutions and action planning. This innovative problem-solving process called "We Want Zero" was launched by the CEO in early 2014, and takes the format of a one- day highly interactive ‘brainstorming’ workshop. Attendees are carefully selected for their strong operational experience and, above all, capability to be creative, innovative and open-minded enough to embrace change. The workshop leads with the question ‘What are the factors which are preventing us to achieve zero?’, which generates hundreds of potential problems for analysis, which are then divided into three main categories, Organizational, Technical and Cultural, and further clustered into common themes. Applying lateral thinking processes then enables the effective discovery of the true root causes, and only then moving onto the development of targeted action plans, using the Pareto law and emotional tools in order to activate creativity in the process. The brainstorming events are championed by the senior level managers attending the workshop, as they are also in charge of driving the implementation of action plans. This paper will describe how Saipem approached dismantling long-term ineffective solutions, how the methodology was applied across its operating divisions, and the high impact that the process has on the organization's ability to further break the safety plateau and achieve zero fatalities.

Generics and Biosimilars: Barriers and Opportunities

Predictors of Drug Shortages and Association with Generic Drug Prices: A Retrospective Cohort Study

Objective: To increase pharmacy technicians' awareness of national drug shortages, enabling them to understand why drug shortages occur and how they can help ameliorate the effects that a drug shortage may have in their workplace. Data Sources: Articles were identified through searches of MEDLINE and PubMed (1950 through July, 2011) using the following search terms: drug shortages, drug shortages and legislation, drug shortages and law, and drug shortages and safety. Additionally, resources on drug shortages from the American Society of Health-System Pharmacists, the FDA, and the Institute for Safe Medication Practices were used. Study Selection and Data Extraction: Articles describing drug shortages, drug shortages and legislation, and managing drug shortages in the health care setting were included. Data Synthesis: The effects of drug shortages on pharmacy departments and the health care system as a whole can place significant strain on pharmacists. Pharmacy technicians can play a key role in the initial management of a drug shortage by being responsible for such tasks as validating shortage details and duration with manufacturers, determining the institution's current stock and history of use of a medication, and remaining up-to-date on current drug shortages to help keep patients and other health care professionals informed. Conclusions: Pharmacy technicians are a valuable resource for pharmacists in the management of drug shortages and can work with pharmacists to perform operational and assessment tasks after a drug shortage has been identified.