Antimicrobial Shortages: A Global Issue Impacting Infectious Diseases.

Shortages of antimicrobial agents rank second among all pharmaceutical classes and are persistent and increasing. Underlying reasons for shortages include manufacturing and quality issues, market economics, and changes in demand. Antimicrobial shortages result in compromised outcomes, higher treatment costs, contribute to antibiotic resistance, and may lead to increased adverse effects.

Mitigating the impact of blood shortages in England.

The supply of blood components and products in sufficient quantities is key to any effective health care system. This report describes the challenges faced by the English blood service, NHS Blood and Transplant (NHSBT), towards the end of the COVID-19 pandemic, which in October 2022 led to an Amber Alert being declared to hospitals indicating an impending blood shortage. The impact on the hospital transfusion services and clinical users is explained. The actions taken by NHSBT to mitigate the blood supply challenges and ensure equity of transfusion support for hospitals in England including revisions to the national blood shortage plans are described. This report focuses on the collaboration and communication between NHSBT, NHS England (NHSE), Department of Health and Social Care (DHSC), National Blood Transfusion Committee (NBTC), National Transfusion Laboratory Managers Advisory Group for NBTC (NTLM), National Transfusion Practitioners Network, the medical Royal Colleges and clinical colleagues across the NHS.

Comparing Drug Shortages Experienced by Institutions With National Metrics.

Drug shortages have increasingly posed challenges to providers, pharmacists, and patients for more than 20 years. Regardless of the underlying causes, for which there does not appear to be a solution in sight, healthcare providers and patients must deal with the consequences. There is often conflicting and confusing information published that confuses everyone. This article describes the reasons for conflicting information from different sources.

A global analysis of the use of immunoglobulin, shortages in supply, and mitigating measures: A survey of hospital providers (a BEST Collaborative study).

BACKGROUND: Immunoglobulin (IG) therapy is widely used to treat primary and secondary immune deficiencies and as immunomodulatory agent for various disorders. There is great concern that shortages of IG may rise, potentially affecting medical treatment options. STUDY DESIGN AND METHODS: An international survey was developed to study how intravenous immunoglobulins (IVIGs) are used and managed within hospitals in case of shortages. Study data were collected and managed using REDCap electronic data capture tools hosted by the Biomedical Excellence for Safer Transfusion (BEST) Collaborative. The survey was directed to hospital pharmacists and blood bank transfusion professionals and disseminated through members of the BEST Collaborative network. RESULTS: Survey respondents from institutions in the USA, Canada, Europe, Japan, and Australia (n = 13) confirmed that the primary specialties utilizing IG are neurology, hematology, and immunology. More than 60% of respondents reported IG supply shortages, but mitigation strategies were not well developed. DISCUSSION: As IG is the leading driver in plasma demand, more studies are needed to understand current and future demand for IG from the clinical perspective. Necessity lies in establishing clinical guidance to address shortages.

Effects of the valsartan recall on heart failure patients: A nationwide analysis.

BACKGROUND: Valsartan is commonly used for cardiac conditions. In 2018, the Food and Drug Administration recalled generic valsartan due to the detection of impurities. Our objective was to determine if heart failure patients receiving valsartan at the recall date had a greater likelihood of unfavorable outcomes than patients using comparable antihypertensives. METHODS: We conducted a cohort study of Optum's de-identified Clinformatics® Datamart (July 2017-January 2019). Heart failure patients with commercial or Medicare Advantage insurance who received valsartan were compared to persons who received non-recalled angiotensin receptor blockers (ARBs) and angiotensin converting enzyme-inhibitors (ACE-Is) for 1 year prior and including the recall date. Outcomes included a composite for all-cause hospitalization, emergency department (ED), and urgent care (UC) use and a measure of cardiac events which included hospitalizations for acute myocardial infarction and hospitalizations/ED/UC visits for stroke/transient ischemic attack, heart failure or hypertension at 6-months post-recall. Cox proportional hazard models with propensity score weighting compared the risk of outcomes between groups. RESULTS: Of the 87 130 adherent patients, 15% were valsartan users and 85% were users of non-recalled ARBs/ACE-Is. Valsartan use was not associated with an increased risk of all-cause hospitalization/ED/UC use six-months post-recall (HR 1.00; 95% CI 0.96-1.03), compared with individuals taking non-recalled ARBs/ACE-Is. Similarly, cardiac events 6-months post-recall did not differ between individuals on valsartan and non-recalled ARBs/ACE-Is (HR 1.04; 95% CI 0.97-1.12). CONCLUSIONS: The valsartan recall did not affect short-term outcomes of heart failure patients. However, the recall potentially disrupted the medication regimens of patients, possibly straining the healthcare system.

Drug supply and assurance: a cross-sectional study of drug shortage monitoring varieties in China.

BACKGROUND: Drug shortage is a worldwide problem that seriously threatens public health. China released the most comprehensive list of key drug shortage monitoring varieties ever in 2022. We aim to analyze the attributes and characteristics of the medicines within the list to provide a reference for improving China's supply security of shortage drugs. METHODS: We used public data to extract information on drug types, dosage forms, indications, classification of clinical uses, whether they were included in medical catalogs such as the National Essential Drugs, and the number of drug and active pharmaceutical ingredient (API) manufacturers. A descriptive statistical analysis was used. RESULTS: Of the 980 drugs on the list, 99.59% were chemicals and 92.65% were injectables. Drugs for blood and hematopoietic organs, the cardiovascular system, and the digestive tract and metabolism ranked among the top three shortages. Verification of the medical catalogs showed that 90.41% of the drugs belonged to the national essential drugs, 95.10% were medicare drugs, 2.55% were volume-based procurement drugs, and 14.70% were for rare diseases, and 42.04% were for children. In terms of drug supply capacity, 21.33% of drug approvals are less than 10, and there were even 26 drugs for exclusive production, close to 90% of manufacturers need to purchase APIs from outside. Among the 256 APIs included in the list, 152 APIs had less than 10 manufacturers, and there were even 5 APIs produced by only one enterprise nationwide. CONCLUSIONS: The situation of drug shortages in China was severe and complex, with serious shortages of medicines adapted to basic medical and healthcare needs and clinically necessary medicines, and a need to improve the production capacity of drugs and the ability to supply APIs. We recommend strengthening drug monitoring and stockpiling and accelerating the approval of shortage drugs to improve drug supply security.

The diagnostic yield of inferior petrosal sinus sampling in Cushing syndrome in the era of ovine CRH shortage.

PURPOSE: The ovine corticotropin-releasing hormone (oCRH) stimulation test has been routinely used in the diagnostic work-up of ACTH-dependent Cushing syndrome (CS). With oCRH currently being out-of-stock in Europe, we aimed at evaluating the diagnostic performance of inferior petrosal sinus sampling (IPSS) without oCRH stimulation. METHODS: We compared the values of 40 patients with ACTH-dependent CS and negative MRI findings in whom ACTH was measured before and after oCRH stimulation. RESULTS: The ratio of central-to-peripheral ACTH measurement (IPS:P) before the combined 3, 5, and 10 min of oCRH stimulation yielded diminished sensitivity (85% vs. 97%), alongside markedly decreased specificity (57% vs. 71%), as well as reduced positive and negative predictive values (90% vs. 94% and 44% vs. 83%), respectively. CONCLUSIONS: With the current drug shortages in Europe, ACTH measurements without oCRH stimulation in IPSS cannot be recommended. Thus, we call for desmopressin or the commercially available human CRH as a potential alternative in the confirmation of ACTH excess by IPSS in equivocal MRI findings.

Identifying Medicine Shortages With the Twitter Social Network: Retrospective Observational Study.

BACKGROUND: Early identification is critical for mitigating the impact of medicine shortages on patients. The internet, specifically social media, is an emerging source of health data. OBJECTIVE: This study aimed to explore whether a routine analysis of data from the Twitter social network can detect signals of a medicine shortage and serve as an early warning system and, if so, for which medicines or patient groups. METHODS: Medicine shortages between January 31 and December 1, 2019, were collected from the Dutch pharmacists' society's national catalog Royal Dutch Pharmacists Association (KNMP) Farmanco. Posts on these shortages were collected by searching for the name, the active pharmaceutical ingredient, or the first word of the brand name of the medicines in shortage. Posts were then selected based on relevant keywords that potentially indicated a shortage and the percentage of shortages with at least 1 post was calculated. The first posts per shortage were analyzed for their timing (median number of days, including the IQR) versus the national catalog, also stratified by disease and medicine characteristics. The content of the first post per shortage was analyzed descriptively for its reporting stakeholder and the nature of the post. RESULTS: Of the 341 medicine shortages, 102 (29.9%) were mentioned on Twitter. Of these 102 shortages, 18 (5.3% of the total) were mentioned prior to or simultaneous to publication by KNMP Farmanco. Only 4 (1.2%) of these were mentioned on Twitter more than 14 days before. On average, posts were published with a median delay of 37 (IQR 7-81) days to publication by KNMP Farmanco. Shortages mentioned on Twitter affected a greater number of patients and lasted longer than those that were not mentioned. We could not conclusively relate either the presence or absence on Twitter to a disease area or route of administration of the medicine in shortage. The first posts on the 102 shortages were mainly published by patients (n=51, 50.0%) and health care professionals (n=46, 45.1%). We identified 8 categories of nature of content. Sharing personal experience (n=44, 43.1%) was the most common category. CONCLUSIONS: The Twitter social network is not a suitable early warning system for medicine shortages. Twitter primarily echoes already-known information rather than spreads new information. However, Twitter or potentially any other social media platform provides the opportunity for future qualitative research in the increasingly important field of medicine shortages that investigates how a larger population of patients is affected by shortages.

Choosing and accessing COVID-19 treatment options: a qualitative study with patients, caregivers, and health care providers in Lebanon.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has strained healthcare systems globally, particularly in terms of access to medicines. Lebanon has been greatly affected by the pandemic, having faced concomitant financial and economic crises. The objective of the study was to understand the experiences of patients with COVID-19 in Lebanon, as well as those of their families, and healthcare providers, with regards to their treatment decisions and accessibility to COVID-19 medicines. METHODS: For this qualitative study, we conducted 28 semi-structured interviews. We used purposive sampling to recruit participants with a diverse range of perspectives. The data collection phase spanned from August to November 2021 and was conducted virtually. After transcribing and translating the interviews, we employed thematic analysis to identify recurring themes and patterns. RESULTS: In total, 28 individuals participated in this study. Participants highlighted challenges owing to the COVID-19 pandemic and economic crisis. Accessing COVID-19 medicines posed major hurdles for physicians and patients, given limited availability, global shortages, local circumstances, community hoarding and stockpiling by pharmacies. Providers based treatment decisions on research, local and international practice guidelines, experiences and expert feedback. Patients sought information from social media, community members and physicians, as well as through word of mouth. Accessing medicines involved navigating the healthcare system, the black market, charities, personal networks and political parties and sourcing from abroad. The medicines were either free, subsidized or at inflated costs. CONCLUSIONS: This study highlights the diversity and complexity of factors influencing decision-making and accessing medicines during the COVID-19 pandemic in Lebanon. Future research should explore strategies for ensuring medicine access during crises, drawing insights from comparative studies across different countries.

Job crafting as retention strategy: An ethnographic account of the challenges faced in crafting new nursing roles in care practice.

Nursing shortages in the global north are soaring. Of particular concern is the high turnover among bachelor-trained nurses. Nurses tend to leave the profession shortly after graduating, often citing a lack of appreciation and voice in clinical and organisational decision-making. Healthcare organisations seek to increase the sustainability of the nursing workforce by enhancing nursing roles and nurses' organisational positions. In the Netherlands, hospitals have introduced pilots in which nurses craft new roles. We followed two pilots ethnographically and examined how nurses and managers shaped new nursing roles and made sense of their (expected) impact on workforce resilience. Informed by the literature on professional ecologies and job crafting, we show how managers and nurses defined new roles by differentiating between training levels and the uptake of care-related organisational responsibilities beyond the traditional nursing role. We also show how, when embedding such new roles, nurses needed to negotiate specific challenges associated with everyday nursing practice, manifested in distinct modes of organising, work rhythms, embodied expertise, socio-material arrangements, interprofessional relationships, and conventions about what is considered important in nursing. We argue that our in-depth case study provides a relational and socio-material understanding of the organisational politics implicated in organising care work in the face of workforce shortages.

No place for young women? The impact of internal migration on adult sex ratios in rural East Germany.

Shortages of women in rural areas occur in many highly urbanized countries. Rural East Germany is an ideal case for studying this phenomenon because of its low adult sex ratio (ASR)-men greatly outnumber women-coupled with high outmigration among young adults. This study identifies how internal migration between rural and urban areas contributes to the shortage of young adult women. We use data on inter-county migration flows (for years 2002-21) to decompose the impacts of migration flows on ASRs. We find that the low ASRs in rural East Germany have been driven by sex-selective migration. In the early 2000s the main destination of sex-selective outflows was West Germany, while in the 2010s urban areas in East Germany were the key destinations. We find that moves among 18-24-year-olds increased the shortage of women in the rural population, whereas moves among 25-29-year-olds contributed to more balanced ASRs.

A Transformative Decade: An Evaluation of the Francophone African Group of Pediatric Oncology's Training Program (2014-2024).

Childhood cancer in Africa faces significant challenges due to workforce shortages and limited training opportunities. The French African Group for Pediatric Oncology (GFAOP) established the African School of Pediatric Oncology and introduced a pediatric oncology teaching called the "Diplome Universitaire de Cancérologie Pédiatrique" (DUCP) training program. This report evaluates the contributions of the DUCP program to pediatric oncology in Africa and discusses the sustainability of the program. The DUCP program trained six cohorts of healthcare professionals from French-speaking African countries since 2014. An evaluation was done on the participant demographics and regional contributions. Data were collected from trainee records and DUCP records. The DUCP program was evaluated based on the domains developed by the Education Program Assessment Tool (EPAT). Over the 10-year period, the DUCP program trained 107 healthcare professionals from 20 Francophone countries of which 99% were retained in Africa. Of the 83 graduates, 55 (66%) actively practice in pediatric oncology. Of the 18 francophone countries, 17 countries increased the number of pediatric oncologists and 16 improved the ratio of pediatric oncologists to children under 15 years. Nine new pediatric oncology services were established by the graduates thus far. Despite challenges, such as the COVID-19 pandemic, the program remains sustainable because of continued financial support, collaborations with the international pediatric oncology community, and adapting the program content to participant and local setting needs. Retention of graduates in childhood cancer services remains a challenge that necessitates governmental involvement. The DUCP program is impactful and sustainable and improves access for children to cancer services in Africa. By fostering continued collaboration with governments, addressing the needs of an increasing African population, and expanding support for similar initiatives, the program's longevity and positive impact can be further ensured.

Nurse Corps' impact on increasing registered nurse staffing in critical shortage areas and facilities, 2017 to 2022.

BACKGROUND: The registered nurse (RN) workforce experienced critical pre-pandemic and pandemic shortages of labor in some areas in the United States. People living in these health professional shortage areas (HPSAs) may have less access to health services. The Bureau of Health Workforce within the Health Resources and Services Administration administers Nurse Corps scholarship and loan repayment programs to increase healthcare access by increasing the supply and distribution of RNs, nurse practitioners, and nurse faculty to HPSAs. The American Rescue Plan Act of 2021 (ARPA) made available considerable new resources for the program. PURPOSE: This paper reports on Nurse Corps applications, awards, and distribution in 2 cohorts in the period 2017 to 2022 to assess the impact of receiving an additional $200 million appropriated in 2021. DISCUSSION: Additional funds through ARPA were associated with nearly threefold increases in the number of Nurse Corps awards. Program participants worked in a total of 1,316 counties (42% of all U.S. counties) in 2020 to 2022, a 76% increase from 749 counties in 2017 to 2019. CONCLUSION: Increased funding for scholarship and loan repayment can help to improve the distribution of nurse labor to a greater number of critical shortage areas in the United States.

Australian specialised mental healthcare labour shortages: Potential interventions for consideration and further research.

OBJECTIVE: Specialised mental healthcare delivery is highly labour intensive, and the COVID-19 pandemic has exacerbated workforce shortfalls. We explore the information on the mental healthcare labour supply in Australia from a health policy viewpoint. Our purpose is to stimulate discussion, further research and development of interventions. CONCLUSIONS: The mental healthcare labour market has a number of features that make it prone to shortages and other distortions. These include: the labour-intensive nature of healthcare work;, long-training periods; that traditional policy levers like pay are only partially effective; as well as other challenges in retaining and recruiting mental health nurses and psychiatrists, especially in public mental health services. Further research is needed to develop and evaluate effective interventions.

The changing psychiatry workforce in Australia: Still lacking in rural and remote regions.

INTRODUCTION: There is a long standing and worsening shortage of psychiatrists in Australia particularly in rural areas. The majority of psychiatrists work in major cities. OBJECTIVE: To identify recent trends in the Australian rural psychiatrist workforce compared with the metropolitan workforce. DESIGN: We descriptively analysed population-level data from the National Health Workforce Data Set (NHWDS), the Australian Institute of Health and Welfare (AIHW) and the Australian Bureau of Statistics (ABS). A descriptive analysis of the numbers (count) and gender of psychiatrists from 1995 to 2022 working in Australia was conducted. For the period 2013 to 2022, we analysed for rurality, gender, years' experience, hours worked, Medicare-subsidised services provided and proportions of Specialist International Medical Graduates (SIMG) by sex, with a focus on the rural workforce. For international comparison, psychiatrist numbers were obtained for other OECD countries. The number of psychiatrists working in Australia, as per NHWDS and AIHW, was quantified. We analysed trends in demographics, hours worked and rurality of psychiatrists working in Australia in a serial cross-sectional design. FINDINGS: Most psychiatrists are maldistributed to major cities, while outer regional and remote areas have few resident psychiatrists. Outer regional New South Wales (NSW) and South Australia (SA) have the lowest numbers of psychiatrists per capita. The full-time equivalent (FTE) of psychiatrists per 100 000 has increased from 12.6 in 2000 to 15.2 in 2022. However, the average hours worked by psychiatrists has declined. In total, available psychiatrist hours worked per 100 000 population has increased by 6.1% since the beginning of the millennium. DISCUSSION: Rural areas in NSW and SA have the greatest shortage of psychiatrists. Specialist International Medical Graduates and females (43% of the overall workforce) are the predominant workforce in rural areas. Although Medicare-subsidised services per 1000 people have increased in rural areas, they remain lower than for those living in major cities. CONCLUSION: There remains an acute shortage of psychiatrists in many regional and remote areas of Australia, with an increasing proportion of SIMGs and females working in these areas, in the context of future increased demand.

Employment of Certified Peer Specialists in Mental Health Professional Shortage Areas.

The current demand for mental health services is exacerbated by an ongoing shortage of behavioral health care providers in the United States. The Health Resources and Services Administration has identified 5,833 Mental Health Professional Shortage Areas (MHPSAs), many of which are rural, and could be served by Certified Peer Specialists (CPSs). This paper examines the relationship between CPS employment and MHPSA residency. Data are from a 2020 survey of 572 CPS certified in one of four states. Random effects logistic regression models were used to test the relationship between MHPSA residence and employment outcomes. Of 166 unique counties identified by participant zip codes, 47 were characterized as being MHPSAs with 14% of participants residing in one of these counties. A higher proportion of those living in MHPSAs were employed in peer support jobs (rather than other job types or unemployed) compared to those living in non-MHPSAs (68% vs. 54%, p = .020). MHPSA residential status was not a significant predictor of employment status (OR = 1.14, p = .728) but was significantly associated with greater likelihood of employment in peer support compared to other jobs, both for the entire sample (OR = 2.13, p = .026), and among those currently employed (OR = 2.90, p = .032). The greater likelihood of working in peer support among those residing in MHPSAs suggests that CPSs may leverage their credential to address shortages. As a result, peer support may become a more necessary part of the traditional service array. Policies that enable CPS to practice in MHPSAs should be encouraged.

[Drug shortages : a fatality ?] / Médicaments indisponibles : une fatalité ?

In recent years, the number of drug shortages has risen alarmingly both in Belgium and internationally. Between 2010 and 2020, the number of reported shortages is almost 27 times higher, according to the French Agency for the Safety of Medicines and Health Products. A recent survey conducted by the European Association of Hospital Pharmacists showed that 95 % of hospital pharmacists consider drug shortages to be a major problem. The drug classes most affected include anti-infectives, analgesics and anaesthetics. The sudden and unpredictable occurrence of drug shortages has a negative impact on the daily lives of healthcare professionals and patients. Doctors are sometimes forced to prescribe alternative treatments that are considered less effective or even less well tolerated. These alternatives make it more difficult for patients to adhere to their treatment and generate an additional risk of medication errors. There are several possible solutions to minimize these shortages: relocating production sites to Europe, imposing penalties on offending companies, adopting a common European policy for managing shortages of medicines of major therapeutic interest,... As a corollary to these proposals, legal texts have been adopted to regulate and guarantee the supply of medicines in Belgium.

Depuis ces dernières années, le nombre de médicaments indisponibles a augmenté de manière inquiétante, tant en Belgique qu'au niveau international. Entre 2010 et 2020, le nombre de pénuries signalées sont près de 27 fois plus élevées, selon l'Agence Française de Sécurité du Médicament et des Produits de Santé. Une récente enquête réalisée par l'Association Européenne des Pharmaciens Hospitaliers a montré que 95 % des pharmaciens hospitaliers considèrent ces pénuries médicamenteuses comme un problème majeur. Parmi les classes médicamenteuses les plus touchées se retrouvent, notamment, les anti-infectieux, les analgésiques et les agents anesthésiques. De survenue soudaine et imprévisible, les ruptures entachent le quotidien tant des professionnels de la santé que des patients. Les médecins sont, parfois, contraints de prescrire des traitements alternatifs jugés moins efficaces, voire moins bien tolérés. Ces alternatives complexifient l'adhérence thérapeutique du patient en générant un risque supplémentaire d'erreur médicamenteuse. Pour pallier ces indisponibilités, certaines pistes de solutions peuvent être dégagées : relocaliser en Europe les sites de production, sanctionner les firmes fautives, adopter une politique européenne commune de gestion des pénuries de médicaments d'intérêt thérapeutique majeur,… En corollaire de ces propositions, des textes juridiques ont été édictés afin d'encadrer et de garantir l'approvisionnement en médicaments en Belgique.

Methotrexate Scarcity Among Children's Oncology Group Institutions: Results of a Multinational Survey.

Shortages of curative chemotherapy agents for children and adults with cancer are ubiquitous. These shortages directly result in compromised outcomes, increased medication errors, heightened cost to health systems, and patient deaths. Methotrexate is a staple of many curative childhood cancer regimens and is frequently in scarcity. No national guidance to manage methotrexate and other chemotherapy shortages exists. To assess the effect of the current methotrexate shortage, a multinational survey of Children's Oncology Group (COG) member institutions was conducted. Wide variation in the scope of methotrexate shortage in the US was demonstrated; some centers experienced significant scarcity while others experienced no shortage. Methotrexate mitigation strategies differed by COG site, resulting in potential to exacerbate differential access to life-saving medication and inequities in care. Preventing chemotherapy shortages remains a challenge. In the interim, standard guidance to assist clinicians to equitably and fairly cope with methotrexate and related drug shortages is needed.

Current Programs and Incentives to Overcome Rural Physician Shortages in the United States: A Narrative Review.

Access to healthcare continues to be a top priority and prominent challenge in rural communities, with 20% of the total U.S. population living in rural areas while only 10% of physicians practice in rural areas. In response to physician shortages, a variety of programs and incentives have been implemented to recruit and retain physicians in rural areas; however, less is known about the types and structures of incentives that are offered in rural areas and how that compares to physician shortages. The purpose of our study is to conduct a narrative review of the literature to identify and compare current incentives that are offered by rural physician shortage areas to better understand how resources are being allocated to vulnerable areas. We reviewed published peer-reviewed articles from 2015-2022 to identify incentives and programs designed to address physician shortages in rural areas. We augment that review by examining the gray literature, including reports and white papers on the topic. Identified incentive programs were aggregated for comparison and translated into a map that depicts high, medium, and low levels of geographically designated Health Professional Shortage Areas (HPSAs) and the number of incentives offered by state. Surveying current literature regarding different types of incentivization strategies while comparing to primary care HPSAs provides general insights on the potential influence of incentive programs on shortages, allows easy visual review, and may provide greater awareness of available support for potential recruits. Providing a broad overview of the incentives offered in rural areas will help illuminate whether diverse and appealing incentives are offered in the most vulnerable areas and guide future efforts to address these issues.

Drug shortages. Part 1. Definitions and harms.

Drug shortages are repeatedly in the news. The earliest drug shortages were reported during the First World War, but the numbers of shortages have increased in recent years. In the first part of this two-part review, we discuss definitions of drug shortages and so-called stockouts, which are localized shortages, and the harms that they can cause. Drug shortages make it difficult or impossible to meet the therapeutic needs of individual patients or populations, but we lack an adequate definition. The problems are too complicated to be encompassed in a brief intensional dictionary-style definition, and that is reflected in the many different attempts at definition that have been proposed. We therefore propose an extensional operational definition that incorporates the processes by which products are manufactured, the causes of shortages and the contributory factors. A definition of this sort allows one to identify the main causes of a particular drug shortage and therefore the remedies that might prevent, mitigate or manage it. In the second part of the review we discuss the causes and solutions in more detail. Adverse drug reactions and medication errors attributable to shortages occur but are not often reported. Adverse reactions to substitute medicines are possible, and errors can occur because of unfamiliarity or unnecessary treatment with replacement medicines. Other harmful outcomes include withdrawal reactions, undertreatment, treatment delays and cancellations, failure of alternatives and disruption of clinical trials.