Drug shortages are a persistent public health issue that increased during the COVID-19 pandemic. Both the US and Canada follow similar regulatory standards and require reporting of drug-related supply chain issues that may result in shortages. However, it is unknown what proportion are associated with meaningful shortages (defined by a significant decrease in drug supply) and whether differences exist between Canada and the US.

To compare how frequently reports of drug-related supply chain issues in the US vs Canada were associated with drug shortages.

Longitudinal cross-sectional study conducted from January 2023 to March 2024 using drug-related reports of supply chain issues from 2017 to 2021 that were less than 180 days apart in Canada and the US. Shortages were assessed using data from the IQVIA Multinational Integrated Data Analysis database, comprising 89% of US and 100% of Canadian drug purchases.

Country (Canada vs US), timing of report issuance (before vs after the COVID-19 pandemic), and characteristics of the supply chain prior to the reports of drug-related supply chain issues (including World Health Organization essential medicine status, Health Canada tier 3 medicine [moderate risk classification], whether there was sole-source manufacturing of the drug, the formulation, the price per unit, ≥20 years since drug approval, and the number of therapeutic alternatives).

A drug shortage (a decrease of ≥33% in monthly purchased standardized drug units) within 12 months, relative to the average units purchased during the 6 months prior to the report of supply chain issues to a US or Canadian reporting system.

Among the 104 drug-related reports of supply chain issues in both countries, 49.0% (95% CI, 39.3%-59.7%) were associated with drug shortages in the US vs 34.0% (95% CI, 25.0%-45.0%) in Canada (adjusted hazard ratio [HR], 0.53 [95% CI, 0.36-0.79]). The lower risk of drug shortages in Canada vs the US was consistent before the COVID-19 pandemic (adjusted HR, 0.47 [95% CI, 0.30-0.75]) and after the pandemic (adjusted HR, 0.31 [95% CI, 0.15-0.66]). After combining reports of supply chain issues in both countries, the shortage risk was double for sole-sourced drugs (adjusted HR, 2.58 [95% CI, 1.57-4.24]) and nearly half for Canadian tier 3 medicines (moderate risk) (adjusted HR, 0.56 [95% CI, 0.32-0.98]).

Drug-related reports of supply chain issues were 40% less likely to result in meaningful drug shortages in Canada compared with the US. These findings highlight the need for international cooperation between countries to curb the effects of drug shortages and improve resiliency of the supply chain for drugs.

Parkinson's disease (PD) is a common age-related neurodegenerative disorder, which may be largely due to the mitochondrial dysfunction and impaired mitophagy. Thus, it is of great importance to seek novel therapeutic strategies for PD targeting mitochondrial function and mitophagy. Cytarabine is a marine-derived antimetabolite used in the treatment of acute leukemia, which is also used in the study of the nervous system. In this study, we found that cytarabine pretreatment significantly inhibited the apoptosis and necrosis in the ROT-induced SH-SY5Y cell PD model and reduced the oxidative stress, as evidenced by the reduced MDA levels and the increased levels of SOD, GSH, and total antioxidant capacity. Cytarabine can also enhance mitochondrial vitality, improve mitochondrial respiratory function, and preserve mitochondrial morphology. Cytarabine also enhanced the expression of the mitophagy-related proteins PINK1, Parkin, VDAC1, and DJ-1, and its actions can be reversed by treatment with AMPK inhibitor - Compound C (CC), suggesting that AMPK activation may be involved in cytarabine-enhanced mitophagy. Furthermore, cytarabine can also ameliorate the motor symptoms in the MPTP-induced PD-like mice model, and attenuate the neuropathy in the substantia nigra (SN) of PD mice, while Compound C antagonized cytarabine's beneficial effects. In summary, marine-derived compound cytarabine could resist neurological damage both in vitro and in vivo by activating AMPK to increase PINK1/Parkin-induced mitophagy, serving as a promising disease modulator for treating neurodegenerative disease.

Chemotherapy is widely recognized as an effective approach for treating cancer due to its ability to eliminate cancer cells using chemotherapeutic drugs. However, traditional chemotherapy suffers from various drawbacks, including limited solubility and stability of drugs, severe side effects, low bioavailability, drug resistance, and challenges in tracking treatment efficacy. These limitations greatly hinder its widespread clinical application. In contrast, supramolecular chemotherapy, which relies on host-guest interactions, presents a promising alternative by offering highly efficient and minimally toxic anticancer drug delivery. In this review, an overview of recent advancements in supramolecular chemotherapy based on host-guest interactions is provided. The significant role it plays in guiding cancer therapy is emphasized. Drawing on a wealth of cutting-edge research, herein, a timely and valuable resource for individuals interested in the field of supramolecular chemotherapy or cancer therapy, is presented. Furthermore, this review contributes to the progression of the field of supramolecular chemotherapy toward clinical application.

To increase awareness, outline strategies, and offer clinical guidance on navigating the complexities of treatment planning amid antineoplastic drug shortages.

A multidisciplinary panel of oncologists, ethicists, and patient advocates was assembled to provide rapid clinical guidance to help providers navigate appropriate patient care in cases where rationing or alternative therapies must be considered. The groups of content experts developed general principles for resource allocation during shortages and clinical guidance on alternative therapies for specific disease sites. The recommendations are supported by evidence when available.

A total of 44 volunteers with content expertise formed the Advisory Group that developed general guidance on the prioritization of antineoplastic agents in limited supply. Disease site-specific clinical guidance was then produced by subgroups on the basis of members' specialties and expertise. The majority of alternative treatment options were developed in consideration of cisplatin and carboplatin shortages. All guidance is posted on ASCO's website.

The prioritization of antineoplastic agents in limited supply should be based on specific goals of the therapy where evidence-based medicine has shown survival outcome and life-extending benefit in both early and advanced stages. Recommendations for specific disease sites are presented. While management options vary according to the disease site, alternatives are presented. For settings in which there are no alternatives with comparable efficacy and safety, it is recommended that patients are referred to an area where the necessary drug is available or can be obtained.Additional information is available at asco.org/drug-shortages.

Shortages and rationing are common in health care, yet we know little about the consequences. We examine an 18-month shortage of the pediatric Haemophilus Influenzae Type B (Hib) vaccine. Using insurance claims data and variation in shortage exposure across birth cohorts, we find that the shortage reduced uptake of high-value primary doses by 4 percentage points and low-value booster doses by 26 percentage points. This suggests providers largely complied with rationing recommendations. In the long-run, catch-up vaccination occurred but was incomplete: shortage-exposed cohorts were 4 percentage points less likely to have received the ir booster dose years later. We also find that the shortage and rationing caused provider switches, extra provider visits, and negative spillovers to other care.

The study estimated the shortages of oncology medicines in Pakistan, their causes, impacts, mitigation strategies, and possible interventions.

Cross-sectional survey.

Oncology pharmacists working at 43 oncology settings (out of 80) from five regions of Pakistan (four provinces (Punjab, Sindh, Khyber Pakhtunkhwa and Baluchistan) and one federal territory (Islamabad)) were approached.

Oncology pharmacists with more than 1 year of experience were selected using stratified random sampling, and data were collected using a questionnaire from September 2021 to January 2022.

To estimate the prevalence of oncology medicine shortages in Pakistan and establish recommendations to overcome them.

Of 167 responded pharmacists, 87% experienced shortages in their practice. Most respondents (50%) experienced both oncology and support agent shortages. It was a current problem in hospitals (58%) and increased with time, but the situation varied across regions (p=0.007). Mainly shortages occur half-yearly (p=0.001) and last for <3 months. Injectable (56.8%) and branded drugs (44.9%) were short. The most frequently mentioned drugs affected by shortages were etoposide, paclitaxel, dacarbazine, bleomycin and carboplatin. Usually, distributors (51.5%) notify the pharmacists about the shortages, and federal agencies (36%) are responsible for these shortages. Distributors (53.4%) were the main source of supply, and shortages were encountered by them as well. The impacts included delayed care (25%) and suboptimal outcomes (23%) on patients, extra time (32%) for staff, prioritisation issues (31%) for pharmacists, delayed clinical trials (60.5%) and increased drugs prices (52.1%). Some hospitals have reporting systems (39.5%) and recording (29.3%) drug shortages. The shortages were managed using available alternative options (21%) and redistributing (21%) the currently available stock.

Pakistan's healthcare system is affected by oncology medicine shortages. The government should establish a cancer registry and drug shortage platform, revise drug prescribing/pricing policies and practice penalties for breaching regulations. Oncology medicines must be widely available to avoid the grey market.

The political instability, economic crisis, and devaluation of the national currency left Lebanese females suffering from a scarcity of oral contraceptive pills (OCPs). Therefore, we aimed to identify the incidence of OCPs shortage in Lebanon and its impact on women's sexual and reproductive health, as well as physical and psychological well-being.

Community pharmacies were selected randomly across Lebanon, using a stratified sampling approach, where female clients asking for OCPs were interviewed using a standardized data collection form.

A total of 440 females were interviewed. More than three-quarters of the participants (76.4%) reported not finding their preferred OCPs brands, almost 40% were affected by the increased prices, and 28.4% declared stockpiling OCPs. More than half of the participants using OCPs for pregnancy prevention reported adopting alternative traditional contraceptive methods (55.3%). Unplanned pregnancy was reported by 9.5% of participants, where 75% of them disclosed intentional abortion while the remaining (25%) reported experiencing a spontaneous miscarriage. Other consequences of OCPs shortage included mood disturbances (52.3%), dysregulation of menses (49.7%), dysmenorrhea (21.1%), weight gain (19.6%), acne (15.7%), and hirsutism (12.5%). Of the participants taking OCPs for birth control, 48.6% reported a reduced frequency of sexual intercourse, which led to conflicts with their partners (46%) and a decreased libido (26.7%).

OCPs shortage has seriously and negatively exposed women to various undesirable consequences including unplanned pregnancy and dysregulation of menses. Therefore, there is an urgent need to bring the attention of healthcare authorities to support the national pharmaceutical industry in manufacturing affordable OCPs generics to meet women's reproductive health demands.

This study aimed to examine the current situation of anti-cancer drug shortages in Pakistan, namely its determinants, impacts, adopted mitigation strategies, and proposed solutions. Qualitative semi-structured, in-depth interviews were conducted with 25 pharmacists in oncology hospitals in Pakistan from August to October 2021. Data were collected in person and online, recorded, and subjected to inductive thematic analysis after being transcribed verbatim. Most participants experienced anti-cancer drug shortages that increased during the pandemic. Etoposide, paclitaxel, vincristine, dacarbazine, and methotrexate were frequently short. Important causes included the compromised role of regulatory authorities, lack of local production, and inventory mismanagement. The impacts were delayed/suboptimal treatment and out-of-pocket costs for patients, patients' prioritization, increased workload, negative work environment, and patients' trust issues for pharmacists. The participants proposed that a cautious regulator's role is needed to revise policies for all stakeholders and support all stakeholders financially at their level to increase access to these medicines. Based on the outcomes, it is clear that anti-cancer medicine shortages are a current issue in Pakistan. Governmental authorities need to play a role in revising policies for all levels of the drug supply chain and promoting local production of these drugs. Stakeholders should also collaborate and manage inventory.

Although the coronavirus disease 2019 (COVID-19) pandemic has reached all over the world population, it has demonstrated a heterogeneous impact on different populations. The most vulnerable communities which coexist daily with the social inequalities like low access to hygiene and personal protection products, crowded residences, and higher levels of chronic diseases have a higher risk of contact and the spread of infection, beyond unfavorable clinical outcomes. The elevation of the risk of infection exposure can be related to gender due to the presence of a larger contingent of women in essential services, as well as frontline and cleaning professionals who regardless of gender have the greatest exposure to the virus. Such exposures can contribute to the development of fear of contaminating themselves or their family members associated also with the work stress, both of which are related to the emergence of mental disturbances in these populations. Furthermore, conditions of unsanitary living and low socioeconomic status, populations at war, pre-existing social barriers, and ethnicity have contributed to more impact of the pandemic both in the exposure to the virus and access to health services, COVID-19 management, and management of other pathologies. At the same time, factors such as the closing of non-essential services, the loss of jobs, and the increase in household spending aggravated the social vulnerabilities and impacted the family economy. Lastly, the COVID-19 pandemic contributed still more to the impact on women's health since it propitiated a favorable environment for increasing domestic violence rates, through the segregation of women from social life, and increasing the time of the victims with their aggressors.

Drug shortages are a clear and growing challenge. Prominent shortages included oncology medications and supportive care products essential for the care of patients with cancer. Oncology drug shortages often result in disruptions in the timing of chemotherapy treatments, alterations in the dose or regimen administered, or even missed doses when alternative agents are unavailable. The purpose of this survey was to characterize the impact of oncology drug shortages across the United States, including the experiences of health care organizations, resource implications, and the impact on patient safety, patient care, and clinical trials.

A 36-item online survey was distributed to membership of the Hematology/Oncology Pharmacy Association to gather information on shortages of oncology drugs (ie, all drugs essential in the care of patients with cancer, including supportive care agents).

Sixty-eight US organizations participated in the survey between December 2019 and July 2020. Sixty-three percent of institutions reported one or more drug shortages per month, with a 34% increase in 2019 from 2018. Treatment delays, reduced doses, or alternative regimens were reported by 75% of respondents. The most difficult agents to obtain were vincristine, vinblastine, intravenous immunoglobulin, leucovorin, and Bacillus Calmette-Guerin.

A survey of US oncology pharmacists indicated that oncology drug shortages occurred frequently in 2020. Shortages led to delays in chemotherapy and changes in treatment or omission, complicated clinical research, and increased risk of medication errors and adverse outcomes.

Cancer is a major public health problem worldwide, and traditional chemotherapy or a single therapeutic strategy often fails to achieve expected results in cancer treatment. Thus, the development of a method to realize controlled drug delivery and synergistic therapy is required. Herein, MOF-based nanoparticles named RhI-DOX-GOD@ZIF-90 are synthesized using RhI (a near-infrared fluorescent dye), DOX (an anti-cancer drug) and GOD (glucose oxidase). RhI and DOX are encapsulated inside the ZIF-90 framework and GOD is loaded on the surface of ZIF-90. Owing to the fact that the ATP level in cancer cells is abnormally higher than that in normal cells, RhI-DOX-GOD@ZIF-90 nanoparticles are destructed only in cancer cells. RhI is released to give outstanding NIR emission and realize controlled drug delivery. DOX is released and cancer cells are killed by chemotherapy. Also, GOD is released to consume glucose and achieve the purpose of starving the cancer cells. By making full use of the advantages of near-infrared emission, RhI-DOX-GOD@ZIF-90 nanoparticles can be used to image ATP in tumor-bearing mice. At the same time, DOX and GOD can be released accurately at tumor sites of mice and excellent anti-tumor efficiency by synergistic chemotherapy and starvation therapy is achieved.

A near-infrared (NIR) fluorescence nanoprobe named RhI-DOX@ZIF-90 has been synthesized by wrapping the guest molecule (RhI and DOX) into ZIF-90 framework. The nanoprobe itself is non-fluorescent and the drug (DOX) is inactive. Upon the addition of ATP, the structure of RhI-DOX@ZIF-90 is degraded. The fluorescence of RhI is recovered and DOX is released. The nanoprobe can detect ATP with high sensitivity and selectivity. There is good linear relationship between the nanoprobe and ATP concentration from 0.25 to 10 mM and the detection limit is 0.10 mM. The nanoprobe has the ability to monitor the change of ATP level in living cells and DOX is released inducing apoptosis of cancer cells. RhI-DOX@ZIF-90 is capable of targeting mitochondria, which provides a basis for improving the efficiency of drug delivery by mitochondrial administration. In particular, the nanoprobe is preferentially accumulated in the tumor sites and detect ATP in tumor mice by fluorescence imaging using near-infrared fluorescence. At the same time, DOX can be released accurately in tumor sites and have good anti-tumor efficiency. So, this nanoprobe is a reliable tool to realize early diagnosis of cancer and improve effect of anticancer drug.

With more than 5 million cases and 333,212 deaths, COVID-19 (or SARS-CoV-2) continues to spread. General symptoms of this disease are similar to that of many other viral respiratory diseases, including fever, cough, dyspnea, and fatigue, with a chance of progression to more severe complications. However, the virus does not affect all people equally, and cases with comorbidities such as malignancies, cardiovascular diseases, respiratory diseases, and kidney diseases are at higher risk of developing severe events, including requiring intensive ventilation, intensive care unit (ICU) admission, and death. Patients with cancer are more likely to be infected with COVID-19, which is possibly due to their immunological dysfunction or frequent clinic visits. Also, there is a higher chance that these patients experience severe events because of the medication they receive. In this chapter, we will review the main clinical manifestations of COVID-19 in patients with cancer. Recommendations and challenges for managing resources, organizing cancer centers, treatment of COVID-19-infected cancer patients, and performing cancer research during this pandemic will also be discussed.

Diosgenin (DG), a steroidal saponin, is mainly found in yam tubers. DG and its derivatives displayed significant pharmacological activities against inflammatory, hyperlipidemia, and various cancers. DG was selected to modify the cancer chemotherapeutic agent cytarabine (Ara-C) due to its anti-tumor activities as well as lipophilicity. After characterization, the biomembrane affinity and the kinetic thermal processes of the obtained DG-Ara-C conjugate were evaluated by differential scanning calorimetry (DSC). Thin hydration method with sonication was applied to prepare the DG-Ara-C liposomes without cholesterol since the DG moiety has the similar basic structure with cholesterol with more advantages. Dynamic Light Scattering (DLS) analysis and cytotoxic analysis were employed to characterize the DG-Ara-C liposomes and investigate their biological activities, respectively. The results indicated that DG changed the biomembrane affinity of Ara-C and successfully replaced the cholesterol during the liposome preparation. The DG-Ara-C liposomes have an average particle size of around 116 nm with a narrow size distribution and revealed better anti-cancer activity against leukemia cells and solid tumor cells than that of free DG or Ara-C. Therefore, it can be concluded that DG displayed the potential application as an anti-cancer drug carrier to improve the bio-activities, since DG counted for a critical component in modulating the biomembrane affinity, preparation of liposome, and release of hydrophilic Ara-C from lipid vesicles.

Drug shortages continue at crisis levels in the United States, with no end in sight. Extensive research in disparate areas has been conducted to explore the impact that shortages have on patients and the healthcare system. We conducted a scoping review to categorize existing work in order to identify opportunities for further research. We considered peer-reviewed and non-peer-reviewed articles involving non-vaccine, human drug shortages in the United States published in English between January 2001 and May 2019. In total, 430 papers were charted according to the following categories: causes, impacts on care, health outcomes, costs, management, prevention, and federal government response. Of these, 112 papers considered causes; 199 discussed effects, 158 considered management strategies, and 140 discussed prevention. We provide a resource to navigate the vast literature on drug shortages in the United States, identifying areas in need of further research. This review highlights the widespread negative effects that drug shortages have on patients, providers, and health system costs in the United States. Evidence of their ramifications should be sufficient to justify policy change. Future work should move from characterizing the problem to working toward solutions to reduce the impact, occurrence, and effects of shortages.

New cases of the novel coronavirus, also known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), are increasing around the world. Currently, health care services are mainly focused on responding to and controlling the unique challenges of the coronavirus disease 2019 (COVID-19) pandemic. These changes, along with the higher susceptibility of patients with cancer to infections, have profound effects on other critical aspects of care and pose a serious challenge for the treatment of such patients. During the COVID-19 pandemic, it is important to provide strategies for managing the treatment of patients with cancer to limit COVID-19-associated risks at this difficult time. The present study set out to summarize the latest research on epidemiology, pathogenesis, and clinical features of COVID-19. We also address some of the current challenges associated with the management of patients with cancer during the COVID-19 pandemic and provide practical guidance to clinically deal with these challenges.

The outbreak of coronavirus disease 2019 (COVID-19) has rapidly spread globally since being identified as a public health emergency of major international concern and has now been declared a pandemic by the World Health Organization (WHO). In December 2019, an outbreak of atypical pneumonia, known as COVID-19, was identified in Wuhan, China. The newly identified zoonotic coronavirus, severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), is characterized by rapid human-to-human transmission. Many cancer patients frequently visit the hospital for treatment and disease surveillance. They may be immunocompromised due to the underlying malignancy or anticancer therapy and are at higher risk of developing infections. Several factors increase the risk of infection, and cancer patients commonly have multiple risk factors. Cancer patients appear to have an estimated twofold increased risk of contracting SARS-CoV-2 than the general population. With the WHO declaring the novel coronavirus outbreak a pandemic, there is an urgent need to address the impact of such a pandemic on cancer patients. This include changes to resource allocation, clinical care, and the consent process during a pandemic. Currently and due to limited data, there are no international guidelines to address the management of cancer patients in any infectious pandemic. In this review, the potential challenges associated with managing cancer patients during the COVID-19 infection pandemic will be addressed, with suggestions of some practical approaches. IMPLICATIONS FOR PRACTICE: The main management strategies for treating cancer patients during the COVID-19 epidemic include clear communication and education about hand hygiene, infection control measures, high-risk exposure, and the signs and symptoms of COVID-19. Consideration of risk and benefit for active intervention in the cancer population must be individualized. Postponing elective surgery or adjuvant chemotherapy for cancer patients with low risk of progression should be considered on a case-by-case basis. Minimizing outpatient visits can help to mitigate exposure and possible further transmission. Telemedicine may be used to support patients to minimize number of visits and risk of exposure. More research is needed to better understand SARS-CoV-2 virology and epidemiology.

The Centers for Medicare and Medicaid Services (CMS) has released quality measures regarding potentially avoidable hospitalizations visits in the 30 days after receipt of outpatient chemotherapy. This study evaluated the proportions of patients treated by Medicare-reimbursed clinicians and Veterans Health Administration (VA) clinicians who experienced avoidable acute care in order to evaluate differences in health system performance.

This retrospective evaluation of Medicare and VA administrative data used a cohort of cancer decedents (fiscal years 2010-2014). Cohort members were veterans aged 66 years or older at death who were dually enrolled in Medicare and the VA. Chemotherapy was identified through International Classification of Diseases, Ninth Revision and Current Procedural Terminology (ICD-9) codes. CMS defines avoidable hospitalizations as those related to anemia, dehydration, diarrhea, emesis, fever, nausea, neutropenia, pain, pneumonia, or sepsis in the 30 days after chemotherapy. Following CMS guidance, this study compared the proportions of patients with potentially avoidable hospitalizations, using hierarchical generalized estimating equations.

There were 27,443 patients who received outpatient chemotherapy. Patients receiving Medicare chemotherapy were significantly more likely to have potentially avoidable hospitalizations than patients receiving VA chemotherapy (adjusted odds ratio, 1.58; 95% confidence interval, 1.41-1.78; P < .001). In predicted estimates, 7.1% of Medicare-treated veterans had potentially avoidable hospitalizations in the 30 days after chemotherapy, compared with 4.6% of VA-treated veterans.

Results indicate veterans with cancer receiving chemotherapy in the VA have higher quality care with respect to avoidable hospitalizations than veterans receiving chemotherapy through Medicare. As more veterans seek care in the private sector under the Maintaining Internal Systems and Strengthening Integrated Outside Networks (MISSION) Act, concerted efforts may be warranted to ensure that veterans do not experience a decline in care quality.