Twenty dogs received a potentially lethal (15 mg/kg) dose of brodifacoum, a halogenated coumarin-type anticoagulant poison. Eleven were immediately treated with vitamin K1 daily for 5 days, either by intramuscular injections (2 mg/kg) or oral tablets (1 mg/kg). It was necessary to give further doses of vitamin K1 to most of the dogs for up to 2 weeks after the first treatment period to reduce their P times to normal levels (< 10 seconds). Four dogs were not given further vitamin K1 and two of these died of acute blood loss from an intrathoracic hemorrhage. Nine dogs received vitamin K1 (2 mg/kg by intramuscular injection) when clinical signs of anticoagulant poisoning were observed. Two dogs died suddenly without premonitory clinical signs of poisoning. The remaining 7 dogs showed various signs of anticoagulant poisoning 4 to 8 days after dosing and they received a 5 day course of vitamin K1. After this period one dog had a transient rise in its P time but this returned to normal without treatment, while another dog was treated on days 16, 20, 29 and 30. In conclusion, the authors recommended vitamin K1 therapy, 2 mg/kg by tablet or injection, daily for 3 weeks in cases of known or suspected brodifacoum poisoning in dogs.

Background

Providers are often unaware of poor adherence to prescribed medications for their patients with chronic diseases.

Objective

To develop brief, computer-administered patient-reported measures in English and Spanish assessing adherence behaviors and barriers. Design, Participants, and Main Measures: Item pools were constructed from existing measures of medication adherence behaviors and barriers, which informed development of a patient concept elicitation interview guide to identify medication adherence behavior and barrier-related concepts. Two hundred six patients either living with HIV (PLWH) or without were interviewed. Interviews were coded, concepts matched to item pool content, and new items were developed for novel concepts. A provider/investigator team highlighted clinically relevant items. Cognitive interviews were conducted with patients on final candidate items (n = 37). The instruments were administered to 2081 PLWH.

Key results

Behavioral themes from concept elicitation interviews included routines incorporating time of day, placement, visual cues, and intentionality to miss or skip doses. Barrier themes included health-related (e.g. depressed mood, feeling ill), attitudes/beliefs (e.g., need for medication), access (e.g., cost/insurance problems), and circumstantial barriers (e.g., lack of privacy, disruption of daily routine). The final instruments included 6 behavior items, and 1 barrier item with up to 23 response options. PLWH endorsed a mean (SD) of 3.5 (1.1) behaviors. The 201 PLWH who missed ≥2 doses in the previous week endorsed a mean (SD) of 3.1 (2.5) barriers. The intraclass correlation coefficient (ICC) for the numbers of behaviors endorsed in 61 PLWH after 4-16 days was 0.54 and for the number of barriers for the 20 PLWH with ≥2 missed doses the ICC was 0.89, representing fair and excellent test-retest reliability.

Conclusion

Measures of medication adherence behaviors and barriers were developed for use with patients living with chronic diseases focusing on clinical relevance, brevity, and content validity for use in clinical care.

Background

Low health literacy is associated with poor medication adherence and poor health outcomes. Limited understanding of prescribed medications may decrease validity of patient-reported adherence measures.

Objectives

To assess knowledge of names and purposes of prescribed medications among patients with multiple chronic conditions.

Methods

Individual interviews were conducted with a convenience sample of patients from six U.S. primary care clinics. Participants (n = 57) were English and/or Spanish-speaking patients prescribed 3+ medications for chronic conditions, for which non-adherence may lead to disability or death. In individual interviews, patients were asked to name their medications, explain the purpose of each, and to explain how they distinguish them from one another. Interviews were audio recorded, transcribed, and coded; coded content was quantified by 1) whether or not the patient could name medications; 2) method of categorizing medications; 3) whether or not the purpose of the medication was understood. Descriptive statistics were compiled using Fisher's exact test to determine the relationship between patient knowledge and medication characteristics.

Results

Thirty percent of patients could not name at least one of their medications; 19% did not know their purpose; 30% held misconceptions about the purpose of one or more medications. There was no significant difference in ability to name medications or state their medication's purpose between patients using medi-sets, pre-packaged rolls, or blister packs, and patients who stored pills in their original containers (p = 0.56 and p = 0.73, respectively), or across demographic groups (p = 0.085 to 0.767).

Conclusions

Many patients demonstrated difficulty identifying the name and purpose of prescribed medications; this did not differ by demographic group or medication storage type. Patients may benefit from routine review of medications with their provider in order to improve health literacy, outcomes, and patient-reported adherence measurement.

Background

Human immunodeficiency virus and acquired immune deficiency syndrome (HIV/AIDS) is still among the leading causes of disease burden and mortality in sub-Saharan Africa (SSA), and the world is not on track to meet targets set for ending the epidemic by the Joint United Nations Programme on HIV/AIDS (UNAIDS) and the United Nations Sustainable Development Goals (SDGs). Precise HIV burden information is critical for effective geographic and epidemiological targeting of prevention and treatment interventions. Age- and sex-specific HIV prevalence estimates are widely available at the national level, and region-wide local estimates were recently published for adults overall. We add further dimensionality to previous analyses by estimating HIV prevalence at local scales, stratified into sex-specific 5-year age groups for adults ages 15-59 years across SSA.

Methods

We analyzed data from 91 seroprevalence surveys and sentinel surveillance among antenatal care clinic (ANC) attendees using model-based geostatistical methods to produce estimates of HIV prevalence across 43 countries in SSA, from years 2000 to 2018, at a 5 × 5-km resolution and presented among second administrative level (typically districts or counties) units.

Results

We found substantial variation in HIV prevalence across localities, ages, and sexes that have been masked in earlier analyses. Within-country variation in prevalence in 2018 was a median 3.5 times greater across ages and sexes, compared to for all adults combined. We note large within-district prevalence differences between age groups: for men, 50% of districts displayed at least a 14-fold difference between age groups with the highest and lowest prevalence, and at least a 9-fold difference for women. Prevalence trends also varied over time; between 2000 and 2018, 70% of all districts saw a reduction in prevalence greater than five percentage points in at least one sex and age group. Meanwhile, over 30% of all districts saw at least a five percentage point prevalence increase in one or more sex and age group.

Conclusions

As the HIV epidemic persists and evolves in SSA, geographic and demographic shifts in prevention and treatment efforts are necessary. These estimates offer epidemiologically informative detail to better guide more targeted interventions, vital for combating HIV in SSA.

The safe, highly effective measles vaccine has been recommended globally since 1974, yet in 2017 there were more than 17 million cases of measles and 83,400 deaths in children under 5 years old, and more than 99% of both occurred in low- and middle-income countries (LMICs)^1-4. Globally comparable, annual, local estimates of routine first-dose measles-containing vaccine (MCV1) coverage are critical for understanding geographically precise immunity patterns, progress towards the targets of the Global Vaccine Action Plan (GVAP), and high-risk areas amid disruptions to vaccination programmes caused by coronavirus disease 2019 (COVID-19)^5-8. Here we generated annual estimates of routine childhood MCV1 coverage at 5 × 5-km² pixel and second administrative levels from 2000 to 2019 in 101 LMICs, quantified geographical inequality and assessed vaccination status by geographical remoteness. After widespread MCV1 gains from 2000 to 2010, coverage regressed in more than half of the districts between 2010 and 2019, leaving many LMICs far from the GVAP goal of 80% coverage in all districts by 2019. MCV1 coverage was lower in rural than in urban locations, although a larger proportion of unvaccinated children overall lived in urban locations; strategies to provide essential vaccination services should address both geographical contexts. These results provide a tool for decision-makers to strengthen routine MCV1 immunization programmes and provide equitable disease protection for all children.

Background

Understanding the magnitude of cancer burden attributable to potentially modifiable risk factors is crucial for development of effective prevention and mitigation strategies. We analysed results from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 to inform cancer control planning efforts globally.

Methods

The GBD 2019 comparative risk assessment framework was used to estimate cancer burden attributable to behavioural, environmental and occupational, and metabolic risk factors. A total of 82 risk-outcome pairs were included on the basis of the World Cancer Research Fund criteria. Estimated cancer deaths and disability-adjusted life-years (DALYs) in 2019 and change in these measures between 2010 and 2019 are presented.

Findings

Globally, in 2019, the risk factors included in this analysis accounted for 4·45 million (95% uncertainty interval 4·01-4·94) deaths and 105 million (95·0-116) DALYs for both sexes combined, representing 44·4% (41·3-48·4) of all cancer deaths and 42·0% (39·1-45·6) of all DALYs. There were 2·88 million (2·60-3·18) risk-attributable cancer deaths in males (50·6% [47·8-54·1] of all male cancer deaths) and 1·58 million (1·36-1·84) risk-attributable cancer deaths in females (36·3% [32·5-41·3] of all female cancer deaths). The leading risk factors at the most detailed level globally for risk-attributable cancer deaths and DALYs in 2019 for both sexes combined were smoking, followed by alcohol use and high BMI. Risk-attributable cancer burden varied by world region and Socio-demographic Index (SDI), with smoking, unsafe sex, and alcohol use being the three leading risk factors for risk-attributable cancer DALYs in low SDI locations in 2019, whereas DALYs in high SDI locations mirrored the top three global risk factor rankings. From 2010 to 2019, global risk-attributable cancer deaths increased by 20·4% (12·6-28·4) and DALYs by 16·8% (8·8-25·0), with the greatest percentage increase in metabolic risks (34·7% [27·9-42·8] and 33·3% [25·8-42·0]).

Interpretation

The leading risk factors contributing to global cancer burden in 2019 were behavioural, whereas metabolic risk factors saw the largest increases between 2010 and 2019. Reducing exposure to these modifiable risk factors would decrease cancer mortality and DALY rates worldwide, and policies should be tailored appropriately to local cancer risk factor burden.

Funding

Bill & Melinda Gates Foundation.

The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 provides a rules-based synthesis of the available evidence on levels and trends in health outcomes, a diverse set of risk factors, and health system responses. GBD 2019 covered 204 countries and territories, as well as first administrative level disaggregations for 22 countries, from 1990 to 2019. Because GBD is highly standardised and comprehensive, spanning both fatal and non-fatal outcomes, and uses a mutually exclusive and collectively exhaustive list of hierarchical disease and injury causes, the study provides a powerful basis for detailed and broad insights on global health trends and emerging challenges. GBD 2019 incorporates data from 281 586 sources and provides more than 3·5 billion estimates of health outcome and health system measures of interest for global, national, and subnational policy dialogue. All GBD estimates are publicly available and adhere to the Guidelines on Accurate and Transparent Health Estimate Reporting. From this vast amount of information, five key insights that are important for health, social, and economic development strategies have been distilled. These insights are subject to the many limitations outlined in each of the component GBD capstone papers.

Background

In estimating the global burden of cancer, adolescents and young adults with cancer are often overlooked, despite being a distinct subgroup with unique epidemiology, clinical care needs, and societal impact. Comprehensive estimates of the global cancer burden in adolescents and young adults (aged 15-39 years) are lacking. To address this gap, we analysed results from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019, with a focus on the outcome of disability-adjusted life-years (DALYs), to inform global cancer control measures in adolescents and young adults.

Methods

Using the GBD 2019 methodology, international mortality data were collected from vital registration systems, verbal autopsies, and population-based cancer registry inputs modelled with mortality-to-incidence ratios (MIRs). Incidence was computed with mortality estimates and corresponding MIRs. Prevalence estimates were calculated using modelled survival and multiplied by disability weights to obtain years lived with disability (YLDs). Years of life lost (YLLs) were calculated as age-specific cancer deaths multiplied by the standard life expectancy at the age of death. The main outcome was DALYs (the sum of YLLs and YLDs). Estimates were presented globally and by Socio-demographic Index (SDI) quintiles (countries ranked and divided into five equal SDI groups), and all estimates were presented with corresponding 95% uncertainty intervals (UIs). For this analysis, we used the age range of 15-39 years to define adolescents and young adults.

Findings

There were 1·19 million (95% UI 1·11-1·28) incident cancer cases and 396 000 (370 000-425 000) deaths due to cancer among people aged 15-39 years worldwide in 2019. The highest age-standardised incidence rates occurred in high SDI (59·6 [54·5-65·7] per 100 000 person-years) and high-middle SDI countries (53·2 [48·8-57·9] per 100 000 person-years), while the highest age-standardised mortality rates were in low-middle SDI (14·2 [12·9-15·6] per 100 000 person-years) and middle SDI (13·6 [12·6-14·8] per 100 000 person-years) countries. In 2019, adolescent and young adult cancers contributed 23·5 million (21·9-25·2) DALYs to the global burden of disease, of which 2·7% (1·9-3·6) came from YLDs and 97·3% (96·4-98·1) from YLLs. Cancer was the fourth leading cause of death and tenth leading cause of DALYs in adolescents and young adults globally.

Interpretation

Adolescent and young adult cancers contributed substantially to the overall adolescent and young adult disease burden globally in 2019. These results provide new insights into the distribution and magnitude of the adolescent and young adult cancer burden around the world. With notable differences observed across SDI settings, these estimates can inform global and country-level cancer control efforts.

Funding

Bill & Melinda Gates Foundation, American Lebanese Syrian Associated Charities, St Baldrick's Foundation, and the National Cancer Institute.