Metal acetylacetonates are coordination complexes derived from the acetylacetonate anion (CH 3COCHCOCH− 3) and metal ions, usually transition metals. The bidentateligand
acetylacetonate is often abbreviated acac. Typically both oxygen atoms
bind to the metal to form a six-membered chelate ring. The simplest
complexes have the formula M(acac)3 and M(acac)2. Mixed-ligand complexes, e.g. VO(acac)2,
are also numerous. Variations of acetylacetonate have also been
developed with myriad substituents in place of methyl (RCOCHCOR′−). Many such complexes are soluble in organic solvents, in contrast to the related metal halides. Because of these properties, acac complexes are sometimes used as catalyst precursors and reagents. Applications include their use as NMR "shift reagents" and as catalysts for organic synthesis, and precursors to industrial hydroformylation catalysts. C 5H 7O− 2
in some cases also binds to metals through the central carbon atom;
this bonding mode is more common for the third-row transition metals
such as platinum(II) and iridium(III).
Synthesis
The usual synthesis involves treatment of a metal salt with acetylacetone, acacH:
Mz+ + z Hacac ⇌ M(acac)z + z H+
Addition of base assists the removal of a proton from acetylacetone
and shifts the equilibrium in favour of the complex. Both oxygen centres
bind to the metal to form a six-membered chelate ring. In some cases
the chelate effect is so strong that no added base is needed to form the complex. Some complexes are prepared by metathesis using Tl(acac).
Structure and bonding
In the majority of its complexes acac forms six-membered C3O2M chelate rings. The M(acac) ring is planar with a symmetry plane bisecting the ring.
The acacM ring generally exhibits aromatic character, consistent with delocalized bonding in the monoanionic C3O2
portion. Consistent with this scenario, in some complexes, the acac
ligand is susceptible to electrophilic substitution, akin to electrophilic aromatic substitution (in this equation Me = CH3):
Co(O2C3Me2H)3 + 3NO2+ → Co(O2C3Me2NO2)3 + 3H+
In terms of electron counting, neutral bidentate O,O-bonded acac ligand is an "L-X ligand", i.e. a combination of a Lewis base (L) and a pseudohalide (X).
Treatment of TiCl4 with acetylacetone gives TiCl2(acac)2, a red-coloured, octahedral complex with C2symmetry:
TiCl4 + 2 Hacac → TiCl2(acac)2 + 2 HCl
This reaction requires no base. The complex TiCl2(acac)2 is fluxional in solution, the NMR spectrum exhibiting a single methyl resonance at room temperature.
Unlike Ti(IV), both Zr(IV) and Hf(IV) bind four bidentate acetylacetonates, reflecting the larger radius of these metals. Hafnium acetylacetonate and zirconium acetylacetonate adopt square antiprismatic structures.
Regarding acetylacetonates of titanium(III), Ti(acac)3 is well studied. This blue-colored compound forms from titanium trichloride and acetylacetone.
Vanadium triad
Vanadyl acetylacetonate is a blue complex with the formula V(O)(acac)2. This complex features the vanadyl(IV) group, and many related compounds are known. The molecule is square pyramidal, with idealized C2v symmetry. The complex catalyzes epoxidation of allylic alcohols by peroxides. Vanadium(III) acetylacetonate
is a dark-brown solid. Vanadium β-diketonate complexes are used as
precatalysts in the commercial production of ethylene-propylene-diene
elastomers (EPDM). They are often evaluated for other applications
related to redox flow batteries, diabetes and enhancing the activity of
insulin, and as precursors to inorganic materials by CVD.
Chromium triad
Chromium(III) acetylacetonate, Cr(acac)3, is a typical octahedral complex containing three acac−
ligands. Like most such compounds, it is highly soluble in nonpolar
organic solvents. This particular complex, which has a three unpaired
electrons, is used as a spin relaxation agent to improve the sensitivity
in quantitative carbon-13 NMR spectroscopy. Chromium(II) acetylacetonate is a highly oxygen-sensitive, light brown compound. The complex adopts a square planar structure, weakly associated into stacks in the solid state. It is isomorphous with Pd(acac)2 and Cu(acac)2.
Manganese triad
Mn(acac)3 has been prepared by the comproportionation of the manganese(II) compound Mn(acac)2 with potassium permanganate in the presence of additional acetylacetone. Alternatively the direct reaction of acetylacetone with potassium permanganate. In terms of electronic structure, Mn(acac)3 is high spin. Its distorted octahedral structure reflects geometric distortions due to the Jahn–Teller effect.
The two most common structures for this complex include one with
tetragonal elongation and one with tetragonal compression. For the
elongation, two Mn–O bonds are 2.12 Å while the other four are 1.93 Å.
For the compression, two Mn–O bonds are 1.95 Å and the other four are
2.00 Å. The effects of the tetragonal elongation are noticeably more
significant than the effects of the tetragonal compression.
In organic chemistry, Mn(acac)3 has been used as a one-electron oxidant for coupling phenols.
The electron transfer rates for Mn(acac)3 have been evaluated.
Iron triad
Iron(III) acetylacetonate, Fe(acac)3, is a red high-spin
complex that is highly soluble in organic solvents. It is a high-spin
complex with five unpaired electrons. It has occasionally been
investigated as a catalyst precursor. Fe(acac)3 has been partially resolved into its Δ and Λ isomers. The ferrous complex Fe(acac)2 is oligomeric.
Like iron, Ru(III) forms a stable tris(acetylacetonate). Reduction of this Ru(III) derivative in the presence of other ligands affords mixed ligand complexes, e.g. Ru(acac)2(alkene)2.
Cobalt triad
Tris(acetylacetonato)cobalt(III), Co(acac)3, is low-spin, diamagnetic complex. Like other compounds of the type M(acac)3, this complex is chiral (has a non-superimposable mirror image).
The synthesis of Co(acac)3 involves the use of an oxidant since the cobalt precursors are divalent:
The complex "Co(acac)2", like the nickel complex with
analogous stoichiometry, is typically isolated with two additional
ligands, i.e. octahedral Co(acac)2L2. The anhydrous form exists as the tetramer [Co(acac)2]4. Like the trimeric nickel complex, this tetramer shows ferromagnetic interactions at low temperatures.
Ir(acac)3 and Rh(acac)3 are known. A second linkage isomer of the iridium complex is known, trans-Ir(acac)2(CH(COMe)2)(H2O). This C-bonded derivative is a precursor to homogeneous catalysts for C–H activation and related chemistries.
Two well-studied acetylacetonates of rhodium(I) and iridium(I) are Rh(acac)(CO)2 and Ir(acac)(CO)2. These complexes are square-planar, with C2v symmetry.
Nickel triad
Nickel(II) bis(acetylacetonate) exists as the trimetallic complex [Ni(acac)2]3. Bulky beta-diketonates give red, monomeric, square-planar complexes. Nickel(II) bis(acetylacetonate) reacts with water to give the octahedral adduct[Ni(acac)2(H2O)2], a chalky green solid.
Cu(acac)2 is prepared by treating acetylacetone with aqueous Cu(NH 3)2+ 4. It is available commercially, catalyzes coupling and carbene transfer reactions.
Unlike the copper(II) derivative, copper(I) acetylacetonate is an air-sensitive oligomeric species. It is employed to catalyze Michael additions.
Zinc triad
The monoaquo complex Zn(acac)2H2O (m.p. 138–140 °C) is pentacoordinate, adopting a square pyramidal structure. The complex is of some use in organic synthesis. Dehydration of this species gives the hygroscopic anhydrous derivative (m.p. 127 °C). This more volatile derivative has been used as a precursor to films of ZnO.
Acetylacetonates of the other elements
Colourless, diamagnetic Al(acac)3 is structurally similar to other tris complexes, e.g. [Fe(acac)3]. The trisacetylacetonates of the lanthanides often adopt coordination numbers above 8.
Variants of acac
Many variants of acetylacetonates are well developed. Hexafluoroacetylacetonates and trifluoroacetylacetonates
form complexes that are often structurally related to regular
acetylacetonates, but are more Lewis acidic and more volatile. The
complex Eufod, Eu(OCC(CH3)3CHCOC3F7)3, features an elaborate partially fluorinated ligand. This complex is a Lewis acid, forming adducts with a variety of hard bases.
One or both oxygen centers in acetylacetonate can be replaced by RN groups, giving rise to Nacac and Nacnac ligands.
C 5H 7O− 2
in some cases also binds to metals through the central carbon atom
(C3); this bonding mode is more common for the third-row transition
metals such as platinum(II) and iridium(III). The complexes Ir(acac)3 and corresponding Lewis-base adducts Ir(acac)3L (L = an amine) contain one carbon-bonded acac ligand. The IR spectra of O-bonded acetylacetonates are characterized by relatively low-energy νCO bands of 1535 cm−1,
whereas in carbon-bonded acetylacetonates, the carbonyl vibration
occurs closer to the normal range for ketonic C=O, i.e. 1655 cm−1.
Global health is the health of the populations in the worldwide context; it has been defined as "the area of study, research, and practice that places a priority on improving health and achieving equity in health for all people worldwide". Problems that transcend national borders or have a global political and economic impact are often emphasized. Thus, global health is about worldwide health improvement (including mental health), reduction of disparities, and protection against global threats that disregard national borders,including the most common causes of human death and years of life lost from a global perspective.
One way global health can be measured is through the prevalence of various global diseases in the world and their threat to decrease life expectancy
in the present day. Estimates suggest that in a pre-modern, poor world,
life expectancy was around 30 years in all regions of the world (mainly
due to high infant mortality). Another holistic perspective called One Health can be used to address global health challenges and to improve global health security.
Both individuals and organizations working in the domain of global health often face many questions regarding ethical and human rights.
Critical examination of the various causes and justifications of health
inequities is necessary for the success of proposed solutions. Such
issues are discussed at the bi-annual Global Summits of National
Ethics/Bioethics Councils.
Global health as a discipline is widely acknwoledged to be of
imperial origin and the need for its decolonisation has been widely
recognised.
The global health ecosystem has also been criticised as having a feudal
structure, acting for a small group of institutions and individuals
based in high-income countries which acts similar to an imperial
"Crown". Some key leaders of the decolonising global health movement are Seye Abimbola and Madhukar Pai.
At a United Nations Summit in 2000, member nations declared eight Millennium Development Goals (MDGs), which reflected the major challenges facing human development globally, to be achieved by 2015.
The declaration was matched by unprecedented global investment by donor
and recipient countries. According to the UN, these MDGs provided an
important framework for development and significant progress has been
made in a number of areas. However, progress has been uneven and some of the MDGs were not fully realized including maternal, newborn and child health and reproductive health. Building on the MDGs, a new Sustainable Development Agenda with 17 Sustainable Development Goals (SDGs) has been established for the years 2016–2030. The first goal being an ambitious and historic pledge to end poverty. On 25 September 2015, the 193 countries of the UN General Assembly adopted the 2030 Development Agenda titled Transforming our world: the 2030 Agenda for Sustainable Development.
In 2015 a book titled "To Save Humanity" was published, with nearly 100 essays regarding today's most pressing global health issues. The essays were authored by global figures in politics, science, and advocacy ranging from Bill Clinton to Peter Piot, and addressed a wide range of issues including vaccinations, antimicrobial resistance, health coverage, tobacco use, research methodology, climate change, equity, access to medicine, and media coverage of health research.
The DALY is a summary measure that combines the impact of illness, disability,
and mortality by measuring the time lived with disability and the time
lost due to premature mortality. One DALY can be thought of as one lost
year of "healthy" life. The DALY for a disease is the sum of the years
of life lost due to premature mortality and the years lost due to
disability for incident cases of the health condition.
QALYs combine expected survival with expected quality of life
into a single number: if an additional year of healthy life is worth a
value of one (year), then a year of less healthy life is worth less than
one (year). QALY calculations are based on measurements of the value
that individuals place on expected years of survival. Measurements can
be made in several ways: by techniques that replicate gambles about
preferences for alternative states of health, with surveys or analyses
that infer willingness to pay for alternative states of health, or
through instruments that are based on trading off some or all likely
survival time that a medical intervention might provide in order to gain
less survival time of higher quality.
Infant mortality and child mortality for children under age 5 are
more specific than DALYs or QALYs in representing the health in the
poorest sections of a population, and are thus especially useful when
focusing on health equity.
Morbidity measures include incidence rate, prevalence, and cumulative incidence,
with incidence rate referring to the risk of developing a new health
condition within a specified period of time. Although sometimes loosely
expressed simply as the number of new cases during a time period,
morbidity is better expressed as a proportion or a rate.
Diarrhea is the second most common cause of child mortality worldwide, responsible for 17% of deaths of children under age 5. Poor sanitation
can increase transmission of bacteria and viruses through water, food,
utensils, hands, and flies. Dehydration due to diarrhea can be
effectively treated through oral rehydration therapy with dramatic reductions in mortality. Important nutritional measures include the promotion of breastfeeding and zinc supplementation. While hygienic measures alone may be insufficient for the prevention of rotavirus diarrhea, it can be prevented by a safe and potentially cost-effective vaccine.
The HIV/AIDS epidemic
has highlighted the global nature of human health and welfare and
globalization has given rise to a trend toward finding common solutions
to global health challenges. Numerous international funds have been set
up in recent times to address global health challenges such as HIV.
Since the beginning of the epidemic, more than 70 million people have
been infected with the HIV virus and about 35 million people have died
of HIV. Globally, 36.9 million [31.1–43.9 million] people were living
with HIV at the end of 2017. An estimated 0.8% [0.6–0.9%] of adults aged
15–49 years worldwide are living with HIV, although the burden of the
epidemic continues to vary considerably between countries and regions.
The WHO African region remains most severely affected, with nearly 1 in
every 25 adults (4.1%) living with HIV and accounting for nearly
two-thirds of the people living with HIV worldwide. Human immunodeficiency virus (HIV) is transmitted through unprotected sex, unclean needles, blood transfusions, and from mother to child during birth or lactation. Globally, HIV is primarily spread through sexual intercourse. The risk-per-exposure with vaginal sex in low-income countries from female to male is 0.38% and male to female is 0.3%. The infection damages the immune system, leading to acquired immunodeficiency syndrome (AIDS) and eventually, death. Antiretroviral drugs prolong life and delay the onset of AIDS by minimizing the amount of HIV in the body.
Malaria is a mosquito-borne infectious disease caused by the parasites of the genus Plasmodium.
Symptoms may include fever, headaches, chills, muscle aches and nausea.
Each year, there are approximately 500 million cases of malaria
worldwide, most commonly among children and pregnant women in developing
countries.
The WHO African Region carries a disproportionately high share of the
global malaria burden. In 2016, the region was home to 90% of malaria
cases and 91% of malaria deaths. The use of insecticide-treated bed nets is a cost-effective way to reduce deaths from malaria, as is prompt artemisinin-based combination therapy, supported by intermittent preventive therapy in pregnancy. International travelers to endemic zones are advised chemoprophylaxis with antimalarial drugs like Atovaquone-proguanil, doxycycline, or mefloquine.
Global consumption and international trade in deforestation-associated
commodities could also indirectly influence malaria risk. Many primary
commodities cause deforestation and deforestation can increase malaria
transmission. Consumption of such commodities in developed nations could
increase malaria risk in developing nations.
Bacterial pathogens
A GBD study reported global estimates of death rates from (33) bacterial pathogens, finding such infections are contributing to one in 8 deaths (or ~7.7 million deaths), which could make it the second largest cause of death globally in 2019.
More than one billion people were treated for at least one neglected tropical disease in 2015. For instance, neglected tropical diseases are a diverse group of infectious diseases that are endemic in tropical and subtropical
regions of 149 countries, primarily effecting low and middle income
populations in Africa, Asia, and Latin America. They are variously
caused by bacteria (Trachoma, Leprosy), viruses (Dengue, Rabies), protozoa (Human African trypanosomiasis, Chagas), and helminths (Schistosomiasis, Onchocerciasis, Soil transmitted helminths).
The Global Burden of Disease Study concluded that neglected tropical
diseases comprehensively contributed to approximately 26.06 million disability-adjusted life years in 2010, as well as significant deleterious economic effects.
In 2011, the World Health Organization launched a 2020 Roadmap for
neglected tropical diseases, aiming for the control or elimination of 10
common diseases. The 2012 London Declaration builds on this initiative, and called on endemic countries and the international community to improve access to clean water and basic sanitation, improved living conditions, vector control, and health education, to reach the 2020 goals. In 2017, a WHO report cited 'unprecedented progress' against neglected tropical diseases since 2007, especially due to mass drug administration of drugs donated by pharmaceutical companies.
Pandemic prevention is the organization and management of preventive measures against pandemics.
Those include measures to reduce causes of new infectious diseases and
measures to prevent outbreaks and epidemics from becoming pandemics.
It is not to be mistaken for pandemic preparedness or mitigation (e.g. against COVID-19)
which largely seek to mitigate the magnitude of negative effects of
pandemics, although the topics may overlap with pandemic prevention in
some respects.
Some biosafety and public health researchers contend that certain
pandemic prevention efforts themselves carry risk of triggering
pandemics (e.g. wildlife virus sampling), though not engaging in any
form of sampling also carries the risk of being unprepared for future
spillover events and being unaware of future pandemic pathogens.
Prevention of future pandemics requires steps to identify future
causes of pandemics and to take preventive measures before the disease
moves uncontrollably into the human population.
For example, influenza is a rapidly evolving disease which has
caused pandemics in the past and has potential to cause future
pandemics. The World Health Organisation collates the findings of 144
national influenza centres worldwide which monitor emerging flu viruses.
Virus variants which are assessed as likely to represent a significant
risk are identified and can then be incorporated into the next seasonal
influenza vaccine program.
In a press conference on 28 December 2020, Mike Ryan, head of the WHO
Emergencies Program, and other officials said the current COVID-19
pandemic is "not necessarily the big one" and "the next pandemic may be
more severe." They called for preparation. The WHO and the UN, have warned the world must tackle the cause of pandemics and not just the health and economic symptoms.
The global health approach could foster international collaboration
in medical research and development and share of its results such as
vaccines, optimizing overall global health for citizens. The U.S. Agency for International Development's
new Global Health Research and Development Strategy 2023-2028 includes
plans to coordinate with such stakeholders in support of innovative
global health product development and work with other agencies like the CDC and National Institutes of Health. Another approach to health would be the innovation of vaccines. The Washington Post
reported the US government's new five billion dollar budget on vaccines
to prevent Covid variants because the Vaccines' access and
public-private partnerships are important.
Often the relevance of mechanisms to stimulate research and development
is limited by national scopes and "by the transnational nature of the
problem which asks for an international approach". Financing models, creation of evidence-based recommendations, and logistics may be part of that.
Complications of pregnancy and childbirth are the leading causes of death among women of reproductive age. In many developing countries, a woman dies from complications from childbirth approximately every minute. According to the World Health Organization's 2005 World Health Report, poor maternal conditions are the fourth leading cause of death for women worldwide, after HIV/AIDS, malaria, and tuberculosis. Most maternal deaths and injuries can be prevented, and such deaths have been largely eradicated in the developed world. Targets for improving maternal health include increasing and assisting the number of deliveries accompanied by skilled birth attendants. 68 low-income countries tracked by the WHO- and UNICEF-led collaboration Countdown to 2015 are estimated to hold for 97% of worldwide maternal and child deaths.
In 2010, about 104 million children were underweight, and undernutrition contributes to about one third of child deaths around the world. (Undernutrition is not to be confused with malnutrition, which refers to poor proportion of food intake and can thus refer to obesity.) Undernutrition impairs the immune system, increasing the frequency, severity, and duration of infections (including measles, pneumonia, and diarrhea). Infection can further contribute to malnutrition.
Deficiencies of micronutrients, such as vitamin A, iron, iodine, and zinc, are common worldwide and can compromise intellectual potential, growth, development, and adult productivity. Interventions to prevent malnutrition include micronutrient supplementation, fortification of basic grocery foods, dietary diversification, hygienic measures to reduce spread of infections, and the promotion of breastfeeding.
Approximately 80% of deaths linked to non-communicable diseases occur in developing countries. For instance, urbanization and aging
have led to increasing poor health conditions related to
non-communicable diseases in India. The fastest-growing causes of
disease burden over the last 26 years were diabetes (rate increased by 80%) and ischemic heart disease (up 34%). More than 60% of deaths, about 6.1 million, in 2016 were due to NCDs, up from about 38% in 1990. Increases in refugee urbanization, has led to a growing number of people diagnosed with chronic non-communicable diseases.
In September 2011, the United Nations is hosting its first
General Assembly Special Summit on the issue of non-communicable
diseases.
Noting that non-communicable diseases are the cause of some 35 million
deaths each year, the international community is being increasingly
called to take measures for the prevention and control of chronic
diseases and mitigate their impacts on the world population, especially
on women, who are usually the primary caregivers.
For example, the rate of type 2 diabetes, associated with obesity,
has been on the rise in countries previously troubled by hunger. In
low-income countries, the number of individuals with diabetes is
expected to increase from 84 million to 228 million by 2030. Obesity, a preventable condition, is associated with numerous chronic diseases, including cardiovascular conditions, stroke, certain cancers, and respiratory disease. About 16% of the global burden of disease, measured as DALYs, has been accounted for by obesity.
Considering that 360 million people across the world live with
disabling hearing loss, including 32 million children and nearly 180
million older adults, and that chronic ear diseases, such as chronic
suppurative otitis media, can lead to hearing loss and may cause
life-threatening complications, the seventieth World Health Assembly on
May 31, 2017 signed the resolution WHA70.13 (Agenda item 15.8) urging
member states to integrate strategies for ear and hearing care within
the framework of their primary health care systems, under the umbrella
of universal health coverage.
A World Report on Hearing (WRH) was published in response to the
resolution (WHA70.13), to provide guidance for Member States to
integrate ear and hearing care into their national health plans.
Lifestyle disease may soon have an impact on the workforce and
the cost of health care. Treating these non-communicable diseases can be
expensive.
It can be critical for the patients health to receive primary
prevention and identify early symptoms of these non-communicable
diseases. These lifestyle diseases are expected to increase throughout
the years if people do not improve their lifestyle choices.
Some commenters maintain a distinction between diseases of longevity and diseases of civilization or diseases of affluence. Certain diseases, such as diabetes, dental caries
and asthma, appear at greater rates in young populations living in the
"western" way; their increased incidence is not related to age, so the
terms cannot accurately be used interchangeably for all diseases.
Some causes listed include deaths also included in more specific
subordinate causes, and some causes are omitted, so the percentages may
only sum approximately to 100%. The causes listed are relatively
immediate medical causes, but the ultimate cause of death might be
described differently. For example, tobacco smoking often causes lung disease or cancer, and alcohol use disorder can cause liver failure or a motor vehicle accident. For statistics on preventable ultimate causes, see preventable causes of death.
Violence against women
has been defined as: "physical, sexual and psychological violence
occurring in the family and in the general community, including battering, sexual abuse, dowry-related violence, rape, female genital mutilation and other traditional practices harmful to women, non-spousal violence and violence related to exploitation, sexual harassment and intimidation at work, in educational institutions and elsewhere, trafficking in women, forced prostitution and violence perpetrated or condoned by the state." In addition to causing injury, violence may increase "women's long-term risk of a number of other health problems, including chronic pain, physical disability, drug and alcohol abuse, and depression".
The WHO Report on global and regional estimates on violence against
women found that partner abuse causes women to have 16% more chances of
suffering miscarriages, 41% more occurrences of pre-term birth babies and twice the likeliness of having abortions and acquiring HIV or other STDs.
Although statistics can be difficult to obtain as many cases go
unreported, it is estimated that one in every five women faces some form
of violence during her lifetime, in some cases leading to serious
injury or even death. Risk factors for being an offender include low education, past exposure to child maltreatment or witnessing violence between parents, harmful use of alcohol, attitudes accepting of violence, and gender inequality. Equality of women has been addressed in the Millennium development goals. Now, Gender Equality is Sustainable Development Goal 5. Preventing the violence against women needs to form an essential part of the public health reforms in the form of advocation and evidence gathering. Primary prevention in the form of raising women economic empowerment facilities, microfinance and skills training social projects related to gender equality should be conducted.
Activities promoting relationship and communication skills among
couples, reducing alcohol access and altering societal ideologies should
be organized. Childhood interventions, community and school-based
education, raising media-oriented awareness and other approaches should
be carried out to challenge social norms and stereotypical thought processes to promote behavioral change
among men and raise gender equality. Trained health care providers
would play a vital role in secondary and tertiary prevention of abuse by
performing early identification of women suffering from violence and
contributing to the addressing of their health and psychological needs.
They could be highly important in prevention of the recurrence of
violence and the mitigation of its effects on the health of the abused
women and their children.
The Member States of the World Health Assembly endorsed a plan in 2016
for reinforcing the health system's role in addressing the global
phenomenon of violence against women and girls and working towards their
health and protection.
Global surgery
Halfdan T. Mahler, the 3rd Director-General of the World Health Organization (WHO),
first brought attention to the disparities in surgery and surgical care
when he stated, "‘the vast majority of the world’s population has no
access whatsoever to skilled surgical care and little is being done to
find a solution,".
While significant progresses have been made in fields within global health such as infectious diseases, maternal and child health, and even other non-communicable diseases over the past several decades, the provision of surgery and surgical care
in resource-limited settings have largely remained unmet with about 5
billion people lacking access to safe and affordable surgical and
anesthesia care.
This is especially true in the poorest countries, which account for
over one-third of the population but only 3.5% of all surgeries that
occur worldwide. In fact, it has been estimated that up to 30% of the total global burden of disease (GBD) could be attributable to surgical conditions, which include a mix of injuries, malignancies, congenital anomalies, and complications of pregnancy. As a result, global surgery has become an emerging field within global health as 'the multidisciplinary
enterprise of providing improved and equitable surgical care to the
world's population, with its core belief as the issues of need, access
and quality' and has often been described as the 'neglected stepchild of
global health,' a term coined by Dr. Paul Farmer to highlight the urgent need for further work in this area. Furthermore, Jim Young Kim, the former President of the World Bank,
proclaimed in 2014 that “surgery is an indivisible, indispensable part
of health care and of progress towards universal health coverage."
In 2015, the Lancet Commission on Global Surgery (LCoGS)
published the landmark report titled "Global Surgery 2030: evidence and
solutions for achieving health, welfare, and economic development,"
describing the large, pre-existing burden of surgical diseases in low-
and middle-income countries (LMICs) and future directions for increasing
universal access to safe surgery by the year 2030. The Commission highlighted that 143 million additional procedures were needed every year to prevent further morbidity and mortality from treatable surgical conditions as well as a $12.3 trillion loss in economic productivity by the year 2030. It emphasized the need to significantly improve the capacity for Bellwether procedures – laparotomy, caesarean section, open fracture care
– which are considered a minimum level of care that first-level
hospitals should be able to provide in order to capture the most basic
emergency surgical care.
In order to address these challenges and track progress, the Commission
defined the following core indicators for assessing access to safe and
affordable surgical d anesthesia care:
Core Indicators
Definition
Target
Access to timely essential surgery
The proportion of the population that can access, within 2 hours, a
facility that can do cesarean delivery, laparotomy, and treatment of
open fracture (the Bellwether Procedures)
A minimum of 80% coverage of essential surgical and anesthesia services per country by 2030
Specialist surgical workforce density
The number of specialist surgical, anaesthetic, and obstetric physicians who are working, per 100,000 population
100% of countries with at least 20 surgical, anaesthetic, and obstetric physicians per 100, 000 population by 2030
Surgical volume
The number of procedures done in an operating theatre, per 100,000 population per year
80% of countries by 2020 and 100% of countries by 2030 tracking
surgical volume; a minimum of 5000 procedures per 100,000 population by
2030
Perioperative mortality
All-cause death rate before discharge in patients who have undergone
a procedure in an operating theatre, divided by the total number of
procedures, presented as a percentage
80% of countries by 2020 and 100% of countries by 2030 tracking
perioperative mortality; in 2020, assess global data and set national
targets for 2030
Protection against impoverishing expenditure
The proportion of households protected against impoverishment from
direct out-of-pocket payments for surgical and anesthesia care
100% protection against impoverishment from out-of-pocket payments for surgical and anaesthesia care by 2030
Protection against catastrophic expenditure
The proportion of households protected against catastrophic
expenditure from direct out-of-pocket payments for surgical and
anesthesia care
100% protection against catastrophic expenditure from out-of-pocket payments for surgical and anaesthesia care by 2030
Data from WHO and the World Bank indicate that scaling up
infrastructure to enable access to surgical care in regions where it is
currently limited or is non-existent is a low-cost measure relative to
the significant morbidity and mortality caused by lack of surgical
treatment. In fact, a systematic review found that the cost-effectiveness ratio
– dollars spent per DALYs averted – for surgical interventions is on
par or exceeds those of major public health interventions such as oral rehydration therapy, breastfeeding promotion, and even HIV/AIDS antiretroviral therapy.
This finding challenged the common misconception that surgical care is
financially prohibitive endeavor not worth pursuing in LMICs.
In terms of the financial impact on the patients, the lack of
adequate surgical and anesthesia care has resulted in 33 million
individuals every year facing catastrophic health expenditure – the
out-of-pocket healthcare cost exceeding 40% of a given household's
income.
In alignment with the LCoGS call for action, the World Health Assembly
adopted the resolution WHA68.15 in 2015 that stated, "Strengthening
emergency and essential surgical care and anesthesia as a component of
universal health coverage." This not only mandated the WHO
to prioritize strengthening the surgical and anesthesia care globally,
but also led to governments of the member states recognizing the urgent
need for increasing capacity in surgery and anesthesia. Additionally,
the third edition of Disease Control Priorities (DCP3), published in 2015 by the World Bank, declared surgery as essential and featured an entire volume dedicated to building surgical capacity.
A key policy framework that arose from this renewed global
commitment towards surgical care worldwide is the National Surgical
Obstetric and Anesthesia Plan (NSOAP).
NSOAP focuses on policy-to-action capacity building for surgical care
with tangible steps as follows: (1) analysis of baseline indicators, (2)
partnership with local champions, (3) broad stakeholder engagement, (4)
consensus building and synthesis of ideas, (5) language refinement, (6)
costing, (7) dissemination, and (8) implementation. This approach has
been widely adopted and has served as guiding principles between
international collaborators and local institutions and governments.
Successful implementations have allowed for sustainability in terms of
longterm monitoring, quality improvement, and continued political and
financial support.
The NIHR Global Health Research Unit on Global Surgery
Seven surgical research Hubs in Benin, Ghana, India, Mexico, Nigeria, Rwanda and South Africa with an extensive network of urban and rural ‘Spoke’ hospitals have joined to create the NIHR. The NIHR Global Health Research Unit on Global Surgery is led by the University of Birmingham which provides overall oversight in relation to the Unit strategy, infrastructure and delivery, research and finance.
The network prioritized surgical topics that needed research and
has performed multiple surgical studies. The network resulted in many
research groups including GlobalSurg I, II, III and COVIDSurg and many other trials with worldwide collaborations as project FALCON and CHEETAH.
The research was published in over 40 articles in high impact journals in topics like Surgical site infections, COVID-19 and mortality.
Other Global Surgery Collaborations
More trials have emerged to assess surgical outcomes around the World
using big data from thousands of centers. Other notable trials include:
Global PaedSurg; The study was published in The Lancet examined
the risk of mortality for nearly 4000 babies born with birth defects in
264 hospitals around the world. The study found babies born with birth
defects involving the intestinal tract have a two in five chance of
dying in a low-income country compared to one in five in a middle-income
country and one in twenty in a high-income country.
APORG: The African Perioperative Research Group (APORG) was launched in South Africa
ASOS and ASOS-2; The studies showed that death after surgery is a
major public health problem in Africa. Surgical patients in Africa are
twice as likely to die in hospital following surgery when compared to
the global average.
ACCCOS
Global Health Research Group on Children’s Non-Communicable Diseases Collaborative
Many scholars from around the world have participated in overlapping
trials whether as Principal Investigators, Dissemination Committee or
Regional leaders to promote the research and oversee data collection.
Notable collaborators from these networks include The list included key
figures from around the World as Prof Bruce Biccard (South Africa), Prof
Adesoji Ademuyiwa (Nigeria), Prof Kokila Lakhoo (Oxford, UK), Dr Naomi
Wright (Oxford, UK), Dr Emrah Aydin (Turkey), Prof Mahmoud Elfiky
(Egypt) and Prof Milind Chitnis (South Africa).
Multimorbidity, age-related diseases and aging
Multimorbidity
is "a growing public health problem worldwide", "likely driven by the
ageing population but also by factors such as high body-mass index,
urbanisation, and the growing burden of NCDs (such as type 2 diabetes) and tuberculosis in low- and middle-income countries (LMICs)". Around the world, many people do not die from one isolated condition but from a multitude of factors and conditions. A study suggested there is a paucity of multimorbidity and comorbidity data globally and mapped comorbidity patterns.
With aging populations, there is a rise of age-related diseases which puts major burdens on healthcare systems as well as contemporary economies or contemporary economics and their appendant societal systems. Healthspan extension and anti-aging research
seek to extend the span of health in the old as well as slow aging or
its negative impacts such as physical and mental decline. Modern
anti-senescent and regenerative technology with augmented decision
making could help "responsibly bridge the healthspan-lifespan gap for a future of equitable global wellbeing".
Aging is "the most prevalent risk factor for chronic disease, frailty
and disability, and it is estimated that there will be over 2 billion
persons age > 60 by the year 2050",
making it a large global health challenge that demands substantial (and
well-orchestrated or efficient) efforts, including interventions that
alter and target the inborn aging process.
Global interventions for improved child health and survival include the promotion of breastfeeding, zinc supplementation, vitamin A fortification, salt iodization, hygiene interventions such as hand-washing, vaccinations, and treatments of severe acute malnutrition. The Global Health Council suggests a list of 32 treatments and health interventions that could potentially save several million lives each year.
Many populations face an "outcome gap", which refers to the gap
between members of a population who have access to medical treatment
versus those who do not. Countries facing outcome gaps lack sustainable
infrastructure. In Guatemala, a subset of the public sector, the Programa de Accessibilidad a los Medicamentos
("Program for Access to Medicines"), had the lowest average
availability (25%) compared to the private sector (35%). In the private
sector, the highest- and lowest-priced medicines were 22.7 and 10.7
times more expensive than international reference prices respectively.
Treatments were generally unaffordable, costing as much as 15 days wages
for a course of the antibiotic ceftriaxone. The public sector in Pakistan,
while having access to medicines at a lower price than international
reference prices, has a chronic shortage of and lack of access to basic
medicines.
Journalist Laurie Garrett
argues that the field of global health is not plagued by a lack of
funds, but that more funds do not always translate into positive
outcomes. The problem lies in the way these funds are allocated, as they
are often disproportionately allocated to alleviating a single disease.
Labor shortages
In its 2006 World Health Report, the WHO estimated a shortage of almost 4.3 million doctors, midwives, nurses, and support workers worldwide, especially in sub-Saharan Africa. A 2022 study estimated that, "in 2019, the world had 104.0 million (95% uncertainty interval 83.5–128.0) health workers,
including 12.8 million (9.7–16.6) physicians, 29.8 million (23.3–37.7)
nurses and midwives, 4.6 million (3.6–6.0) dentistry personnel, and 5.2
million (4.0–6.7) pharmaceutical personnel" and found that sub-Saharan
Africa, south Asia, and north Africa and the Middle East had the lowest
densities of human resources for health. However, even when only considering current technologies and processes (such as only little use of telehealth
as of 2022), overall numbers of personnel and shortages don't consider
sub-national geographic distribution of various types of health workers
(or expertise).
Global health security
The COVID-19 pandemic has highlighted how global health security
is reliant on all countries around the world, including low- and
middle-income countries, having strong health systems and at least a
minimum of health research capacities. In an article 2020 in Annals of
Global Health,
the ESSENCE group outlined a mechanism for review of investment in
health research capacity building in low- and middle-income countries.
The review mechanism will give funders of research for health the
information to identify the gaps in the capacity that exist in low- and
middle-income countries and the opportunity to work together to address
those disparities. The overall goal is increased, coordinated support of
research on national health priorities as well as improved pandemic
preparedness in LMICs, and, eventually, fewer countries with very
limited health research capacity.
Global factors impacting health
Climate change
The effects of climate change on human health are increasingly well studied and quantified. Direct effects include heat waves and extreme weather events. Indirect effects take place through changes in the biosphere. Examples are changes in water and air quality, food security and displacement. Factors such as age, gender or socioeconomic status influence to what extent these effects become wide-spread risks to human health. Health risks are unevenly distributed across the world. Disadvantaged populations are especially vulnerable to climate change effects. For example, young children and older people are the most vulnerable to extreme heat.
The relationship between health and heat includes several aspects. One is the exposure of vulnerable populations to heatwaves. Another is heat-related mortality. Reduced labour capacity for outdoor workers and effects on mental health are others. Extreme weather events have a big impact on health. These include floods, hurricanes, droughts and wildfires. They cause injuries, diseases, and air pollution in the case of wildfires. Other indirect health effects from climate change may be rising food insecurity, undernutrition and water insecurity.
A range of climate-sensitive infectious diseases may increase in some regions. These include mosquito-borne diseases, zoonoses, cholera and some waterborne diseases.
Climate change will also impact where infectious diseases are likely to
be able to spread in the future. Many infectious diseases will spread
to new geographic areas where people do not yet have suitable immune
systems.
The health effects of climate change are increasingly a matter of
concern for the international public health policy community. Already
in 2009, a publication in the general medical journal The Lancet stated: "Climate change is the biggest global health threat of the 21st century". The World Health Organization reiterated this in 2015. In 2019, the Australian Medical Association formally declared climate change a health emergency.
Studies have found that communications on climate change that present it
as a health concern rather than just an environmental matter are more
likely to engage the public.
A comprehensive annually scheduled study finds climate change is
"undermining every dimension of global health monitored" and reports
dire conclusions from tracking of impact indicators.
The effects of climate change have also increased the risk of health
conditions, such as lung disease or asthma which are caused by air
pollution. These medical conditions are caused due to extreme heatwaves or by "higher concentrations of ground-level ozone".
Antimicrobial resistance
Antimicrobial resistance (AMR) occurs when microbes evolve mechanisms that protect them from the effects of antimicrobials (drugs used to treat infections). All classes of microbes can evolve resistance where the drugs are no longer effective. Fungi evolve antifungal resistance. Viruses evolve antiviral resistance. Protozoa evolve antiprotozoal resistance, and bacteria evolve antibiotic
resistance. Together all of these come under the umbrella of
antimicrobial resistance. Microbes resistant to multiple antimicrobials
are called multidrug resistant (MDR) and are sometimes referred to as superbugs.
Although antimicrobial resistance is a naturally occurring process, it
is often the result of improper usage of the drugs and management of the
infections.
Antibiotic resistance is a major subset of AMR, that applies specifically to bacteria that become resistant to antibiotics. Resistance in bacteria can arise naturally by genetic mutation, or by one species acquiring resistance from another. Resistance can appear spontaneously because of random mutations, but also arises through spreading of resistant genes through horizontal gene transfer. However, extended use of antibiotics appears to encourage selection for mutations which can render antibiotics ineffective.
Antifungal resistance is a subset of AMR, that specifically applies to
fungi that have become resistant to antifungals. Resistance to
antifungals can arise naturally, for example by genetic mutation or
through aneuploidy. Extended use of antifungals leads to development of antifungal resistance through various mechanisms.
Clinical conditions due to infections caused by microbes containing AMR cause millions of deaths each year. In 2019 there were around 1.27 million deaths globally caused by bacterial AMR.
Infections caused by resistant microbes are more difficult to treat,
requiring higher doses of antimicrobial drugs, more expensive
antibiotics, or alternative medications which may prove more toxic. These approaches may also cost more.
The prevention of antibiotic misuse, which can lead to antibiotic resistance, includes taking antibiotics only when prescribed.Narrow-spectrum antibiotics are preferred over broad-spectrum antibiotics
when possible, as effectively and accurately targeting specific
organisms is less likely to cause resistance, as well as side effects.
For people who take these medications at home, education about proper
use is essential. Health care providers can minimize spread of resistant
infections by use of proper sanitation and hygiene, including handwashing and disinfecting between patients, and should encourage the same of the patient, visitors, and family members.
Rising drug resistance is caused mainly by use of antimicrobials
in humans and other animals, and spread of resistant strains between the
two.
Growing resistance has also been linked to releasing inadequately
treated effluents from the pharmaceutical industry, especially in
countries where bulk drugs are manufactured. Antibiotics increase selective pressure
in bacterial populations, killing vulnerable bacteria; this increases
the percentage of resistant bacteria which continue growing. Even at
very low levels of antibiotic, resistant bacteria can have a growth
advantage and grow faster than vulnerable bacteria.
Similarly, the use of antifungals in agriculture increases selective
pressure in fungal populations which triggers the emergence of
antifungal resistance.
As resistance to antimicrobials becomes more common there is greater
need for alternative treatments. Calls for new antimicrobial therapies
have been issued, but there is very little development of new drugs
which would lead to an improved research process.
Antimicrobial resistance is increasing globally due to increased prescription and dispensing of antibiotic drugs in developing countries.
Estimates are that 700,000 to several million deaths result per year
and continues to pose a major public health threat worldwide. Each year in the United States,
at least 2.8 million people become infected with bacteria that are
resistant to antibiotics and at least 35,000 people die and US$55
billion is spent on increased health care costs and lost productivity.According to World Health Organization (WHO) estimates, 350 million deaths could be caused by AMR by 2050. By then, the yearly death toll will be 10 million, according to a United Nations report.
There are public calls for global collective action to address the threat that include proposals for international treaties on antimicrobial resistance. The burden of worldwide antibiotic resistance is not completely identified, but low-and middle- income countries with weaker healthcare systems are more affected, with mortality being the highest in sub-Saharan Africa. During the COVID-19 pandemic, priorities changed with action against antimicrobial resistance slowing due to scientists and governments focusing more on SARS-CoV-2 research. At the same time the threat of AMR has increased during the pandemic.
AMR has been described as a leading global health issue. Globally, 1.27
million deaths in 2019 were attributable to AMR. That year, AMR may
have contributed to 5 million deaths and one in five people who died due
to AMR were children under five years old.
Organization
Governmental or inter-governmental organizations focused on global health include:
A study of select global health related organizations and initiatives
suggests that major trends in global health governance appear to be
"towards more discretionary funding and away from core or longer-term
funding; towards defined multi-stakeholder governance and away from
traditional government-centred representation and decision-making; and
towards narrower mandates or problem-focused vertical initiatives and
away from broader systemic goals". There is a growing willingness to use militaries in state-led
support of global health efforts which have capabilities ranging from
"research, surveillance, and medical expertise to rapidly deployable,
large-scale assets for logistics, transportation, and security".
Global Health Security Agenda
The Global Health Security Agenda (GHSA) is "a multilateral,
multi-sector effort that includes 60 participating countries and
numerous private and public international organizations focused on
building up worldwide health security capabilities toward meeting such
threats" as the spread of infectious disease. On March 26–28, 2018, the
GHSA held a high-level meeting in Tbilisi, Georgia, on biosurveillance
of infectious disease threats, "which include such modern-day examples
as HIV/AIDS, severe acute respiratory syndrome (SARS), H1N1 influenza, multi-drug resistant tuberculosis — any emerging or reemerging disease that threatens human health and global economic stability".
This event brought together GHSA partner countries, contributing
countries of Real-Time Surveillance Action Package, and international
partner organizations supporting the strengthening of capacities to
detect infectious disease threats within the Real-Time Surveillance
Action Package and other cross-cutting packages.
GHSA works through four main mechanisms of member action, action
packages, task forces and international cooperation. In 2015, the
Steering Group of the GHSA agreed upon the implementation of their
commitments through 11 Action Packages. Action Packages are a commitment
by member countries and their partners to work collaboratively towards
development and implementation of International Health Regulations
(IHR).
Action packages are based on GHSA's aim to strengthen national and
international capacity to prevent, detect, and respond to infectious
disease threats. Each action package consists of five-year targets,
measures of progress, desired impacts, country commitments, and list of
baseline assessments.
The Joint External Evaluation process, derived as part of the IHR
Monitoring and Evaluation Framework is an assessment of a country's
capacity for responding to public health threats.
So far, G7 partners and EU have made a collective commitment to assist
76 countries whereas the US committed to helping 32 countries to achieve
GHSA targets for IHR implementation. In September 2014, a pilot tool
was developed to measure progress of the Action Packages and applied in
countries (Georgia, Peru, Uganda, Portugal, the United Kingdom, and
Ukraine) that volunteered to participate in an external assessment.