Two decades of imipenem therapy

Imipenem, the first carbapenem discovered, was developed more than two decades ago in response to an unmet need for a highly potent, broad-spectrum antimicrobial agent with a strong safety profile. It has since been used to treat more than 26 million patients. In an era where antibiotic use has driven antibiotic resistance, choosing appropriate initial therapy for serious infection is critical. Appropriate antibiotic regimens must cover all likely pathogens, be administered promptly at the correct dosage and dosing interval, be well tolerated and prevent the emergence of resistance. While imipenem was initially reserved for use in intractable, serious infections, the benefits of early aggressive therapy are now known, making imipenem a core agent in de-escalation therapy due to proven efficacy and safety for indications such as nosocomial pneumonia, intra-abdominal infection, sepsis and febrile neutropenia. De-escalation therapy with an agent such as imipenem minimizes resistance development by initiating aggressive initial treatment and then tailoring therapy based on patient response and culture results, switching to a less expensive, narrower spectrum antibiotic regimen or shortening the duration of therapy. Imipenem has maintained sustained clinical efficacy, tolerability and in vitro activity against important bacterial pathogens for two decades. We review the factors that continue to make imipenem as appropriate an agent for de-escalation therapy now as it was 20 years ago.     

Two decades of advances in diterpenoid alkaloids with cytotoxicity activities

The important pharmacological activities and structural complexity of diterpenoid alkaloids have long stimulated strong scientific interest; some of these naturally abundant compounds have been reported to be highly promising for treating cancer. From 2008 to 2018, the cytotoxicity activities of more than 250 diterpenoid alkaloids were tested against several cancer cell lines. This review focuses on the progress of diterpenoid alkaloids with different structures derived from Ranunculaceae plants and some of their derivatives with potential anticancer activities. Then, we discuss the application prospects and development of active diterpenoid alkaloids.

The important pharmacological activities and structural complexity of diterpenoid alkaloids have long stimulated strong scientific interest; some of these naturally abundant compounds have been reported to be highly promising for treating cancer.     

Tuberculosis and HIV disease: Two decades of a dual epidemic

The HIV epidemic is currently in its third decade without any sign of abating. Tuberculosis (TB) is responsible for a third of all AIDS deaths, 99% of which occur in developing countries. The two epidemics fuel each other, together making up the leading infectious causes of mortality worldwide. Tuberculosis-HIV coinfection presents special diagnostic and therapeutic challenges and constitutes an immense burden on the health care systems of heavily infected countries. Despite major gains that have been made in the past two decades, important questions still remain. To cope with the challenge of TB-HIV coinfection, further research in the design of diagnostic tests for tuberculosis, detection of drug resistant Mycobacterium tuberculosis strains in HIV-positive people, as well as development of more effective therapeutic agents and vaccines are urgently needed. It has become evident that this dual epidemic will persist unless comprehensive measures are instituted through the provision of sufficient funding in addition to expanding and strengthening current control strategies adopted by governments and international organizations.     

Two decades of the synthesis of mono- and bis-aminomercapto[1,2,4]triazoles

4-Amino-5-mercapto[1,2,4]triazole and its 3-substituted derivatives have proven to be of biological interest and provide access to a new class of biologically active heterocyclic compounds for biomedical applications. This study will be helpful for scientific researchers interested in the chemistry of bifunctional versatile compounds as it provides a collection of all the methods for the preparation of 3-substituted-4-amino-5-mercapto[1,2,4]triazoles with aliphatic, aromatic, and heterocyclic moieties during the period from 2000 to mid-2020.

4-Amino-5-mercapto[1,2,4]triazole and its 3-substituted derivatives have proven to be of biological interest and provide access to a new class of biologically active heterocyclic compounds for biomedical applications.     

Two decades of recent advances of Ugi reactions: synthetic and pharmaceutical applications

Multicomponent reactions (MCRs) are powerful synthetic tools in which more than two starting materials couple with each other to form multi-functionalized compounds in a one-pot process, the so-called “tandem”, “domino” or “cascade” reaction, or utilizing an additional step without changing the solvent, the so-called a sequential-addition procedure, to limit the number of synthetic steps, while increasing the complexity and the molecular diversity, which are highly step-economical reactions. The Ugi reaction, one of the most common multicomponent reactions, has recently fascinated chemists with the high diversity brought by its four- or three-component-based isonitrile. The Ugi reaction has been introduced in organic synthesis as a novel, efficient and useful tool for the preparation of libraries of multifunctional peptides, natural products, and heterocyclic compounds with stereochemistry control. In this review, we highlight the recent advances of the Ugi reaction in the last two decades from 2000–2019, mainly in the synthesis of linear or cyclic peptides, heterocyclic compounds with versatile ring sizes, and natural products, as well as the enantioselective Ugi reactions. Meanwhile, the applications of these compounds in pharmaceutical trials are also discussed.

We highlight the recent advances of the Ugi reaction in the last two decades from 2000–2019, mainly in the synthesis of linear or cyclic peptides, heterocyclic compounds with versatile ring sizes, and natural products, as well as the enantioselective Ugi reactions.     

Two decades of experience with the Haemophilus influenzae serotype b conjugate vaccine in the United Kingdom

BackgroundThe Haemophilus influenzae serotype b (Hib) conjugate vaccine was introduced into the UK national childhood immunization program in 1992 after clinical trials reported the vaccine to be highly immunogenic in infants as young as two months of age.ObjectiveThe goal of this study was to describe and comment on the impact of routine Hib immunization on the epidemiology of invasive Hib disease in the United Kingdom. In addition, the development of Hib polysaccharide and conjugate vaccines was reviewed.MethodsA literature search was conducted of PubMed for invasive Hib disease epidemiology in the United Kingdom. The UK Health Protection Agency Web site was also searched for relevant publications.ResultsThe incidence of invasive Hib incidence in children aged <5 years fell from 21/100,000 to 44/100,000 in the prevaccine era to 0.63/100,000 in 1998, with an estimated vaccine failure rate of 2.2/100,000 vaccinees. After 1999, however, invasive Hib disease increased, particularly in toddlers, and peaked in 2003. Potential reasons for the resurgence included a greater-than-expected decline in Hib antibodies after primary immunization, waning of herd immunity offered by the initial catch-up campaign, and use of a less immunogenic Hib combination vaccine containing acellular pertussis in 2000–2001. In response to the resurgence, a Hib combination vaccine containing whole-cell pertussis was reintroduced in 2002, followed by a childhood Hib booster campaign in 2003. In 2004, the recommended infant vaccine was changed to a different Hib/acellular pertussis combination vaccine containing inactivated polio, which had a satisfactory Hib response, was less reactogenic, and eliminated the risk of vaccine-associated paralytic poliomyelitis. This action was followed by introduction of a routine 12-month Hib booster in 2006. Together, these measures led to a decline in invasive Hib disease across all age groups. In 2010, there were only 30 invasive Hib cases, with 6 reported in children aged <5 years and no deaths in this age group since 2007.ConclusionsControl of Hib disease is currently the best that has been achieved since the introduction of the routine Hib vaccination almost 20 years ago.     

Strategic deployment. Two decades of experience provide important lessons on how to deploy emergency resources

When it comes to deployment, one size (approach) doesn't fit all. Progressive public safety and EMS systems will recognize that a successful plan can thoughtfully balance system performance and human needs. Inventive people who learned how to do things better, cheaper and faster built America. Providing optimum system coverage, improved response times and quality care for patients fits the same mold. Sophisticated and accountable EMS systems readily accept this as part of their mandate.     

Two decades of British newspaper coverage regarding do not attempt cardiopulmonary resuscitation decisions: Lessons for clinicians

ObjectiveTo review UK newspaper reports relating to Do Not Attempt Cardiopulmonary Resuscitation (DNACPR) decisions in order to identify common themes and encourage dialogue.MethodsAn online media database (LexisNexis^®) was searched for UK Newspaper articles between 1993 and 2013 that referenced DNACPR decisions. Legal cases, concerning resuscitation decisions, were identified using two case law databases (Lexis Law^® and Westlaw^®), and referenced back to newspaper publications. All articles were fully reviewed.ResultsThree hundred and thirty one articles were identified, resulting from 77 identifiable incidents. The periods 2000–01 and 2011–13 encompassed the majority of articles. There were 16 high-profile legal cases, nine of which resulted in newspaper articles. Approximately 35 percent of newspaper reports referred to DNACPR decisions apparently made without adequate patient and/or family consultation. “Ageism” was referred to in 9 percent of articles (mostly printed 2000–02); and “discrimination against the disabled” in 8 percent (mostly from 2010–12). Only five newspaper articles (2 percent) discussed patients receiving CPR against their wishes. Eighteen newspaper reports (5 percent) associated DNACPR decisions with active euthanasia.ConclusionsRegarding DNACPR decision-making, the predominant theme was perceived lack of patient involvement, and, more recently, lack of surrogate involvement. Negative language was common, especially when decisions were presumed unilateral. Increased dialogue, and shared decision-making, is recommended.     

Amiodaron: decades of administration

The review of long-term international clinical experience with amiodaron covers pharmacological properties of the drug, mechanisms of development of its pharmacodynamic effects basing on its action on ionic channels, receptors, impact on thyroid function. Unique pharmacokinetics of amiodaron, high antiarrhythmic efficacy of the drug in supraventricular and ventricular arrhythmia, positive experience in primary and secondary prevention of sudden death are characterized. Amiodaron is effective in patients with atrial fibrillation including those with organic heart disease and chronic cardiac failure. It is safe in relation to different cardiac side effects which are minimal but has some non-cardiac side effects which require control during long-term treatment.     

Digestive endoscopy in five decades

The world of gastroenterology changed forever when flexible endoscopes became available in the 1960s. Diagnostic and therapeutic techniques proliferated and entered the mainstream of medicine, not without some controversy. Success resulted in a huge service demand, with the need to train more endoscopists and to organise large endoscopy units and teams of staff. The British health service struggled with insufficient numbers of consultants, other staff and resources, and British endoscopy fell behind that of most other developed countries. This situation is now being addressed aggressively, with many local and national initiatives aimed at improving access and choice, and at promoting and documenting quality. Many more consultants are needed and some should be relieved of their internal medicine commitment to focus on their specialist skills. New instruments and procedures are stretching the diagnostic boundaries and changing the interface with sister disciplines like radiology, surgery and pathology. The old distinctions, particularly between gastroenterology and surgery, are increasingly irrelevant and unhelpful. The future is bright for gastroenterology and for endoscopy, but unpredictable. In this fast-changing world it will be essential to remain flexible, with our goals firmly focused on the best interests of our patients.     

Two decades have passed ... and still it is her eyes that I remember: reflections of a pediatric nurse

A pediatric nurse reflects on her practice by recounting her experience while caring for a child with Guillian Barre 20 years ago. Principles and lessons relevant to guide pediatric nursing practice in today's health care environment are identified.