Managing community acquired pneumonia in the elderly – the next generation of pharmacotherapy on the horizon

Introduction: Community acquired pneumonia (CAP) is associated with high rates of morbidity and mortality, especially among the elderly. Antibiotic treatment for CAP in the elderly is particularly challenging for many reasons, including compliance issues, immunosuppression, polypharmacy and antimicrobial resistance. There are few available antibiotics that are able to address these concerns.

Areas covered: After a systematic review of the current literature, we describe seven novel antibiotics that are currently in advanced stages of development (phase 3 and beyond) and show promise for the treatment of CAP in those over the age of 65. These antibiotics are: Solithromycin, Pristinamycin, Nemonaxacin, Lefamulin, Omadacycline, Ceftobiprole and Delafloxacin. Using a novel conceptual framework designed by the present authors, known as the ‘San Antonio NIPS model’, we evaluate their strengths and weaknesses based on their ability to address the unique challenges that face the elderly.

Expert opinion: All seven antibiotics have potential value for effective utilization in the elderly, but to varying degrees based on their NIPS model score. The goal of this model is to reorganize a clinician’s focus on antibiotic choices in the elderly and bring attention to a seldom discussed topic that may potentially become a health-care crisis in the next decade.     

盐酸帕罗西汀治疗胃肠疾病433例分析

常见胃肠疾病的临床症状常是非特异性及多样性,其中或多或少受到精神因素的影响［１］。为探索针对调整神经功能失调药物在治疗胃肠疾病中的作用,自１９９７年５月至１９９８年７月,我们在常规药物治疗的基础上加用盐酸帕罗西汀（赛乐特）治疗常见胃肠疾病４３３例,疗效满意,现报告如下。材料与方法一、研究对象４３３例胃肠疾病均依据临床表现、内镜、实验室及影象学检查明确诊断,其表１　主要胃肠道症状及治疗效果（例）恶心呕吐腹痛腹胀暖气大便次数及习惯改变吞咽障碍或吞咽不协调病例数１５６１２８８２４３１０有效数１３２１１…     

Severe congenital absence of skin in a preterm infant

A severe case of aplasia cutis congenita in a preterm infant is described. Although major problems with thermoregulation and fluid balance were anticipated, these parameters were relatively easy to control once the patient was stabilized. Meticulous skin care and rapid formation of a membranous-like fibrous tissue layer covering the denuded areas probably played an important role in minimizing excessive fluid and heat loss. The prognosis in aplasia cutis congenita is determined by the underlying associated anomalies, the severity of skin lesions and, in our case, the maturity of the infant who died from complications of prematurity.     

Neonatal Marfan syndrome: A case report

A case of neonatal Marfan syndrome is presented. The patient was noted to have cardiomegaly and tricuspid regurgitation on antenatal ultrasound scan. She was born with long, slender fingers and toes, an aged appearance and non-paralytic hypotonia. Echocardiogram revealed a dilated right atrium, right ventricle, dysplastic tricuspid valve and severe tricuspid regurgitation. She subsequently died of severe heart failure. Post-mortem examination showed the pathological features of lobar emphysema and cystic medial necrosis of the aorta. These features supported the diagnosis of neonatal Marfan syndrome. Nucleotide sequencing showed substitution of G by A at codon 1032 in exon 25 located in the long arm of chromosome 15. This resulted in the substitution of a cysteine by a tyrosine. A de novo mutation is suggested by the absence of affected family members.     

The descent of human herpesvirus 8.

Analysis of conserved herpesvirus genes shows that human herpesvirus 8 (HHV8) belongs to a clade of primate herpesviruses within the gamma2 sublineage. Overall, this clade has developed by cospeciation with host species. Seventeen genes of HHV8 and its nearest relatives lack simple homologues in other herpesviruses, and eight of these have known mammalian homologues, presumed to be the sources of the HHV8 versions. Comparative analyses yield further insights into the source or time of acquisition for several of these genes. All were acquired by the HHV8 lineage in the very distant past. Two unusual processes are manifest in the contemporary evolution of HHV8. First, the K1 gene is uniquely undergoing a process of extensive and positively selected substitution, of unknown significance. Secondly, the K15 gene has been substituted in some lineages by a distant homologue, presumably by recombination with an unknown herpesvirus. While available data are otherwise compatible with a cospeciational relationship between HHV8 and the human species, they do not exclude relatively recent transfer to humans from another primate host.     

Relative roles of climatic suitability and anthropogenic influence in determining the pattern of spread in a global invader

Because invasive species threaten the integrity of natural ecosystems, a major goal in ecology is to develop predictive models to determine which species may become widespread and where they may invade. Indeed, considerable progress has been made in understanding the factors that influence the local pattern of spread for specific invaders and the factors that are correlated with the number of introduced species that have become established in a given region. However, few studies have examined the relative importance of multiple drivers of invasion success for widespread species at global scales. Here, we use a dataset of >5,000 presence/absence records to examine the interplay between climatic suitability, biotic resistance by native taxa, human-aided dispersal, and human modification of habitats, in shaping the distribution of one of the world's most notorious invasive species, the Argentine ant (Linepithema humile). Climatic suitability and the extent of human modification of habitats are primarily responsible for the distribution of this global invader. However, we also found some evidence for biotic resistance by native communities. Somewhat surprisingly, and despite the often cited importance of propagule pressure as a crucial driver of invasions, metrics of the magnitude of international traded commodities among countries were not related to global distribution patterns. Together, our analyses on the global-scale distribution of this invasive species provide strong evidence for the interplay of biotic and abiotic determinants of spread and also highlight the challenges of limiting the spread and subsequent impact of highly invasive species.     

Implementation of an image-guided radiation therapy program: Lessons learnt and future challenges

The aim of this paper is to detail the experience obtained in implementing an image-guided radiation therapy program at the Northern Sydney Cancer Centre. This required retrofitting a Varian Clinac 21EX with an on-board imager. The commissioning and quality assurance procedures, organisation of a multidisciplinary image guided radiation therapy group, and the development of clinical protocols for orthogonal kV and cone beam computed tomography implementation are described. Reassessment of the image-guided radiation therapy program has continued as new equipment and software versions were made available in the department.     

Optimal stem cell source for allogeneic stem cell transplantation for hematological malignancies

Hematopoietic stem cell transplant (HSCT) is a standard treatment for many hematological malignancies. Three different sources of stem cells, namely bone marrow (BM), peripheral blood stem cells (PBSC) and cord blood (CB) can be used for HSCT, and each has its own advantages and disadvantages. Randomized controlled trials (RCTs) suggest that there is no significant survival advantage of PBSC over BM in Human Leukocyte Antigen-matched sibling transplant for adult patients with hematological malignancies. PBSC transplant probably results in lower risk of relapse and hence better disease-free survival, especially in patients with high risk disease at the expense of higher risks of both severe acute and chronic graft-versus-host disease (GVHD). In the unrelated donor setting, the only RCT available suggests that PBSC and BM result in comparable overall and disease-free survivals in patients with hematological malignancies; and PBSC transplant results in lower risk of graft failure and higher risk of chronic GVHD. High level evidence is not available for CB in comparison to BM or PBSC. The risks and benefits of different sources of stem cells likely change with different conditioning regimen, strategies for prophylaxis and treatment of GVHD and manipulation of grafts. The recent success and rapid advance of double CB transplant and haploidentical BM and PBSC transplants further complicate the selection of stem cell source. Optimal selection requires careful weighing of the risks and benefits of different stem cell source for each individual recipient and donor. Detailed counseling of patient and donor regarding risks and benefits in the specific context of the patient and transplant method is essential for informed decision making.