Impact of a Standardized Titration Protocol with Carvedilol in Heart Failure: Safety,Tolerability, and Efficacy—A Report from the GESICA Registry

Grupo de Estudio de la Sobrevida en la Insuficiencia Cardiaca en Argentina (GESICA) studied whether a standardized protocol for the initiation and titration of the β-blocker carvedilol in a multicenter, open-label program would optimize β-blocker use in heart failure (HF) patients. The program included: (1) the carvedilol initiation and titration period, and (2) long-term follow-up at 6 and 12 months. Of 1299 patients in the registry, 504 were excluded due to current therapy; of the remaining 795 eligible patients, 293 were excluded due to contraindications. Of the included patients with follow-up data (n = 316), 93.3% tolerated carvedilol initiation and 47.7% of the patients reached the target dose of 50 mg/day for a mean dose of 39 mg/day. Rates were comparable in the elderly (n = 83), of which 53% achieved a target dose for a mean dose of 43.08 mg/day. This protocol improved therapy rates and achieved target doses quickly (average of 4 visits). Concomitant medications did not have to be adjusted and there were low withdrawal rates (10%) and hospital admissions (7.2%) for HF. Patients were able to maintain carvedilol therapy at 6 and 12 months. These results indicate that a standardized titration protocol, as used in GESICA, for the initiation and titration of β-blockers is well tolerated and may improve β-blocker use in carefully selected heart failure patients.The study authors are members of the GESICA Steering Committee and Subcommittees     

Recognition and management of idiopathic systemic capillary leak syndrome: an evidence-based review

Introduction: Idiopathic systemic capillary leak syndrome (SCLS) is a unique disorder characterized by episodes of massive systemic leak of intravascular fluid leading to volume depletion and shock. A typical attack of SCLS consists of prodromal, leak and post-leak phases. Complications, such as compartment syndrome and pulmonary edema, usually develop during the leak and post-leak phases respectively. Judicious intravenous hydration and early use of vasopressors is the cornerstone of management in such cases.

Areas covered: The purpose of the present review is to provide an up-to-date, evidence-based review of our understanding of SCLS and its management in the light of currently available evidence.

Commentary: Idiopathic SCLS was first described in 1960 and, since then, more than 250 cases have been reported. A large number of cases have been reported over the past one decade, most likely due to improved recognition. In the acute care setting, most patients with SCLS are managed as per the Surviving Sepsis guidelines and receive aggressive volume resuscitation – which is not the optimal management strategy for such patients. There is a need to raise awareness amongst physicians and clinicians in order to improve recognition of this disorder and ensure its appropriate management.     

Immune Modulation by Vitamin D and Its Relevance to Food Allergy

Apart from its classical function in bone and calcium metabolism, vitamin D is also involved in immune regulation and has been linked to various cancers, immune disorders and allergic diseases. Within the innate and adaptive immune systems, the vitamin D receptor and enzymes in monocytes, dendritic cells, epithelial cells, T lymphocytes and B lymphocytes mediate the immune modulatory actions of vitamin D. Vitamin D insufficiency/deficiency early in life has been identified as one of the risk factors for food allergy. Several studies have observed an association between increasing latitude and food allergy prevalence, plausibly linked to lower ultraviolet radiation (UVR) exposure and vitamin D synthesis in the skin. Along with mounting epidemiological evidence of a link between vitamin D status and food allergy, mice and human studies have shed light on the modulatory properties of vitamin D on the innate and adaptive immune systems. This review will summarize the literature on the metabolism and immune modulatory properties of vitamin D, with particular reference to food allergy.     

Oral cadmium exposure during rat pregnancy: assessment of transplacental micronutrient transport and steroidogenesis at term

Diet is the main source of cadmium (Cd) exposure. Gastrointestinal absorption increases during pregnancy. Cadmium accumulated in the placenta may interfere with nutrient transport to the foetus. Data on the potential of Cd to act as a steroid disruptor of pregnancy are limited. We evaluated the effects of oral Cd exposure during pregnancy on placental function in micronutrient transfer to the foetus and steroidogenesis in Wistar rats (regular 4‐day cyclers) that mated with unexposed males. Pregnant rats were randomly assigned to a Cd group exposed orally to 50 mg Cd l^–1 (CdCl₂xH₂O dissolved in demineralized water), ≈7.5 mg Cd kg^–1 a day, during 20 days of gestation and control (supplied with demineralized water). Non‐pregnant rats were treated under the same experimental conditions. On day 20, all of the rats were killed and samples were taken for element analyses (by electrothermal atomic absorption spectrometry). Progesterone and testosterone were measured in serum and placenta‐derived samples (by immunoenzymometric assay and/or enzyme‐linked immunosorbent assay). In the exposed rats, Cd increased in blood and organs, more in pregnant rats, and in placenta and foetus whereas zinc increased in liver. Iron decreased in maternal organs and in foetus, whereas zinc decreased in maternal kidney and placenta. Liver copper was lower and kidney copper higher in all pregnant vs. non‐pregnant rats. Steroids in serum and placenta did not change. In conclusion, oral Cd exposure during rat pregnancy does not affect progesterone and testosterone at term. Transplacental iron and zinc handover are disrupted, which may put at risk the maintenance of foetal nutrition and viability. Copyright © 2014 John Wiley & Sons, Ltd.     

Analysis of misoprostol and chlorhexidine policy gains in Pakistan: the advocacy experience of Mercy Corps Pakistan

While Pakistan has made progress toward achieving Millennium Development Goal 5 for maternal health, it is unlikely to achieve the target; further, it is also not on track for Millennium Development Goal 4 regarding child health. Two low-cost, temperature stable and life-saving drugs, misoprostol and chlorhexidine, can respectively avert maternal and newborn deaths, and are particularly pertinent for poor and marginalized areas which bear the brunt of maternal and newborn deaths in Pakistan. In response, Mercy Corps led focused advocacy efforts to promote changes in policies, protocols, and regulatory environments for misoprostol (2012–2014) and for chlorhexidine (2014). These short-duration advocacy projects facilitated significant policy gains, such as inclusion of misoprostol and chlorhexidine into province-specific essential drug lists, development and endorsement of clinical protocols for the two drugs by provincial health departments, inclusion of misoprostol into pre-service training curriculum for several health cadres, and application for registration of chlorhexidine (at the concentration required for newborn care) by two pharmaceutical companies. These results were achieved by a consultative and evidence-based process which generated feedback from community members, program implementers, and policymakers, and ultimately put the government in the driver’s seat to facilitate change. Community Action Dialogue forums were linked with provincial-level Technical Working Groups and Provincial Steering Committees, who passed on endorsed recommendations to the Health Secretary. The key factors which facilitated change were the identification of champions within the provincial health departments, prioritization of relationship building and follow-up, focus on concrete advocacy aims rather than broad objectives, and the use of multi-stakeholder forums to secure an enabling environment for the policy changes to take root. While these advocacy initiatives resulted in significant policy changes in Pakistan’s devolved health system, to ensure these policy changes have an impact on health outcomes, Pakistan should focus on the scale-up of appropriate use of chlorhexidine and misoprostol. Further, future policy initiatives in Pakistan should make use of similar multi-stakeholder policy forums, while ensuring a third party to facilitate the process so that civil society and community voices are not lost in the policy development discussion.     

Towards an internet civil defence against bioterrorism

Approaches towards the public-health prevention of bioterrorism are too little, and too late. New information-based approaches could yield better homeland protection. An internet civil defence is presented where millions of eyes could help to identify suspected cases of bioterrorism, with the internet used to report, confirm, and prevent outbreaks.