Elimination of hepatitis C in Europe: can WHO targets be achieved?

BackgroundChronic hepatitis C virus (HCV) infection affects 71 million people worldwide. The availability of highly efficient direct-acting antivirals has revolutionized the treatment landscape with over 95% cure rates. The WHO has launched a global programme to achieve rather ambitious HCV elimination targets for 2030.ObjectivesThis article aims to provide a critical overview of the current HCV elimination programmes in Europe highlighting the elements that should be implemented to achieve elimination and those that are already in place to promote this process.SourcesReview of the recently published literature and opinion of experts in the field.ContentElimination of hepatitis C as a public health threat appears to be a difficult task, which should be subdivided into smaller targets, the so-called micro-elimination goals, to increase chances of success. Macro-elimination strategies based on mass-screening are difficult to implement. Evidence supporting the efficacy of micro-elimination comes from key populations, such as people who inject drugs. HCV elimination is proceeding at different speeds in Europe. Some countries are on target with the WHO's objectives whereas others lack economic support and political advocacy, and have insufficient infrastructures to achieve this. The absence of an effective prophylactic vaccine is hampering the process and should be overcome.ImplicationsElimination of hepatitis C worldwide appears plausible, but in several countries probably not within the time frame suggested by the WHO. In the absence of vaccination, universal access to HCV treatment would act as a ‘therapeutic’ option to reduce transmission, especially in high-risk populations.     

Zoster-associated pain: what is known, who is at risk and how can it be managed?

Herpes zoster episodes commence with a prodromal period of about 4 days with symptoms including pain and malaise. This is followed by a rash lasting approximately 2-4 weeks, with possible subacute herpetic neuralgia for up to 3 months, followed, in some patients, by a period of post-herpetic neuralgia (PHN) lasting months or possibly years. Severe acute pain is more likely in older females and those with a prodrome or severe rash. Two separate mechanisms of PHN have been proposed: the first is that the excitability of primary afferent neurons is increased after nerve damage, causing irritable nociceptors and central sensitization, resulting in pain and allodynia; the second involves the degeneration of nociceptive neurons, which leads to deafferentation with central hyperactivity, causing pain but without allodynia. Both mechanisms may co-exist in an individual patient. Treatments for acute herpes zoster and PHN include established antivirals, alone or in combination with steroids, analgesics and neural blockade with local anaesthetics. Commonly used pain relief includes acetaminophen/paracetamol, non-steroidal anti-inflammatory drugs (NSAIDs), opioid analgesics, tricyclic antidepressants, gabapentin, pregabalin and topical analgesics. Effective and long-lasting pain relief in herpes zoster and PHN remains a largely unmet medical need.     

Viruses and other infections in stillbirth: what is the evidence and what should we be doing?

In Australia, as in other developed countries, approximately 40-50% of stillbirths are of unknown aetiology. Emerging evidence suggests stillbirths are often multifactorial. The absence of a known cause leads to uncertainty regarding the risk of recurrence, which can cause extreme anguish for parents that may manifest as guilt, anger or bewilderment. Further, clinical endeavours to prevent recurrences in future pregnancies are impaired by lack of a defined aetiology. Therefore, efforts to provide an aetiological diagnosis of stillbirth impact upon all aspects of care of the mother, and inform many parts of clinical decision making. Despite the magnitude of the problem, that is 7 stillbirths per 1000 births in Australia, diagnostic efforts to discover viral aetiologies are often minimal. Viruses and other difficult to culture organisms have been postulated as the aetiology of a number of obstetric and paediatric conditions of unknown cause, including stillbirth. Reasons forwarded for testing stillbirth cases for infectious agents are non-medical factors, including addressing all parents' need for diagnostic closure, identifying infectious agents as a sporadic cause of stillbirth to reassure parents and clinicians regarding risk for future pregnancies, and to reduce unnecessary testing. It is clear that viral agents including rubella, human cytomegalovirus (CMV), parvovirus B19, herpes simplex virus (HSV), lymphocytic choriomeningitis virus (LCMV), and varicella zoster virus (VZV) may cause intrauterine deaths. Evidence for many other agents is that minimal or asymptomatic infections also occur, so improved markers of adverse outcomes are needed. The role of other viruses and difficult-to-culture organisms in stillbirth is uncertain, and needs more research. However, testing stillborn babies for some viral agents remains a useful adjunct to histopathological and other examinations at autopsy. Modern molecular techniques such as multiplex PCR, allow searches for multiple agents. Now that such testing is available, it is important to assess the clinical usefulness of such testing.     

Orthographic and associative neighborhood density effects: What is shared,what is different?

Words with many orthographic neighbors elicit a larger N400 than words with few orthographic neighbors. This has been interpreted as stronger overall semantic activation due to orthographic neighbors activating their semantic representations. To investigate this claim, we manipulated the number of associates of words (NoA), a variable directly affecting overall semantic activation, and compared this to the ERP effect of the number of orthographic neighbors (N) in a lexical decision task. Words with high NoA and with high N produced a very similar increase of the N400. In addition, a higher N increased the amplitude of the Late Positive Complex. The common N400 effect suggests that N affects semantic activation, like NoA does. The late positive effect specific to N could occur because words with few orthographic neighbors initially elicit little activity in the orthographic system, thereby resembling nonwords, which leads to distinct processing.     

Interlimb coordination during locomotion: what can be adapted and stored?

Interlimb coordination is critically important during bipedal locomotion and often must be adapted to account for varying environmental circumstances. Here we studied adaptation of human interlimb coordination using a split-belt treadmill, where the legs can be made to move at different speeds. Human adults, infants, and spinal cats can alter walking patterns on a split-belt treadmill by prolonging stance and shortening swing on the slower limb and vice versa on the faster limb. It is not known whether other locomotor parameters change or if there is a capacity for storage of a new motor pattern after training. We asked whether adults adapt both intra- and interlimb gait parameters during split-belt walking and show aftereffects from training. Healthy subjects were tested walking with belts tied (baseline), then belts split (adaptation), and again tied (postadaptation). Walking parameters that directly relate to the interlimb relationship changed slowly during adaptation and showed robust aftereffects during postadaptation. These changes paralleled subjective impressions of limping versus no limping. In contrast, parameters calculated from an individual leg changed rapidly to accommodate split-belts and showed no aftereffects. These results suggest some independence of neural control of intra- versus interlimb parameters during walking. They also show that the adult nervous system can adapt and store new interlimb patterns after short bouts of training. The differences in intra- versus interlimb control may be related to the varying complexity of the parameters, task demands, and/or the level of neural control necessary for their adaptation.     

Patient blood management in adults and children: What have we achieved,and what still needs to be addressed?

An overview of Patient Blood Management (PBM), with its main scope to preserve the patient’s own blood to improve the patient’s outcome, is presented here, including the research gaps that needs to be addressed, particularly in the pediatric age group. Next, novel techniques to analyse PBM data and the challenges and strategies of PBM implementation will also be discussed.     

Clinical management of genital herpes: what can be done in pregnancy?

Neonatal herpes infection is the major complication of genital herpes even if it occurs in less than 1/10,000 births. A great number of recent studies illustrates the natural history of genital herpes. The importance of viral transmission by asymptomatic shedding is now well established. The widespread use of viral diagnosis strategies is the prerequisite to efficient genital herpes prevention in order to eradicate viral mother-to-child transmission. This starts with the detection of at-risk situations such as primary infection in late pregnancy. Once the at-risk situation is known there should be concern about the adaptation of treatment strategies including antiviral therapy. The following work proposes different strategies facing each at-risk situation in order to discuss the efficiency of new diagnostic and treatment tools.     

Addressing men's health policy concerns in Australia: what can be done?

There is a lack of consensus about what men's health constitutes in Australia. The absence of a widely accepted definition has been problematic for establishing state and national men's health policies. I consider that one impediment to the implementation of state and federal men's health policies has been a lack of willingness to approach men's health from a broad public health perspective. In particular, scant attention has been paid to exploring lay perspectives of how men define and understand health, and in turn, how these relate to significant policy problems such as men's health service use. I conclude by suggesting that a focus on men's lay perspectives of their health emerging from the United Kingdom and the Republic of Ireland provides a useful framework to guide men's health policy discussion in Australia.     

Biogenic amine receptors in parasitic nematodes: what can be learned from Caenorhabditis elegans?

The biogenic amines, serotonin, octopamine, tyramine and dopamine regulate many essential processes in parasitic nematodes, such as pharyngeal pumping, muscle contraction, and egg-laying, as well as more complex behaviors, such as mechanosensation and foraging, making biogenic amine receptors excellent targets for drug discovery. This review is designed to summarize our knowledge of nematode biogenic amine signaling and preliminarily identify some of the key receptors involved in the regulation of biogenic amine-dependent behaviors through an analysis of the free-living nematode, Caenorhabditis elegans.     

What is empathy, and how can it be promoted during clinical clerkships?

The ability of medical students to empathize often declines as they progress through the curriculum. This suggests that there is a need to promote empathy toward patients during the clinical clerkships. In this article, the authors attempt to identify the patient interviewing style that facilitates empathy and some practice habits that interfere with it. The authors maintain that (1) empathy is a multistep process whereby the doctor's awareness of the patient's concerns produces a sequence of emotional engagement, compassion, and an urge to help the patient; and (2) the first step in this process--the detection of the patient's concerns--is a teachable skill. The authors suggest that this step is facilitated by (1) conducting a "patient-centered" interview, thereby creating an atmosphere that encourages patients to share their concerns, (2) enquiring further into these concerns, and (3) recording them in the section traditionally reserved for the patient's "chief complaint." Some practice habits may discourage patients from sharing their concerns, such as (1) writing up the history during patient interviewing, (2) focusing too early on the chief complaint, and (3) performing a complete system review. The authors conclude that sustaining empathy and promoting medical professionalism among medical students may necessitate a change in the prevailing interviewing style in all clinical teaching settings, and a relocation of a larger proportion of clinical clerkships from the hospital setting to primary care clinics and chronic care, home care, and hospice facilities, where students can establish a continuing relationship with patients.     

Development of analysis of drugs and toxic substances that can play an immediate role in emergency medical service: what is to be analyzed?

Our laboratory was capable of analyzing less than 20 drugs and toxic substances at the time of the establishment of the Center in 1994. Since the poisoning crimes in 1998, such as the curry poisoning with arsenic in Wakayama, the sodium azide poisoning in Niigata, and the potassium cyanide poisoning in Nagano, we have introduced methods for rapid qualitative analysis of arsenic compounds, cyanides and azides, and developed methods for qualitative analysis of three types of surfactants (cationic, anionic, and nonionic) on the basis of the statistics for intoxication patients transferred to the Center. In 1999, the Analysis Method Investigation Committee of the Japanese Society for Clinical Toxicology requested individual medical institutions to analyze 15 selected intoxicating substances, focusing on the following three aspects. 1. Intoxication with a high degree of fatality. 2. Intoxication where analysis plays an immediate role in treatment. 3. Intoxication with a high frequency of requests by clinical physicians for analysis. The selected substances included methanol, barbital drugs, benzodiazepines, tricyclic or tetracyclic antidepressants, methamphetamine, acetaminophen, salicylic acid, bromovalerylurea, organophosphorus pesticides, carbamate pesticides, paraquat, glufosinate, cyanides, arsenic, and theophylline. Responding to the Committee's request, out laboratory has been making efforts so that analysis of drugs and intoxicating substances can play an immediate role in emergency medical service, giving the highest priority to the aforementioned 15 substances. As a result, anyone of us can now rapidly analyze about 35 substances, including those listed by the Society, day and night.     

Maternal nutrition: how is Eastern and Southern Africa faring and what needs to be done?

Background

The progress in key maternal health indicators in the Eastern and Southern Africa Region (ESAR) over the past two decades has been slow.

Objective

This paper analyzed available information on nutrition programs and nutrition-specific interventions targeting maternal nutrition in the ESAR and proposes steps to improve maternal nutrition in this region.

Methods

Search was conducted in relevant databases. Meta-analysis was done where there was sufficient data, while data from the nutrition programs was abstracted for objectives, settings, beneficiaries, stakeholders, impact of interventions and barriers encountered during implementation.

Results

Findings from our review suggest that multiple nutrition programs are in place in the ESAR; including programs that directly address nutrition indicators and those that integrate corresponding sectors like agriculture, health, education, and water and sanitation. However, their scale and depth differ considerably. These programs have been implemented by a diverse range of players including respective government ministries, international agencies, non government organisations and the private sector in the region. Most of these programs are clustered in a few countries like Kenya, Uganda and Ethiopia while others e.g. Comoros, Somalia and Swaziland have only had a limited number of initiatives.

Conclusion

These programs have been associated with some improvements in overall maternal health and nutritional indicators; however these are insufficient to significantly contribute to the progress in the region. Efforts should be prioritized in countries with the greatest burden of maternal undernutrition and associated risk factors with a focus on existing promising interventions to improve maternal nutrition.