Economic evaluations can inform decisions about the efficiency and allocation of resources to implementation strategies—strategies explicitly designed to inform care providers and patients about the best available research evidence and to enhance its use in their practices. These strategies are increasingly popular in health care, especially in light of growing concerns about quality of care and limits on resources. But such concerns have hardly motivated health authorities and other decision-makers to spend on some form of economic evaluation in their assessments of implementation strategies. This editorial addresses the importance of economic evaluation in the context of implementation science—particularly, how these analyses can be most efficiently incorporated into decision-making processes about implementation strategies. Economic evaluation assesses the efficiency and allocation of resources to interventions that may improve health care and health outcomes. Economic evaluation applies not only to decisions about interventions or services that directly target patients, like pharmacological treatments and medical devices, but also to decisions about implementation strategies, which are explicitly designed to inform care providers and patients about the best available research evidence and to enhance its use in their practices.Many inefficiencies in health-care delivery result from overuse of unnecessary services, underuse of beneficial interventions, or medical errors . In lighEmpirical studies of the effects of implementation strategies related to behavior change and health outcomes have become more numerous ,3. Many But although the prominence of implementation science in health services is increasing, relatively little attention has been paid to another important aspect of implementation strategies: these efforts demand resources, and thus, have costs. Depending on the perspective of the decision-maker and their objective(s), the cost of implementation may include the following: 1) costs associated with executing implementation strategies; 2) the excess cost of service delivery as uptake or implementation changes; 3) the opportunity cost to providers and patients partaking in the implementation activities; and 4) research and development-related expenses resulting from the process of implementing change in health care. Unless the budget for implementation is sufficient, not all possible implementation projects can be supported. Trade-offs must be made, and these trade-offs merit an analysis that can compare costs to their benefits and that can identify the opportunity cost of choices—in other words, an economic evaluation.This editorial addresses the importance of economic evaluation in the context of implementation science—in particular, how these analyses can be most efficiently incorporated into decision-making processes about implementation strategies Figure .Figure 1a The number of economic evaluations contrasts sharply with the number of studies on implementation strategies assessing only their effect on behavior change and health outcomes.Despite the prevalence of economic evaluation in health services research, its use is not standard practice in assessing implementation strategies. Recent reviews revealed fewer than 60 studies of the efficiency of strategies for implementing clinical practice guidance before 2008 , with noWhy are implementation decisions so seldom guided by economic evaluation? Some of the more plausible reasons include divergent views on cost and cost-effectiveness, limited resources for evaluative research, and the paucity of data for decision-making.Views on the appropriate role of economics in evaluating implementation strategies may differ importantly between people and over time. Some revert to basic ethical tenets and moral obligations to discard information on cost completely; others view, more realistically, considerations of cost as secondary or complementary to other criteria, such as clinical effectiveness. But regardless of the differences of opinion and how they impact evaluation and decision-making, particular implementation strategies do have costs. Simply ignoring these implications can have undesirable consequences, such as inefficiencies and inequities that compromise the accessibility and delivery of health services—the very reason why spending on implementation of research evidence is considered initially.Limits on research capacity and appropriate data seem plausible reasons for decision-makers not to base implementation decisions on some form of economic evaluation, but in fact conceal a paradox: implementation decisions need economic evaluations that produce good-quality data for these decisions to be well-informed; economic evaluations need decisions that utilize their results for these evaluations to be supported.Methods—cost/cost-consequences analysis, cost-effectiveness/utility analysis, or cost-benefit analysis—do not need to pose a burden to performing economic evaluation of implementation strategies. The approach is similar to the economic evaluation of the services being implemented, while explicitly accounting for the resources used in developing and executing implementation strategies as a cost of ensuring appropriate service delivery ,9. DeterCommon to all forms of economic evaluation is the analysis of cost. Properly conducted—collecting adequate data on the use of all relevant resources on implementation and assigning appropriate tariffs or prices to those resources—cost analysis can help decision-makers address a not unimportant question: How much more will it cost to pursue implementation efforts?  But information from cost analysis, such as budget impact analyses or patient level cost-minimization studies, generally is insufficient to determine whether intervening in implementation problem(s) makes economic sense. Unless the potential alternative strategies are certain to have the same health outcomes across provider and patient practices over time—which is unlikely—implementation decisions will require a joint comparison of costs and outcomes by full economic evaluation.At the simplest level, economic evaluation entails the mere listing of all cost/benefit implications of each potential choice, as in cost-consequences analyses . This foAnalyses like these have distinct uses. They provide information for spending decisions to address problems in health care, when possible implementation strategies are expected to have outcomes that are too disparate to be combined meaningfully. Cost-consequences analyses permit value judgments without having to fully specify a relation between all the different measures of outcomes. And yet listing the cost/benefit implications of implementation strategies alone fails an important objective of economic evaluation—to make explicit the opportunity costs of alternative resource uses.These opportunity costs can be assessed directly using other forms of economic evaluation: cost-effectiveness or cost-utility analyses. Incremental cost-effectiveness ratios are established by dividing the difference in costs of various implementation strategies by the corresponding difference in health outcomes. Again, the measure(s) of outcomes most appropriate for ratio calculations depends, to an important extent, on the objective of decision-making and the perspective of analysis. Common metrics typically used include incremental cost per life-year gain or per quality-adjusted life-year (QALY).Ratios of cost-effectiveness—absolute and relative—can vary considerably across targeted providers, patients, behaviors, practices, and services. A sample of cost-effectiveness studies and calculated incremental cost-effectiveness ratios are found in Table Wide variation in outcomes is not uncommon given the many types of information inputs used in cost-effectiveness studies. One obvious and important determinant is the cost of implementation; economies of scale and scope may apply as implementation strategies target larger groups of providers and patients, and multiple behaviors and practices. But the cost-effectiveness of such strategies also depends critically on the effect they have on provider and patient behaviors—as measured by guideline adherence and patient compliance—and on the differential outcomes of care between services being implemented. The greater the difference in expected outcomes between usual care and the change being implemented, and the more widespread the implementation, the more likely a strategy is to be cost-effective.Translating cost-effectiveness ratios into resource allocation decisions can be difficult—even when potential implementation projects are comparable in scale and scope, and information about all the analysis inputs is so precise that the outcomes can be regarded as certain. Strategies that improve health and lower costs should be accepted; rejected should be those that worsen outcomes at higher costs. But what if a strategy is expected to improve (worsen) health outcomes but also cost more (less)?In such cases, health or safety gains from implementation strategies need to be valued in monetary units, reflecting the budget constraints and opportunity cost of alternative resource uses. Common thresholds for choices of pharmacological treatments and other health services range from €20,000 to €80,000 per life-year or QALY—and similar threshold values may well apply to accept-reject decisions in an implementation context. Yet the critical question is: Do current thresholds fully incorporate the cost of implementation of ‘cost-effective’ health services?When assigned appropriate thresholds, cost-effectiveness data can be transformed to a more comprehensive measure of implementation strategy efficiency—the net benefit. As earlier applications of this concept suggested ,15, the Once the methods for evaluation (including cost-effectiveness thresholds) are agreed upon, economic evaluation becomes a useful tool in the studying and planning of strategies for implementing change in health care. The question then becomes as follows: How can economic evaluation be performed most efficiently?Economic evaluations are more efficient if data collection on outcomes is limited. One approach is to confine the study to the measures of the care process, say cost per change in professional guidance adherence or patient compliance to medication, instead of measuring actual health outcomes. For example, in a Dutch quasi-experiment on the use of financial incentives as an implementation strategy , incentiOther ways to improve efficiency by limiting data collection include shortening the length of patient or provider follow-up or by relying on studies of less rigorous design for data collection.However, limiting data collection can have undesirable consequences, such as reducing confidence in the accuracy of the conclusions drawn from the analysis. Consider the Dutch study of financial incentives : can thePractical considerations suggest yet another approach to economic evaluation and efficiency improvement: the use of decision analytic models. In modeling studies, economic data on implementation strategies may be synthesized from a range of sources, including theory on behavioral change, rather than from a single trial or observational study. For example, in a Dutch study of the implementation of intensified glycemic control in type 2 diabetes, the comparison of audit and feedback to primary care providers versus usual care was based on an economic model . The modDecision analytic models have many more uses along these lines—for example, they can provide estimates of the expected value of information to form a basis for deciding whether additional data collection is necessary ,21. DespThe greatest gain in efficiency for implementation decisions may not be the method of economic evaluation but rather the timing. Economic evaluations are typically being performed ex-post—after some inefficiency has been identified as a problem of implementation and after designing and testing a set of strategies.Step 1: Assess the expected returns  from promoting the implementation of research evidence or any further change in clinical management or health policy through the use of value of implementation analysis ,20,21.Step 2: Make predictions of the implementation cost, which may include research and development-related expenses and the opportunity cost of care providers and patients partaking in the implementation activities.Step 3: Set  against Instead of carrying out economic evaluations after the fact, a 3-step ex-ante process of evaluation and decision-making is potentially much more efficient:Early economic assessment can help eliminate cost-ineffective implementation studies early on, allowing resources to be directed toward problems in care where intervening is likely to be more beneficial. Knowledge of the practicality of health service implementation is essential. If valid and meaningful estimates of resource allocation requirements for implementation can be made, the cost of implementation could be considered much sooner in the health-care decision-making process—namely, when the decisions about care components are being made .how economic evaluation can most efficiently be incorporated into implementation decisions, not whether it should.Performing economic evaluations is not rocket science. Already commonly used in the assessment of health services, economic evaluation is a potentially useful tool for making decisions on strategies for implementing research knowledge into clinical practice, management, or health policy. Confronted with a problem of implementation, decision-makers who wish to derive the greatest benefits from available resources must spend on some form of economic evaluation. Only by comparing each potential choice across both costs and benefits can the opportunity cost of implementation strategies be assessed. As more economic evaluations are performed and decision-makers leverage analytic techniques such as modeling and value of implementation analysis, the contribution of economic evaluation to decision-making processes will increase. The question is aA comprehensive search in PubMed for English language publications from 1 January 2008 to 1 July 2014, using the terms : ‘economic eval* OR cost-effect*’, ‘implementation strateg* OR quality improv*’, revealed 284 records, most of which recorded publications of studies that did not report any cost of implementation or that refrained to perform an economic evaluation of the reported implementation or quality improvement strategy in terms of cost of implementation.


In everyday life, multiple sensory channels jointly trigger emotional experiences and one channel may alter processing in another channel. For example, seeing an emotional facial expression and hearing the voice’s emotional tone will jointly create the emotional experience. This example, where auditory and visual input is related to social communication, has gained considerable attention by researchers. However, interactions of visual and auditory emotional information are not limited to social communication but can extend to much broader contexts including human, animal, and environmental cues. In this article, we review current research on audiovisual emotion processing beyond face-voice stimuli to develop a broader perspective on multimodal interactions in emotion processing. We argue that current concepts of multimodality should be extended in considering an ecologically valid variety of stimuli in audiovisual emotion processing. Therefore, we provide an overview of studies in which emotional sounds and interactions with complex pictures of scenes were investigated. In addition to behavioral studies, we focus on neuroimaging, electro- and peripher-physiological findings. Furthermore, we integrate these findings and identify similarities or differences. We conclude with suggestions for future research. In daily life, a wide variety of emotional cues from the environment reaches our senses. Typically, multiple sensory channels, for example vision and audition are integrated to provide a complete assessment of the emotional qualities of a situation or an object. For example, when someone is confronted with a dog, the evaluation of its potential dangerousness or friendliness will be more effective if visual  and auditory information (growling vs. friendly barking) can be integrated. While some of the information carried in either one of the channels may be redundant, the channels may also interact; i.e., a fierce bark may boost visual attention to the dog’s bared teeth.Despite the obvious relevance of multimodal perception in everyday life, emotion research has typically only investigated unimodal cues – with an apparent emphasis on visual stimuli. To cope with (a) limited processing capacities within a sensory modality and (b) the need to detect information which is relevant for survival, emotionally relevant cues have been suggested to modulate attention and selectively enhance perception .visual domain it has been shown that emotional cues – especially with threatening, but also with appetitive content – are preferentially processed in very early sensory areas  contexts. These contexts are certainly not limited to social situations. Examples for non-social situations of high biological significance may be a growling bear, swirling wasps, or an approaching thunderstorm. In these examples congruent visual and auditory information is transmitted , whose prioritized processing may help the organism to survive. The first obvious advantage of multimodal information is that uncertainties in one sensory channel can be easily compensated and complemented by the other channel. In addition, even if the  information conveyed by ear and eye is obviously redundant, multisensory integration effects can be clearly distinguished from redundancy effects within one modality. Again, the only empirical evidence supporting this claim stems from research on face–voice pairings. Redundant emotional information within the same modality leads to (post-) perceptual interferences shown by a lesser accuracy and longer response latencies within an emotional expression discrimination task. In contrast, congruent information of faces and voices was integrated early and pre-attentive with a clear perceptual benefit . Thus, bEmpirical evidence for multifaceted differences between human communication and scene stimuli comes from the visual domain. On the peripher-physiological level, Thus, investigations with affective scene cues which have been consistently demonstrated to elicit emotional responses on behavioral and physiological levels  are needed to answer research questions about multi-modal emotion processing beyond face-voice stimuli.Compared to visual cues, sounds are still investigated only rarely. It is likely that this is due to the development of research traditions according to practical considerations rather than a reflection of the relative importance of auditory cues. Compared to pictures, sounds may be somewhat less amenable to experimental designs in the laboratory. However, sounds can clearly prompt strong emotional responses as has been shown in a large internet-based survey . The devImportantly, in an fMRI-study  there waA recent study from our research group investigated the processing of emotional sounds from the IADS within the auditory cortex . BecauseFurther support for this observation comes from an MEG-Study investigating the influence of emotional content of complex sounds on auditory-cortex activity, both during anticipation and hearing of emotional and neutral sounds . Indeed,In sum, there is now considerable evidence that complex highly arousing pleasant and unpleasant sounds are processed more intensively on a peripheral as well as on early sensory processing levels. Thus, using standardized emotional sounds  can serve as a useful research tool to elicit emotions and investigate emotion processing.Generally, emotional sound and picture processing is very comparable. The pattern of behavioral and physiological and electrophysiological reactions elicited by emotional sounds is comparable to emotional pictures . HoweverTo sum up, emotional pictures and sounds mainly elicit similar reactions on the level of self-report, behavioral, physiological, and neuronal – both types of stimuli strongly activate appetitive and defensive motivational circuits . The repGenerally and beyond the emotional domain, it is well established that visual information can foster early stages of auditory processing and vice versa. For example, auditory speech perception can be strongly influenced by the viewing of visual speech stimuli on the perceptual  as well On a behavioral level, a recent study investigated the influence of emotional IAPS pictures on the classification of high and low pitch tones but did not find an effect of picture valence on the auditory classification .On the physiological level, it is well-known that emotional visual stimuli can modulate the acoustic startle reflex elicited by loud, abrupt, and unexpected sounds: negative pictures enhance, positive pictures dampen the blink magnitude in response to the unexpected sound e.g., . MoreoveRegarding electrophysiological responses, the presentation of unpleasant pictures has a significant impact on event-related potentials of the EEG to strongly deviant tones. During the presentation of unpleasant pictures, high deviant tones elicited larger N1 and P2 responses than during the presentation of pleasant pictures which was interpreted as a sensitization to potentially significant deviant events (N1) and enhanced attention (P2) to regular external events . SimilarFurther support for crossmodal influences of emotion is provided by a MEG study showing that unpleasant pictures diminish auditory sensory gating in response to repeated neutral tones as an index of neuronal habituation . PresentTaken together, emotional cues in the visual domain are able to enhance concurrent as well as subsequent auditory processing even at very early processing stages with no or low costs for emotion processing.To the best of our knowledge, evidence that emotion cues from the auditory modality can also influence non-emotional (basic) visual information processing is nearly missing. One study investigated the influence of emotional sounds on visual attention in a spatial cueing paradigm . Here, nAnother study used spoken emotional and neutral words that were followed by a visually presented neutral target word . It was both modalities. Regarding that question, self-report data of an internet-based survey suggest that sound stimuli were significantly perceived as more horrible when they were accompanied by pictures that show associated information  compared to pictures with unassociated pictures  sounds clearly influence emotional picture processing . We coulTaken together, the above mentioned studies strongly suggest that emotion processing in one sensory modality can strongly affect emotion processing of another modality during very early stages of neuronal processing, as well as on the self-report level.Table 1.For a short overview of the here reviewed studies see As the review summarized at the beginning, the majority of research on unimodal auditory emotion processing provides clear evidence that complex emotional auditory stimuli (mainly investigated with IADS) elicit similarly intensive emotional reactions on behavioral, physiological, and on neuronal levels as traditionally used complex visual emotional scenes. Furthermore, emotional cues from both modalities guide selective attention and receive enhanced processing. This preferential processing can even alter  information processing in other sensory channels. Specifically, there is evidence that the processing of complex emotional information in one sensory modality can strongly affect (emotion) processing of another modality during very early stages of neural processing, as well as self-reported emotions, and that these effects are bidirectional. As hitherto existing research mainly focused on stimuli of human communication such as faces and voices, the here reviewed work expands the concept of multimodality to a broader variety of human, animal, and environmental cues. However, as this review also indicates research in this field is in its infancy. Consequently, to carve out similarities and differences between the different classes of stimuli, disentangling emotional from social relevance  and emotional (in)congruence in multimodality which is usually confounded in face–voice pairings. Similarly important is the dissociation of (task) difficulty from incongruence in multimodal emotion integration . FurtherRegarding the impact of attention and automaticity, there has been a controversy for unimodal emotional cues whether they are processed outside of explicit attention or whether attentional disengagement can reduce neural responses and behavioral output . For exaWith regards to other electrophysiological indices of preferential processing and attention, the N2Pc or steady-state visual evoked potentials (ssVEPS) which are established in the visual domain , would lTo make research more ecological valid and to evolve a broader and more complete concept of emotional multimodality, future research should not only concentrate on audiovisual emotion processing but should also incorporate cues from other sensory channels as, e.g., olfactory , somatosAnother issue that is of great theoretical and practical importance is the consideration of different populations in the context of multimodal emotion processing. From a clinical perspective, the consideration of multimodal emotional processing is promising for the understanding of several mental disorders . Here, contextual  information contributes to the acquisition and maintenance of the disorder . AccordiFor the most part, the here reviewed interactions between emotional stimuli in the two senses can be explained on the background of the motivational priming theory . AccordiIndependent of the sensory modality, emotional information is thought to activate the appetitive or defensive motivational system. Consequently, the engaged motivational system modulates other (brain) processing operations which means that  processing of other emotional information can be facilitated or inhibited. These modulatory effects are shown crossmodally, thus, there also seem to be independent of the stimulus modality (see, e.g., interactions of emotional information. However, the motivational priming theory does not make any assumptions of how multisensory emotional inputs are combined and integrated. Actually, no specific model exists which accounts for the integration of multisensory emotional information. Generally, one can assume that multisensory integration of emotional information follows similar principles as multisensory integration of other types of complex information (see, e.g., Taken together, the motivational priming theory is able to explain audiovisual The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Cast treatment can serve both as a nonsurgical treatment option and as a means for providing postoperative protection. However, with the duration of immobilization intervals, the benefits of cast treatment, especially in hand surgery, are at risk of being outweighed by undesired drawbacks such as joint stiffening and contracture formation. In order to minimize potential complications commonly associated with cast treatment, efforts to further improve cast making must attempt to reconcile two conflicting objectives: (1) to achieve stability and rigidity at the site of injury  and (2) to allow free range of joint movement as early as possible. In addition, in order to assure patient compliance, modern cast treatments should aim to improve wearing-comfort of the cast. This paper describes modern cast designs for four common types hand injuries, with sample cases highlighting the clinical outcome of each treatment. Cast treatment not only is well established as a nonsurgical treatment option for a variety of posttraumatic conditions of the hand but also is an indispensable tool for providing postoperative protection, for example, for reduced fractures, reconstructed ligaments, tendons, or nerves. Immobilization, however, also has well-known drawbacks which can negatively impact the time of return to “normal hand activity” and the overall clinical outcome as a whole . Common  early functional treatment principle first proposed by Bunnell ) remains a well-accepted treatment option for certain indications—especially in the immediate posttraumatic interval when soft-tissue swelling and primary wound healing occur [ Pascal's law of hydrostatics in developing his bracing technique, which avoids joint-immobilization in connection with the treatment of long bone fractures  without compromising fracture retention and stability [ bracing technique uses the soft tissue surrounding bone to stabilize a fracture site by preventing it from changing volume by means of a circular cast. Additional lessons for achieving the required level of stability while minimizing immobilization of adjacent joints can be drawn from the three-point-pressure principle in fracture retention, which was first widely promoted by Charnley in the 1940s [Although the traditional plaster cast  reduce the time of immobilization and (ii) minimize the restriction of active or passive joint movement [Immobilization by means of cast treatment remains a well-established treatment option for a variety of posttraumatic conditions of the hand , 22. Howmovement , 24. ModThe utility of the cast making technique presented in this paper is not limited to the four sample cases presented in this paper but can be adapted to a great variety of clinical settings using a modular approach . In addi


The power of the randomised controlled trial depends upon its capacity to operate in a closed system whereby the intervention is the only causal force acting upon the experimental group and absent in the control group, permitting a valid assessment of intervention efficacy. Conversely, clinical arenas are open systems where factors relating to context, resources, interpretation and actions of individuals will affect implementation and effectiveness of interventions. Consequently, the comparator  can be difficult to define and variable in multi-centre trials. Hence outcomes cannot be understood without considering usual care and factors that may affect implementation and impact on the intervention.Using a fieldwork approach, we describe PICU context, ‘usual’ practice in sedation and weaning from mechanical ventilation, and factors affecting implementation prior to designing a trial involving a sedation and ventilation weaning intervention. We collected data from 23 UK PICUs between June and November 2014 using observation, individual and multi-disciplinary group interviews with staff.Pain and sedation practices were broadly similar in terms of drug usage and assessment tools. Sedation protocols linking assessment to appropriate titration of sedatives and sedation holds were rarely used (9 % and 4 % of PICUs respectively). Ventilator weaning was primarily a medical-led process with 39 % of PICUs engaging senior nurses in the process: weaning protocols were rarely used (9 % of PICUs). Weaning methods were variably based on clinician preference. No formal criteria or use of spontaneous breathing trials were used to test weaning readiness. Seventeen PICUs (74 %) had prior engagement in multi-centre trials, but limited research nurse availability. Barriers to previous trial implementation were intervention complexity, lack of belief in the evidence and inadequate training. Facilitating factors were senior staff buy-in and dedicated research nurse provision.We examined and identified contextual and organisational factors that may impact on the implementation of our intervention. We found usual practice relating to sedation, analgesia and ventilator weaning broadly similar, yet distinctively different from our proposed intervention, providing assurance in our ability to evaluate intervention effects. The data will enable us to develop an implementation plan; considering these factors we can more fully understand their impact on study outcomes. Many trials in intensive care require a pragmatic design. In contrast to explanatory trials, performed to test whether an intervention works under optimal situations akin to a closed system, pragmatic trials evaluate the effectiveness of interventions in real-life current practice conditions that are influenced by various factors operating in open systems . BecauseDespite the importance of optimising sedation and minimising time on mechanical ventilation, there is limited guidance in the paediatric literature to direct practice on reducing sedation and discontinuing ventilation. Consensus guidelines on sedation developed in the United Kingdom (UK) and Germany , 5 recomP = 0.01). Two small pilot studies using computer-based weaning protocols also reported reductions in duration of total ventilation, albeit non-significant [With regards discontinuing mechanical ventilation, there is no standard method of weaning. A review of weaning and extubation reported that most paediatric studies either described weaning practice in single PICUs or retrospectively sought to identify predictors of successful weaning . Prospecnificant , 13. Thenificant , but as nificant . ExistinTrials of sedation and ventilator weaning are complex because they involve a number of components that act inter-dependently. These include patient monitoring and assessment, measurement and evaluation of sedation and ventilation requirements, practitioner education and training, and inter-professional collaboration. The multi-component structure of such an intervention can challenge evaluation because it needs to provide information on whether the intervention was delivered as intended . It follThere is extensive and convincing evidence confirming the strong impact of careful implementation on outcomes . A revieWe used a fieldwork approach to gather baseline information framed around the fieldwork process outlined by the National Institute of Health and Care Excellence . To undeDiscussions with PHA R&D Division and the University’s Research Governance and Integrity Office established that the fieldwork was not considered to be research, therefore an ethical review or additional governance approvals were not required.A trial outline was presented at a Paediatric Intensive Care Society Specialist Group (PICS SG) in September 2013 and the topic was ranked as the highest priority in the prioritisation survey of PICS members. We subsequently presented the trial proposal at a PICS SG meeting in June 2014. We approached PICU consultant intensivists attending the meeting, and emailed those not attending to request permission to visit their units to discuss the trial with key multi-professional staff: we followed this up with an email to confirm.Fieldwork was conducted mainly by BB and LT together and on four occasions by LT alone. Our aim was to obtain relevant information on factors that may affect the implementation process. These factors were derived from the work of Durlak and DuPre , adaptedQuantitative data relating to staff numbers and unit beds were collated in an Excel database and summarised using descriptive statistics . Narrative and observational textual data relating to each of the factors outlined in the data collection sheet were entered into tables in Word for ease of documenting. These factors were categorised and summarised for reporting.The 23 PICUs ranged in size from 5 to 31  funded beds for intensive care patients. All hospitals visited had high-dependency beds ranging from 2 to 15  that could be used as intensive care beds if necessary: three hospitals had separate high-dependency units. Each PICU had a 1:1 registered nurse to patient ratio for invasively ventilated children. The consultant to patient ratio varied depending on time of day and the size of the unit, from 1:23 (overnight) in larger units to 1:5 in the day for smaller units. Consultant medical staff were always resident 24 hours a day/7 days a week in three larger units, otherwise they were present during daytime and early evening hours and covered on-call from home at night. Clinical patient information was recorded by electronic clinical information systems exporting physiological data directly to electronic health records in eight (35 %) PICUs; the others used paper-based recording charts. In 11 (48 %) PICUs, medical staff conducted morning handover in a conference room before undertaking a walk-around ward round.Analgesia and sedation medication types varied according to the child’s age and condition. All units used intravenous morphine as the primary opiate with 20 PICUs (87 %) using morphine in combination with midazolam for sedation. In six units , clonidine was administered either as the main sedative drug or for children younger than 3–6 months. Clonidine was administered intravenously in all but one unit where it was prescribed orally. Use of neuromuscular blockade was generally rare and reserved for cases such as those with ‘difficult and precarious airways’; severe traumatic brain injuries; post-operative cardiac surgical infants with delayed sternal closure; children receiving extracorporeal membrane oxygenation; or children with unstable pulmonary to systemic blood flow.Pain was not formally scored in three PICUs (13 %). In 20 (87 %) units that scored pain levels, age-appropriate tools were used , nurses were authorised to titrate intravenous sedative and analgesic infusions within a medically prescribed infusion range or administer an intravenous bolus according to patient assessment. In one PICU, nurses could not alter the infusion rate without medical staff sanction, but were authorised to administer up to three intravenous boluses. When probed about assessment and subsequent management, nurses reported their decisions to titrate intravenous sedative medication were seldom associated with the scores on the sedation assessment tool and they revealed they were more likely to increase than decrease medication. Furthermore, the trends in daily sedation level scores were rarely discussed in ward rounds and were not considered in formulating sedation plans. Nurse compliance with sedation scoring was reported to be a problem in many units.In nine PICUs (39 %), a proportion of senior nurses were engaged in weaning children from mechanical ventilation and this included reducing ventilator support to a pre-extubation level (five PICUs) or to extubation (four PICUs). Weaning was undertaken by nurses following a locally developed weaning protocol (two PICUs), based on senior clinical experience (three PICUs), or following successful completion of an academic weaning ventilation course (four PICUs).None of the PICUs reported having a formal set of criteria to determine readiness to wean or extubate. Spontaneous breathing trials (SBTs) were conducted infrequently in PICUs: one PICU reported it was common practice to conduct an SBT using either 5 cmH20 continuous positive airway pressure (CPAP) for 30–120 minutes and three PICUs reported it was occasionally practised. Methods of weaning varied across and within PICUs, although three PICUs used a common ‘rules of five′ (or six) for 2 hours to test readiness for extubation referring to CPAP 5 cm H20, positive end-expiratory pressure 5 cm H20 and pressure support 5 cm H20. Only one unit used an automated weaning mode  although many of the ventilators used could support this application. Weaning to extubation was generally only conducted during the day shift unless there was adequate on-site senior medical cover at night.Our fieldwork data indicated that each PICU had at least one nurse educator responsible for providing mandatory in-service training courses and new staff induction. On-site training included pain and sedation assessment and generally mechanical ventilation, although specific training in weaning patients from mechanical ventilation was not. Academically accredited weaning courses were delivered on-site in four PICUs within two hospital sites and attended by a small proportion of senior nurses depending on local PICU needs. The majority of sites used the COMFORT  sedationSeventeen PICUs 17/23 74 %) had been involved in large multi-centre interventional paediatric trials (Control of Hyperglycaemia in Paediatric intensive care (CHIP) , Safety /23 74 % It was important to explore the staff’s perceptions and belief in the need for the sedation and ventilator weaning protocol, because implementation will be enhanced if staff are committed to the study, feel confident in their ability to undertake the intervention and possess the essential skills. Fieldwork interviews revealed that all units visited were receptive to the intervention and expressed keenness to participate in the trial; this came across most strongly from nursing staff. Those units unable to provide an assurance to participate did so because of their organisational capacity and engagement in other trials (n = 2)A collaboration meeting was held on 25 November 2014 and was attended by 42 participants. These included nurses and doctors from 20 PICUs who had expressed an interest in participating in the trial; and the research team including clinical trialists, methodologists, statisticians and health economists. Summarised feedback on usual care practices from the visited PICUs was presented at the collaboration meeting. Subsequent discussions ensued about the design of the trial and its impact on PICUs, the implementation strategy and the intervention itself. The aims of the meeting were to discuss incongruities, and encourage a shared vision and buy-in from sites. We collected further information on usual care practices pertaining to sedation and ventilator weaning and through discussion established a compromise on an evidence-based intervention that would be agreeable to participating sites.Broadly speaking, the new intervention will be designed to engage all PICU staff from the junior bedside nurse to the medical consultant in sedation and weaning tailored to their level of experience. The intervention protocol will include monitoring and assessing sedation levels and titrating intravenous infusions to achieve optimal sedation within a prescribed range, daily assessment of the child’s readiness for an SBT using an agreed set of clinical criteria, followed by a maximum 2-hour SBT if the criteria are met. Participants agreed that ventilation parameters for the SBT should be considerably lower than those in the readiness criteria in order to more reliably ascertain the child’s ability to tolerate spontaneous breathing and extubation.This pre-trial exploration of baseline practice is the first in the UK paediatric intensive care population to have reported a rigorous process using an evidence-based framework prior to trial set-up to ascertain usual care and factors that might affect implementation. As a result, it has provided valuable information about ‘usual care’ in the open system of UK PICU practice around sedation and ventilation weaning. The methods we used in gathering this information may also provide useful guidance for future clinical trial design.We found that pain and sedation practices in UK PICUs are broadly similar in terms of drug usage, pain and sedation assessment tools and timing. Sedation assessment was commonly scheduled hourly to 4-hourly during the day, but scores were rarely linked to actions for drug titration. This resulted in reported low compliance with scheduled assessment times. Relatively few PICUs (30 %) had written sedation guidelines and only one PICU practised sedation holds. This is in contrast to adult intensive care units where sedation withholding is a recommended part of the ‘ventilator care bundle’, as outlined by the UK Department of Health , the InsWeaning from mechanical ventilation is principally practised according to PICU clinician preference with no common consensus in methods among consultant medical staff. Senior nursing staff and nurses with accredited courses are engaged in weaning, but rarely according to any formalised weaning protocol. In addition, they comprised a relatively small proportion of the nursing staff, which affected continuity of ventilator weaning. In general, the PICUs did not use readiness to wean criteria and SBTs as a method for testing readiness for weaning. In contrast, SBT protocols are the most common weaning methods used in adult ICU studies where protocols have been shown to significantly reduce duration of mechanical ventilation in comparison with non-protocolised weaning . SBTs, iWith regards trial planning, it is clear the majority of PICUs have limited resources in terms of research nurse capacity. In trials requiring individual patient consent, when research nurse time is funded as part of a trial, there is good participation and recruitment in large interventional multi-centre studies, as evidenced by the CHIP and CATCH trials in particular. Our fieldwork findings suggest that our proposed trial will require a proportion of research nurse support for each participating site.Our fieldwork was conducted in 23 from a total of 29 National Health Services in England, Wales and Northern Ireland. We purposively did not collect data from the two Scottish children’s hospitals as laws in Scotland governing informed consent preclude their participation in our proposed trial. The data we collected on usual sedation and ventilation weaning practices show broad similarity across the PICUs. We are confident, therefore, that these practices reflect a generalizable trend across hospitals.Our data were collected from available PICU staff during fieldwork visits and we have not verified the accuracy of these data objectively. However, by meeting a broad range of staff and collecting data in this face-to-face manner, we feel we elicited greater depth of insight than that which could be gained by survey alone. In addition, the visits afforded us the opportunity to obtain copies of relevant guidelines, observations charts and information to corroborate the data.We used an evidence-based framework to identify the variance in contextual, organisational and usual care practices that operated within 23 PICUs. This approach was extremely useful in helping us to describe and define some of the ‘openness’ that is so often a feature within pragmatic trials. The benefit of undertaking this baseline work prior to trial commencement is that it has enabled us to plan a robust implementation strategy and consider how identified factors may impact on trial outcomes. We found that usual PICU practices relating to sedation, analgesia and ventilator weaning were broadly similar in England, Wales and Northern Ireland. There was a noticeable lack of sedation and ventilator weaning protocols to guide and support staff in patient assessment and management in these areas. We are confident, having explored factors affecting implementation, that this intervention is compatible with the values and missions of the participating sites. Nevertheless, we are not naïve in understanding the complexities of multi-site research. We intend to extend our evaluation of factors that may impact on implementation by conducting a process evaluation alongside the trial. The process evaluation, informed by the Promoting Action on Research Implementation in Health Services (PARIHS) framework , will fo


So far most studies on adult neurogenesis aimed to unravel mechanisms and molecules regulating the integration of newly generated neurons in the mature brain parenchyma. The exceedingly abundant amount of results that followed, rather than being beneficial in the perspective of brain repair, provided a clear evidence that adult neurogenesis constitutes a necessary feature to the correct functioning of the hosting brain regions. In particular, the rodent olfactory system represents a privileged model to study how neuronal plasticity and neurogenesis interact with sensory functions. Until recently, the vomeronasal system (VNS) has been commonly described as being specialized in the detection of innate chemosignals. Accordingly, its circuitry has been considered necessarily stable, if not hard-wired, in order to allow stereotyped behavioral responses. However, both first and second order projections of the rodent VNS continuously change their synaptic connectivity due to ongoing postnatal and adult neurogenesis. How the functional integrity of a neuronal circuit is maintained while newborn neurons are continuously added—or lost—is a fundamental question for both basic and applied neuroscience. The VNS is proposed as an alternative model to answer such question. Hereby the underlying motivations will be reviewed. In the olfactory epithelia, ciliated and microvillus neurons, supporting cells and ensheating glial cells are constantly renewed during pre- and postnatal development  hormone metabolites and other small molecules possibly contained in urine and bodily secretions; V2Rs, activated mainly by high molecular weight (HMW) peptidic compounds such as lipocalins, or smaller MHC peptides; formyl peptide receptors (FPRs), involved in the immune cell response to infections  each OSN expresses only one of them. In the VNO this rule is not followed since each VSN may express more than one receptor gene  layer of the AOB look clearly partitioned by the segregated V1R/Gai2 and V2R/Gao afferent fibers. Axonal projections from these two neuronal populations establish synaptic contact with either the anterior (aAOB) or posterior (pAOB) AOB, respectively. This separation is visible in the PC layer neuropil , external (ECL), and internal (ICL) cellular layers  are classified in periglomerular (PG), short axon (SA) and external tufted (ET) cells, based on their neurochemistry, morphology, and connectivity. Juxtaglomerular cells can be divided in two main GABAergic chemotypes based on the expression of different isoforms of the GABA synthesis enzyme—GAD-65, GAD-67—together with other markers such as dopamine (DA), or its synthesis enzyme tyrosine hydroxylase (TH), calbindin, calretinin, and others , respectively. Evidence showed the vast majority of newborn cells reaching the AOB is represented by internal granule cells  has been proved Yang, . These nIt is not known whether SVZ-derived interneurons migrating to the AOB belong to the same lineage of those in the MOB. It is possible that genetically distinct populations of interneurons are heterogeneously distributed in the two OB sub-regions. Recently, viral fate-mapping experiments revealed the mosaic nature of the SVZ proliferative domains giving rise to different and heterogeneous pools of GABAergic interneurons (Merkle et al., As shown by olfactory enrichment or deprivation studies, the maturation and survival of newborn neurons in the MOB depends on sensory inputs (Cummings et al., Although renewing at a slower rate (Oboti et al., The presence of gender related differences in AOB neurogenesis is controversial (no differences in CD1 mice Oboti et al., A few comparative considerations with the MOB elementary functional unit—the olfactory column—can be insightful in defining the impact of newborn neurons on AOB network activity. The MOB olfactory column is considered equivalent to the cortical columns and barrels in the visual and somatosensory cortices (Shepherd, ex-vivo VNO-AOB intact preparation showed that this is indeed the case (Meeks et al., The AOB appears structurally similar to the MOB, although it retains some peculiar features in both hodology and cell types. However, the occurrence of similar plastic events in both structures motivates the same reasoning done for the MOB. Olfactory glomeruli in the AOB are on average smaller than those in the MOB and appear to be clustered in pseudostratified formations. Contrarily to MOB glomeruli, they receive multiple inputs from different types of VSNs (Takami and Graziadei, The limited extent by which AOB PGs are regenerated by SVZ-derived progenitors, together with the above mentioned lack of TH, could be explained by the lack of TH/GAD-67 cells in the AOB. Alternatively, since TH expression levels in PGs are traditionally used as a proxy for olfactory input (Nadi et al., Conversely, granule cells in the AOB are the most represented cell type among newly generated neurons (Oboti et al., Overall these observations suggest that newly generated GABAergic interneurons differently contribute to mature AOB circuits, if compared to the MOB. The different nature of GABAergic modulation of AOB output signals is further supported by the firing of AOB PCs, which appears to be longer sustained, if compared to MOB mitral cells (Meeks et al., pheromone-detector in the nasal cavity of mammals or other vertebrates (Eisthen and Wyatt, pheromone sensing. Indeed studying the molecular and genetic mechanisms underlying the neuroendocrine physiology of sociality may yield insights on the etiology of associated anomalies, even in those mammalian species, human included, in which this sensory pathway is not present. For this reason the rodent VNS may represent the unique opportunity to dissect this issue in an animal model in which these features strongly rely on its functional integrity and—plausibly—its capability of cell renewal through adult neurogenesis.Overall the considerations made in this manuscript are meant to underline that the VNS is not only constitutively plastic but also that this plasticity may constitute the basis for its peculiar function. Eventually the VNS circuitry cannot be considered hardwired but rather able to adjust its connectivity to environmental changes. If the function of the VNS described so far (see for critical views on this point Eisthen and Wyatt, Figure


Sensory deafferentation resulting from the loss of photoreceptors during retinal degeneration (rd) is often accompanied by a paradoxical increase in spontaneous activity throughout the visual system. Oscillatory discharges are apparent in retinal ganglion cells in several rodent models of rd, indicating that spontaneous activity can originate in the retina. Understanding the biophysical mechanisms underlying spontaneous retinal activity is interesting for two main reasons. First, it could lead to strategies that reduce spontaneous retinal activity, which could improve the performance of vision restoration strategies that aim to stimulate remnant retinal circuits in blind patients. Second, studying emergent network activity could offer general insights into how sensory systems remodel upon deafferentation. Here we provide an overview of the work describing spontaneous activity in the degenerating retina, and outline the current state of knowledge regarding the cellular and biophysical properties underlying spontaneous neural activity. For centuries it has been known that when people suffer vision loss they often experience differing degrees of visual hallucinations Ffytche, . Some ofThe finding of increased spontaneous activity in ganglion cells in retinae with degenerating photoreceptors has now been repeated by many labs and in several different animal strains including rd1 mice , which mediate oscillatory activity in other parts of the brain , an increase in oscillation amplitude and a decrease in oscillation frequency  completely abolishes oscillatory synaptic input to retinal ganglion cells , strongly modulating the membrane potential (from −80 to 0 mV) does not abolish spontaneous membrane oscillations  Osc+ channels are present in AII amacrine cells in wild type retinae, and AII amacrine cells are extensively coupled to each other as well as to ON cone bipolar cells in wild type retinae, why do these components only contribute to the generation of network wide oscillations in rd retinae? Critical insights into the mechanism underlying oscillations came from pharmacological experiments in wild type retinae showing that hyperpolarizing the AII amacrine/ON cone bipolar cell network by pharmacologically blocking photoreceptor output led to the emergence of ~10 Hz oscillations in wild type AII amacrine/ON cone bipolar cells (Figure + channels by bringing them out of an inactivated state, and thereby induce oscillations (Trenholm et al., Finally, if TTX-sensitive Nas Figure . These ps Figure , suggests Figure . These fs Figure . Membran+ channels are required for driving the oscillation. Fourth, bipolar cells appear to play a key role in setting the membrane potential of the coupled network into a state in which it can oscillate, and active membrane properties of bipolar cells, including Ih, regulate the amplitude and frequency of oscillations. Finally, no major rewiring of the retina appears to be required for driving oscillations, as pharmacologically blocking photoreceptor output or photo-bleaching the wild type retina generates similar pacemaker activity. Future work targeting the different components that modulate this spontaneous activity may allow for this spontaneous noise to be dampened in order to heighten the effectiveness of vision restoration strategies. Indeed, such work has already commenced (Toychiev et al., in vivo, such as injecting pharmacological agents into the eye while monitoring spontaneous activity in higher visual centers, will be important for outlining which strategies for mitigating spontaneous retinal activity have the best chance of translating from the lab to the clinic.Taken together, these experiments reveal several key features of the retina following photoreceptor degeneration and these are outlined in Figure The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Myocarditis can lead to acute heart failure, cardiogenic shock, or sudden death and later, dilated cardiomyopathy (DCM) with chronic heart failure. We report the cases of two DCM induced by acute and past myocarditis in the same family and expressed by its two main complications within few weeks: an hemodynamic presentation as a fulminant myocarditis rapidly leading to cardiac tranplantation and a rythmologic presentation as an electrical storm leading to catheter ablation of ventricular tachycardia. These cases ask the question of the family predisposition to viral myocarditis leading to DCM. A family history of dilated cardiomyopathy (DCM) is found in about one-third to one-half of patients with idiopathic DCM, who are considered to have familial DCM. DCM can also be the consequence of myocarditis, but not every acute myocarditis develops DCM. These findings suggest that there could be familial predisposition to infection in some patients. Familial DCM is commonly reattached to genetic mutations that affect myocardial functions but there is no data to support the possibility of mutation affecting sensibility to infection.We report two cases of DCM developing in the same family within a few weeks, with confirmed infectious aetiology in one of them.A 14-year-old boy referred for fulminant myocarditis diagnosed by cardiac magnetic resonance imaging (MRI): left ventricle was dilated with an left ventricle ejection fraction (LVEF) of 15% and apical thrombus, lateral wall displays hypersignal in the T2 weight sequences  panel 1ATwo months later, his father, a previously healthy 47-year-old man with no cardiovascular history, was referred for an electrical storm. There was no family history of sudden death. The ECG revealed monomorphic sustained ventricular tachycardia with a right side behind right axis. Coronary artery disease was excluded by coronary angiography. Cardiac MRI was performed showing a DC with severe impairment of the LVEF, functional mitral regurgitation  panel 2CThis family history of myocarditis underlies a genetic susceptibility. Most of viruses in myocarditis are common cough viruses and the reason why some people develop myocardial damages remains unclear. Studies show that inflammation and viral persistence in the myocardium are associated with progressive impairment of left ventricle function . During Familial DCM may have its origin in myocarditis, and therefore identification of genes implicated and of immunes responses could improve therapies.


This review explores the proposal that vulnerability to psychological symptoms, particularly anxiety, originates in constitutional differences in the control of bodily state, exemplified by a set of conditions that include Joint Hypermobility, Postural Tachycardia Syndrome and Vasovagal Syncope. Research is revealing how brain-body mechanisms underlie individual differences in psychophysiological reactivity that can be important for predicting, stratifying and treating individuals with anxiety disorders and related conditions. One common constitutional difference is Joint Hypermobility, in which there is an increased range of joint movement as a result of a variant of collagen. Joint hypermobility is over-represented in people with anxiety, mood and neurodevelopmental disorders. It is also linked to stress-sensitive medical conditions such as irritable bowel syndrome, chronic fatigue syndrome and fibromyalgia. Structural differences in “emotional” brain regions are reported in hypermobile individuals, and many people with joint hypermobility manifest autonomic abnormalities, typically Postural Tachycardia Syndrome. Enhanced heart rate reactivity during postural change and as recently recognized factors causing vasodilatation  is characteristic of Postural Tachycardia Syndrome, and there is a phenomenological overlap with anxiety disorders, which may be partially accounted for by exaggerated neural reactivity within ventromedial prefrontal cortex. People who experience Vasovagal Syncope, a heritable tendency to fainting induced by emotional challenges (and needle/blood phobia), are also more vulnerable to anxiety disorders. Neuroimaging implicates brainstem differences in vulnerability to faints, yet the structural integrity of the caudate nucleus appears important for the control of fainting frequency in relation to parasympathetic tone and anxiety. Together there is clinical and neuroanatomical evidence to show that common constitutional differences affecting autonomic responsivity are linked to psychiatric symptoms, notably anxiety. Influential theories argue that bodily states of arousal are a key component to emotions, and are the basis to emotional feeling states. Emotional processes are intrinsically coupled to autonomic bodily responses through shared neural substrates. Exaggerated patterns of autonomic responsivity can enhance the expression of panic or anxiety symptoms. Some of the vulnerability to psychological symptoms, particularly anxiety, originates in constitutional differences in the control of bodily states of arousal. Joint Hypermobility, Postural Tachycardia Syndrome and Vasovagal Syncope represent common conditions in which there is evidently a stronger association. The mechanisms underlying these brain-body interactions can be defined by combining brain imaging with detailed physiological monitoring of psychiatric and neurological patients and healthy controls. Ultimately, these interactions are relevant to the recognition, understanding and treatment of individuals with anxiety, and also for stress-sensitive medical disorders. By characterizing the interplay between brain and body in detail, clinically relevant insights can be gained into the mechanisms that underpin both adaptive and maladaptive psychological and physical states. This in turn will lead to targeted interventions for the personalized treatment of symptoms, for enhancing health and resilience and for mitigating adverse events, e.g., drug side effects. We argue that there are specific yet common constitutional variants  in physiological reactivity  that have major influences on emotional state and by extension on vulnerability to psychiatric disorder. Below we discuss the relevance of three of these “neurovisceral phenotypes”  to psychiatric symptoms.Syndrome (synonymous with Ehlers-Danlos Hypermobility Type–formerly Type III) . Conditions associated with joint hypermobility go beyond rheumatology to include Chronic Fatigue Syndrome  as assessed by administration of isoproterenol)  or a heart rate of >120 beats per minute without orthostatic hypotension within the initial 10 min of orthostasis or head up tilt. Postural Tachycardia Syndrome has only relatively recently 1993) been clearly described  and co-existing physiological   and reported in previous studies .Cerebral hypoperfusion resulting in transient loss of consciousness can be induced by a variety of physiological—or in some cases of vasovagal syncope, psychological–phenomena that lead to either inadequate cerebral perfusion pressure or abnormally high cerebral vascular resistance. Causes of syncope are heterogeneous but can be classified into three categories: Low arterial blood pressure; Increased resistance to cerebral blood flow; and other causes of cerebral dysfunction . It is characterized by a sudden transient loss of consciousness and postural tone caused by cerebral hypoperfusion provoked by physiological or emotional stressors. The term “vasovagal” derives from sympathetic vasoconstrictor withdrawal causing vasodilatation and increased vagal nerve activity causing bradycardia, these leading to hypotension and resultant loss of consciousness. vasovagal syncope accounts for around 40% of syncopal events, making it the most common cause of syncope  panic (20%), and depression (15%) and higher anxiety scores  was significantly positively correlated with fainting frequency  and log[fainting frequency]   and frequency of syncope in vasovagal syncope participants. Moreover, emotional state, notably anxiety, is well recognized as a predisposing factor to syncope in vulnerable vasovagal syncope individuals  and influences cardiovascular autonomic regulation , emotional numbing, feelings of disembodiment and memory recall deficits relating to the personalization but not retrieval of memory  with functional neuroimaging, finds that depersonalization disorder patients produce decreased hypothalamic and amygdala blood oxygen level dependent (BOLD) responses during presentation of happy and sad expressions respectively . A detailed understanding of these processes in clinical and non-clinical groups, alongside greater clinical recognition of neurovisceral phenotypes and their expression across neuropsychiatric disorders, will inform the innovative development of pharmacological and biobehavioral interventions for the management of psychosomatic symptoms, panic and anxiety states.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


In sub-Saharan Africa, the capacity of human resources for health (HRH) managers to create positive practice environments that enable motivated, productive, and high-performing HRH is weak. We implemented a unique approach to examining HRH management practices by comparing perspectives offered by mid-level providers (MLPs) of emergency obstetric care (EmOC) in Tanzania to those presented by local health authorities, known as council health management teams (CHMTs).Health Systems Strengthening for Equity: The Power and Potential of Mid-Level Providers project. Survey data was obtained from 837 mid-level providers, 83 of whom participated in a critical incident interview whose aim was to elicit negative events in the practice environment that induced intention to leave their job. HRH management practices were assessed quantitatively in 48 districts with 37 members of CHMTs participating in semi-structured interviews.This study was guided by the basic strategic human resources management (SHRM) component model. A convergent mixed-method design was utilized to assess qualitative and quantitative data from the The eight human resources management practices enumerated in the basic SHRM component model were implemented unevenly. On the one hand, members of CHMTs and mid-level providers agreed that there were severe shortages of health workers, deficient salaries, and an overwhelming workload. On the other hand, members of CHMTs and mid-level providers differed in their perspectives on rewards and allocation of opportunities for in-service training. Although written standards of performance and supervision requirements were available in most districts, they did not reflect actual duties. Members of CHMTs reported high levels of autonomy in key HRH management practices, but mid-level providers disputed the degree to which the real situation on the ground was factored into job-related decision-making by CHMTs.The incongruence in perspectives offered by members of CHMTs and mid-level providers points to deficient HRH management practices, which contribute to poor practice environments in acute obstetric settings in Tanzania. Our findings indicate that members of CHMTs require additional support to adequately fulfill their HRH management role. Further research conducted in low-income countries is necessary to determine the appropriate package of interventions required to strengthen the capacity of members of CHMTs. Poor practice environments alternately induce and exacerbate low levels of health worker performance in sub-Saharan Africa, thus undermining delivery of maternal health services needed to reduce the maternal mortality burden in the region. Women lack access to skilled providers when personnel shun service in poor practice environments. Poor practice environments are characterized by inadequate compensation and supervision, lack of basic equipment and supplies, and ill-maintained facilities –7. NegatAccording to the International Collaborating Partners of the Positive Practice Environment CampaignIn sub-Saharan Africa, the capacity of human resources for health (HRH) managers to strategically plan for and deploy health personnel is weak. In 26 countries assessed, HRH managers were found to lack adequate infrastructure, training, and work experience to fulfill even basic management activities . The abiAs in other sub-Saharan African countries, the HRH management capacity in the United Republic of Tanzania is considered weak. The decentralized health system in Tanzania grants local (district) authorities, known as council health management teams (CHMTs)Simultaneously, maternal mortality in Tanzania is high with 398 deaths per 100 000 live births; maternal mortality contributes significantly to the national burden of disease and is designated a priority health area . CriticaTanzania’s response to its dual crises, high maternal mortality and scarce HRH, has been to train and license mid-level providers (MLPs) to perform an expanded set of basic and comprehensive emergency obstetric care (EmOC)Acute obstetric care is delivered in clinical settings typically characterized by unpredictable fluctuations in patient volume and acuity by a wide range of providers . In ordeOne such study conducted by McAuliffe and colleagues found that nursing and medical staff in Malawi responding to the Healthcare Provider Work Index (HPWI) rated their practice environments poorly largely due to weak supervision and inadequate resources . DemonstHealth Systems Strengthening for Equity: The Power and Potential of Mid-Level Providers (HSSE) collectively endorsed utilizing supervisory mechanisms to create supportive practice environments centered on helping health workers achieve their patient care goals , 4140, 4We completed an analysis of data from the HSSE study utilizing a descriptive convergent mixed-method approach. The HSSE study is described in detail elsewhere , 38, 42.Procedures used to select facilities from which participants in the HSSE study were recruited have been described elsewhere . MLPs weOnce necessary ethical approvals were obtained, instruments developed by the HSSE study team based on previously validated instruments were used to gather interview and survey data during October and November of 2008. The research team obtained information from members of CHMTs to complete the 32-item HRH Information Survey, comprising dichotomous, nominal, and Likert-type questions. MLPs completed the Provider Survey, a 298-item questionnaire comprising dichotomous, nominal, and Likert-type questions, plus 15 items that were part of a discrete choice experiment. The CHMT HRH Information Survey and the Provider Survey encompassed the quantitative branch of the study. In the qualitative arm, trained interviewers conducted semi-structured interviews using the CHMT Interview Guide and the Provider Critical Incident Analysis instrument. MLPs participating in the critical incident interview were asked to identify and elaborate on a work-related event causing loss of motivation and inducing intention to leave in the 3 months prior to encounter with the research team. Trained interviewers met with members of CHMTs at predetermined locales and times. MLPs were usually interviewed at their place of work although scheduling preferences were accommodated. Following informed consent, participants were enrolled in the study. The interviews were conducted in Swahili, audio recorded, and transcribed verbatim. Transcripts were then translated into English in Microsoft Word  prior to analysis.Interview data were systematically compressed or coded into categories from which an inference could be made using conventional content analysis –49. Two U test with the Bonferroni correction applied to account for multiple comparisons  my dead body.Excessive patient volume created difficult work environments for under-resourced and understaffed MLPs who mentioned extending themselves to fulfill the professional obligation to meet patients’ needs. One nurse midwife reported “…you know when a woman comes for delivery you have to find a way to help her you just can’t leave her.” Sometimes helping patients meant sacrificing personal well-being as in the case of one public health nurse working in a seaside community:…even if I decide that I’m leaving them alone, or say I get angry and stop attending patients, citizens will suffer. It could be that he or she is my neighbor or my relative…Participants rationalized their motivation to overcome the difficult work environment similar to this nurse midwife:Additional coping mechanisms attributed to influence MLPs to remain in their posts included hope for a better future, religious faith, and support networks comprising spouses, relatives, and friends. Some felt other facilities were similar to their own; it was pointless to uproot life in one area to face similar difficulties in another.… those seniors [in authority], even if he went [to district authorities] last week, this week he will just be paid. But for those who have been waiting for six months we get told that there’s no money. But for him, there is no problem because he is the boss …Salaries were a major source of dissatisfaction among MLPs. Late salaries, low salaries, partial payment of salaries, and superficial understanding of salary structures were the dominant grievances. A CO interviewed in October 2008 reported that “from May we have not been paid.” Members of CHMTs were said to promise but not compensate personnel for overtime hours worked or reimburse personal funds spent on patient-related activities, such as hiring a car to transport patient to higher levels of care when an ambulance was not available. A nurse assistant reported that “you are just told to fill in the forms but you don’t get paid.” Attempts to resolve salary discrepancies through administrative channels were challenging due to expenses accrued during repeated visits to district headquarters, apathetic response by officials, and inability to fully advocate for oneself. Further aggravating MLPs was the perception that members of CHMTs were exempt from salary predicaments. One nurse midwife explained:…there are few workers who have been trained here so you find that patient care is not done to an expected standard because there are few trained workers.MLPs reported severe personnel shortages. One nurse described the impact:…I found this woman who has just given birth in a very bad situation. So I had to call the doctor and the doctor told me to put her a drip but there was no drip so I had to rush back to the doctor to take [the drip] and I did but when I got back she was even worse. So I had to come to call the doctor but bad enough is when we got back to realize that she was already dead.Commensurate with inadequate personnel were longer work hours, a heavier workload, and greater patient dissatisfaction due to long wait times. Poor outcomes occurred when precious moments during medical emergencies were wasted locating medications and supplies instead of administering life-saving interventions as in the instance reported by a nurse assistant:MLPs reported lack of proper protective barriers when their work exposed them to potentially infectious bodily fluids, frequent stock outs of essential medications, unreliable electricity, and inadequate water supply. Patients and family members verbalized their dissatisfaction with poor quality of care towards MLPs as one registered nurse stated “…they do complain a lot and sometimes they insult you with harsh words.”I stayed there a second village from here. There was a day when I was called at 3 am in the midnight to come to attend a pregnant woman who had failed to give birth. I came with a kerosene lamp from there in the night… I did not have a torch…For many respondents, opportunities for both in-service training and advanced professional qualifications were out of reach due to unfair selection criteria applied by members of CHMTs and disqualification based on tenure and education requirements. MLPs were demoralized when members of CHMTs continually selected the same personnel to attend in-service training. Inadequate staffing prevented some MLPs from exploiting available training opportunities to avoid leaving health facilities unattended. Short-term training workshops are highly desired opportunities to obtain new knowledge, earn extra income from stipends, travel away from home, and interact with other attendees. MLPs who were not selected reported their personal and professional growth was stunted. Exposure to poor living conditions constantly reminded MLPs of their inability to advance themselves according to this nurse midwife.…You are working in a situation with anger and hatred. Our intention is to save people’s lives but not to build anger.Sometimes low morale caused tension among MLPs leading to negative interpersonal interactions. One nurse midwife reported:…the research you are conducting. We would request that if it is possible people in the ministry should be involved directly. We know that these are the people who make policies… They would come directly and ask us questions and give them our views. In this way I believe that the policies which they make would be better.Emerging from MLP narratives was the view that they are essential partners in the endeavor for better health outcomes; through collaboration with the government, seemingly intractable health system problems could be overcome. Using interviews to air concerns, one CO asked that policies reflect the true reality of clinical practice “now we beg the government to think about us.” A public health nurse suggested:The role of government as a reservoir and distributor of technical, fiscal, and human resources influenced the preference for public sector jobs, which are seen to confer greater job security than in the private sector. A CO stated “there are other benefits which are not offered in private facilities.” Pensions are one such benefit.Narratives drawn from interviews of 37 members of CHMTs were analyzed following the same procedure used to sort and compress into categorical data obtained from the MLPs resulting in the six themes presented here.A shortage in all the cadres was acknowledged by all members of CHMTs. Interviewees reported that UAP are more readily available than cadres with higher levels of training. One district health secretary summarized the situation as follows: “we have few health workers while we have great demand.” Recruitment and retention of personnel, particularly for posts in rural areas, was challenging for members of CHMTs. Factors attributed to deter health workers from rural areas include poor infrastructure, traditional housing not connected to the electrical grid, ill-equipped health facilities, low and late salaries, family commitments favoring urban residence, and socio-cultural biases against unmarried personnel.…but after she returns from the malaria course you find she goes to do something else not related to malaria. So after a short time those learned skills starts to disappear due to issue of not using them.According to interviewees, the push to enhance maternal child health services in Tanzania has driven up demand for additional training while leading to an increase in workshops and seminars offered for personnel to gain new knowledge and update skills. Members of CHMTs pointed to personnel shortages as a major factor known to limit the number of health workers who can take advantage of available opportunities. One district health secretary put it this way: “…if the station has one person and that person needs to go for training, this is a problem.” Cadres reported to have the most access to in-service training were COs, nurses, and midwives. We learned that sometimes health workers were taught skills that could not be implemented in their facilities due to lack of resources or personnel were assigned to areas where newly acquired training was not relevant or useful. A district health secretary told us:Of course for the best performance there is a gift. For example this year during May Day we gave a gift to one of our workers… She was the best workers. So there is something like that which motivates people.The CHMT interviews mentioned May Day  as an annual event when special gifts are awarded in recognition of exemplary performance:…Then there is a book MTUHA No. 2 in which we write and after the supervision we write what we did, we write the date, what we found and the directives we gave. So next time you to visit again you just open your book and see if improvements are done…Members of CHMTs expressed the view that they communicated expected performance standards to MLPs through the published Health Management Information System, also known by its Swahili acronym, MTUHA. A district medical officer described the process:In addition to MTUHA, reinforcement of performance standards was reported to occur via various media, including morning staff meetings and during training workshops and seminars.…you will find one health provider works in antenatal, to provide vaccination, weighing children, providing counseling to mother with children, providing counseling to mothers to come for family planning. One person will provide all these services. Still there are mothers who want to give birth. Therefore you will find that the workload is bigger than workers who are there.In their interviews, members of CHMTs revealed that procedures to match workload to staffing reported in their surveys were impossible to achieve in reality due to severe personnel shortages. One reproductive and child health coordinator reported that:…That form is supposed to be filled with year aims so every worker is supposed to work accordingly to this form. So the head of department is supposed to make follow up if those aims are fulfilled and if not there should be reasons why so.Interviewees conveyed the integration of the OPRAS, a formal performance assessment tool and checklist, into the supervision process utilized by members of CHMTs. The degree of objectivity introduced through OPRAS demanded accountability from MLPs, which appealed to members of CHMTs. One reproductive and child health coordinator stated:Some members of CHMTs reported that operationalizing OPRAS was problematic. A complete grasp of the performance metrics and the rationale for selecting specific measures still eluded some members of CHMTs. Scheduled supervision visits were postponed on occasion for reasons such as lack of transportation and instances when members of CHMTs were compelled to abandon their supervisory duties and assume the clinician role to relieve personnel burdened by overwhelming patient volume.…As I said earlier director is the one who is responsible for employing and firing or punishing. As heads of department we can only advice or suggest therefore we must advise our director. So we are advising but we cannot make decision on human resource.With regard to participation of members of CHMTs in matters related to HRH in their districts, interviewees spoke of playing a largely advisory role. Final policy decisions were said to rest with the district executive director but based on real-time intelligence gathered by members of CHMTs concerning the HRH situation on the ground. One district medical officer explained:Our analysis revealed that HRH management is implemented unevenly across the representative sample of 48 districts we examined. We discovered areas in which responses from members of CHMTs and MLPs were concordant, for example, personnel shortages were endorsed by all. In other areas, discordant perspectives were apparent. A summary of qualitative and quantitative results is presented in Table The fragmented HRH management and coexistent poor practice environments in our findings reflect the broader context in which important gaps in implementation of Tanzania’s national HRH strategic plan set the stage for lapses at the district level . DespiteAccording to the Ministry of Health and Social Welfare (MoHSW), key national HRH targets are missed partly because personnel issues are ranked low in priority and also due to inability to effectively appeal for necessary resources from crucial government partners, such as the Ministry of Finance . DifficuBesides circumstances arising at the national level, members of CHMTs also contend with their mandate within the decentralized health system in Tanzania, which is to engage community members and nongovernmental partners in setting and achieving district health goals . For meaThe case for building the capacity of members of CHMTs to create positive practice environments in which MLPs deliver EmOC is grounded in evidence that patients can suffer harmful consequences, including death, when frontline workers are denied proper organizational support. Although the series of seminal studies we report here were conducted in Europe and the USA, their implications are relevant even in low-resource settings. Aiken and colleagues demonstrated that hospital and nursing characteristics, such as workload, educational achievement, and skill mix, had a significant effect on the odds of patient mortality and failure-to-rescue  –65. In 1In our study, both members of CHMTs and MLPs indicated various instances when obstacles in their practice environments threatened or even overshadowed patient care. The lone nurse assistant preoccupied with searching for intravenous fluids instead of administering emergency aid to a critically ill postpartum patient or MLPs taking time off from work responsibilities to seek resolution of salary discrepancies were some emerging themes. At the same time, the capacity of members of CHMTs to address challenges encountered by MLPs in their practice environments was undermined by budget deficits and bureaucratic red tape. These factors prevented members of CHMTs from completing scheduled supervisory visits, relieving payroll bottlenecks that lead to personnel attrition, and meeting staffing guidelines.Regrettably, narratives depicting poor practice environments have been widely reported across a range of clinical settings in low-income countries and are not unique to Tanzania. Well documented in the global health literature are accounts of personnel dissatisfaction with elements of their practice environments, for example, poor pay in Lebanon  and burdAlthough interest in some elements of professional models of work organization has been reported in low-income countries, there is no evidence that they have been fully implemented in these regions . FindingOur findings point to four additional target areas as policymakers in Tanzania take incremental steps to improve practice environments encountered by MLPs. First, HRH policy dictates that personnel are entitled to various allowances as inducements to complement their base salary, but these incentives are awarded unevenly , 75–77. Restructuring HRH management requires upfront fiscal investments and time dedicated to installing related infrastructure and processes. We did not find any studies conducted in low-income countries to estimate costs of implementing comprehensive HRH management reforms. But, we can extrapolate from US facilities fulfilling all of the arduous requirements of the Magnet® model mentioned earlier. Operating costs associated with delivery of inpatient care in these facilities increased by 2.5 % on average and they reached their break-even point within 2–3 years . The finTaken together, qualitative and quantitative data gathered from members of CHMTs and MLPs revealed crucial gaps in HRH management practices implemented in Tanzanian facilities that deliver EmOC. Our analysis found a dearth of empirical evidence generated in low-income countries that can be used to support a package of interventions to strengthen the capacity of members of CHMTs, and such studies are urgently needed. In the absence of pertinent exemplars from low-income countries, we were compelled to rely on findings from studies carried out in high-income countries. Additional research should be conducted to test the effectiveness of recommended interventions aimed at enhancing CHMT operation competencies and improving their familiarity with OPRAS. Effects of interventions to bolster the capacity of members of CHMTs can be compared against quality of practice environments reported by MLPs and measured at distinct time intervals utilizing validated tools, such as the HPWI. Quality of practice environments can also be compared against MLP-sensitive patient outcomes, such as morbidity, mortality, and satisfaction.negative aspects of the practice environment attributed to induce intention to leave. Concerns that comparing negative MLP perspectives to findings from members of CHMTs may have introduced a bias were dispelled for two reasons. First, the 83 MLPs interviewed were a subset of the 837 MLPs who completed the Provider Survey. As a result, we were able to ascertain that themes elicited from the critical incident interview narratives resembled responses made by the larger pool of participants responding to the Provider Survey. Secondly, themes derived from the critical incident interviews overwhelmingly identified deficient HRH management practices as a major source of their dissatisfaction. In fact, despite being asked to speak about only negative events, MLPs voluntarily described positive factors that enabled them to cope with their challenging work environments, such as commitment to the citizens of Tanzania, strong support networks, their own resilience, faith, and hope for the future.It is important to note that MLPs participating in the critical incident interview were asked to relay only The mixed-method approach utilized in this study was particularly valuable in sorting through the quantitative and qualitative HSSE data to form a unified profile of the state of HRH management practices utilized by members of CHMTs to deploy and manage MLPs. Interview narratives were useful in expanding the meaning of responses provided in the survey data and vice versa. Responses from members of CHMTs either corroborated or contradicted those given by MLPs to generate deeper insight on the HRH management practice reality. Lastly, our study demonstrated the utility of reaching across disciplinary divides for a framework to understand complex phenomena in public health. Wright, Dunford, and Snell’s basic SHRM component model , 41 is tThis study was subject to shortcomings associated with self-reports made by members of CHMTs and MLPs. Either group may have attempted to exaggerate positive or negative aspects of the practice environment in order to maintain social desirability. However, the triangulation of data sources and use of quantitative and qualitative data in tandem to inform the research question allowed our findings to converge on the true state of HRH management practice.The purposeful sampling strategy used in this study constitutes a nonrandom sampling method, which limits generalizations that can be made from the quantitative arm of the study . HoweverMissing data posed a potential problem during the quantitative analysis phase because it was not possible to revisit participants to obtain missing data or clarify responses. Less than 10 % of the data in each variable we analyzed was missing, and missing variables were scattered randomly across participants. Therefore, cases were not excluded from the analysis based on missing data . MembersOur study sheds light on some HRH management practices that are detrimental to practice environments encountered by MLPs in Tanzania. But far from placing responsibility solely on members of CHMTs, our findings affirm the need for additional support in their HRH management role. Additional research conducted in low-income countries is necessary to outline the best way to strengthen the capacity of HRH managers to create positive practice environments for MLPs to deliver consistently high-quality maternal care.AMO, assistant medical officer; CHMT, council health management team; CO, clinical officer; EmOC, emergency obstetric care; HPWI, Healthcare Providers Work Index; HRH, human resources for health; HSSE, Health Systems Strengthening for Equity: The Power and Potential of Mid-Level Providers; MDGs, Millennium Development Goals; MLPs, mid-level providers; OPRAS, Open Performance Review and Appraisal System; SHRM, strategic human resources management; UAP, unlicensed assistive personnel