[Recommendations for the development of resilient health systems in the AmericasRecomendações para o desenvolvimento de sistemas de saúde resilientes nas Américas]. / Recomendaciones para el desarrollo de sistemas de salud resilientes en las Américas.

This article offers opinion and analysis outlining strategic lines of action to build resilient health systems while promoting recovery in the post-COVID-19 pandemic period, with a view to maintaining and protecting public health gains. It contextualizes the challenges and opportunities in the Region of the Americas and offers recommendations for implementation of the strategic lines.It is urgent to promote the development of resilient health systems through the implementation of four lines of action defined in the strategy adopted by the Member States of the Pan American Health Organization in September 2021. The transformation of health systems must be based on the adoption of an integrated model of primary health care, a priority focus on the essential public health functions, strengthening of integrated health service networks, and increased public funding, especially for the first level of care. Implementation of these lines of action is focused not only on consolidating immediate crisis response; it is also framed within efforts toward the recovery and sustainable development of health systems, reducing their structural vulnerabilities to better prepare the response to future crises.

Este artigo de opinião e análise descreve linhas de ação estratégicas para desenvolver sistemas de saúde resilientes ao mesmo tempo em que se promove a recuperação pós-pandemia de COVID-19 a fim de manter e proteger os ganhos em saúde pública. Além disso, apresenta uma contextualização dos desafios e oportunidades na região das Américas e oferece recomendações para sua implementação. Há uma necessidade urgente de promover o desenvolvimento de sistemas de saúde resilientes por meio da implementação das quatro linhas de ação definidas na estratégia adotada pelos Estados Membros da Organização Pan-Americana da Saúde em setembro de 2021. A transformação dos sistemas de saúde deve se basear na adoção de um modelo integral de atenção primária à saúde; na priorização das funções essenciais de saúde pública; no fortalecimento de redes integrais de serviços de saúde; e no aumento do financiamento público, especialmente para o primeiro nível de atenção. A implementação dessas linhas de ação busca não apenas consolidar a resposta imediata à crise, mas também enquadrá-la nos esforços de recuperação e desenvolvimento sustentável dos sistemas de saúde, reduzindo suas vulnerabilidades estruturais para que fiquem mais bem preparados para responder a futuras crises.

Recomendaciones para el desarrollo de sistemas de salud resilientes en las Américas

[RESUMEN]. En este artículo de opinión y análisis se describen las líneas de acción estratégicas para desarrollar siste- mas de salud resilientes y al mismo tiempo promover la recuperación en la etapa posterior a la pandemia de COVID-19, a fin de mantener y proteger los logros de la salud pública. Asimismo, se presenta una contextuali- zación de los desafíos y oportunidades en la Región de las Américas, y se ofrecen recomendaciones para su implementación. Urge impulsar el desarrollo de sistemas de salud resilientes a través de la implementación de cuatro líneas de acción definidas en la Estrategia adoptada por los Estados Miembros de la Organización Panamericana de la Salud en septiembre de 2021. La transformación de los sistemas de salud debe basarse en la adopción de un modelo integral de atención primaria de la salud, un enfoque priorizado sobre las funciones esenciales de salud pública, el fortalecimiento de las redes integrales de servicios de salud, y el aumento en el financiamiento público, sobre todo para el primer nivel de atención. La implementación de estas líneas de acción no solo busca consolidar la respuesta inmediata a las crisis, sino también enmarcarla en los esfuerzos de recuperación y desarrollo sostenible de los sistemas de salud, reduciendo sus vulnerabi- lidades estructurales y así poder estar mejor preparados para responder a futuras crisis.

[ABSTRACT]. This article offers opinion and analysis outlining strategic lines of action to build resilient health systems while promoting recovery in the post-COVID-19 pandemic period, with a view to maintaining and protecting public health gains. It contextualizes the challenges and opportunities in the Region of the Americas and offers recommendations for implementation of the strategic lines. It is urgent to promote the development of resilient health systems through the implementation of four lines of action defined in the strategy adopted by the Member States of the Pan American Health Organization in Sep- tember 2021. The transformation of health systems must be based on the adoption of an integrated model of primary health care, a priority focus on the essential public health functions, strengthening of integrated health service networks, and increased public funding, especially for the first level of care. Implementation of these lines of action is focused not only on consolidating immediate crisis response; it is also framed within efforts toward the recovery and sustainable development of health systems, reducing their structural vulnerabilities to better prepare the response to future crises.

[RESUMO]. Este artigo de opinião e análise descreve linhas de ação estratégicas para desenvolver sistemas de saúde resilientes ao mesmo tempo em que se promove a recuperação pós-pandemia de COVID-19 a fim de manter e proteger os ganhos em saúde pública. Além disso, apresenta uma contextualização dos desafios e oportu- nidades na região das Américas e oferece recomendações para sua implementação. Há uma necessidade urgente de promover o desenvolvimento de sistemas de saúde resilientes por meio da implementação das quatro linhas de ação definidas na estratégia adotada pelos Estados Membros da Organização Pan-Ameri- cana da Saúde em setembro de 2021. A transformação dos sistemas de saúde deve se basear na adoção de um modelo integral de atenção primária à saúde; na priorização das funções essenciais de saúde pública; no fortalecimento de redes integrais de serviços de saúde; e no aumento do financiamento público, espe- cialmente para o primeiro nível de atenção. A implementação dessas linhas de ação busca não apenas consolidar a resposta imediata à crise, mas também enquadrá-la nos esforços de recuperação e desenvolvi- mento sustentável dos sistemas de saúde, reduzindo suas vulnerabilidades estruturais para que fiquem mais bem preparados para responder a futuras crises.

Mindfulness-Based Group Therapy for Chronic Pain Management in Older Adults.

OBJECTIVES: There were two quality improvement goals for this project: (1) to evaluate the outcomes of an 8-week geriatric-focused mindfulness-based group therapy program for chronic pain management called "Mindfulness-based Chronic Pain Care" offered at a senior community center affiliated with a geriatric primary care clinic, and (2) to obtain feedback from participants to make relevant modifications for future groups. METHODS: The program consisted of eight 150-minute weekly sessions. Thirteen community-dwelling older adults aged 60 and older participated in the program. The study utilized a non-randomized control-group pretest-posttest design. Participants completed pre- and post-program evaluations measuring pain and related psychosocial outcomes and were also asked to evaluate the importance of the group. Intervention and control groups were compared by t-test, chi-square likelihood ratio, Fischer's exact test, and multivariate analysis of variance with repeated measures. RESULTS: There were statistically significant improvements in three areas: 1) increased activity level, 2) increased "pain willingness," and 3) decreased generalized anxiety symptoms. Qualitative analysis highlighted how this intervention was important to participants. CONCLUSIONS: The results of this pilot program indicate promising outcomes for older adults suffering from chronic pain. CLINICAL IMPLICATIONS: The Mindfulness-based Chronic Pain Care program was a practical, feasible, and acceptable approach for pain management among program participants.

Identifying access barriers faced by rural and dispersed communities to better address their needs: implications and lessons learned for rural proofing for health in the Americas and beyond.

INTRODUCTION: Universal access to health services and universal health coverage are needed to achieve good health for all, yet rural communities face a variety of access barriers. As part of an effort to 'rural proof' health systems, it is therefore imperative to identify and act on the factors limiting access to health services by rural and indigenous communities. This article provides a comprehensive overview of the wide range of access barriers faced by rural and remote communities in two countries where barrier assessments were conducted. It also discusses the potential for barrier assessments to contribute evidence for rural proofing of national health policies, strategies, plans and programs. METHODS: The study applied a concurrent triangulation design to collect and analyze data obtained from narrative-style literature reviews, in-depth interviews with local health authorities, and secondary analyses of existing household data on Guyana and Peru. These two countries were selected because they have some of the largest rural and indigenous populations in Latin America and the Caribbean, and have national policies in place for providing free, essential health services for these communities. Both quantitative and qualitative data were collected separately, and results were interpreted together. The main objective was to corroborate and cross-validate findings looking for convergence between the separate data analyses. RESULTS: Seven dominant themes were identified across the two countries: use of traditional medicine and practice; decision making, gender, and family power dynamics; ethnicity and trust; knowledge and health literacy; geographic accessibility, health personnel and intercultural skills; and financial accessibility. The findings suggest that the interaction between these barriers may be as important as the singular role played by each factor, thereby highlighting the complex and multifactorial nature of accessing services in rural settings. Issues with limited availability of human resources for health were compounded by inadequate supplies and infrastructure. Financial barriers were often linked to the indirect costs of transport and geographic location, and further exacerbated by reduced socioeconomic status of rural communities, a majority of which are indigenous and have a strong preference for traditional medicines. Importantly, rural and indigenous communities experience considerable non-financial barriers related to issues of acceptability, which requires adaptation of health personnel and health service delivery models to the context-specific needs and realities of each rural community. CONCLUSION: This study presented an approach for data collection and analysis that is both feasible and effective for evaluating access barriers in rural and remote communities. While this study explored access barriers through general health services in two rural settings, the issues identified reflect the structural deficiencies of many health systems. These challenges and singularities require adaptive organizational models for the provision of health services that respond to the specific characteristics of rural and indigenous communities. This study indicates the potential relevance of conducting assessments of barriers to health services as part of a wider approach to rural proofing and supports the notion that a mixed-methods approach, linking secondary analysis of existing relevant national survey data with focused key-informant interview data, may be an effective and efficient way to transform data into the knowledge policymakers need to rural proof health policies.

Recomendaciones para el desarrollo de sistemas de salud resilientes en las Américas / Recommendations for the development of resilient health systems in the Americas / Recomendações para o desenvolvimento de sistemas de saúde resilientes nas Américas

RESUMEN En este artículo de opinión y análisis se describen las líneas de acción estratégicas para desarrollar sistemas de salud resilientes y al mismo tiempo promover la recuperación en la etapa posterior a la pandemia de COVID-19, a fin de mantener y proteger los logros de la salud pública. Asimismo, se presenta una contextualización de los desafíos y oportunidades en la Región de las Américas, y se ofrecen recomendaciones para su implementación. Urge impulsar el desarrollo de sistemas de salud resilientes a través de la implementación de cuatro líneas de acción definidas en la Estrategia adoptada por los Estados Miembros de la Organización Panamericana de la Salud en septiembre de 2021. La transformación de los sistemas de salud debe basarse en la adopción de un modelo integral de atención primaria de la salud, un enfoque priorizado sobre las funciones esenciales de salud pública, el fortalecimiento de las redes integrales de servicios de salud, y el aumento en el financiamiento público, sobre todo para el primer nivel de atención. La implementación de estas líneas de acción no solo busca consolidar la respuesta inmediata a las crisis, sino también enmarcarla en los esfuerzos de recuperación y desarrollo sostenible de los sistemas de salud, reduciendo sus vulnerabilidades estructurales y así poder estar mejor preparados para responder a futuras crisis.

ABSTRACT This article offers opinion and analysis outlining strategic lines of action to build resilient health systems while promoting recovery in the post-COVID-19 pandemic period, with a view to maintaining and protecting public health gains. It contextualizes the challenges and opportunities in the Region of the Americas and offers recommendations for implementation of the strategic lines. It is urgent to promote the development of resilient health systems through the implementation of four lines of action defined in the strategy adopted by the Member States of the Pan American Health Organization in September 2021. The transformation of health systems must be based on the adoption of an integrated model of primary health care, a priority focus on the essential public health functions, strengthening of integrated health service networks, and increased public funding, especially for the first level of care. Implementation of these lines of action is focused not only on consolidating immediate crisis response; it is also framed within efforts toward the recovery and sustainable development of health systems, reducing their structural vulnerabilities to better prepare the response to future crises.

RESUMO Este artigo de opinião e análise descreve linhas de ação estratégicas para desenvolver sistemas de saúde resilientes ao mesmo tempo em que se promove a recuperação pós-pandemia de COVID-19 a fim de manter e proteger os ganhos em saúde pública. Além disso, apresenta uma contextualização dos desafios e oportunidades na região das Américas e oferece recomendações para sua implementação. Há uma necessidade urgente de promover o desenvolvimento de sistemas de saúde resilientes por meio da implementação das quatro linhas de ação definidas na estratégia adotada pelos Estados Membros da Organização Pan-Americana da Saúde em setembro de 2021. A transformação dos sistemas de saúde deve se basear na adoção de um modelo integral de atenção primária à saúde; na priorização das funções essenciais de saúde pública; no fortalecimento de redes integrais de serviços de saúde; e no aumento do financiamento público, especialmente para o primeiro nível de atenção. A implementação dessas linhas de ação busca não apenas consolidar a resposta imediata à crise, mas também enquadrá-la nos esforços de recuperação e desenvolvimento sustentável dos sistemas de saúde, reduzindo suas vulnerabilidades estruturais para que fiquem mais bem preparados para responder a futuras crises.

The Neurostimulation Appropriateness Consensus Committee (NACC): Recommendations on Best Practices for Cervical Neurostimulation.

INTRODUCTION: The International Neuromodulation Society convened a multispecialty group of physicians based on expertise with international representation to establish evidence-based guidance on the use of neurostimulation in the cervical region to improve outcomes. This Neurostimulation Appropriateness Consensus Committee (NACC) project intends to provide evidence-based guidance for an often-overlooked area of neurostimulation practice. MATERIALS AND METHODS: Authors were chosen based upon their clinical expertise, familiarity with the peer-reviewed literature, research productivity, and contributions to the neuromodulation literature. Section leaders supervised literature searches of MEDLINE, BioMed Central, Current Contents Connect, Embase, International Pharmaceutical Abstracts, Web of Science, Google Scholar, and PubMed from 2017 (when NACC last published guidelines) to the present. Identified studies were graded using the US Preventive Services Task Force criteria for evidence and certainty of net benefit. Recommendations are based on the strength of evidence or consensus when evidence was scant. RESULTS: The NACC examined the published literature and established evidence- and consensus-based recommendations to guide best practices. Additional guidance will occur as new evidence is developed in future iterations of this process. CONCLUSIONS: The NACC recommends best practices regarding the use of cervical neuromodulation to improve safety and efficacy. The evidence- and consensus-based recommendations should be utilized as a guide to assist decision making when clinically appropriate.

Towards applying the essential public health functions for building health systems resilience: A renewed list and key enablers for operationalization.

The COVID-19 pandemic, climate change-related events, protracted conflicts, economic stressors and other health challenges, call for strong public health orientation and leadership in health system strengthening and policies. Applying the essential public health functions (EPHFs) represents a holistic operational approach to public health, which is considered to be an integrated, sustainable, and cost-effective means for supporting universal health coverage, health security and improved population health and wellbeing. As a core component of the Primary Health Care (PHC) Operational Framework, EPHFs also support the continuum of health services from health promotion and protection, disease prevention to treatment, rehabilitation, and palliative services. Comprehensive delivery of EPHFs through PHC-oriented health systems with multisectoral participation is therefore vital to meet population health needs, tackle public health threats and build resilience. In this perspective, we present a renewed EPHF list consisting of twelve functions as a reference to foster country-level operationalisation, based on available authoritative lists and global practices. EPHFs are presented as a conceptual bridge between prevailing siloed efforts in health systems and allied sectors. We also highlight key enablers to support effective implementation of EPHFs, including high-level political commitment, clear national structures for institutional stewardship on EPHFs, multisectoral accountability and systematic assessment. As countries seek to transform health systems in the context of recovery from COVID-19 and other public health emergencies, the renewed EPHF list and enablers can inform public health reform, PHC strengthening, and more integrated recovery efforts to build resilient health systems capable of managing complex health challenges for all people.

Burst Occipital Nerve Stimulation for Chronic Migraine and Chronic Cluster Headache.

BACKGROUND: Occipital nerve stimulation (ONS) is widely used for headache syndromes including chronic migraine (CM) and chronic cluster headache (CCH). The paraesthesia associated with tonic stimulation can be bothersome and can limit therapy. It is now clear in spinal cord stimulation that paraesthesia-free waveforms can produce effective analgesia, but this has not been reported in ONS for CM or CCH. MATERIALS AND METHODS: Seventeen patients (12 CM and 5 CCH) were treated with bilateral burst pattern ONS, including 4 who had previously had tonic ONS. Results were assessed in terms of the frequency of headaches (number of headache days per month for CM, and number of attacks per day for CCH) and their intensity on the numeric pain rating scale. RESULTS: Burst ONS produced a statistically significant mean reduction of 10.2 headache days per month in CM. In CCH, there were significant mean reductions in headache frequency (92%) and intensity (42%). CONCLUSION: Paraesthesia is not necessary for good quality analgesia in ONS. Larger studies will be required to determine whether the efficacies of the two stimulation modes differ. Burst ONS is imperceptible and therefore potentially amenable to robustly blinded clinical trials.

Burst or Conventional Peripheral Nerve Field Stimulation for Treatment of Neuropathic Facial Pain.

BACKGROUND: Trigeminal Neuropathic Pain (TNP) is a chronic facial pain syndrome caused by a lesion or disease affecting one or more branches of the trigeminal nerve. It may, for example, result from accidental injury to a branch of the trigeminal nerve by trauma or during surgery; it may also be idiopathic. TNP is typically constant, in contrast to most cases of the commoner trigeminal neuralgia. In some cases, pain may be refractory to pharmacological treatment. Peripheral nerve field stimulation is recognized as an effective minimally invasive surgical treatment option for this debilitating condition. To date, stimulation has used conventional tonic waveforms, which generate paraesthesia in the stimulated area. This is the first report of the use of paraesthesia-free burst pattern stimulation for TNP. METHODS: Seven patients were treated at the John Radcliffe Hospital for TNP from 2016 to 2018. Mean duration of preoperative symptoms was five years. All patients had exhausted pharmacological measures to limited effect. The initial three patients had tonic stimulation with the subsequent four having burst stimulation. Outcome was assessed using the numeric pain rating scale preoperatively and postoperatively at three and six months and one year. Side-effects and complications were also assessed as well as reduction in analgesic medication use. RESULTS: All patients achieved pain reduction of at least 50% at 6 months (range 50-100%, mean 81%, p = 0.0082). Those in the burst stimulation group were paraesthesia free. One patient developed a postoperative infection for which the system had to be removed and is awaiting reimplantation. There were no other complications in either group. CONCLUSION: Burst stimulation conferred similar pain control to tonic stimulation in our small cohort, and there were similar reductions in pain medication use. An additional benefit of burst stimulation is freedom from paraesthesia. Larger scale studies are needed to further evaluate burst stimulation and compare its efficacy with that of tonic stimulation.

The Neuromodulation Appropriateness Consensus Committee on Best Practices for Dorsal Root Ganglion Stimulation.

INTRODUCTION: The Neuromodulation Appropriateness Consensus Committee (NACC) is dedicated to improving the safety and efficacy of neuromodulation and thus improving the lives of patients undergoing neuromodulation therapies. With continued innovations in neuromodulation comes the need for evolving reviews of best practices. Dorsal root ganglion (DRG) stimulation has significantly improved the treatment of complex regional pain syndrome (CRPS), among other conditions. Through funding and organizational leadership by the International Neuromodulation Society (INS), the NACC reconvened to develop the best practices consensus document for the selection, implantation and use of DRG stimulation for the treatment of chronic pain syndromes. METHODS: The NACC performed a comprehensive literature search of articles about DRG published from 1995 through June, 2017. A total of 2538 article abstracts were then reviewed, and selected articles graded for strength of evidence based on scoring criteria established by the US Preventive Services Task Force. Graded evidence was considered along with clinical experience to create the best practices consensus and recommendations. RESULTS: The NACC achieved consensus based on peer-reviewed literature and experience to create consensus points to improve patient selection, guide surgical methods, improve post-operative care, and make recommendations for management of patients treated with DRG stimulation. CONCLUSION: The NACC recommendations are intended to improve patient care in the use of this evolving therapy for chronic pain. Clinicians who choose to follow these recommendations may improve outcomes.

The Efficacy and Safety of Dorsal Root Ganglion Stimulation as a Treatment for Neuropathic Pain: A Literature Review.

OBJECTIVE: Dorsal root ganglion stimulation (DRGS) received its first regulatory approval (CE marking in Europe) in late 2011, and so its use is now almost six years old. Several thousand patients have already been treated, and a landmark trial in lower limb complex regional pain syndrome (CRPS) and causalgia has recently been published. METHODS: In this review we have summarized the literature to date on the use of DRGS in the treatment of neuropathic pain. RESULTS: The results so far are encouraging, with reports of successful use in treating a wide range of indications including postsurgical pain, CRPS, and phantom pain. Treatment of failed back surgery syndrome (FBSS) appears less successful. The therapy is still young, and long term results are not yet available. There is now good randomized clinical trial (RCT) evidence that DRGS provides superior pain relief to spinal cord stimulation for CRPS and causalgia of the lower limb, and produces stimulation that is more posturally stable, with more precise paraesthesia coverage. However evidence of this quality for other indications and pain locations is lacking. CONCLUSION: There is now Class A RCT evidence that DRGS provides superior pain relief to SCS for CRPS and causalgia of the lower limb. In the coming years we hope that randomized controlled trials will be performed on an indication-by-indication basis, which, together with the publication of longer term follow-up data, will provide a more complete understanding of the role of DRGS in the treatment of neuropathic pain syndromes.

Oscillatory neural representations in the sensory thalamus predict neuropathic pain relief by deep brain stimulation.

OBJECTIVE: Understanding the function of sensory thalamic neural activity is essential for developing and improving interventions for neuropathic pain. However, there is a lack of investigation of the relationship between sensory thalamic oscillations and pain relief in patients with neuropathic pain. This study aims to identify the oscillatory neural characteristics correlated with pain relief induced by deep brain stimulation (DBS), and develop a quantitative model to predict pain relief by integrating characteristic measures of the neural oscillations. APPROACH: Measures of sensory thalamic local field potentials (LFPs) in thirteen patients with neuropathic pain were screened in three dimensional feature space according to the rhythm, balancing, and coupling neural behaviours, and correlated with pain relief. An integrated approach based on principal component analysis (PCA) and multiple regression analysis is proposed to integrate the multiple measures and provide a predictive model. MAIN RESULTS: This study reveals distinct thalamic rhythms of theta, alpha, high beta and high gamma oscillations correlating with pain relief. The balancing and coupling measures between these neural oscillations were also significantly correlated with pain relief. SIGNIFICANCE: The study enriches the series research on the function of thalamic neural oscillations in neuropathic pain and relief, and provides a quantitative approach for predicting pain relief by DBS using thalamic neural oscillations.

Mindfulness-based forgiveness groups for older adults.

Interventions that enable individuals to be more forgiving toward themselves and others are important for older adults. This article describes a group intervention for adults aged 60 or older that integrates forgiveness-related skills with a mindfulness approach. The Mindfulness-based Forgiveness Group was designed to meet for eight sessions. The skills taught included: recognizing one's own expectations and unenforceable rules, broadening one's perspectives about the context of the transgression, and discovering positive intentions through exercises as well as a variety of meditations to cultivate mindfulness, self-compassion and forgiveness. Data from five Mindfulness-Based Forgiveness Groups were collected. Based on pre- and post-test measures, analyses indicate that participants improved significantly in relation to forgiveness, mindfulness/self-compassion, and mental health. Using qualitative post-test data from participants, we identify elements of the intervention that appear to be helpful. Suggestions are provided for social workers seeking to replicate and build upon this promising intervention.

Stimulating at the right time: phase-specific deep brain stimulation.

SEE MOLL AND ENGEL DOI101093/AWW308 FOR A SCIENTIFIC COMMENTARY ON THIS ARTICLE: Brain regions dynamically engage and disengage with one another to execute everyday actions from movement to decision making. Pathologies such as Parkinson's disease and tremor emerge when brain regions controlling movement cannot readily decouple, compromising motor function. Here, we propose a novel stimulation strategy that selectively regulates neural synchrony through phase-specific stimulation. We demonstrate for the first time the therapeutic potential of such a stimulation strategy for the treatment of patients with pathological tremor. Symptom suppression is achieved by delivering stimulation to the ventrolateral thalamus, timed according to the patient's tremor rhythm. Sustained locking of deep brain stimulation to a particular phase of tremor afforded clinically significant tremor relief (up to 87% tremor suppression) in selected patients with essential tremor despite delivering less than half the energy of conventional high frequency stimulation. Phase-specific stimulation efficacy depended on the resonant characteristics of the underlying tremor network. Selective regulation of neural synchrony through phase-locked stimulation has the potential to both increase the efficiency of therapy and to minimize stimulation-induced side effects.

Successful treatment of pelvic girdle pain with dorsal root ganglion stimulation.

The authors report the first case of successful implantation of a dorsal root ganglion stimulator at L1 and L2 for sustained improvement in chronic pelvic girdle pain.

Tractography Study of Deep Brain Stimulation of the Anterior Cingulate Cortex in Chronic Pain: Key to Improve the Targeting.

BACKGROUND: Deep brain stimulation (DBS) of the anterior cingulate cortex (ACC) is a new treatment for alleviating intractable neuropathic pain. However, it fails to help some patients. The large size of the ACC and the intersubject variability make it difficult to determine the optimal site to position DBS electrodes. The aim of this work was therefore to compare the ACC connectivity of patients with successful versus unsuccessful DBS outcomes to help guide future electrode placement. METHODS: Diffusion magnetic resonance imaging (dMRI) and probabilistic tractography were performed preoperatively in 8 chronic pain patients (age 53.4 ± 6.1 years, 2 females) with ACC DBS, of whom 6 had successful (SO) and 2 unsuccessful outcomes (UOs) during a period of trialing. RESULTS: The number of patients was too small to demonstrate any statistically significant differences. Nevertheless, we observed differences between patients with successful and unsuccessful outcomes in the fiber tract projections emanating from the volume of activated tissue around the electrodes. A strong connectivity to the precuneus area seems to predict unsuccessful outcomes in our patients (UO: 160n/SO: 27n), with (n), the number of streamlines per nonzero voxel. On the other hand, connectivity to the thalamus and brainstem through the medial forebrain bundle (MFB) was only observed in SO patients. CONCLUSIONS: These findings could help improve presurgical planning by optimizing electrode placement, to selectively target the tracts that help to relieve patients' pain and to avoid those leading to unwanted effects.

The nature of tremor circuits in parkinsonian and essential tremor.

Tremor is a cardinal feature of Parkinson's disease and essential tremor, the two most common movement disorders. Yet, the mechanisms underlying tremor generation remain largely unknown. We hypothesized that driving deep brain stimulation electrodes at a frequency closely matching the patient's own tremor frequency should interact with neural activity responsible for tremor, and that the effect of stimulation on tremor should reveal the role of different deep brain stimulation targets in tremor generation. Moreover, tremor responses to stimulation might reveal pathophysiological differences between parkinsonian and essential tremor circuits. Accordingly, we stimulated 15 patients with Parkinson's disease with either thalamic or subthalamic electrodes (13 male and two female patients, age: 50-77 years) and 10 patients with essential tremor with thalamic electrodes (nine male and one female patients, age: 34-74 years). Stimulation at near-to tremor frequency entrained tremor in all three patient groups (ventrolateral thalamic stimulation in Parkinson's disease, P=0.0078, subthalamic stimulation in Parkinson's disease, P=0.0312; ventrolateral thalamic stimulation in essential tremor, P=0.0137; two-tailed paired Wilcoxon signed-rank tests). However, only ventrolateral thalamic stimulation in essential tremor modulated postural tremor amplitude according to the timing of stimulation pulses with respect to the tremor cycle (e.g. P=0.0002 for tremor amplification, two-tailed Wilcoxon rank sum test). Parkinsonian rest and essential postural tremor severity (i.e. tremor amplitude) differed in their relative tolerance to spontaneous changes in tremor frequency when stimulation was not applied. Specifically, the amplitude of parkinsonian rest tremor remained unchanged despite spontaneous changes in tremor frequency, whereas that of essential postural tremor reduced when tremor frequency departed from median values. Based on these results we conclude that parkinsonian rest tremor is driven by a neural network, which includes the subthalamic nucleus and ventrolateral thalamus and has broad frequency-amplitude tolerance. We propose that it is this tolerance to changes in tremor frequency that dictates that parkinsonian rest tremor may be significantly entrained by low frequency stimulation without stimulation timing-dependent amplitude modulation. In contrast, the circuit influenced by low frequency thalamic stimulation in essential tremor has a narrower frequency-amplitude tolerance so that tremor entrainment through extrinsic driving is necessarily accompanied by amplitude modulation. Such differences in parkinsonian rest and essential tremor will be important in selecting future strategies for closed loop deep brain stimulation for tremor control.

Phase dependent modulation of tremor amplitude in essential tremor through thalamic stimulation.

High frequency deep brain stimulation of the thalamus can help ameliorate severe essential tremor. Here we explore how the efficacy, efficiency and selectivity of thalamic deep brain stimulation might be improved in this condition. We started from the hypothesis that the effects of electrical stimulation on essential tremor may be phase dependent, and that, in particular, there are tremor phases at which stimuli preferentially lead to a reduction in the amplitude of tremor. The latter could be exploited to improve deep brain stimulation, particularly if tremor suppression could be reinforced by cumulative effects. Accordingly, we stimulated 10 patients with essential tremor and thalamic electrodes, while recording tremor amplitude and phase. Stimulation near the postural tremor frequency entrained tremor. Tremor amplitude was also modulated depending on the phase at which stimulation pulses were delivered in the tremor cycle. Stimuli in one half of the tremor cycle reduced median tremor amplitude by ∼10%, while those in the opposite half of the tremor cycle increased tremor amplitude by a similar amount. At optimal phase alignment tremor suppression reached 27%. Moreover, tremor amplitude showed a non-linear increase in the degree of suppression with successive stimuli; tremor suppression was increased threefold if a stimulus was preceded by four stimuli with a similar phase relationship with respect to the tremor, suggesting cumulative, possibly plastic, effects. The present results pave the way for a stimulation system that tracks tremor phase to control when deep brain stimulation pulses are delivered to treat essential tremor. This would allow treatment effects to be maximized by focussing stimulation on the optimal phase for suppression and by ensuring that this is repeated over many cycles so as to harness cumulative effects. Such a system might potentially achieve tremor control with far less power demand and greater specificity than current high frequency stimulation approaches, and may lower the risk for tolerance and rebound.

Zinc decreases C-reactive protein, lipid peroxidation, and inflammatory cytokines in elderly subjects: a potential implication of zinc as an atheroprotective agent.

BACKGROUND: Chronic inflammation and oxidative stress are common risk factors for atherosclerosis. Zinc is an essential micronutrient that can function as an antiinflammatory and antioxidative agent, and as such, it may have atheroprotective properties. OBJECTIVE: We hypothesized that zinc down-regulates the production of atherosclerosis-related cytokines/molecules in humans. DESIGN: To examine these effects, we conducted a randomized, double-blinded, placebo trial of zinc supplementation in elderly subjects. We recruited 40 healthy elderly subjects (aged 56-83 y) and randomly assigned them to 2 groups. One group was given an oral dose of 45 mg zinc/d as a gluconate for 6 mo. The other group was given a placebo. Cell culture models were conducted to study the mechanism of zinc as an atheroprotective agent. RESULTS: After 6 mo of supplementation, the intake of zinc, compared with intake of placebo, increased the concentrations of plasma zinc and decreased the concentrations of plasma high-sensitivity C-reactive protein (hsCRP), interleukin (IL)-6, macrophage chemoattractant protein 1 (MCP-1), vascular cell adhesion molecule 1 (VCAM-1), secretory phospholipase A2, and malondialdehyde and hydroxyalkenals (MDA+HAE) in elderly subjects. Regression analysis showed that changes in concentrations of plasma zinc were inversely associated with changes in concentrations of plasma hsCRP, MCP-1, VCAM-1, and MDA+HAE after 6 mo of supplementation. In cell culture studies, we showed that zinc decreased the generation of tumor necrosis factor-alpha, IL-1beta, VCAM-1, and MDA+HAE and the activation of nuclear transcription factor kappaB and increased antiinflammatory proteins A20 and peroxisome proliferator-activated receptor-alpha in human monocytic leukemia THP-1 cells and human aortic endothelial cells compared with zinc-deficient cells. CONCLUSION: These findings suggest that zinc may have a protective effect in atherosclerosis because of its antiinflammatory and antioxidant functions.