The state of primary health care in south Asia.

The south Asian region (SAR) is home to 1·74 billion people, corresponding to 22% of the global population. The region faces several challenges pertaining to changing epidemiology, rapid urbanisation, and social and economic concerns, which affect health outcomes. Primary health care (PHC) is a cost-effective strategy to respond to these challenges through integrated service delivery, multi-sectoral action, and empowered communities. The PHC approach has historically been an important cornerstone of health policy in SAR countries. However, the region is yet to fully reap the benefits of PHC-oriented health systems. Our introductory paper in this Lancet Series on PHC in the SAR describes the existing PHC delivery structure in five SAR nations (ie, Bangladesh, India, Nepal, Pakistan, and Sri Lanka) and critically appraises PHC performance to identify its enablers and barriers. The paper proposes investing in a shared culture of innovation and collaboration for revitalisation of PHC in the region.

Improving urban health through primary health care in south Asia.

South Asia is rapidly urbanising. The strains of rapid urbanisation have profound implications for the health and equity of urban populations. This Series paper examines primary health care (PHC) in south Asian cities. Health and its social determinants vary considerably across south Asian cities and substantial socioeconomic inequities are present. Although cities offer easy geographical access to PHC services, financial hardship associated with health care use and low quality of care are a concern, particularly for low-income residents. Providing better PHC in south Asia requires a multi-sectoral response, with effective and resourced urban local bodies; increased public financing for health care; and new service delivery models aimed at low-income urban communities that involve strengthening public sector services, strengthening government engagement with private providers where necessary, and engaging with low-income communities and the PHC providers that serve them.

Copper nanoparticles loaded gelatin/ polyvinyl alcohol/ guar gum-based 3D printable multimaterial hydrogel for tissue engineering applications.

Hydrogels are becoming increasingly significant in tissue engineering because of their numerous benefits, including biocompatibility, biodegradability, and their ability to provide a supportive structure for cell proliferation. This study presents the synthesis and characterization of a new multimaterial hydrogel with 3D-printing capabilities composed of copper nanoparticle-reinforced gelatin, polyvinyl alcohol (PVA), and guar gum-based biomaterials intended for tissue engineering applications. Combining CuNPs aims to enhance the hydrogel's antibacterial properties, mechanical strength, and bioactivity, which are essential for successful tissue regeneration. Hydrogels are chemically cross-linked with glyoxal and analyzed through different assessments to examine the compressive behavior, surface morphology, sorbing capacity, biocompatibility, thermal stability, and degradation properties. The results demonstrated that including CuNPs significantly improved the hydrogel's compressive modulus (4.18 MPa) for the hydrogel with the CuNPs and provided better antibacterial activity against common pathogens with controlled degradation. All the hydrogels exhibited a lower coefficient of friction, which was below 0.1. In vitro cell culture studies using chondrocytes indicated that the CuNPs-loaded hydrogel supported cell proliferation and growth of chondrogenic genes such as collagen type II (COL2) and aggrecan (ACAN). The biocompatibility and enhanced mechanical properties of the multimaterial hydrogel make it a promising candidate for developing customized, patient-specific tissue engineering scaffolds.

Diltiazem Hydrochloride Floating Matrix Tablet: Formulation and in vitro-in vivo Evaluation.

BACKGROUND: Diltiazem hydrochloride is a calcium channel-blocker with a plasma elimination half-life of 4.4 ± 1.3 h and has a narrow absorption window. So, this work aimed to prepare a gastro-retentive floating matrix tablet. METHODS: The direct compression method was used to manufacture tablets. 32 factorial design was applied for optimization, taking Hydroxypropyl Methylcellulose K100M (HPMC K 100M) and the amount of sodium bicarbonate as independent factors and cumulative percentage release at 1 h, at 6 h, and at 12 h and floating lag time as dependent variables. RESULTS: The high amount of HPMC K100M and sodium bicarbonate shows good results. The optimized preparation was evaluated for differential scanning calorimetry, in-vivo gastric retention in male albino rabbits, kinetic modeling, and stability study. An in vivo study revealed gastric retention of tablets up to 6 h in healthy male Albino rabbits. The stability study indicated no significant change in the buoyancy and release profiles of the drug. CONCLUSION: From this study, it can be concluded that the gastro-retentive diltiazem hydrochloride floating matrix tablet was successfully prepared and retained inside the rabbit stomach for up to 6 h and was stable under accelerated stability study.

Voting with their feet: Primary care provider choice and its implications for public sector primary care services in India.

Expanding networks of government primary health centers (PHCs) to bring health services closer to communities is a longstanding policy objective in LMICs. In pluralistic health systems, where public and private providers compete for patients, PHCs are often not the preferred source for care. This study analyzes the market for primary care services in the Indian state of Bihar to understand how choice of primary care provider is influenced by distance, cost and quality of care. This study is based on linked surveys of rural households, PHCs, and private primary care providers conducted in 2019 and 2020. Most rural residents lived in proximity to a primary care provider, though not a qualified one. Within a 5-km distance, 60% of villages had a PHC, 90% had an informal provider, 35% an Indian systems of medicine practitioner, and 10% a private MBBS doctor. Most patients sought care from informal providers irrespective of PHC distance; only 25% of patients living in the PHC's vicinity sought care there. Reducing distance to the PHC by 1 km marginally increased the likehood of the PHC being selected, and reduced the likelihood of private clinics being selected. Reducing patient's costs at PHCs increased the likelihood of the PHC being selected and reduced the likelihood of private clinics and private hospitals being selected. Improved clinical quality at PHCs had no effect on patient selection of PHCs, private clinics, or hospitals. Illness severity reduced the likelihood of PHCs or private clinics being selected, and increased the likelihood of private hospitals selected. Wealthier patients were marginally more likely to use PHCs, substantially more likely to use private hospitals, and less likely to use private clinics. Expanding PHC network coverage or improving their quality of care is not sufficient to make PHCs more relevant to local health needs. An orientation towards essential public health functions, as well as, a community-centered approach to the organization of primary health care system is necessary.

Evolutionary analysis reveals the origin of sodium coupling in glutamate transporters.

Secondary active membrane transporters harness the energy of ion gradients to concentrate their substrates. Homologous transporters evolved to couple transport to different ions in response to changing environments and needs. The bases of such diversification, and thus principles of ion coupling, are unexplored. Employing phylogenetics and ancestral protein reconstruction, we investigated sodium-coupled transport in prokaryotic glutamate transporters, a mechanism ubiquitous across life domains and critical to neurotransmitter recycling in humans. We found that the evolutionary transition from sodium-dependent to independent substrate binding to the transporter preceded changes in the coupling mechanism. Structural and functional experiments suggest that the transition entailed allosteric mutations, making sodium binding dispensable without affecting ion-binding sites. Allosteric tuning of transporters' energy landscapes might be a widespread route of their functional diversification.

ADVANCEMENTS IN MINIMALLY INVASIVE SURGERY: A COMPREHENSIVE ANALYSIS OF ROBOTIC SURGERY, ENDOSCOPIC TECHNIQUES, AND NATURAL ORIFICE TRANSLUMENAL ENDOSCOPIC SURGERY.

The term "Natural Orifice Transluminal Endoscopic Surgery" (NOTES) defines a surgical approach that leverages the body's natural orifices to access the abdominal cavity, presenting a patient-centric perspective by highlighting its potential to eliminate abdominal wall aggression, mitigate postoperative discomfort, and offer benefits comparable to laparoscopic surgery. This comprehensive paper aims to not only review the existing landscape of NOTES techniques but also to propose advancements in flexible tools augmenting established endoscopic platforms, while also exploring the revolutionary concept of robotic structures grounded in micromechatronics and communication technologies. The thorough analysis encompasses the assessment of advantages and limitations associated with flexible devices and robotic platforms, coupled with an in-depth evaluation of the current array of devices used in NOTES, informed by pertinent literature. The authors' comprehensive approach entails scrutinizing technological breakthroughs and offering viable solutions, fostering a comprehensive understanding. Furthermore, the study encompasses an exhaustive evaluation and juxtaposition of state-of-the-art NOTES devices, supplemented by a nuanced discourse on the merits and demerits of flexible devices and robotic platforms, with a focused emphasis on their inherent strengths and weaknesses. Within this context, the discourse extends to strategic suggestions aimed at refining extant designs and cultivating robust, dependable autonomous robotic platforms purpose-built for NOTES. This narrative encapsulates the multifaceted exploration of benefits, challenges, and potential remedies directed towards enhancing prevailing designs and forging a dependable foundation for the future of NOTES.

THE ROLE OF GENETICS IN DISEASE DIAGNOSIS AND TREATMENT MITOCHONDRIAL RESPIRATORY CHAIN DYSREGULATION IN GENOMIC MEDICINE.

Although mitochondrial DNA respiration circuit abnormalities are among the most common metabolic diseases to manifest in children, identification can be difficult due to their medical variability. Given the multisystem nature of the condition and its diverse and generalized manifestations, making a final diagnosis often takes a long time. Within this summary, they give an in-depth account of the physical signs of adolescent Mitochondrial Respiratory Chain Disorders (MRCDs),analyze the available diagnostics and treatment possibilities, and emphasize current developments in this field of study. During the discovery of fresh biomarkers and the development of next generation sequencing (NGS) technology, extensive research over the years has considerably enhanced the regularity that precise diagnoses are produced. Given the intricate nature of mitochondrial DNA biology and its double genomic investments, Sequencing has made significant progress in identifying the genetic basis of Mitochondrial Respiratory Chain Disorders (MRCDs). Research studies have been created employing a variety of various methods of therapy in an effort to shift the goal on therapy that is mainly curative to possibly having a positive impact on the natural course of the trouble. That's because there is gained a greater awareness of the underlying causes of this category of ailments.

Methamphetamine-associated catatonia: Case series and systematic review of the literature from 1943-2020.

BACKGROUND: Catatonia due to a general medical condition may result from a variety of causes, including substance intoxication and withdrawal. Stimulants are occasionally associated with catatonia, though there has been little investigation of methamphetamine's relationship to catatonia. Here we present 5 cases of catatonia associated with methamphetamine use and a systematic review of the associated literature from 1943 to 2020. METHODS: We performed a systematic review of the literature and present 5 cases of catatonia evaluated using the Bush-Francis Catatonia Rating Scale and KANNER catatonia rating scale. RESULTS: Methamphetamine use was associated with catatonia in a small number of cases in the literature. However, some of these reports included other possible etiologies. The patients in our case series met DSM-5 criteria for catatonia due to a general medical condition, with all reporting recent methamphetamine use and testing positive for amphetamines on urine drug screen. CONCLUSIONS: Given the ongoing rise in methamphetamine use in the United States, it is important that clinicians understand that methamphetamine use can be associated with catatonia. Patients with methamphetamine-associated catatonia may respond favorably to lorazepam and require shorter hospital stays than other catatonic patients. Lastly, methamphetamine-associated catatonia highlights how alteration in dopamine function and projections may be a critical neural mechanism underlying catatonia in general.

Is there an association between serum soluble interleukin-2 receptor levels and syndrome severity in persistent Complex Regional Pain Syndrome?

OBJECTIVE: A potentially useful biomarker for Complex Regional Pain Syndrome (CRPS) is the serum soluble interleukin-2 receptor (sIL-2R) level, which is a marker for T-cell activation. Elevated serum sIL-2R levels have been described in CRPS patients compared to healthy controls. In T-cell mediated inflammatory diseases such as sarcoidosis and rheumatoid arthritis, the serum sIL-2R levels correlate with disease severity. In this study, we investigate whether an association exists between serum sIL-2R levels in CRPS patients and CRPS severity. METHODS: A cross-sectional cohort study was conducted in a tertiary pain referral center in the Netherlands. Adult CRPS patients diagnosed by the IASP criteria were included between October 2018 until October 2022. The main study parameters were serum sIL-2R levels and the CRPS severity score. RESULTS: Fifty-three CRPS patients were included with a mean syndrome duration of 84 months (Q3 - Q1:180 - 48). The majority had persistent CRPS with a syndrome duration >1 year (n = 52, 98%). The median pain Numerical Rating Score (NRS) was 7 (Q3 - Q1: 8 - 5) and the mean CRPS severity score was 11 (SD ± 2.3). The median serum sIL-2R level was 330 U/mL (Q3 - Q1:451 - 256). No statistically significant correlation was observed between serum sIL-2R levels and the CRPS severity score (rs = 0.15, P = .28). CONCLUSIONS: Our findings suggest that serum sIL-2R levels cannot be used as a biomarker for syndrome severity in persistent CRPS (syndrome duration >1 year). Serial measurements of serum sIL-2R from early CRPS to persistent CRPS are needed to investigate whether serum sIL-2R levels can be used to monitor T-cell mediated inflammatory syndrome activity.

Environmentally Ultrasensitive Fluorine Probe to Resolve Protein Conformational Ensembles by 19F NMR and Cryo-EM.

Limited chemical shift dispersion represents a significant barrier to studying multistate equilibria of large membrane proteins by 19F NMR. We describe a novel monofluoroethyl 19F probe that dramatically increases the chemical shift dispersion. The improved conformational sensitivity and line shape enable the detection of previously unresolved states in one-dimensional (1D) 19F NMR spectra of a 134 kDa membrane transporter. Changes in the populations of these states in response to ligand binding, mutations, and temperature correlate with population changes of distinct conformations in structural ensembles determined by single-particle cryo-electron microscopy (cryo-EM). Thus, 19F NMR can guide sample preparation to discover and visualize novel conformational states and facilitate image analysis and three-dimensional (3D) classification.

Intermittent versus continuous esketamine infusions for long-term pain modulation in complex regional pain syndrome: protocol of a randomized controlled non-inferiority study (KetCRPS-2).

BACKGROUND: Complex regional pain syndrome (CRPS) is a chronic pain condition of an extremity. While achieving pain relief in CRPS is challenging, esketamine infusions can accomplish pain relief for several weeks post-infusion in a subgroup of CRPS patients. Unfortunately, CRPS esketamine protocols are very heterogeneous in advice on dosage, administration and treatment setting. Currently, no trials are available that study differences between intermittent and continuous esketamine infusions for CRPS. With the current situation of bed shortages, it is difficult to admit patients for several consecutive days for inpatient esketamine treatments. In this study, we investigate whether 6 intermittent outpatient esketamine treatments are not inferior to a continuous 6-day inpatient esketamine treatment in establishing pain relief. In addition, several secondary study parameters will be assessed in order to investigate mechanisms responsible for pain relief by esketamine infusions. Furthermore, the cost-effectiveness will be analyzed. METHODS: In this RCT, the primary objective is to demonstrate that an intermittent esketamine dosing regimen is non-inferior to a continuous esketamine dosing regimen at 3 months follow-up. We will include 60 adult CRPS patients. The inpatient treatment group receives a continuous intravenous esketamine infusion for 6 consecutive days. The outpatient treatment group receives a 6-hour intravenous esketamine infusion every 2 weeks for 3 months. Esketamine dose will be individually tailored and is started at 0.05 mg/kg/h and can be increased to a maximum of 0.2 mg/kg/h. Each patient will be followed for 6 months. The primary study parameter is perceived pain intensity, measured by an 11-point Numerical Rating Scale. Secondary study parameters are conditioned pain modulation, quantitative sensory testing, adverse events, thermography, blood inflammatory parameter, questionnaires about functionality, quality of life and mood and costs per patient. DISCUSSION: If our study reveals non-inferiority between intermittent and continuous esketamine infusions, these findings can be beneficial to increase the availability and flexibility of esketamine infusions through outpatient treatments. Furthermore, the costs of outpatient esketamine infusions could be lower than inpatient esketamine infusions. In addition, secondary parameters may predict response to esketamine treatment. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT05212571 , date of registration 01-28-2022. PROTOCOL VERSION: Version 3, February 2022.

Assessment and Comparison of Database Search Engines for Peptidomic Applications.

Protein database search engines are an integral component of mass spectrometry-based peptidomic analyses. Given the unique computational challenges of peptidomics, many factors must be taken into consideration when optimizing search engine selection, as each platform has different algorithms by which tandem mass spectra are scored for subsequent peptide identifications. In this study, four different database search engines, PEAKS, MS-GF+, OMSSA, and X! Tandem, were compared with Aplysia californica and Rattus norvegicus peptidomics data sets, and various metrics were assessed such as the number of unique peptide and neuropeptide identifications, and peptide length distributions. Given the tested conditions, PEAKS was found to have the highest number of peptide and neuropeptide identifications out of the four search engines in both data sets. Furthermore, principal component analysis and multivariate logistic regression were employed to determine whether specific spectral features contribute to false C-terminal amidation assignments by each search engine. From this analysis, it was found that the primary features influencing incorrect peptide assignments were the precursor and fragment ion m/z errors. Finally, an assessment employing a mixed species protein database was performed to evaluate search engine precision and sensitivity when searched against an enlarged search space containing human proteins.

Improving quality of non-communicable disease services at primary care facilities in middle-income countries: A scoping review.

Health systems in middle-income countries face important challenges in managing the high burden of Non-Communicable Diseases (NCD). Primary health care is widely recognized as key to managing NCDs in communities. However, the effectiveness of this approach is limited by poor quality of care (QoC), among others. This scoping review identifies the types of interventions that have been used in middle-income countries to improve the quality of NCD services at primary care facilities. Further, it identifies the range of outcomes these quality interventions have influenced. This scoping review covered both the grey and peer-reviewed literature. The 149 articles reviewed were classified into four domains - governance, service-delivery systems, health workforce, and patients and communities. There was a remarkable unevenness in the geographic distribution of studies - lower middle-income countries and some regions (Middle East, North Africa, and South East Asia) had a scarcity of published studies. NCDs such as stroke and cardiovascular disease, mental health, cancer, and respiratory disorders received less attention. The thrust of quality interventions was directed at the practice of NCD care by clinicians, facilities, or patients. Few studies provided evidence from interventions at the organizations or policy levels. Overall, effectiveness of quality interventions was mixed across domains. In general, positive or mixed effects on provider clinical skills and behavior, as well as, improvements in patient outcomes were found across interventions. Access to care and coverage of screening services were positively influenced by the interventions reviewed. This review shows that quality improvement interventions tried in middle-income countries mostly focused at the provider and facility level, with few focusing on the organizational and policy level. There is a need to further study the effectiveness of organizational and policy level interventions on the practice and outcomes of NCD care.

Systemic Colonization of Potato Plants by Verticillium dahliae Leads to Infection of Tubers and Sprouting Buds.

A green fluorescent protein (GFP)-tagged isolate of Verticillium dahliae was used to study its colonization in potato plants and tubers. Three-week-old potato plants of the highly susceptible cultivar 'Shepody' were inoculated with a conidial suspension of a GFP-tagged isolate of V. dahliae using a wound inoculation method. Colonization was studied using confocal microscopy combined with tissue sections. Conidia germinated and hyphae grew along the root hairs, elongation zones, and root caps between 24 and 96 h postinoculation (HPI). At 7 days postinoculation (DPI), the pathogen advanced to cortical tissues and grew into the root vascular bundles. At 8 weeks postinoculation (WPI), the stem epidermal cells, cortical tissues, vascular elements, and petioles were fully colonized by the mycelium of V. dahliae. At 11 WPI, the pathogen was detected in the stolon and progeny tubers, as confirmed by both GFP signals in tissues and reisolation of the pathogen on the semiselective NP-10 medium. Progeny potato tubers were harvested from the inoculated potato plants, and the GFP-signal was observed in the epidermal cells and vascular elements of sprouting buds that emerged from the harvested tubers. The infection rate of progeny tubers detected on semiselective NP-10 medium ranged from 34.55 to 55.56%, with an average of 45.31%. In conclusion, we report, for the first time, the entire progression of colonization by V. dahliae in potato plant tissues, progeny tubers, as well as of the sprouting buds that emerged from progeny tubers.

Incontinence as a catatonic sign.

BACKGROUND: Incontinence (urinary or fecal) is not included in DSM-5 criteria for catatonia or in most catatonia rating scales. However, there is a historical basis for the inclusion or consideration of incontinence as a catatonic sign. METHODS: We performed a review of the literature and found references to urinary disturbances and fecal incontinence in 19th- and 20th-century literature. We did a computerized literature review using the terms "catatonia," "catatonic," and "incontinence." RESULTS: We highlight 2 cases in which urinary or fecal incontinence was a presenting or predominant feature of catatonia. Clinical improvement was associated with improvement in incontinence. CONCLUSIONS: These preliminary findings suggest that urinary and fecal incontinence may be an uncommon presentation of catatonia. Furthermore, incontinence may improve at the same time catatonia improves with treatment. The neural circuitry that controls micturition and the sphincter involves neural pathways and multiple neurotransmitters. Catatonia can cause a reemergence of involuntary or reflex maturation, leading to urinary incontinence. This may lead to the need for additional custodial care for patients. Thus, the detection and monitoring of urinary and fecal incontinence may help us better understand the pathophysiology and impairment associated with catatonia.

Building the health-economic case for scaling up the WHO-HEARTS hypertension control package in low- and middle-income countries.

Generally, hypertension control programs are cost-effective, including in low- and middle-income countries, but country governments and civil society are not likely to support hypertension control programs unless value is demonstrated in terms of public health benefits, budget impact, and value-for-investment for the individual country context. The World Health Organization (WHO) and the Pan American Health Organization (PAHO) established a standard, simplified Global HEARTS approach to hypertension control, including preferred antihypertensive medicines and blood pressure measurement devices. The objective of this study is to report on health economic studies of HEARTS hypertension control package cost (especially medication costs), cost-effectiveness, and budget impact and describe mathematical models designed to translate hypertension control program data into the optimal approach to hypertension care service delivery and financing, especially in low- and middle-income countries. Early results suggest that HEARTS hypertension control interventions are either cost-saving or cost-effective, that the HEARTS package is affordable at between US$ 18-44 per person treated per year, and that antihypertensive medicines could be priced low enough to reach a global standard of an average

En general, los programas de control de la hipertensión son costo-eficaces, incluso en los países de ingresos bajos y medios. Aun así, es poco probable que los gobiernos nacionales y la sociedad civil apoyen los programas de control de la hipertensión a menos que se demuestre su valor en términos de beneficios para la salud pública, impacto presupuestario y valor de la inversión para el contexto individual del país. La Organización Mundial de la Salud (OMS) y la Organización Panamericana de la Salud (OPS) implementaron la iniciativa HEARTS, un enfoque mundial estandarizado y simplificado para el control de la hipertensión, que incluye los medicamentos antihipertensivos y los dispositivos de medición de la presión arterial de preferencia. El objetivo de este estudio es informar sobre los estudios en el ámbito de la economía de la salud relativos al costo de las medidas de control de la hipertensión previstas en HEARTS (especialmente, de los medicamentos), la costo-efectividad y el impacto presupuestario, así como describir los modelos matemáticos diseñados para traducir los datos de este programa en un enfoque óptimo para la prestación y el financiamiento de los servicios de atención de la hipertensión, especialmente en países de ingresos medianos y bajos. Los primeros resultados indican que las intervenciones de HEARTS para el control de la hipertensión son de bajo costo o costo-eficaces, que el conjunto de medidas HEARTS es asequible, a un precio que oscila entre US$ 18 y US$ 44 al año por paciente tratado, y que los medicamentos antihipertensivos podrían tener un precio lo suficientemente bajo como para alcanzar un estándar medio mundial de

Geralmente, os programas de controle de hipertensão são custo-efetivos, inclusive em países de baixa e média renda, mas os governos dos países e a sociedade civil provavelmente não apoiarão tais programas a menos que demonstrem valor em termos de benefícios à saúde pública, impacto orçamentário e retorno sobre o investimento no contexto individual do país. A Organização Mundial da Saúde (OMS) e a Organização Pan-Americana da Saúde (OPAS) criaram a Global HEARTS, uma abordagem padrão e simplificada ao controle da hipertensão arterial, que inclui medicamentos anti-hipertensivos preferidos e dispositivos para aferição da pressão arterial preferidos. O objetivo deste estudo é relatar os estudos de economia em saúde que analisaram o custo (especialmente custos de medicamentos), custo-benefício e impacto orçamentário do pacote HEARTS para controle da hipertensão e descrever modelos matemáticos elaborados para traduzir os dados do programa de controle de hipertensão em uma abordagem ideal para a prestação e financiamento de serviços de atenção às pessoas com hipertensão, especialmente em países de baixa e média renda. Os primeiros resultados sugerem que as intervenções HEARTS para controle da hipertensão são de baixo custo ou custo-efetivas, que o pacote HEARTS é acessível (custando de US$ 18 a 44 por pessoa tratada por ano) e que o preço dos medicamentos anti-hipertensivos poderia ser baixo o suficiente para atingir uma média global de

Building the health-economic case for scaling up the WHO-HEARTS hypertension control package in low- and middle-income countries

[ABSTRACT]. Generally, hypertension control programs are cost-effective, including in low- and middle-income countries, but country governments and civil society are not likely to support hypertension control programs unless value is demonstrated in terms of public health benefits, budget impact, and value-for-investment for the individual country context. The World Health Organization (WHO) and the Pan American Health Organization (PAHO) established a standard, simplified Global HEARTS approach to hypertension control, including preferred antihypertensive medicines and blood pressure measurement devices. The objective of this study is to report on health economic studies of HEARTS hypertension control package cost (especially medication costs), cost-effectiveness, and budget impact and describe mathematical models designed to translate hypertension control program data into the optimal approach to hypertension care service delivery and financing, especially in lowand middle-income countries. Early results suggest that HEARTS hypertension control interventions are either cost-saving or cost-effective, that the HEARTS package is affordable at between US$ 18-44 per person treated per year, and that antihypertensive medicines could be priced low enough to reach a global standard of an average <US$ 5 per patient per year in the public sector. This health economic evidence will make a compelling case for government ownership and financial support for national scale hypertension control programs.

[RESUMEN]. En general, los programas de control de la hipertensión son costo-eficaces, incluso en los países de ingresos bajos y medios. Aun así, es poco probable que los gobiernos nacionales y la sociedad civil apoyen los programas de control de la hipertensión a menos que se demuestre su valor en términos de beneficios para la salud pública, impacto presupuestario y valor de la inversión para el contexto individual del país. La Organización Mundial de la Salud (OMS) y la Organización Panamericana de la Salud (OPS) implementaron la iniciativa HEARTS, un enfoque mundial estandarizado y simplificado para el control de la hipertensión, que incluye los medicamentos antihipertensivos y los dispositivos de medición de la presión arterial de preferencia. El objetivo de este estudio es informar sobre los estudios en el ámbito de la economía de la salud relativos al costo de las medidas de control de la hipertensión previstas en HEARTS (especialmente, de los medicamentos), la costo-efectividad y el impacto presupuestario, así como describir los modelos matemáticos diseñados para traducir los datos de este programa en un enfoque óptimo para la prestación y el financiamiento de los servicios de atención de la hipertensión, especialmente en países de ingresos medianos y bajos. Los primeros resultados indican que las intervenciones de HEARTS para el control de la hipertensión son de bajo costo o costo-eficaces, que el conjunto de medidas HEARTS es asequible, a un precio que oscila entre US$ 18 y US$ 44 al año por paciente tratado, y que los medicamentos antihipertensivos podrían tener un precio lo suficientemente bajo como para alcanzar un estándar medio mundial de <US$ 5 por paciente al año en el sector público. Estos datos del ámbito de la economía de la salud serán argumentos convincentes para que los gobiernos se involucren en los programas de control de la hipertensión a escala nacional y les brinden apoyo financiero.

[RESUMO]. Geralmente, os programas de controle de hipertensão são custo-efetivos, inclusive em países de baixa e média renda, mas os governos dos países e a sociedade civil provavelmente não apoiarão tais programas a menos que demonstrem valor em termos de benefícios à saúde pública, impacto orçamentário e retorno sobre o investimento no contexto individual do país. A Organização Mundial da Saúde (OMS) e a Organização Pan-Americana da Saúde (OPAS) criaram a Global HEARTS, uma abordagem padrão e simplificada ao controle da hipertensão arterial, que inclui medicamentos anti-hipertensivos preferidos e dispositivos para aferição da pressão arterial preferidos. O objetivo deste estudo é relatar os estudos de economia em saúde que analisaram o custo (especialmente custos de medicamentos), custo-benefício e impacto orçamentário do pacote HEARTS para controle da hipertensão e descrever modelos matemáticos elaborados para traduzir os dados do programa de controle de hipertensão em uma abordagem ideal para a prestação e financiamento de serviços de atenção às pessoas com hipertensão, especialmente em países de baixa e média renda. Os primeiros resultados sugerem que as intervenções HEARTS para controle da hipertensão são de baixo custo ou custo-efetivas, que o pacote HEARTS é acessível (custando de US$ 18 a 44 por pessoa tratada por ano) e que o preço dos medicamentos anti-hipertensivos poderia ser baixo o suficiente para atingir uma média global de <US$ 18 por paciente por ano no setor público. Estas evidências do campo da economia em saúde serão um argumento convincente para que os governos se responsabilizem por programas de controle de hipertensão em escala nacional e os dotem de recursos financeiros.

Krankheitsreste: The residual signs of catatonia. A case series.

BACKGROUND: Catatonic signs were first described by 19th- and 20th-century researchers. An important concept known as "Krankheitsreste," or the residual signs of catatonia, was described by Kraepelin in 1896. Modern researchers describe patients who demonstrate "partial response to the treatment of catatonia with residual signs." Kraepelin observed that these signs occurred between catatonic episodes as part of the natural course of illness. Modern psychiatrists see residual signs after intervention or treatment. The determination of residual signs of catatonia is necessary to evaluate the most effective treatment approach to the patient. METHODS: In this case series, we describe 3 patients whose catatonia improved with treatment, but each exhibited continued residual signs of the syndrome. Appropriate consent was obtained from the patients and we identified the varying levels of catatonic signs using the Bush-Francis Catatonia Rating Scale (BFCRS) and the KANNER scale. RESULTS: Scores on both the BFCRS and KANNER scale decreased on followup in all 3 patients, with varying levels of success. The BFCRS score for the patient in Case 1 dropped 4 points upon follow-up, and their score on Part 2 of the KANNER scale decreased 12 points. The patient in Case 2 experienced a 5-point drop in their BFCRS score at follow-up and their score on Part 2 of the KANNER scale decreased 4 points. In Case 3, the patient's BFCRS score dropped 10 points at follow-up and their score on Part 2 of the KANNER scale decreased 20 points. CONCLUSIONS: These 3 patients demonstrate Krankheitsreste, or "partial response to the treatment of catatonia with residual signs." Each patient had a developmental disorder and 2 had autism spectrum disorder. They exhibited improved self-care and greater independence and required less restrictive living environments.