Estenosis aórtica severa e hipercolesterolemia familiar

Homozygous familial hypercholesterolemia (HFH) is a rare and life-threatening disease that can manifest as coronary artery disease or severe aortic stenosis before twenties. We present the case of a male adolescent who was hospitalized with a clinical diagnosis of HFH and severe aortic stenosis. He underwent aortic valve replacement with mechanical prosthesis and aortic annulus enlargement, and two aortocoronary bypasses were implanted due to an intraoperative complication. The patient evolved favourably and was discharged with combination therapy with high-intensity statins and ezetimibe.La hipercolesterolemia familiar homocigota (HFH) es una enfermedad infrecuente y potencialmente mortal que se puede manifestar como enfermedad coronaria o estenosis aórtica severa antes de los 20 años de edad. Presentamos el caso de un adolescente de sexo masculino que fue hospitalizado con diagnóstico clínico de HFH y estenosis aórtica severa. Se le realizó cirugía de reemplazo de válvula aórtica con prótesis mecánica y ampliación de anillo, y se implantaron dos baipases aortocoronarios debido a una complicación intraoperatoria. El paciente evolucionó favorablemente y fue dado de alta con terapia combinada con estatinas de alta intensidad y ezetimibe

Propuesta de manejo inicial del infarto de miocardio con elevación del segmento ST no complicado en centros sin capacidad de intervención coronaria percutánea en el Perú

ST-segment elevation myocardial infarction (STEMI) is a clinical entity whose adequate treatment will depend on its prompt recognition, accurate diagnosis, and management in reperfusion networks. The first contact with these patients is generally done in centers without reperfusion capacity, attended by non-cardiologist doctors, and in centers far from hospitals with greater resolution capacity, something that is well known in our country. This manuscript proposes a strategy for the diagnosis and treatment of STEMI in centers without percutaneous coronary intervention capacity of the public health system in Peru, emphasizing not losing sight of electrocardiographic patterns compatible with coronary artery occlusion, adequate fibrinolysis and management of its complications, the treatment of infarction in special populations and highlighting the importance of the pharmacoinvasive strategy as the main form of reperfusion treatment in our country.El infarto de miocardio con elevación del segmento ST (IMCEST) es una entidad clínica cuyo tratamiento adecuado dependerá de su pronto reconocimiento, diagnóstico certero y manejo en redes de reperfusión. El primer contacto con estos pacientes es generalmente en centros sin capacidad de reperfusión, atendidos por médicos no cardiólogos y en centros alejados de hospitales de mayor capacidad resolutiva, algo que es bien conocido en nuestro país. Este manuscrito propone la estrategia de diagnóstico y tratamiento del IMCEST para centros sin capacidad de intervención coronaria percutánea del sistema público de salud en el Perú, haciendo hincapié en no perder de vista patrones electrocardiográficos compatibles con oclusión de la arteria coronaria, fibrinolisis adecuada y manejo de sus complicaciones, el tratamiento del infarto en poblaciones especiales y resaltando la importancia de la estrategia farmacoinvasiva como forma de tratamiento de reperfusión principal en nuestro país

Proposal for initial management of uncomplicated ST elevation myocardial infarction in centers without percutaneous coronary intervention capacity in Peru

El infarto de miocardio con elevación del segmento ST (IMCEST) es una entidad clínica cuyo tratamiento adecuado dependerá de su pronto reconocimiento, diagnóstico certero y manejo en redes de reperfusión. El primer contacto con estos pacientes es generalmente en centros sin capacidad de reperfusión, atendidos por médicos no cardiólogos y en centros alejados de hospitales de mayor capacidad resolutiva, algo que es bien conocido en nuestro país. Este manuscrito propone la estrategia de diagnóstico y tratamiento del IMCEST para centros sin capacidad de intervención coronaria percutánea del sistema público de salud en el Perú, haciendo hincapié en no perder de vista patrones electrocardiográficos compatibles con oclusión de la arteria coronaria, fibrinolisis adecuada y manejo de sus complicaciones, el tratamiento del infarto en poblaciones especiales y resaltando la importancia de la estrategia farmacoinvasiva como forma de tratamiento de reperfusión principal en nuestro país.ST-segment elevation myocardial infarction (STEMI) is a clinical entity whose adequate treatment will depend on its prompt recognition, accurate diagnosis, and management in reperfusion networks. The first contact with these patients is generally done in centers without reperfusion capacity, attended by non-cardiologist doctors, and in centers far from hospitals with greater resolution capacity, something that is well known in our country. This manuscript proposes a strategy for the diagnosis and treatment of STEMI in centers without percutaneous coronary intervention capacity of the public health system in Peru, emphasizing not losing sight of electrocardiographic patterns compatible with coronary artery occlusion, adequate fibrinolysis and management of its complications, the treatment of infarction in special populations and highlighting the importance of the pharmacoinvasive strategy as the main form of reperfusion treatment in our country

Tratamiento del infarto agudo de miocardio en el Perú y su relación con eventos adversos intrahospitalarios: resultados del Segundo Registro Peruano de Infarto de Miocardio con elevación del segmento ST (PERSTEMI-II)

  Background. ST-segment elevation myocardial infarction (STEMI), is an important cause of morbidity and mortality worldwide, and myocardial reperfusion, when adequate, reduces the complications of this entity. The aim of the study was to describe the clinical and treatment characteristics of STEMI in Peru and the relationship of successful reperfusion with in-hospital adverse events. Materials and methods. Prospective, multicenter cohort of STEMI patients attended during 2020 in public hospitals in Peru. We evaluated the clinical, therapeutic characteristics and in-hospital adverse events, also the relationship between successful reperfusion and adverse events. Results. A total of 374 patients were included, 69.5% in Lima and Callao. Fibrinolysis was used in 37% of cases (pharmacoinvasive 26% and alone lysis 11%), primary angioplasty with < 12 hours of evolution in 20%, late angioplasty in 9% and 34% did not access adequate reperfusion therapies, mainly due to late presentation. Ischemia time was longer in patients with primary angioplasty compared to fibrinolysis (median 7.7 hours (RIQ 5-10) and 4 hours (RIQ 2.3-5.5) respectively). Mortality was 8.5%, the incidence of post-infarction heart failure was 27.8% and of cardiogenic shock 11.5%. Successful reperfusion was associated with lower cardiovascular mortality (RR:0.28; 95%CI: 0.12-0.66, p=0.003) and lower incidence of heart failure during hospitalization (RR: 0.61; 95%CI: 0.43-0.85, p=0.004). Conclusions. Fibrinolysis continues to be the most frequent reperfusion therapy in public hospitals in Peru. Shorter ischemia-to-reperfusion time was associated with reperfusion success, and in turn with fewer in-hospital adverse events.  Antecedentes. El infarto de miocardio con elevación del segmento ST (IMCEST), es una de las principales causas de morbimortalidad a nivel global, la reperfusión adecuada del miocardio consigue disminuir las complicaciones de esta entidad. El objetivo del estudio fue describir las características clínicas y terapéuticas del IMCEST en el Perú y la relación de la reperfusión exitosa con los eventos adversos intrahospitalarios. Materiales y métodos. Cohorte prospectiva, multicéntrica de pacientes con IMCEST atendidos durante el año 2020 en hospitales públicos del Perú. Se evaluaron las características clínicas, terapéuticas y eventos adversos intrahospitalarios, además de la relación entre la reperfusión exitosa del infarto y los eventos adversos. Resultados. Se incluyeron 374 pacientes, 69,5% en Lima y Callao. La fibrinólisis fue usada en 37% de casos (farmacoinvasiva 26% y sola 11%), angioplastia primaria con < 12 h de evolución en 20%, angioplastia tardía en 9% y 34% no accedieron a terapias de reperfusión adecuadas, principalmente por presentación tardía. El tiempo de isquemia fue mayor en pacientes con angioplastia primaria en comparación a fibrinólisis (mediana 7,7 h [RIQ 5-10] y 4 h [RIQ 2,3-5,5] respectivamente). La mortalidad fue de 8,5%, la incidencia de insuficiencia cardiaca posinfarto fue de 27,8% y de choque cardiogénico de 11,5%. El éxito de la reperfusión se asoció con menor mortalidad cardiovascular (RR: 0,28; IC95%: 0,12-0,66, p=0,003) y menor incidencia de insuficiencia cardiaca (RR: 0,61; IC95%: 0,43-0,85, p=0,004). Conclusiones. La fibrinólisis sigue siendo la terapia de reperfusión más frecuente en hospitales públicos del Perú. El menor tiempo de isquemia a reperfusión se asoció con el éxito de esta y, a su vez, a menores eventos adversos intrahospitalarios

Precision rehabilitation for aphasia by patient age, sex, aphasia severity, and time since stroke? A prespecified, systematic review based, individual participant data network subgroup meta-analysis

Background: Stroke rehabilitation interventions are routinely personalized to address individuals’ needs, goals, and challenges based on evidence from aggregated randomized controlled trials (RCT) data and meta-syntheses. Individual participant data (IPD) meta-analyses may better inform the development of precision rehabilitation approaches, quantifying treatment responses while adjusting for confounders and reducing ecological bias. Aim: We explored associations between speech and language therapy (SLT) interventions frequency (days/week), intensity (h/week), and dosage (total SLT-hours) and language outcomes for different age, sex, aphasia severity, and chronicity subgroups by undertaking prespecified subgroup network meta-analyses of the RELEASE database. Methods: MEDLINE, EMBASE, and trial registrations were systematically searched (inception-Sept2015) for RCTs, including ⩾ 10 IPD on stroke-related aphasia. We extracted demographic, stroke, aphasia, SLT, and risk of bias data. Overall-language ability, auditory comprehension, and functional communication outcomes were standardized. A one-stage, random effects, network meta-analysis approach filtered IPD into a single optimal model, examining SLT regimen and language recovery from baseline to first post-intervention follow-up, adjusting for covariates identified a-priori. Data were dichotomized by age (⩽/> 65 years), aphasia severity (mild–moderate/ moderate–severe based on language outcomes’ median value), chronicity (⩽/> 3 months), and sex subgroups. We reported estimates of means and 95% confidence intervals. Where relative variance was high (> 50%), results were reported for completeness. Results: 959 IPD (25 RCTs) were analyzed. For working-age participants, greatest language gains from baseline occurred alongside moderate to high-intensity SLT (functional communication 3-to-4 h/week; overall-language and comprehension > 9 h/week); older participants’ greatest gains occurred alongside low-intensity SLT (⩽ 2 h/week) except for auditory comprehension (> 9 h/week). For both age-groups, SLT-frequency and dosage associated with best language gains were similar. Participants ⩽ 3 months post-onset demonstrated greatest overall-language gains for SLT at low intensity/moderate dosage (⩽ 2 SLT-h/week; 20-to-50 h); for those > 3 months, post-stroke greatest gains were associated with moderate-intensity/high-dosage SLT (3–4 SLT-h/week; ⩾ 50 hours). For moderate–severe participants, 4 SLT-days/week conferred the greatest language gains across outcomes, with auditory comprehension gains only observed for ⩾ 4 SLT-days/week; mild–moderate participants’ greatest functional communication gains were associated with similar frequency (⩾ 4 SLT-days/week) and greatest overall-language gains with higher frequency SLT (⩾ 6 days/weekly). Males’ greatest gains were associated with SLT of moderate (functional communication; 3-to-4 h/weekly) or high intensity (overall-language and auditory comprehension; (> 9 h/weekly) compared to females for whom the greatest gains were associated with lower-intensity SLT ( 9 h over ⩾ 4 days/week. Conclusions: We observed a treatment response in most subgroups’ overall-language, auditory comprehension, and functional communication language gains. For some, the maximum treatment response varied in association with different SLT-frequency, intensity, and dosage. Where differences were observed, working-aged, chronic, mild–moderate, and male subgroups experienced their greatest language gains alongside high-frequency/intensity SLT. In contrast, older, moderate–severely impaired, and female subgroups within 3 months of aphasia onset made their greatest gains for lower-intensity SLT. The acceptability, clinical, and cost effectiveness of precision aphasia rehabilitation approaches based on age, sex, aphasia severity, and chronicity should be evaluated in future clinical RCTs

Precision rehabilitation for aphasia by patient age, sex, aphasia severity, and time since stroke? A prespecified, systematic review-based, individual participant data, network, subgroup meta-analysis

Background: Stroke rehabilitation interventions are routinely personalized to address individuals’ needs, goals, and challenges based on evidence from aggregated randomized controlled trials (RCT) data and meta-syntheses. Individual participant data (IPD) meta-analyses may better inform the development of precision rehabilitation approaches, quantifying treatment responses while adjusting for confounders and reducing ecological bias. Aim: We explored associations between speech and language therapy (SLT) interventions frequency (days/week), intensity (h/week), and dosage (total SLT-hours) and language outcomes for different age, sex, aphasia severity, and chronicity subgroups by undertaking prespecified subgroup network meta-analyses of the RELEASE database. Methods: MEDLINE, EMBASE, and trial registrations were systematically searched (inception-Sept2015) for RCTs, including ⩾ 10 IPD on stroke-related aphasia. We extracted demographic, stroke, aphasia, SLT, and risk of bias data. Overall-language ability, auditory comprehension, and functional communication outcomes were standardized. A one-stage, random effects, network meta-analysis approach filtered IPD into a single optimal model, examining SLT regimen and language recovery from baseline to first post-intervention follow-up, adjusting for covariates identified a-priori. Data were dichotomized by age (⩽/> 65 years), aphasia severity (mild–moderate/ moderate–severe based on language outcomes’ median value), chronicity (⩽/> 3 months), and sex subgroups. We reported estimates of means and 95% confidence intervals. Where relative variance was high (> 50%), results were reported for completeness. Results: 959 IPD (25 RCTs) were analyzed. For working-age participants, greatest language gains from baseline occurred alongside moderate to high-intensity SLT (functional communication 3-to-4 h/week; overall-language and comprehension > 9 h/week); older participants’ greatest gains occurred alongside low-intensity SLT (⩽ 2 h/week) except for auditory comprehension (> 9 h/week). For both age-groups, SLT-frequency and dosage associated with best language gains were similar. Participants ⩽ 3 months post-onset demonstrated greatest overall-language gains for SLT at low intensity/moderate dosage (⩽ 2 SLT-h/week; 20-to-50 h); for those > 3 months, post-stroke greatest gains were associated with moderate-intensity/high-dosage SLT (3–4 SLT-h/week; ⩾ 50 hours). For moderate–severe participants, 4 SLT-days/week conferred the greatest language gains across outcomes, with auditory comprehension gains only observed for ⩾ 4 SLT-days/week; mild–moderate participants’ greatest functional communication gains were associated with similar frequency (⩾ 4 SLT-days/week) and greatest overall-language gains with higher frequency SLT (⩾ 6 days/weekly). Males’ greatest gains were associated with SLT of moderate (functional communication; 3-to-4 h/weekly) or high intensity (overall-language and auditory comprehension; (> 9 h/weekly) compared to females for whom the greatest gains were associated with lower-intensity SLT ( 9 h over ⩾ 4 days/week. Conclusions: We observed a treatment response in most subgroups’ overall-language, auditory comprehension, and functional communication language gains. For some, the maximum treatment response varied in association with different SLT-frequency, intensity, and dosage. Where differences were observed, working-aged, chronic, mild–moderate, and male subgroups experienced their greatest language gains alongside high-frequency/intensity SLT. In contrast, older, moderate–severely impaired, and female subgroups within 3 months of aphasia onset made their greatest gains for lower-intensity SLT. The acceptability, clinical, and cost effectiveness of precision aphasia rehabilitation approaches based on age, sex, aphasia severity, and chronicity should be evaluated in future clinical RCTs

Complex speech-language therapy interventions for stroke-related aphasia: the RELEASE study incorporating a systematic review and individual participant data network meta-analysis

Background: People with language problems following stroke (aphasia) benefit from speech and language therapy. Optimising speech and language therapy for aphasia recovery is a research priority. Objectives: The objectives were to explore patterns and predictors of language and communication recovery, optimum speech and language therapy intervention provision, and whether or not effectiveness varies by participant subgroup or language domain. Design: This research comprised a systematic review, a meta-analysis and a network meta-analysis of individual participant data. Setting: Participant data were collected in research and clinical settings. Interventions: The intervention under investigation was speech and language therapy for aphasia after stroke. Main outcome measures: The main outcome measures were absolute changes in language scores from baseline on overall language ability, auditory comprehension, spoken language, reading comprehension, writing and functional communication. Data sources and participants: Electronic databases were systematically searched, including MEDLINE, EMBASE, Cumulative Index to Nursing and Allied Health Literature, Linguistic and Language Behavior Abstracts and SpeechBITE (searched from inception to 2015). The results were screened for eligibility, and published and unpublished data sets (randomised controlled trials, non-randomised controlled trials, cohort studies, case series, registries) with at least 10 individual participant data reporting aphasia duration and severity were identified. Existing collaborators and primary researchers named in identified records were invited to contribute electronic data sets. Individual participant data in the public domain were extracted. Review methods: Data on demographics, speech and language therapy interventions, outcomes and quality criteria were independently extracted by two reviewers, or available as individual participant data data sets. Meta-analysis and network meta-analysis were used to generate hypotheses. Results: We retrieved 5928 individual participant data from 174 data sets across 28 countries, comprising 75 electronic (3940 individual participant data), 47 randomised controlled trial (1778 individual participant data) and 91 speech and language therapy intervention (2746 individual participant data) data sets. The median participant age was 63 years (interquartile range 53-72 years). We identified 53 unavailable, but potentially eligible, randomised controlled trials (46 of these appeared to include speech and language therapy). Relevant individual participant data were filtered into each analysis. Statistically significant predictors of recovery included age (functional communication, individual participant data: 532, n = 14 randomised controlled trials) and sex (overall language ability, individual participant data: 482, n = 11 randomised controlled trials; functional communication, individual participant data: 532, n = 14 randomised controlled trials). Older age and being a longer time since aphasia onset predicted poorer recovery. A negative relationship between baseline severity score and change from baseline (p < 0.0001) may reflect the reduced improvement possible from high baseline scores. The frequency, duration, intensity and dosage of speech and language therapy were variously associated with auditory comprehension, naming and functional communication recovery. There were insufficient data to examine spontaneous recovery. The greatest overall gains in language ability [14.95 points (95% confidence interval 8.7 to 21.2 points) on the Western Aphasia Battery-Aphasia Quotient] and functional communication [0.78 points (95% confidence interval 0.48 to 1.1 points) on the Aachen Aphasia Test-Spontaneous Communication] were associated with receiving speech and language therapy 4 to 5 days weekly; for auditory comprehension [5.86 points (95% confidence interval 1.6 to 10.0 points) on the Aachen Aphasia Test-Token Test], the greatest gains were associated with receiving speech and language therapy 3 to 4 days weekly. The greatest overall gains in language ability [15.9 points (95% confidence interval 8.0 to 23.6 points) on the Western Aphasia Battery-Aphasia Quotient] and functional communication [0.77 points (95% confidence interval 0.36 to 1.2 points) on the Aachen Aphasia Test-Spontaneous Communication] were associated with speech and language therapy participation from 2 to 4 (and more than 9) hours weekly, whereas the highest auditory comprehension gains [7.3 points (95% confidence interval 4.1 to 10.5 points) on the Aachen Aphasia Test-Token Test] were associated with speech and language therapy participation in excess of 9 hours weekly (with similar gains notes for 4 hours weekly). While clinically similar gains were made alongside different speech and language therapy intensities, the greatest overall gains in language ability [18.37 points (95% confidence interval 10.58 to 26.16 points) on the Western Aphasia Battery-Aphasia Quotient] and auditory comprehension [5.23 points (95% confidence interval 1.51 to 8.95 points) on the Aachen Aphasia Test-Token Test] were associated with 20-50 hours of speech and language therapy. Network meta-analyses on naming and the duration of speech and language therapy interventions across language outcomes were unstable. Relative variance was acceptable (< 30%). Subgroups may benefit from specific interventions. Limitations: Data sets were graded as being at a low risk of bias but were predominantly based on highly selected research participants, assessments and interventions, thereby limiting generalisability. Conclusions: Frequency, intensity and dosage were associated with language gains from baseline, but varied by domain and subgroup

Communicating simply, but not too simply: Reporting of participants and speech and language interventions for aphasia after stroke

Purpose: Speech and language pathology (SLP) for aphasia is a complex intervention delivered to a heterogeneous population within diverse settings. Simplistic descriptions of participants and interventions in research hinder replication, interpretation of results, guideline and research developments through secondary data analyses. This study aimed to describe the availability of participant and intervention descriptors in existing aphasia research datasets. Method: We systematically identified aphasia research datasets containing ≥10 participants with information on time since stroke and language ability. We extracted participant and SLP intervention descriptions and considered the availability of data compared to historical and current reporting standards. We developed an extension to the Template for Intervention Description and Replication checklist to support meaningful classification and synthesis of the SLP interventions to support secondary data analysis. Result: Of 11, 314 identified records we screened 1131 full texts and received 75 dataset contributions. We extracted data from 99 additional public domain datasets. Participant age (97.1%) and sex (90.8%) were commonly available. Prior stroke (25.8%), living context (12.1%) and socio-economic status (2.3%) were rarely available. Therapy impairment target, frequency and duration were most commonly available but predominately described at group level. Home practice (46.3%) and tailoring (functional relevance 46.3%) were inconsistently available. Conclusion : Gaps in the availability of participant and intervention details were significant, hampering clinical implementation of evidence into practice and development of our field of research. Improvements in the quality and consistency of participant and intervention data reported in aphasia research are required to maximise clinical implementation, replication in research and the generation of insights from secondary data analysis. Systematic review registration: PROSPERO CRD4201811094

Utilising a systematic review-based approach to create a database of individual participant data for meta- and network meta-analyses: the RELEASE database of aphasia after stroke

Background: Collation of aphasia research data across settings, countries and study designs using big data principles will support analyses across different language modalities, levels of impairment, and therapy interventions in this heterogeneous population. Big data approaches in aphasia research may support vital analyses, which are unachievable within individual trial datasets. However, we lack insight into the requirements for a systematically created database, the feasibility and challenges and potential utility of the type of data collated. Aim: To report the development, preparation and establishment of an internationally agreed aphasia after stroke research database of individual participant data (IPD) to facilitate planned aphasia research analyses. Methods: Data were collated by systematically identifying existing, eligible studies in any language (≥10 IPD, data on time since stroke, and language performance) and included sourcing from relevant aphasia research networks. We invited electronic contributions and also extracted IPD from the public domain. Data were assessed for completeness, validity of value-ranges within variables, and described according to pre-defined categories of demographic data, therapy descriptions, and language domain measurements. We cleaned, clarified, imputed and standardised relevant data in collaboration with the original study investigators. We presented participant, language, stroke, and therapy data characteristics of the final database using summary statistics. Results: From 5256 screened records, 698 datasets were potentially eligible for inclusion; 174 datasets (5928 IPD) from 28 countries were included, 47/174 RCT datasets (1778 IPD) and 91/174 (2834 IPD) included a speech and language therapy (SLT) intervention. Participants’ median age was 63 years (interquartile range [53, 72]), 3407 (61.4%) were male and median recruitment time was 321 days (IQR 30, 1156) after stroke. IPD were available for aphasia severity or ability overall (n = 2699; 80 datasets), naming (n = 2886; 75 datasets), auditory comprehension (n = 2750; 71 datasets), functional communication (n = 1591; 29 datasets), reading (n = 770; 12 datasets) and writing (n = 724; 13 datasets). Information on SLT interventions were described by theoretical approach, therapy target, mode of delivery, setting and provider. Therapy regimen was described according to intensity (1882 IPD; 60 datasets), frequency (2057 IPD; 66 datasets), duration (1960 IPD; 64 datasets) and dosage (1978 IPD; 62 datasets). Discussion: Our international IPD archive demonstrates the application of big data principles in the context of aphasia research; our rigorous methodology for data acquisition and cleaning can serve as a template for the establishment of similar databases in other research areas