Intervention for Cognitive Reserve Enhancement in Delaying the Onset of Alzheimer's Symptomatic Expression (INCREASE) Study: Results from a Randomized Controlled Study of Medication Therapy Management Targeting a Delay in Prodromal Dementia Symptom Progression.

BACKGROUND: Cognitive reserve has been hypothesized as a mechanism to explain differences in individual risk for symptomatic expression of Alzheimer's Disease (AD). Inappropriate medications may diminish cognitive reserve, precipitating the transition from preclinical AD (pAD) to a symptomatic state. To date, there is limited data on the potential impact of medication optimization as a potential tool for slowing the symptomatic expression of AD. OBJECTIVES: (1) To test the efficacy of a medication therapy management intervention designed to bolster cognitive reserve in community-dwelling older adults without dementia. (2) To evaluate the efficacy of intervention by baseline pAD status. DESIGN: A 1-year randomized controlled trial was conducted in community-dwelling older adults without dementia. Randomization was stratified by amyloid ß positron emission tomography levels. SETTING: Community-based, Lexington, Kentucky. PARTICIPANTS: Adults 65 years or older with no evidence of dementia and reporting at least one potentially inappropriate medication as listed in the Beers 2015 criteria were recruited. The study aimed to enroll 90 participants based on the a priori sample size calculation. INTERVENTION: Medication therapy management versus standard of care. MEASUREMENTS: Primary outcomes were: (1) one-year changes in the Medication Appropriateness Index; (2) one-year changes in Trail Making Test B under scopolamine challenge. RESULTS: The medication therapy management intervention resulted in significant improvement in Medication Appropriateness Index scores. Overall, there was no beneficial effect of the medication therapy management on Trail Making Test B scores, however stratified analysis demonstrated improvement in Trail Making Test B challenged scores associated with the medication therapy management for those with elevated amyloid ß positron emission tomography levels consistent with pAD. CONCLUSIONS: Medication therapy management can reduce inappropriate medication use in older adults at risk for AD. Our study indicated beneficial cognitive effects in those with preclinical Alzheimer's Disease. No statistically significant effects were evident in the study group as a whole, or in those without preclinical cerebral amyloidosis. Further work designed to improve the effectiveness of the medication therapy management approach and defining other preclinical pathologic states that may benefit from medication optimization are readily achievable goals for promoting improved cognitive health and potentially delaying the onset of symptomatic AD.

Valores extremos del IMC materno: factores determinantes de peores resultados obstétricos y perinatales / Extreme values of maternal BMI: Determinants of worse obstetric and perinatal outcomes

Objetivo: Conocer la influencia del índice de masa corporal (IMC) materno al inicio del embarazo en los resultados obstétricos-perinatales. Material y métodos: Estudio observacional-ambispectivo. Se incluyeron 1.407 pacientes con gestaciones únicas y partos de fetos>24 semanas entre el 01/12/2017 y el 31/07/2019. La muestra fue estratificada según su IMC según la clasificación de la OMS. Se analizaron variables sobre: enfermedad pregestacional, gestacional, asistencia obstétrica y resultados maternos-perinatales y se compararon entre los grupos estudiados. El programa estadístico utilizado ha sido R Core Team 2020, versión 3.6.3. Un valor de p≤0,05 se consideró significativo. Resultados: Las obesas ii-iii (IMC 35-39 e IMC≥40, respectivamente) tienen mayor riesgo de hipertensión arterial crónica (OR 53,54, IC95% 18,21-229,02), diabetes gestacional (OR 5,24, IC95% 2,87-9,51) y preeclampsia (OR 2,38, IC95% 0,95-5,51; p=0,049). Las de bajo peso tuvieron más fetos con crecimiento intrauterino restringido (OR 3,09, IC95% 1,46-6,17). Las inducciones del parto y las cesáreas aumentan conforme lo hace el IMC (p=0,006). Las pacientes con bajo peso también tuvieron mayor riesgo de cesárea (OR 2,46, IC95% 1,06-5,20). Los ingresos neonatales fueron más frecuentes en mujeres obesas y con bajo peso (OR 2,68, IC95% 1,39-5,00, y OR 2,56, IC95% 1,10-5,44, respectivamente). Las obesas tuvieron más riesgo de peso neonatal>4.000g (OR 3,06, IC95% 1,57-5,77) y las gestantes de bajo peso más riesgo de peso neonatal<2.500g (OR 2,94, IC95% 1,54-5,41). Conclusión: Los valores extremos del IMC materno al inicio de la gestación son factores determinantes para un desenlace obstétrico-perinatal adverso.(AU)

Objective: To study the influence of maternal body mass index (BMI) at the beginning of pregnancy on obstetric-perinatal outcomes. Material and methods: Observational-ambispective study. We recruited 1407 patients with singleton gestations and deliveries of foetuses>24 weeks between 01/12/2017 and 31/07/2019. The sample was stratified according to their BMI following the WHO classification. Variables on pre-pregnancy, gestational disease, obstetric care, and maternal-perinatal outcomes were analysed and compared between the studied groups. The statistical program has been R Core Team 2020, version 3.6.3. P≤.05 was considered significant. Results: Class II-III (BMI 35-39 and BMI≥40 respectively) obese women have a higher risk of chronic arterial hypertension (OR 53.54, 95% CI 18.21-229.02), gestational diabetes (OR 5.24, 95% CI 2.87-9.51) and preeclampsia (OR 2.38, 95% CI 0.95-5.51 with P=.049). The underweight women had more intrauterine growth restriction diagnoses (OR 3.09, 95% CI 1.46-6.17). Inductions of labour and caesarean sections increase as BMI increases (P=.006). Low weight patients also had a higher risk of caesarean section (OR 2.46, 95% CI 1.06-5.20). Neonatal admissions were more frequent in obese and underweight women (OR 2.68, 95% CI 1.39-5.00 and OR 2.56, 95% CI 1.10-5.44 respectively). Obese women had a higher risk of neonatal weight>4000g (OR 3.06, 95% CI 1.57-5.77) and low weight pregnant women had a higher risk of neonatal weight<2500g (OR 2.94, 95% CI 1.54-5.41). Conclusion: Extreme values of maternal BMI at the beginning of gestation are determining factors for an adverse obstetric-perinatal outcome.(AU)

Translational and post-translational regulation of polyamine metabolic enzymes in plants.

Polyamines are small organic and basic polycations that perform essential regulatory functions in all living organisms. Fluctuations in polyamine content have been observed to occur during growth, development and under stress conditions, implying that polyamines play pivotal roles in diverse cellular and physiological processes. To achieve polyamine homeostasis, the entire metabolic pathway is subjected to a fine-tuned regulation of its biosynthetic and catabolic genes and enzymes. In this review, we describe and discuss the most important mechanisms implicated in the translational and post-translational regulation of polyamine metabolic enzymes in plants. At the translational level, we emphasize the role of polyamines in the modulation of upstream open reading frame (uORF) activities that control the translation of polyamine biosynthetic and catabolic mRNAs. At the post-translational level, different aspects of the regulation of polyamine metabolic proteins are depicted, such as the proteolytic activation of enzyme precursors, the importance of dimerization in protein stability as well as in protein intracellular localization.

[Evaluation of effectiveness of corrective measures arising from incident notifications in a paediatric emergency department]. / Evaluación de la efectividad de acciones correctivas derivadas de la notificación de incidentes en urgencias pediátricas.

OBJECTIVE: To analyse the effectiveness of corrective measures arising from the analysis of safety incident notifications in the Paediatric Emergency Unit. METHODS: A quasi-experimental, prospective, and single-centre study was carried out between 2015 and 2018. In the first phase, incidents notified throughout one year were analysed. Corrective measures were then implemented for 5 specific kinds of incidents. These incidents were finally compared to those notified within 12 months after the implementation of those measures. Results were expressed as relative risk and relative risk reduction. RESULTS: A total of 1587 safety incidents were notified (0.9% of patients treated) between January 2015 and December 2017. After implementation of corrective measures, there was a decrease in all kinds of incidents notifications analysed. The incidents related to patient identification were reduced by 60.9% (RR 0.39, 95% CI; 0.25-0.60), and those regarding communication between professionals were reduced by 74.5% (RR 0.25, 95% CI; 0.12-0.55). Incidents related to sedation and analgesic procedures totally disappeared. No significant reduction was found in incidents concerning the triage system, or in those related to rapid intravenous rehydration procedures. CONCLUSIONS: The implementation of improvement actions arising from the analysis of voluntary notification of incidents is an effective strategy to improve patient effective strategy to improve.

Cómo tratamos en nuestra práctica clínica diaria el hipotiroidismo subclínico / How we treat subclinical hypothyroidism in our daily clinical practice

Objetivo. Estudiar el abordaje terapéutico del hipotiroidismo subclínico (HTS): frecuencia de instauración de tratamiento sustitutivo, motivos de inicio, dosis y duración, en la población mayor de 14 años del centro de salud. Material y métodos. Estudio observacional, longitudinal retrospectivo. Se incluyeron 1.156 pacientes con episodio T86 del CIAP en OMI. Excluidos: 10 duplicados, 180 sin criterios de inclusión o imposibilidad para recoger datos, 25 diagnosticados en otro laboratorio y 359 con hipotiroidismo clínico (HTC). Variables. Sexo, edad, cifra de hormona estimulante del tiroides (TSH) al diagnóstico y al iniciar tratamiento, última TSH recogida en la historia clínica (HC) si no tratado, TSH de confirmación diagnóstica, anticuerpos anti-TPO (ATA), presencia de astenia, bocio, síntomas neuropsiquiátricos, hipercolesterolemia; si hay HTS secundario; progresión a HTC; intervalo diagnóstico-inicio tratamiento, dosis de inicio y final, duración y motivos de la interrupción. Resultados. Se incluyeron 582 pacientes: 508 mujeres. Edad media: 43,03 (de 15,97). HTS tratado: 330 (56,7%); TSH al diagnóstico < 10: 81,6%; TSH media en tratados: 11,22 (de 10,49); ATA realizados: 315 (54%)+166 (52,7%); No consta recogido en HC. Astenia: 64%; bocio: 65%. El 67% no fueron tratados: normofunción espontánea. Dosis de inicio: 86% ≤ 50μg. Finales ≤ 50: 43%. Duración del tratamiento: 1-5 años, 41%; > 5 años, 40%. Inicio del tratamiento inmediato al diagnóstico, 38%. Permanecen tratados el 93%. Variables que aumentan la probabilidad de instauración de tratamiento (regresión logística): cifra TSH (OR 32,5; IC 12,8-82,6); ATA+(OR 4,7; IC 2,8-7,7); astenia (OR 2,5; IC 1,5-4); Bocio (OR 3; IC 1,3-6,6). Conclusiones. La decisión de tratar es generalmente adecuada, pero con frecuencia se cronifica un trastorno analítico instaurando tratamientos excesivamente prolongados sin intentos de retirada. Descuidamos la anamnesis y la exploración (AU)

Objective. To study the therapeutic approach to subclinical hypothyroidism (HTS), the frequency of introducing replacement therapy, reasons for starting, doses, and duration, in the population over 14 years-old in a Primary Care Centre. Material and methods. Longitudinal, retrospective observational study of 1156 patients with a hypothyroidism/myxedema episode (T86 in the International Classification of Primary Care (ICPC)) entered in the OMI program were studied. Excluded: 10 duplicates, 180 no inclusion criteria or inability to collect data, 25 diagnosed in another laboratory, 359 with clinical hypothyroidism (HTC). Measurements. Sex, age, TSH value to diagnosis and initiate treatment, or latest TSH recorded in the clinical history (HC) if not treated, TSH diagnostic confirmation, antiTPO antibodies (ATAs), presence of fatigue, goitre, neuropsychiatric symptoms, raised cholesterol, if HTS secondary, progression to HTC, diagnostic-start treatment interval, initial and final dose, duration, reasons for discontinuation. Results. 582 patients: 508 women. Mean age: 43.03 (sd 15.97). HTS treated: 330 (56.7%); TSH at diagnosis < 10: 81.6%; Mean TSH treated: 11.22 (sd 10.49); Made ATAs performed: 315 (54%),+166 (52.7%); Fatigue not recorded in HC: 64%; Goitre: 65%. 67% untreated: returned to normal spontaneously. Starting dose: 86% ≤ 50μg. Final ≤ 50: 43%. Treatment duration: 1-5 years 41%; > 5 years 40%. Immediate treatment after diagnosis 38%. Remain treated 93%. Variables that increase the likelihood of onset of treatment (Logistic Regression): TSH value (OR 32.5, CI 12.8- 82.6), ATAs+(OR 4.7, CI 2.8-7.7); Fatigue (OR 2.5, CI 1.5-4), Goitre (OR 3, CI 1.3-6.6). Conclusions. The decision to treat is generally adequate, but often becomes a chronic analytical disorder, because of unduly prolonged treatment without attempts to withdraw it. Clinical history and physical examination tend to be ignored (AU)

[How we treat subclinical hypothyroidism in our daily clinical practice]. / Cómo tratamos en nuestra práctica clínica diaria el hipotiroidismo subclínico.

OBJECTIVE: To study the therapeutic approach to subclinical hypothyroidism (HTS), the frequency of introducing replacement therapy, reasons for starting, doses, and duration, in the population over 14 years-old in a Primary Care Centre. MATERIAL AND METHODS: Longitudinal, retrospective observational study of 1156 patients with a hypothyroidism/myxedema episode (T86 in the International Classification of Primary Care (ICPC)) entered in the OMI program were studied. Excluded: 10 duplicates, 180 no inclusion criteria or inability to collect data, 25 diagnosed in another laboratory, 359 with clinical hypothyroidism (HTC). MEASUREMENTS: Sex, age, TSH value to diagnosis and initiate treatment, or latest TSH recorded in the clinical history (HC) if not treated, TSH diagnostic confirmation, antiTPO antibodies (ATAs), presence of fatigue, goitre, neuropsychiatric symptoms, raised cholesterol, if HTS secondary, progression to HTC, diagnostic-start treatment interval, initial and final dose, duration, reasons for discontinuation. RESULTS: 582 patients: 508 women. Mean age: 43.03 (sd 15.97). HTS treated: 330 (56.7%); TSH at diagnosis < 10: 81.6%; Mean TSH treated: 11.22 (sd 10.49); Made ATAs performed: 315 (54%),+166 (52.7%); Fatigue not recorded in HC: 64%; Goitre: 65%. 67% untreated: returned to normal spontaneously. Starting dose: 86% ≤ 50µg. Final ≤ 50: 43%. Treatment duration: 1-5 years 41%; > 5 years 40%. Immediate treatment after diagnosis 38%. Remain treated 93%. Variables that increase the likelihood of onset of treatment (Logistic Regression): TSH value (OR 32.5, CI 12.8- 82.6), ATAs+(OR 4.7, CI 2.8-7.7); Fatigue (OR 2.5, CI 1.5-4), Goitre (OR 3, CI 1.3-6.6). CONCLUSIONS: The decision to treat is generally adequate, but often becomes a chronic analytical disorder, because of unduly prolonged treatment without attempts to withdraw it. Clinical history and physical examination tend to be ignored.

Regression of vascular calcification in a patient treated with cinacalcet: a case report.

The purpose of this case report is to describe the regression of vascular calcifications (VC) in a patient with secondary hyperparathyroidism (SHPT) after having added cinacalcet to her treatment. We present the clinical case of a 48-year-old woman with chronic renal failure secondary to tubulointerstitial disease. She was being treated with long-term haemodialysis (HD) and underwent two kidney transplants with transplantectomies. The patient presented with severe SHPT caused by parathyroid gland hypertrophy. The radiology test showed signs of VC in the radial and interdigital arteries, and VC in a linear arrangement were observed in both breasts on the mammography. Cinacalcet was added to her treatment with vitamin D derivatives and phosphate-binding agents, which resulted in a good control of mineral metabolism. The radiology test showed that the calcification in the interdigital artery had disappeared and that the bone appeared to be more structured. The mammography also showed regression of the VC. To conclude, cinacalcet may have potential for regression of VC in patients with SHPT.

Regresión de la calcificación vascular en un paciente tratado con cinacalcet: informe de un caso / Regression of vascular calcification in a patient treated with cinacalcet: A case report

El propósito de este informe de caso es describir la regresión de las calcificaciones vasculares (CV) en una paciente con hiperparatiroidismo secundario (HPTS) tras añadir cinacalcet a su tratamiento. Presentamos un caso clínico de una mujer de 48 años de edad con insuficiencia renal crónica secundaria a nefropatía túbulo-intersticial, tratada con hemodiálisis (HD) de larga duración y sometida a dos trasplantes renales con trasplantectomías. La paciente presentaba HPTS grave causado por la hipertrofia de la glándula paratiroidea; la radiología mostró signos de CV en las arterias radiales e interdigitales y la mamografía, CV lineales múltiples en ambas mamas. Se añadió cinacalcet al tratamiento previo con derivados de la vitamina D y agentes quelantes del fósforo, lo que dio como resultado un buen control del metabolismo mineral. La radiología mostró que las calcificaciones de la arteria interdigital habían desaparecido y que el hueso presentaba un aspecto más estructurado. La mamografía también mostró una regresión de las CV. En conclusión, cinacalcet puede tener potencial para la regresión de las CV en pacientes con HPTS (AU)

The purpose of this case report is to describe the regression of vascular calcifications (VC) in a patient with secondary hyperparathyroidism (SHPT) after having added cinacalcet to her treatment. We present the clinical case of a 48-year-old woman with chronic renal failure secondary to tubulointerstitial disease. She was being treated with long-term haemodialysis (HD) and underwent two kidney transplants with transplantectomies. The patient presented with severe SHPT caused by parathyroid gland hypertrophy. The radiology test showed signs of VC in the radial and interdigital arteries, and VC in a linear arrangement were observed in both breasts on the mammography. Cinacalcet was added to her treatment with vitamin D derivatives and phosphate-binding agents, which resulted in a good control of mineral metabolism. The radiology test showed that the calcification in the interdigital artery had disappeared and that the bone appeared to be more structured. The mammography also showed regression of the VC. To conclude, cinacalcet may have potential for regression of VC in patients with SHPT (AU)

In vitro activities of tigecycline and 10 other antimicrobials against nonpigmented rapidly growing mycobacteria.

We evaluated the in vitro activities of tigecycline and 10 other antibiotics against clinical isolates of nonpigmented rapidly growing mycobacteria. Fifteen collection strains and 165 clinical isolates were included in the study. Tigecycline showed the highest activity among all antibiotics studied: all the strains were inhibited by 1 mg/liter.

Anesthetic management of Klippel-Trénaunay syndrome and attendant gastrointestinal hemorrhage. A case report.

Klippel-Trénaunay syndrome is a congenital malformation characterized by the triad of flat red hemangiomas, soft tissue and bony hypertrophy and varicose veins. In addition, venous malformations or hemangiomas may also be found in the lung, gastrointestinal tract, liver, kidney and bladder, which may result in recurrent hemor-rhage and compromise the affected organs. Involvement of the cerebrum, cerebellum or spinal cord may lead to intracerebral bleeding and compression of neurological structures. Venous thrombosis and pulmonary thromboembolism are both common and may cause pulmonary hypertension and right ventricle failure. In some patients, in addition to flat hemangiomas, cavernous hemangiomas can be seen with a rapid growth rate in the first year of the patient's lifespan, producing high-output congestive heart failure and consumptive coagulopathy (Kasabach-Merritt syndrome). We report the case of a 35-year-old male patient diagnosed with Klippel-Trénaunay syndrome who was scheduled for right hemicolectomy for relapsing gastrointestinal hemorrhage unmanageable with conservative treatment. We also discuss the pathophysiologic and clinical aspects of the Klippel-Trénaunay syndrome. Nowadays, the anesthetic management of these patients remains a matter of controversy.

Canine fresh and cryopreserved semen evaluation.

There is little doubt that objective assessment of multiple parameters related to the functional and morphological characteristics of spermatozoa, increase the predictability of the fertilizing potential of a semen sample. Conventional microscopic methods for sperm evaluation in combination with the more objective computer-assisted sperm motility and morphology analyzers and flow cytometry, have allowed investigators to obtain precise information about the morphofunctional status of spermatozoa, which already has resulted in a better understanding of sperm biology and of some of the mechanisms involved in sperm cryoinjury. In addition, assays based on in vitro fertilization provide valuable information about the functional ability of spermatozoa when interacting with the oocyte. Although objective methods for dog sperm evaluation are available for many researchers, considerable effort has still to be invested in order to standardize physiological sperm parameters for the results to be interpretable under unified criteria. In the present paper some of the classical and new methods currently used for dog sperm evaluation are reviewed, though not exhaustively, covering some aspects of the sperm cell that are useful in estimating its functional ability.

Subarachnoid anesthesia in a patient with type I Gaucher disease.

Gaucher's disease is a rare genetic disorder characterized by lack or functional insufficiency of glucocerebrosidase, an enzyme accountable for intracellular hydrolysis of glucosyl ceramide and other glycosphingolipids, which results in macrophage storage in the mononuclear-macrophage system. The severity of Gaucher's disease is correlated with the extent to which the central nervous system is involved. It is associated with the so-called Gaucher's cells in the bone marrow, but is specifically diagnosed by showing enzyme acid beta-glucosidase activity in a sample of blood leukocyte or cultured macrophages from skin biopsy. In the last 10 years, an enzyme replacement therapy (alglucerase) for the disease has been available, which has significantly changed approaches to its treatment. Here we report the case of a 56-year-old female patient with type I Gaucher's disease who underwent surgery for subcapital hip fracture with subarachnoid anesthesia. Type I Gaucher's disease clinical and pathophysiologic aspects relevant to anesthetic management are discussed. As very few similar cases have been reported in the anesthesiology literature, it is our belief that the present case may help to elucidate some controversial issues relating to the perioperative anesthetic management of patients with type I Gaucher's disease.

[The validity and reliability of a questionnaire for assessing the functional capacity of older persons]. / Validez y fiabilidad de un cuestionario para valorar la capacidad funcional de las personas mayores.

OBJECTIVES: Our aim was to evaluate the validity and reliability of a questionnaire to measure the functional capacity in older people. DESIGN: Observational cross-sectional study. SETTING: Community level. Three basic health areas. PARTICIPANTS: 519 individuals over 64 selected by systematic random sampling taking as sampling units a list of household living at least an individual over 64 years. MEASUREMENTS AND MAIN RESULTS: A new questionnaire was developed starting from the OARS-MFAQ, the CVA. This new questionnaire is shorter but it maintains the same structure. Ten interviews were recorded in a videotape and subsequently analyzed and marked by four different observers to evaluate the inter-observer agreement. To assess the criterion validity the rates of 40 individuals in the CVA were compared with the rates assigned to the same individuals by experts in each area of the questionnaire (physical health, mental health, daily activities, economic resources, and social support). The criterion validity of the version to proxies of CVA (CVA-I) was studied comparing the answers in the CVA of 31 individuals and the answers given in the CVA-I by proxies of the same 31 individuals. The internal consistency in both versions of the questionnaire was studied in 519 individuals, agreement showed values of kappa coefficient between 0.43 and 0.69. Correlation coefficients Interobserver between expert's rates showed values between 0.54 and 0.74. Correlation coefficients between CVA and CVA-I showed values between 0.60 and 0.74 except in the social support dimension (0.16). The Cronbach alpha coefficient were 0.73 for CVA and 0.62 for CVA-I. CONCLUSIONS: The CVA questionnaire showed an acceptable validity and reliability except in the social support dimension of the CVA-I.

[Hemicrania continua]. / Hemicránea continua.

Hemicrania continua is a very rare headache and, as its name implies, is characterised by a continuous, unilateral headache of moderate severity. In most patients, attacks of more intense pain are superimposed. These last from minutes to several days and are sometimes associated with autonomic features. In this review, we shall try to clarify the clinical and pathophysiological features, the nosology, the differential diagnosis and the treatment of this entity.