Hypophosphatemia as a possible biomarker for epileptic seizures at the emergency department.

INTRODUCTION: Hypophosphatemia seems to be temporally associated with seizures, despite not being considered a trigger. We aimed to evaluate hypophosphatemia as a biomarker for seizures. METHODS: Retrospective study, including all consecutive patients admitted at our central hospital's emergency department from 01/01-31/03/2021, screened as "altered consciousness/syncope" or "seizures", with available phosphate levels. RESULTS: 277 patients included, mostly male (61.7%), mean age 64.3 years. Final diagnosis was "seizure" in 34.7% and "other diagnosis" in 65.3%. Patients with seizures were younger (p<0.001), had more frequent epilepsy (p<0.001) and alcoholism (p=0.01). Patients with other diagnosis had more often renal failure (p<0.001) and statin (p=0.02) or diuretic (p=0.003) therapy. Time to blood collection (from the event and from admission) was similar between groups. Patients with seizures had lower mean phosphate levels and more frequent hypophosphatemia (<2.4mg/dL) (p<0.001). Mean CK levels were similar in both groups (p=0.25). HyperCK (>200U/L) was more frequent in the seizure group (p=0.04). Odds ratio (OR) of hypophosphatemia for seizures was 4.330 (CI 95% 2.170-8.640, p<0.001), persisting after correction for confounders. OR of hyperCK was 1.890 (CI 95% 1.060-3.371, p=0.03), losing significance when adjusted. Sensitivity was low for both. Hypophosphatemia was more specific (91.2% vs 79.9%). CONCLUSIONS: Our findings support hypophosphatemia as a seizure biomarker. More studies are needed.

Safety and Effectiveness of Cladribine in Multiple Sclerosis: Real-World Clinical Experience From 5 Tertiary Hospitals in Portugal.

OBJECTIVES: Cladribine is a selective and oral immunological reconstitution treatment, approved in Europe for very active multiple sclerosis (MS) with relapses. Aims were to assess the safety and effectiveness of cladribine in real-world setting, during treatment follow-up. METHODS: This was a multicentric, longitudinal, observational study with retrospective and prospective data collection of clinical, laboratory, and imaging data. This interim analysis reports data from July 1, 2018 (study onset), to March 31, 2021. RESULTS: A total of 182 patients were enrolled: 68.7% were female; mean age at onset was 30.1 ± 10.0 years, and mean age at first cycle of cladribine treatment was 41.1 ± 12.1; 88.5% were diagnosed with relapse-remitting MS and 11.5% with secondary progressive MS. Mean disease duration at cladribine start was 8.9 ± 7.7 years. Most patients (86.1%) were not naive, and median number of previous disease-modifying therapies was 2 (interquartile range, 1-3). At 12 months, we observed no significant Expanded Disability Status Scale score worsening ( P = 0.843, Mann-Whitney U test) and a significantly lower annualized relapse rate (0.9 at baseline to 0.2; 78% reduction). Cladribine treatment discontinuation was registered in 8% of patients, mainly (69.2%) due to disease activity persistence. Most frequent adverse reactions were lymphocytopenia (55%), infections (25.2%), and fatigue (10.7%). Serious adverse effects were reported in 3.3%. No patient has discontinued cladribine treatment because of adverse effects. CONCLUSION: Our study confirms the clinical efficacy and the safety profile of cladribine for treating MS patients with a long-term active disease in the real-world setting. Our data contribute to the body of knowledge of the clinical management of MS patients and the improvement of related clinical outcomes.

Fatores preditores do desfecho do Teste de Provocação Oral na Alergia à Proteína do Leite de Vaca: in natura vs. alimentos processados / Predictors of the outcome of the Oral Food Challenge for Cow's Milk Protein Allergy: raw vs. processed foods

Objetivos: Descrever uma população de crianças com alergia à proteína do leite de vaca (APLV) IgE mediada, submetidas ao teste de provocação oral (TPO) com alimentos processados vs. in natura, e comparar características clínico-epidemiológicas e laboratoriais, avaliando preditores de desfecho ao uso dessas diferentes apresentações de proteína. Métodos: Estudo transversal realizado em ambulatório de alergia de um hospital terciário em Fortaleza, Ceará. A coleta dos dados foi realizada entre outubro de 2018 a setembro de 2019. O questionário foi preenchido com os dados epidemiológicos, clínicos e laboratoriais encontrados no prontuário; amostra total de 49 crianças, com APLV IgE mediada tolerantes ao TPO com alimentos processados ou in natura. Resultados: Na comparação das características clinico-epidemiológicas das populações tolerantes a alimentos in natura vs. processados (respectivamente), a maioria apresentou dados semelhantes, como sexo masculino (60% vs. 57,9%), etnia parda (73,3% vs. 68,4%), idade gestacional a termo (80% vs. 77,8%), sem intercorrências durante a gestação (58,3% vs. 80,0%) ou parto (70% vs. 78,9), média de idade materna (32 anos vs. 35 anos), escolaridade materna (ensino médio completo - 43,3% vs. 47,4%), idade de início dos sintomas de APLV entre 1 e 6 meses (76,7% vs. 68,4%), aleitamento materno exclusivo entre 4 e 6 meses (60% vs. 68,45%), histórico de alergia familiar alimentar (73% vs. 68,4%), sendo as principais comorbidades alérgicas as respiratórias (38,9% vs. 35,7%) e alimentares (38,9% vs. 35,7%). Em relação aos dados laboratoriais, a maioria das frações de proteína no grupo tolerante a alimentos in natura e a alimentos processados apresentou valores ≤ 10 kU/L. Foi constatado que a idade materna (p = 0,006) e a idade de introdução de fórmula complementar (p = 0.020) se correlacionam de forma estatisticamente significante no grupo de pacientes tolerantes a alimentos processados. Conclusões: Foi observado que a idade materna (p = 0,006) e a idade de introdução de fórmula complementar (p=0.020) se correlacionam de forma estatisticamente significante no grupo de pacientes tolerantes alimentos processados. Os dados laboratoriais seguiram distribuição proporcionais entre os dois grupos, com maior frequência de valores ≤ 10 kU/L para todas as frações de proteína do leite de vaca, sem significância estatística. Estudos populacionais semelhantes em populações APLV IgE mediada são importantes para caracterizar melhor esse fenótipo e otimizar ferramentas diagnósticas e protocolos de tratamento. Destaca-se também o papel da terapia baked, que auxilia na aquisição de tolerância a diferentes apresentações da PLV de forma mais breve, melhorando, portanto, a qualidade de vida desses pacientes (AU)

Objectives: To describe the population of children with IgE-mediated CMPA tolerant to processed or raw CMP in the OFC, comparing their clinical, epidemiological and laboratory characteristics and evaluating the possible predictors of outcomes associated with these different presentations of CMP. Methods: Cross-sectional study carried out in an allergy clinic of a tertiary hospital in Fortaleza, Ceará. Data collection was carried out between October 2018 and September 2019. The questionnaire was filled out with epidemiological, clinical and laboratory data found in the medical records. The total sample was composed of 49 children with IgE-mediated CMPA tolerant to processed or raw foods in the OFC. Results: The comparison of the clinical and epidemiological characteristics of populations tolerant to raw foods vs. processed (respectively) showed similarities, such as the predominance of the male gender (60% vs. 57.9%); mixed ethnicity (73.3% vs. 68.4%); delivery at term (80% vs. 77 .8%); no complications during pregnancy (58.3% vs. 80.0%) or childbirth (70% vs. 78.9); mean maternal age (32 years vs. 35 years); level of education of the mothers (complete high school - 43.3% vs. 47.4%); age of onset of CMPA symptoms between 1 and 6 months (76.7% vs. 68.4%); exclusive breastfeeding for 4 to 6 months (60% vs. 68.45%); family history of food allergy (73% vs. 68.4%); and respiratory (38.9% vs. 35.7%) and food allergies (38.9% vs. 35.7%) as the main allergic comorbidities. Regarding laboratory data, most protein fractions had values ≤ 10 kU/L in both groups. It was found that maternal age (p = 0.006) and age of introduction of formula (p = 0.020) were statistically significant in the group of patients tolerant to processed foods. Conclusions: It was observed that maternal age (p = 0.006) and age of introduction of formula (p = 0.020) were statistically significant in the group of patients tolerant to processed foods. Laboratory data were proportionally distributed across the two groups, with a higher frequency of values lower than or equal to 10 kU/L for all CMP fractions, with no statistical significance between the groups. Similar population studies in IgE-mediated CMPA populations are important to better characterize this phenotype and optimize diagnostic tools and treatment protocols. The role of baked therapy is also noteworthy, as it helps patients to develop tolerance to different presentations of CMP more quickly, improving their quality of life (AU)

Fatores preditores do desfecho do Teste de Provocação Oral na Alergia à Proteína do Leite de Vaca: in natura vs. alimentos processados / Predictors of the outcome of the Oral Food Challenge for Cow's Milk Protein Allergy: raw vs. processed foods

RESUMO: Objetivos: Descrever uma população de crianças com alergia à proteína do leite de vaca (APLV) IgE mediada, submetidas ao teste de provocação oral (TPO) com alimentos processados vs. in natura, e comparar características clínico-epidemiológicas e laboratoriais, avaliando preditores de desfecho ao uso dessas diferentes apresentações de proteína. Métodos: Estudo transversal realizado em ambulatório de alergia de um hospital terciário em Fortaleza, Ceará. A coleta dos dados foi realizada entre outubro de 2018 a setembro de 2019. O questionário foi preenchido com os dados epidemiológicos, clínicos e laboratoriais encontrados no prontuário; amostra total de 49 crianças, com APLV IgE mediada tolerantes ao TPO com alimentos processados ou in natura. Resultados: Na comparação das características clinico-epidemiológicas das populações tolerantes a alimentos in natura vs. processados (respectivamente), a maioria apresentou dados semelhantes, como sexo masculino (60% vs. 57,9%), etnia parda (73,3% vs. 68,4%), idade gestacional a termo (80% vs. 77,8%), sem intercorrências durante a gestação (58,3% vs. 80,0%) ou parto (70% vs. 78,9), média de idade materna (32 anos vs. 35 anos), escolaridade materna (ensino médio completo - 43,3% vs. 47,4%), idade de início dos sintomas de APLV entre 1 e 6 meses (76,7% vs. 68,4%), aleitamento materno exclusivo entre 4 e 6 meses (60% vs. 68,45%), histórico de alergia familiar alimentar (73% vs. 68,4%), sendo as principais comorbidades alérgicas as respiratórias (38,9% vs. 35,7%) e alimentares (38,9% vs. 35,7%). Em relação aos dados laboratoriais, a maioria das frações de proteína no grupo tolerante a alimentos in natura e a alimentos processados apresentou valores ≤ 10 kU/L. Foi constatado que a idade materna (p = 0,006) e a idade de introdução de fórmula complementar (p = 0.020) se correlacionam de forma estatisticamente significante no grupo de pacientes tolerantes a alimentos processados. Conclusões: Foi observado que a idade materna (p = 0,006) e a idade de introdução de fórmula complementar (p=0.020) se correlacionam de forma estatisticamente significante no grupo de pacientes tolerantes alimentos processados. Os dados laboratoriais seguiram distribuição proporcionais entre os dois grupos, com maior frequência de valores ≤ 10 kU/L para todas as frações de proteína do leite de vaca, sem significância estatística. Estudos populacionais semelhantes em populações APLV IgE mediada são importantes para caracterizar melhor esse fenótipo e otimizar ferramentas diagnósticas e protocolos de tratamento. Destaca-se também o papel da terapia baked, que auxilia na aquisição de tolerância a diferentes apresentações da PLV de forma mais breve, melhorando, portanto, a qualidade de vida desses pacientes. (AU)

ABSTRACS: Objectives: To describe the population of children with IgE-mediated CMPA tolerant to processed or raw CMP in the OFC, comparing their clinical, epidemiological and laboratory characteristics and evaluating the possible predictors of outcomes associated with these different presentations of CMP. Methods: Cross-sectional study carried out in an allergy clinic of a tertiary hospital in Fortaleza, Ceará. Data collection was carried out between October 2018 and September 2019. The questionnaire was filled out with epidemiological, clinical and laboratory data found in the medical records. The total sample was composed of 49 children with IgE-mediated CMPA tolerant to processed or raw foods in the OFC. Results: The comparison of the clinical and epidemiological characteristics of populations tolerant to raw foods vs. processed (respectively) showed similarities, such as the predominance of the male gender (60% vs. 57.9%); mixed ethnicity (73.3% vs. 68.4%); delivery at term (80% vs. 77 .8%); no complications during pregnancy (58.3% vs. 80.0%) or childbirth (70% vs. 78.9); mean maternal age (32 years vs. 35 years); level of education of the mothers (complete high school - 43.3% vs. 47.4%); age of onset of CMPA symptoms between 1 and 6 months (76.7% vs. 68.4%); exclusive breastfeeding for 4 to 6 months (60% vs. 68.45%); family history of food allergy (73% vs. 68.4%); and respiratory (38.9% vs. 35.7%) and food allergies (38.9% vs. 35.7%) as the main allergic comorbidities. Regarding laboratory data, most protein fractions had values ≤ 10 kU/L in both groups. It was found that maternal age (p = 0.006) and age of introduction of formula (p = 0.020) were statistically significant in the group of patients tolerant to processed foods. Conclusions: It was observed that maternal age (p = 0.006) and age of introduction of formula (p = 0.020) were statistically significant in the group of patients tolerant to processed foods. Laboratory data were proportionally distributed across the two groups, with a higher frequency of values lower than or equal to 10 kU/L for all CMP fractions, with no statistical significance between the groups. Similar population studies in IgE-mediated CMPA populations are important to better characterize this phenotype and optimize diagnostic tools and treatment protocols. The role of baked therapy is also noteworthy, as it helps patients to develop tolerance to different presentations of CMP more quickly, improving their quality of life. (AU)

Seroconversion rate following HBV vaccination in clinical practice: The role of age and DMT treatment.

HBV screening and immunization is recommended in all MS patients and is mandatory before the start of some DMT. However, studies evaluating the immune response to HBV vaccine in MS patients are scarce. We aimed to evaluate the seroprotection rate following HBV immunization in MS patients and to assess if older age and DMT-treatment influenced seroprotection. We conducted a cohort study between 2016 and 2020 and compared the immune response to HBV vaccine in MS patients under different DMTs and in patients 50 years old or younger and older than 50. We found that patients under non-injectable DMT presented lower rates of seroprotection comparing to patients under injectable DMT's or without treatment. In patients older than 50, although the seroprotection rate was similar to the remaining patients, the antibody anti-HBV surface antigen titers following HBV immunization were lower and patients were more likely to require a 4th dose of the vaccine to achieve seroprotection. Our findings highlight to need to consider HBV immunization in MS patients early in the disease course, in order to ensure a proper immune response to the vaccine.

Intensive Blood Pressure Treatment Reduced Stroke Risk in Patients With Albuminuria in the SPRINT Trial.

Background and Purpose- Albuminuria is associated with stroke risk among individuals with diabetes. However, the association of albuminuria with incident stroke among nondiabetic patients is less clear. Methods- We performed a post hoc analysis of the SPRINT (Systolic Blood Pressure Intervention Trial), which examined the effect of higher versus lower intensity blood pressure management on mortality in 8913 participants without diabetes. We fit unadjusted and adjusted Cox proportional hazards models to estimate the association of baseline albuminuria (urinary albumin-to-creatinine ratio ≥30 mg/g versus<30 mg/g) with stroke risk. We also assessed effect modification according to treatment arms. Results- Mean age was 68±9 years, 35% were female, and 30% were black. Median follow-up was 3.2 years, and 19% patients had baseline albuminuria. Incident stroke occurred in 129 individuals during follow-up. Albuminuria was associated with increased stroke risk (unadjusted hazard ratio, 2.24; 95% CI, 1.55-3.23; adjusted hazard ratio 1.73; 95% CI, 1.17-2.56). The association of albuminuria with incident stroke differed according to the randomized treatment arm (P interaction=0.03). In the intensive treatment arm, the association of albuminuria and stroke was nonsignificant (unadjusted hazard ratio, 1.25; 95% CI, 0.69-2.28), whereas, in the standard treatment arm, it was significant (unadjusted hazard ratio, 3.44; 95% CI, 2.11-5.61). Conclusions- In a post hoc analysis of SPRINT, baseline albuminuria (versus not) was associated with a higher risk of incident stroke, but this relationship appeared to be restricted to those in the standard treatment arm. Further studies are required to conclusively determine if reduction of albuminuria in itself is beneficial in reducing stroke risk. Clinical Trial Registration- URL: https://www.clinicaltrials.gov. Unique identifier: NCT01206062.

A multicenter, non-interventional study to evaluate the disease activity in Multiple Sclerosis after withdrawal of Natalizumab in Portugal.

OBJECTIVES: Natalizumab (NTZ) is very effective for treatment of relapsing-remitting multiple sclerosis (RRMS), its use is mainly limited by safety issues. Discontinuation of NTZ is associated with recurrence of disease activity (reactivation and rebound). The best strategy for subsequent therapy and the predictive factors for recurrence in such patients are areas of active research. We aimed to evaluate predictors of reactivation in a multicentric study. PATIENTS AND METHODS: Multicentric retrospective observational study in five portuguese MS referral centers. Demographic, clinical and imagiological data were collected in the year prior, during and in the year following NTZ discontinuation. Predictors of reactivation and rebound after NTZ suspension were studied using a multivariate Cox model. RESULTS: Sixty-nine patients were included. They were mainly non-naïve patients (97%), with a mean age of 29.1 ±â€¯8.3 years at diagnosis, and a mean age of 37.2 ±â€¯10.3 years at NTZ initiation. The mean annualized relapse rate (ARR) previous, during and after NTZ was 1.6 ±â€¯1.2, 0.2 ±â€¯0.5 and 0.6 ±â€¯1.0, respectively. The median EDSS before, during and after NTZ was 3.5 (IQR 3.3), 3.5 (IQR 3.5) and 4.0 (IQR 3.8), respectively. The median number of infusions was 26.0 (IQR 12.5) and the main reason to NTZ discontinuation was progressive multifocal leukoencephalopathy (PML) risk (70%). After NTZ suspension, reactivation was observed in 25 (36%) patients after a median time of 20.0 (IQR 29.0) weeks. Reactivation predictors in our sample included NTZ suspension for reasons other than PML (adjusted HR = 0.228, 95% CI [0.084- 0.616], p = 0.004), ARR before NTZ (adjusted HR = 1.914 95% [CI 1.330-2.754], p < 0.001) and a longer disease duration at time of NTZ initiation (adjusted HR = 1.154, 95% CI [1.020-1.306], p = 0.023). Rebound occurred in 5 (7%) patients after a median time of 20 (IQR 34.5) weeks. CONCLUSION: Significant predictors of disease reactivation in our cohort were discontinuation of NTZ for reasons other than PML risk, higher disease activity before NTZ treatment, and longer disease duration. Our study provides valuable data of portuguese patients after NTZ withdrawal.

Impaired Fasting Glucose and Chronic Kidney Disease, Albuminuria, or Worsening Kidney Function: A Secondary Analysis of SPRINT.

PURPOSE: Diabetes mellitus is a risk factor for the development and progression of chronic kidney disease (CKD). However, the association of prediabetes with adverse kidney outcomes is uncertain. METHODS: We performed a secondary analysis of the Systolic Blood Pressure Intervention Trial (SPRINT), including 9361 participants without diabetes at baseline. We categorized participants according to fasting glucose level as having impaired fasting glucose [≥100 mg/dL (≥5.6 mmol/L)] or normoglycemia [<100 mg/dL (<5.6 mmol/L)]. Unadjusted and adjusted proportional hazards models were fitted to estimate the association of impaired fasting glucose (vs normoglycemia) with a composite outcome of worsening kidney function [≥30% decrease in estimated glomerular filtration rate (eGFR) to <60 mL/min/1.73 m2 in participants without baseline CKD; ≥50% decrease in eGFR or need for long-term dialysis/kidney transplantation in participants with CKD] or incident albuminuria (doubling of urinary albumin/creatinine ratio from <10 mg/g to >10 mg/g). These outcomes were also evaluated separately and according to CKD status at baseline. RESULTS: Participants' mean age was 67.9 ± 9.4 years, 35.5% were female, and 31.4% were black. The median follow-up was 3.3 years, and 41.8% had impaired fasting glucose. Impaired fasting glucose was not associated with higher rates of the composite outcome [hazard ratio (HR): 0.97; 95% CI: 0.8 to 1.16], worsening kidney function (HR: 1.02; 95% CI: 0.75 to 1.37), or albuminuria (HR: 0.98; 95% CI: 0.78 to 1.23). Similarly, there was no association of impaired fasting glucose with outcomes according to baseline CKD status. CONCLUSIONS: Impaired fasting glucose at baseline was not associated with the development of worsening kidney function or albuminuria in participants of SPRINT.

Lower free triiodothyronine levels within the reference range are associated with higher cardiovascular mortality: An analysis of the NHANES.

BACKGROUND: Thyroid hormones play a central role in cardiovascular homeostasis. Lower free triiodothyronine (FT3) levels have been associated with worse prognosis in several conditions. However, contrary to thyrotropin (TSH) and free thyroxine (FT4), the role of FT3 in morbidity and mortality in the general population remains uncertain. Our objective was to evaluate the association between within the normal range FT3 levels and mortality in the general population. METHODS: We evaluated 7116 adults in the National Health and Nutrition Examination Survey (NHANES) 2001-2002, 2007-2008, and 2009-2010 cycles with mortality evaluated as of December 2011. Exclusion criteria were: pregnancy; history of thyroid disease; use of thyroid-related drugs; and TSH, FT4, or FT3 level outside the reference range. RESULTS: During a median follow-up of 45 months, 357 participants died. In unadjusted analysis, lower FT3 levels were associated with higher all-cause (HR per 0.1 pg/mL increase in FT3: 0.82 [95% confidence interval, 0.78-0.87]), cardiovascular (HR 0.74 [0.66-0.83]), cancer-related (HR 0.88 [0.80-0.97]) and other cause-related mortality (HR 0.83 [0.77-0.90]). After adjustment with Cox proportional hazard models, lower FT3 levels remained significantly associated with higher cardiovascular mortality (HR 0.83 [0.75-0.93]), but not with all-cause (HR 0.97 [0.92-1.02]), cancer-related (HR 1.02 [0.89-1.17]), or other cause-related mortality (HR 1.00 [0.92-1.10]). CONCLUSIONS: Lower levels of FT3 within the reference range may independently predict higher cardiovascular mortality in the general population.

[Prescribing of Non-Steroidal Anti-Inflammatory Drugs to Patients with Diabetes Mellitus in Portugal]. / Prescrição de Anti-Inflamatórios Não Esteroides a Doentes com Diabetes Mellitus em Portugal.

INTRODUCTION: Portugal presents the highest incidence of stage 5 chronic kidney disease in Europe. It is speculated that a high consumption of non-steroidal anti-inflammatory drugs (NSAIDS) may contribute to this high incidence. Our aim was to characterize the prescription of non-steroidal anti-inflammatory drugs to patients with diabetes mellitus in Portugal. MATERIAL AND METHODS: We analyzed the national prescription database in triennium 2015 - 2017. In patients with diabetes mellitus, we evaluated the prescription of non-steroidal anti-inflammatory drugs according to age, gender and region of the patient and specialty of the prescribing physician. We evaluated the prescription of non-steroidal anti-inflammatory drugs in all patients with diabetes mellitus, in patients with presumed renal impairment, and in those with concomitant prescription of angiotensin converting enzyme inhibitors or angiotensin receptor antagonists. RESULTS: We analyzed 23 320 620 prescriptions, corresponding to 610 157 adults, including 104 306 patients with diabetes mellitus. The most prescribed non-steroidal anti-inflammatory drugs were ibuprofen (20.1%), metamizole (14.7%), and diclofenac (11.4%). The prescription of non-steroidal anti-inflammatory drugs was higher in females, in patients aged 51 - 70 years and in the Alentejo region. Non-steroidal anti-inflammatory drugs were prescribed to 70.6% of patients with diabetes mellitus, from which 10.6% were prescribed ≥ 10 packages during the three years. Among patients with diabetes mellitus on angiotensin converting enzyme inhibitors/angiotensin receptor antagonists and with presumed reduction in kidney function, 69.3% were prescribed non-steroidal anti-inflammatory drugs and 11.5% were prescribed ≥ 10 packages during the three years. DISCUSSION: The level of prescribing of non-steroidal anti-inflammatory drugs to patients with diabetes mellitus is high. The concern of reducing non-steroidal anti-inflammatory drugs prescription to patients already on angiotensin converting enzyme inhibitors/angiotensin receptor antagonists and/or decreased renal function does not seem to exist. CONCLUSION: In Portugal, the level of prescribing of non-steroidal anti-inflammatory drugs to patients with diabetes mellitus should be reduced, particularly in the subgroups identified with higher prescription and with higher risk of progression to stage 5 chronic kidney disease.

Introdução: Portugal apresenta a incidência mais elevada de doença renal crónica estádio 5 na Europa. Especula-se que o elevado consumo de anti-inflamatórios não esteroides possa contribuir para esta incidência. O objetivo do presente estudo foi caracterizar a prescrição de anti-inflamatórios não esteroides a doentes com diabetes mellitus em Portugal. Material e Métodos: Na Base de Dados Nacional de Prescrições do Ministério da Saúde, triénio 2015 - 2017, analisámos a prescrição de anti-inflamatórios não esteroides em doentes com diabetes mellitus, de acordo com a idade, género e região do doente e a especialidade do médico prescritor. Avaliámos a prescrição de anti-inflamatórios não esteroides no total de doentes com diabetes mellitus, em doentes com diminuição presumida da função renal e naqueles com prescrição concomitante de inibidores da enzima de conversão da angiotensina ou antagonistas dos recetores da angiotensina. Resultados: Analisámos 23 320 620 prescrições, correspondendo a 610 157 adultos, dos quais 104 306 doentes com diabetes mellitus. Os anti-inflamatórios não esteroides mais prescritos foram ibuprofeno (20,1%), metamizol (14,7%) e diclofenac (11,4%). A prescrição foi mais frequente nas mulheres, nos doentes com 51 - 70 anos e no Alentejo. Foram prescritos anti-inflamatórios não esteroides a 70,6% dos doentes com diabetes mellitus, dos quais 10,6% receberam prescrições de ≥ 10 embalagens durante os três anos. Dos doentes com diabetes mellitus medicados com inibidores da enzima de conversão da angiotensina ou antagonistas dos receptores da angiotensina e com diminuição presumida da taxa de filtração glomerular, 69,3% receberam prescrição de anti-inflamatórios não esteroides e 11,5% receberam ≥ 10 embalagens durante os três anos. Discussão: A prescrição de anti-inflamatórios não esteroides na diabetes mellitus é elevada. Não parece existir uma preocupação na menor utilização de anti-inflamatórios não esteroides em doentes simultaneamente medicados com inibidores da enzima de conversão da angiotensina ou antagonistas dos recetores da angiotensina e/ou com diminuição da função renal. Conclusão: A prescrição de anti-inflamatórios não esteroides em Portugal a doentes com diabetes mellitus deverá ser reduzida, particularmente nos subgrupos identificados com prescrição mais elevada e com maior risco de progressão para doença renal crónica estádio 5.

Caffeine consumption and mortality in chronic kidney disease: a nationally representative analysis.

BACKGROUND: An inverse relationship between coffee consumption and mortality has been reported in the general population. However, the association between caffeine consumption and mortality in patients with chronic kidney disease (CKD) remains uncertain. METHODS: We analysed 4863 non-institutionalized USA adults with CKD [defined by an estimated glomerular filtration rate (eGFR) of 15-60 mL/min/1.73 m2 and/or a urinary albumin:creatinine ratio >30 mg/g] in a nationwide study using the National Health and Nutrition Examination Survey (NHANES) 1999-2010. Caffeine consumption was evaluated by 24-h dietary recalls at baseline and all-cause, cardiovascular and cancer mortality were evaluated until 31 December 2011. We also performed an analysis of caffeine consumption according to its source (coffee, tea and soft drinks). Quartiles of caffeine consumption were <28.2 mg/day (Q1), 28.2-103.0 (Q2), 103.01-213.5 (Q3) and >213.5 (Q4). RESULTS: During a median follow-up of 60 months, 1283 participants died. Comparing with Q1 of caffeine consumption, the adjusted hazard ratio for all-cause mortality was 0.74 [95% confidence interval (CI) 0.60-0.91] for Q2, 0.74 (95% CI 0.62-0.89) for Q3 and 0.78 (95% CI 0.62-0.98) for Q4 (P = 0.02 for trend across quartiles). There were no significant interactions between caffeine consumption quartiles and CKD stages or urinary albumin:creatinine ratio categories regarding all-cause mortality. CONCLUSIONS: We detected an inverse association between caffeine consumption and all-cause mortality among participants with CKD.

Caffeine Consumption and Mortality in Diabetes: An Analysis of NHANES 1999-2010.

Aim: An inverse relationship between coffee consumption and mortality has been reported in the general population. However, the effect of coffee consumption in diabetes remains unclear. We aimed to evaluate the association of caffeine consumption and caffeine source with mortality among patients with diabetes. Methods: We examined the association of caffeine consumption with mortality among 1974 women and 1974 men with diabetes, using the National Health and Nutrition Examination Survey (NHANES) 1999-2010. Caffeine consumption was assessed at baseline using 24 h dietary recalls. Cox proportional hazard models were fitted to estimate hazard ratios (HR) for all-cause, cardiovascular, and cancer-related mortality according to caffeine consumption and its source, adjusting for potential confounders. Results: A dose-dependent inverse association between caffeine and all-cause mortality was observed in women with diabetes. Adjusted HR for death among women who consumed caffeine, as compared with non-consumers, were: 0.57 (95% CI, 0.40-0.82) for <100 mg of caffeine/day, 0.50 (95% CI, 0.32-0.78) for 100 to <200 mg of caffeine/day, and 0.39 (95% CI, 0.23-0.64) for ≥200 mg of caffeine/day (p = 0.005 for trend). This association was not observed in men. There was a significant interaction between sex and caffeine consumption (p = 0.015). No significant association between total caffeine consumption and cardiovascular or cancer mortality was observed. Women who consumed more caffeine from coffee had reduced risk of all-cause mortality (p = 0.004 for trend). Conclusion: Our study showed a dose-dependent protective effect of caffeine consumption on mortality among women with diabetes.

BP Reduction, Kidney Function Decline, and Cardiovascular Events in Patients without CKD.

BACKGROUND AND OBJECTIVES: In the Systolic Blood Pressure Intervention Trial (SPRINT), intensive systolic BP treatment (target <120 mm Hg) was associated with fewer cardiovascular events and higher incidence of kidney function decline compared with standard treatment (target <140 mm Hg). We evaluated the association between mean arterial pressure reduction, kidney function decline, and cardiovascular events in patients without CKD. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We categorized patients in the intensive treatment group of the SPRINT according to mean arterial pressure reduction throughout follow-up: <20, 20 to <40, and ≥40 mm Hg. We defined the primary outcome as kidney function decline (≥30% reduction in eGFR to <60 ml/min per 1.73 m2 on two consecutive determinations at 3-month intervals), and we defined the secondary outcome as cardiovascular events. In a propensity score analysis, patients in each mean arterial pressure reduction category from the intensive treatment group were matched with patients from the standard treatment group to calculate the number needed to treat regarding cardiovascular events and the number needed to harm regarding kidney function decline. RESULTS: In the intensive treatment group, 1138 (34%) patients attained mean arterial pressure reduction <20 mm Hg, 1857 (56%) attained 20 to <40 mm Hg, and 309 (9%) attained ≥40 mm Hg. Adjusted hazard ratios for kidney function decline were 2.10 (95% confidence interval, 1.22 to 3.59) for mean arterial pressure reduction between 20 and 40 mm Hg and 6.22 (95% confidence interval, 2.75 to 14.08) for mean arterial pressure reduction ≥40 mm Hg. In propensity score analysis, mean arterial pressure reduction <20 mm Hg presented a number needed to treat of 44 and a number needed to harm of 65, reduction between 20 and <40 mm Hg presented a number needed to treat of 42 and a number needed to harm of 35, and reduction ≥40 mm Hg presented a number needed to treat of 95 and a number needed to harm of 16. CONCLUSIONS: In the intensive treatment group of SPRINT, larger declines in mean arterial pressure were associated with higher incidence of kidney function decline. Intensive treatment seemed to be less favorable when a larger reduction in mean arterial pressure was needed to attain the BP target.

Macrossomias / Macrosomia

O termo macrossomia é utilizado para nomear recém-nascidos com peso superior a 4.000-4.500 gramas. É uma patologia que tem prevalência relativamente alta nos países desenvolvidos, girando em torno de 10%; no Brasil se estima uma média aproximada de 5,3%. Essa diferença pode ser explicada pelo fato de que a sociedade brasileira se encontra inserida em um contexto intermediário de transição nutricional; se tal contexto fosse avançado, poder-se-ia esperar um aumento desta incidência. É importante salientar que são vários os aspectos que contribuem para o nascimento de fetos macrossômicos, que vão desde causas metabólicas, como o diabetes mellitus gestacional, o ganho de peso gestacional excessivo e a obesidade materna, até síndromes essencialmente genéticas. Com base em tal informação, verifica-se a necessidade contínua de estudar essa afecção. Neste estudo se pretende pontuar as principais causas de macrossomia fetal pré-natal, assim como suas características gerais e específicas, os métodos diagnósticos, as principais complicações e as condutas a serem adotadas. Além disso, a questão do aconselhamento genético também será levada em consideração.