Long-term survival in pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension: Insights from a referral center in Portugal.

OBJECTIVES: This study aims to assess the long-term survival of pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH) patients followed in a Portuguese pulmonary hypertension (PH) referral center. METHODS: We studied PAH and CTEPH patients diagnosed between January 2005 and December 2016. Cumulative survival was estimated using the Kaplan-Meier method. Survival trends were compared over two periods (2005-2010 vs. 2011-2016). RESULTS: Of the 142 studied PH patients (age 54±18 years; 31% male), 47 had CTEPH and 95 had group 1 PH. Most patients with CTEPH and idiopathic/heritable PAH (I/HPAH) were in NYHA III-IV at diagnosis (64% and 57%, respectively). At the time of death, 31% of patients with connective tissue disease (CTD)-associated PAH (CTD-PAH) and all I/HPAH patients were on double or triple combination therapy. No patient underwent lung transplantation. Pulmonary endarterectomy or angioplasty were performed in 36% of CTEPH patients. Age at diagnosis tended to increase over time in CTD-PAH (53±15 vs. 63±15 years; p=0.13) and I/HPAH (39±15 vs. 51±19 years; p=0.10). The five-year survival estimates for I/HPAH, CTD-PAH and CTEPH patients were 80%, 52%, and 81%, respectively. Over time, CTD-PAH and CTEPH showed better five-year survival (33 vs. 67% and 77 vs. 84%), but I/HPAH did not (84 vs. 75%). CONCLUSIONS: Our data indicate a trend toward improved survival over time of CTD-PAH and CTEPH patients treated at a Portuguese referral PH center. Earlier diagnosis, increasing use of parenteral prostanoids, and surgical treatment may further improve PH prognosis.

Health-Related Quality of Life in Pulmonary Hypertension and Its Clinical Correlates: A Cross-Sectional Study.

BACKGROUND: Health-related quality of life (HRQoL) impairment is common in pulmonary hypertension (PH), but its clinical predictors are not well established. This study aims to characterize the HRQoL of patients with pulmonary arterial hypertension (PAH) and other precapillary forms of PH (pcPH) and to explore its clinical correlates. MATERIALS AND METHODS: A cross-sectional, observational study of patients with documented PAH and other forms of pcPH. Patients completed two patient-reported outcome measures (PROM): Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR) and Nottingham Health Profile (NHP). Clinical characteristics were retrieved from electronic medical records. RESULTS: Mean CAMPHOR and NHP scores for the study population were indicative of a moderate HRQoL impairment. Patients in World Health Organisation Functional Classes (WHO FC) III/IV showed significantly worse HRQoL. The main clinical correlates of HRQoL were WHO FC, 6-minute walking distance (6MWD), and Borg dyspnoea index. Overall quality of life (QoL), assessed through CAMPHOR's QoL domain, showed patterns comparable to HRQoL measured by both instruments. CONCLUSIONS: HRQoL, measured by two different PROMs, is impaired in Portuguese patients with PAH and other forms of pcPH, particularly in patients with increased disease severity. WHO FC, 6MWD, and Borg dyspnoea index are highly correlated with HRQoL and QoL.

Portuguese validation of the Cambridge pulmonary hypertension outcome review (CAMPHOR) questionnaire.

BACKGROUND: Patients with pulmonary arterial hypertension (PAH) and other forms of precapillary pulmonary hypertension (PH) have impaired quality of life (QoL). The Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR) is a PH-specific patient-reported outcome measure that assesses symptoms, activity limitations and QoL. It was originally developed in UK-English. The main objective of this study was to create an adaptation of the CAMPHOR suitable for a Portuguese-speaking population. METHODS: A multi-step approach was followed: bilingual and lay panel translation; cognitive debriefing interviews; and psychometric testing in repeated postal surveys (2 weeks apart) including assessment of internal consistency, reproducibility and validity. The Nottingham Health Profile (NHP) questionnaire was used as a comparator instrument to test convergent validity. RESULTS: The CAMPHOR was translated without difficulty by the two panels. Cognitive debriefing interviews showed the questionnaire was easily understood and considered relevant to patients' experience with their illness. Psychometric evaluation was performed with 50 PAH patients (47 ± 14 years, 37 women). Cronbach's alpha coefficients showed good internal consistency for the three CAMPHOR scales [Symptoms = 0.95; Activities = 0.93 and QoL = 0.94]. Test-retest coefficients showed that all scales had excellent reliability (Symptoms = 0.94; Activities = 0.89 and QoL = 0.93), indicating low levels of random measurement error. The CAMPHOR correlated as expected with the NHP. The magnitude of correlations followed a similar pattern to those in the original development study. The CAMPHOR also exhibited evidence of known group validity in its ability to distinguish between self-reported severity and general health groups. CONCLUSIONS: A valid and reliable version of the CAMPHOR questionnaire for the European Portuguese-speaking population was developed and is recommended for use.

Prosopagnosia as the Presenting Symptom of Whipple Disease.

Whipple disease is a rare, chronic multisystem infectious disease. The central nervous system (CNS) is secondarily involved in 43% of patients; 5% of patients have isolated or primary CNS involvement. The most frequent CNS symptoms are cognitive changes. Prosopagnosia is an inability to recognize familiar faces, in a person who does not have vision impairments or cognitive alterations. This relatively rare condition is usually related to vascular, traumatic, degenerative, or infectious lesions. We report a 54-year-old woman who presented subacutely with fever, headache, and seizures that led to a diagnosis of infectious meningoencephalitis. She improved temporarily on broad-spectrum antibiotics, but then developed a chronically evolving cognitive impairment with associative prosopagnosia as the major complaint. She had a history of sporadic abdominal pain and mild sacroiliac arthralgia. After a negative duodenal biopsy, we confirmed primary CNS Whipple disease by polymerase chain reaction and brain biopsy. We treated the patient with ceftriaxone for 15 days and then co-trimoxazole for 2 years. At 8-year follow-up, she had no further impairments, but continuing prosopagnosia. To our knowledge, this is the first description of isolated prosopagnosia in a patient with primary CNS Whipple disease. Because CNS Whipple disease can lead to serious, irreversible lesions if not promptly treated, clinicians must suspect the diagnosis, treat with long-term antibiotics, and follow patients carefully to prevent recurrence.

Do MCI patients with vitamin B12 deficiency have distinctive cognitive deficits?

BACKGROUND: Vitamin B12 deficiency is common in older people, and may be responsible for reversible dementia. Low serum vitamin B12 levels were also observed in patients with Mild Cognitive Impairment (MCI). It is not known whether patients with vitamin B12 deficiency have a distinctive profile of cognitive impairment different from the episodic memory deficit usually observed in MCI. RESULTS: From a cohort of 310 patients with MCI followed in a memory clinic in Lisbon, only 10 cases with vitamin B12 deficiency were found. From collaboration with other neurologists, 5 further patients with vitamin B12 deficiency were added. These cases were compared to MCI patients with normal vitamin B12 levels in a ratio 1:3. The duration of subjective cognitive symptoms was significantly shorter in MCI patients with B12 deficiency (1.2±1.0 years) as compared to MCI patients with normal vitamin B12 levels (3.4±3.0 years, p<0.001, Student' t test). There were no statistically significant differences in the neuropsychological tests between MCI patients with and without vitamin B12 deficiency. Vitamin B12 was started in MCI patients with vitamin B12 deficiency, with no noticeable clinical improvement. CONCLUSION: MCI patients with low levels of vitamin B12 had no particular profile of cognitive impairment, however vitamin B12 deficiency might have precipitated the onset of symptoms. The effect of vitamin B12 supplementation in patients with MCI and low vitamin B12 levels should be clarified by future prospective studies.

Montreal Cognitive Assessment (MoCA): validation study for vascular dementia.

The Montreal Cognitive Assessment (MoCA) is a brief instrument developed for the screening of milder forms of cognitive impairment, having surpassed the well-known limitations of the MMSE. The aim of the present study was to validate the MoCA as well as its short version, which was proposed by the NINDS-CSN VCI Harmonization Standards for screening Vascular Dementia (VaD) patients. The results, based on a homogeneous sample of 34 VaD patients, indicate that the MoCA is a psychometrically valid and reliable instrument for cognitive screening in VaD patients, showing excellent discriminant validity. Both the full and short versions of the MoCA had excellent diagnostic accuracy in discriminating VaD patients, exhibiting an area under curve (AUC) higher than the MMSE [AUC(MoCA full version) = .950; 95% IC = .868-.988; AUC(MoCA short version) = .936; 95% IC = .849-.981; AUC(MMSE) = .860; 95% IC = .754-.932]. With a cutoff below 17 on the MoCA full version and 8 on the short version, the results for sensitivity, specificity, positive and negative predictive values, and classification accuracy were superior compared to the MMSE. In conclusion, both versions of the MoCA are valid, reliable, sensitive and accurate screening instruments for VaD patients.