Blood pressure responses to hypertension treatment and trends in cognitive function in patients with initially difficult-to-treat hypertension: a retrospective subgroup analysis of the Observational Study on Cognitive Function and SBP Reduction (OSCAR) study

J Clin Hypertens (Greenwich). 2012;14:78–84. ©2012 Wiley Periodicals, Inc.The Observational Study on Cognitive Function and SBP Reduction (OSCAR) provided opportunities to examine the influence of eprosartan on trends in cognitive performance in a large population of patients with difficult‐to‐treat hypertension (DTTH). A total of 4649 patients diagnosed retrospectively with DTTH, defined as systolic/diastolic blood pressure (SBP/DBP) ≥140/90 mm Hg despite use of at least 3 antihypertensive drugs during the month preceding the baseline visit comprised the intention‐to‐treat (ITT) cohort. The patients were given eprosartan‐based antihypertension therapy (EBT; 600 mg/d). Blood pressure and cognitive function parameters included significant (P<.001) differences for DTTH vs non‐DTTH patients such as older age, body mass index, SBP and pulse pressure (PP), and lower Mini‐Mental State Examination (MMSE) score. After EBT for 6 months, SBP/DBP in DTTH was 138.8±12.2/81.9±7.4 (ΔSBP−26±15.7; ΔDBP−11.4±9.8); PP was 57.0±10.8 (ΔPP−14.5±13.8) (all P<.001 vs baseline and non‐DTTH group). A total of 2576 patients (87.4%) responded to EBT (ie, SBP <140 mm Hg and/or ΔSBP ≥15 mm Hg, or DBP <90 mm Hg and/or ΔDBP ≥10 mm Hg); 1426 DTTH patients (48.4%) achieved normalized SBP/DBP (ie, SBP <140 mm Hg and DBP <90 mm Hg). ΔPP in DTTH‐isolated systolic hypertension (ISH) was −18.0±13.3 mm Hg (P=.003 vs DTTH‐systolic‐diastolic hypertension). End‐of‐EBT mean MMSE was 27.5±3.0 (P<.001 vs baseline). Blood pressure responses after EBT coincided with stabilization/improvement of MMSE in this retrospective investigation in DTTH patients. The average improvement in MMSE in DTTH patients was similar to that in non‐DTTH patients. EBT effects on PP may be relevant to the evolution of MMSE in DTTH‐ISH patients.

The Observational Study on Cognitive Function and SBP Reduction (OSCAR) was designed to examine the safety and tolerability of once‐daily therapy with eprosartan in a very large community‐dwelling population of patients with arterial hypertension recruited in 28 countries and managed in routine primary care. This study provided opportunities to examine the influence of the angiotensin receptor blocker (ARB) eprosartan on trends in cognitive performance in a large population of patients with high blood pressure (BP).The principal findings of OSCAR have been reported previously. ¹ A 6‐month period of antihypertensive therapy based on eprosartan was associated with a significant reduction in mean systolic BP (SBP) and a significant improvement in mean Mini‐Mental State Examination (MMSE) score (P<.0001 for both outcomes). In multiple linear regression, cognitive decline was demonstrated to be independently and inversely correlated with SBP reduction (odds ratio, 0.77; 95% confidence interval [CI], 0.73–0.82).The intention‐to‐treat (ITT) cohort of OSCAR comprised 25,745 adult patients with hypertension. This large number of patients enabled us to identify several large subgroups for further investigation, with the intention of adding to what are still sometimes limited epidemiologic data on specific types of patients.Recent revisions to extant European hypertension guidelines and first reports of new treatment options for this condition ² , ³ , ⁴ are indications that resistant hypertension is a pressing clinical priority. Poorly controlled high BP may be a factor in cognitive decline in older patients. Observations from several thousand patients in a real‐world survey may be instructive for the better management of this condition. Accordingly, we report here our findings in a retrospectively identified cohort of almost 3000 patients from the OSCAR population classified as having difficult‐to‐treat hypertension (DTTH) at baseline.     

Clinical profile and response to steroids in post-fever retinitis: a nine-year experience from a referral institute in the rural hinterland of Central India

Purpose

To describe the demographics, clinical features, and treatment outcomes with systemic steroids in eyes presenting with post-fever retinitis (PFR) from Central India.

Methods

Single-center, retrospective analysis of 147 eyes of 98 PFR cases between 2011 and 2019.

Results

Mean age of the study cohort was 33.46?±?12.76 years, with 72 males and 26 females. The mean interval between the onset of fever and the diminution of vision was 21.10?±?13.54 days (range 0–60 days). The number of PFR cases increased over the nine years with 89 cases (90.1%) presenting during winters. Unilateral involvement was seen in 49 cases, while 49 had bilateral involvement. Clinical characteristics included: multifocal retinitis (n?=?122; 61.2%), hemorrhages (n?=?132; 89.8%), disc edema (n?=?57; 38.8%), anterior chamber reaction (n?=?28; 19%), and vitritis (n?=?103; 70.1%). Treatment included intravenous followed by oral steroids in 70 patients and oral steroids exclusively in 23; five patients denied treatment. The visual acuity improved from 1.09?±?0.52 LogMAR to 0.29?±?0.42 LogMAR (p?<?0.05).

Conclusion

There has been an increase in the prevalence of PFR cases over the last decade with clustering during the winters. Multifocal retinitis, retinal hemorrhages, and vitritis were the most common clinical findings in our series. The retinitis resolved with improvement in vision following steroid therapy in all eyes.

     

Morphometric and Histological Study of Breast Lesions with Special Reference to Proliferative Activity and Invasiveness

Breast carcinoma is the most common cause of carcinoma death in women. Sometimes, difficulty arises to differentiate between premalignant lesions and carcinoma by routine histopathology. Our study was done to establish the role of morphometry and immunohistochemistry to solve this problem. In this study, total 60 cases of different breast lesions were included and 10 controls were also included to compare the results with the normal findings. They were studied by hematoxylin and eosin-stained sections for morphometry and routine histological study; as well as by proliferative markers such as proliferating cell nuclear antigen and p53. Invasiveness was studied using immunohistochemical staining with 34 βE12 monoclonal antibody. Statistically significant differences were found in morphometric parameters and in expression of proliferative markers between most of them. Morphometry and immunohistochemistry help in the proper diagnosis of different breast lesions that lie in the gray zone on routine histopathology.     

Energy Failure

Energy failure from mitochondrial dysfunction is proposed to be a central mechanism leading to neuronal death in a range of neurodegenerative diseases. However, energy failure has never been directly demonstrated in affected neurons in these diseases, nor has it been proved to produce degeneration in disease models. Therefore, despite considerable indirect evidence, it is not known whether energy failure truly occurs in susceptible neurons, and whether this failure is responsible for their death. This limited understanding results primarily from a lack of sensitivity and resolution of available tools and assays and the inherent limitations of in vitro model systems. Major advances in these methodologies and approaches should greatly enhance our understanding of the relationship between energy failure, neuronal dysfunction, and death, and help us to determine whether boosting bioenergetic function would be an effective therapeutic approach. Here we review the current evidence that energy failure occurs in and contributes to neurodegenerative disease, and consider new approaches that may allow us to better address this central issue. Ann Neurol 2013;74:506–516     

Primary sleep disorders seen at a Neurology service-based sleep clinic in India: Patterns over an 8-year period

There is an increasing awareness for recognition of sleep disorders in India; however, there is still a huge gap in the number of people suffering from various sleep disorders, in the community versus those visiting hospital clinics for the same. Ours is a neurology services-based sleep disorders clinic, which has evolved successfully over the last decade. In this study, we aimed to evaluate the changes in referral patterns and distribution of various sleep disorders in the patients presenting to the clinic.

Materials and Methods:

This is a retrospective chart review-based study on all patients seen over an 8-year period, divided into 2 groups comprising of patients seen during the first 4 years versus those seen over the next 4 years. Only those patients who had the sleep disorder as their presenting manifestation and those who had been formally interviewed with a pre-structured questionnaire detailing about the main features of the common sleep disorders according to the ICSD-R were included. Patients, in whom the sleep disorder could be clearly attributable to another neurological or systemic disorder, were excluded. Statistical analysis was carried out to identify the differences between the two groups as regards the distribution of various sleep disorders and other clinical data.

Results:

Among 710 patients registered in the clinic, 469 were included for analysis and 222 patients formed group 1 while 247 formed group 2. The main differences observed were in the form of a clear increase in the percentage of patients with sleep-related breathing disorders, sleep-related movement disorder, and the hypersomnias on comparison of distribution over the first 4 years versus the last 4 years; while a clear decline was seen in the number of patients with insomnia and parasomnias. A 3-fold increase was observed in the number of patients in whom polysomnography was obtained.

Conclusion:

The distribution of various sleep disorders as seen in a neurology service-based sleep clinic is demonstrated in this study. Increasing referrals for sleep-disordered breathing, restless legs syndrome, and fewer referrals for insomnia and parasomnias might reflect on changing physician and patient awareness in our community.     

Multistage antiplasmodial activity of hydroxyethylamine compounds,in vitro and in vivo evaluations

Malaria, a global threat to the human population, remains a challenge partly due to the fast-growing drug-resistant strains of Plasmodium species. New therapeutics acting against the pathogenic asexual and sexual stages, including liver-stage malarial infection, have now attained more attention in achieving malaria eradication efforts. In this paper, two previously identified potent antiplasmodial hydroxyethylamine (HEA) compounds were investigated for their activity against the malaria parasite''s multiple life stages. The compounds exhibited notable activity against the artemisinin-resistant strain of P. falciparum blood-stage culture with 50% inhibitory concentrations (IC₅₀) in the low micromolar range. The compounds'' cytotoxicity on HEK293, HepG2 and Huh-7 cells exhibited selective killing activity with IC₅₀ values > 170 μM. The in vivo efficacy was studied in mice infected with P. berghei NK65, which showed a significant reduction in the blood parasite load. Notably, the compounds were active against liver-stage infection, mainly compound 1 with an IC₅₀ value of 1.89 μM. Mice infected with P. berghei sporozoites treated with compound 1 at 50 mg kg⁻¹ dose had markedly reduced liver stage infection. Moreover, both compounds prevented ookinete maturation and affected the developmental progression of gametocytes. Further, systematic in silico studies suggested both the compounds have a high affinity towards plasmepsin II with favorable pharmacological properties. Overall, the findings demonstrated that HEA and piperidine possessing compounds have immense potential in treating malarial infection by acting as multistage inhibitors.

Malaria, a global threat to the human population, remains a challenge partly due to the fast-growing drug-resistant strains of Plasmodium species.     

Clinical characteristics of bipolar disorder in very young children

BACKGROUND: Clinical information about bipolar disorder (BPD) in preschool-age (3-7 years old) children is extremely limited. This study examined clinical presentations, applicability of the DSM-IV diagnostic criteria, comorbidity, recovery and relapse rates, as well as some treatment strategies used in the management of BPD in preschoolers. METHODS: The charts of 26 outpatient children, ages 3-7, refereed to a child psychiatry outpatient clinic with mood and behavioral symptoms, were retrospectively reviewed. RESULTS: The majority of the patients were referred with the tentative diagnosis of ADHD but the most common diagnoses made by child and adolescent psychiatrists at the time of initial evaluation were BPD NOS (61.5%), followed by BPD I (26.9%), and mood disorder NOS (23.1%). Thirty-eight percent of the patients had one or more comorbid diagnoses. The most common presenting symptoms were irritability (84.6%) and aggression (88.5%). The most widely prescribed class of medications after diagnosis in the clinic was atypical antipsychotics and mood stabilizers. Twenty-six percent of the patients were treated with a combination of atypical antipsychotics and mood stabilizers. LIMITATIONS: Retrospective design; small sample size; lack of a comparison group. CONCLUSIONS: The course of BPD with onset in preschool years is complicated with high recovery and relapse rates. The questions of development of age-appropriate diagnostic criteria, long-term prognosis and treatment strategies used in this population require further intensive investigation.