When and How to Treat Agitation in Alzheimer's Disease Dementia With Citalopram and Escitalopram.

Agitation is a common neuropsychiatric symptom (NPS) in the early and middle stages of Alzheimer's disease (AD) dementia, which is difficult to treat and causes much distress. The U.S. Food and Drug Administration (U.S. FDA) issued black box warnings against the use of antipsychotics in dementia in 2005 and 2008 due to the increased risk of morbidity and mortality, resulting in the reduction in antipsychotic use for treating dementia-related NPS and spurring the quest for safer and more effective pharmacological options. The data favoring the use of citalopram for treating agitation in AD dementia is particularly compelling, and this may be a class effect for all selective serotonin reuptake inhibitors. However, concerns about the cardiac side-effects of citalopram have limited its widespread use for this indication. In this article, available efficacy and safety data for the use of citalopram and escitalopram in treating agitation in AD dementia is reviewed, using a composite case to illustrate key points. Practical recommendations are made to facilitate the use of these medications in routine clinical practice, risk mitigation strategies are discussed and salient issues for future clinical research are emphasized.

Xanthoma of the urinary bladder - A rare entity.

Xanthomas of the urinary bladder are rare. They may be associated with metabolic disorders. We hereby report a case of bladder xanthoma.

Course of Hyposmia and Hypogeusia and their Relationship with Severity of COVID-19 Disease among Indian Population.

AIMS: Hyposmia and hypogeusia are one of the symptoms of COVID-19. Occurrence and course of these symptoms and their relationship with severity of COVID-19 disease are studied. MATERIALS AND METHODS: This was a prospective cohort study, including consenting adult SARS CoV-2 positive patients of both genders, admitted to a Covid Hospital in Puducherry, India. This questionnaire- based study was conducted for a period 4 months from 1st October 2020 to 31st January 2021, and collected data was analyzed using SPSS version 24.0 software. RESULTS: Out of 639 participants, 412 (64.5%) were males, 227 (35.5%) were females. Total cases of new onset hyposmia were 167 (26.1%), and total patients with new onset hypogeusia were 172 (26.91%). 216 (33.80%) had either hyposmia/hypogeusia. First symptom as hyposmia was noted in 49 (7.67%) patients, and as hypogeusia in 20 (3.13%) patients before development of any other symptoms. 216 (33.80%) patients had either smell or taste disturbance as one of their symptoms. By the end of 5 weeks of illness, 96.41% of hyposmic patients, and 97.67% of hypogeusic patients recovered fully. There was no statistically significant difference between presence or absence of hyposmia/hypogeusia and severity of COVID-19 disease (p value = 0.95). CONCLUSION: The occurrence of hyposmia and hypogeusia among Indian COVID-19 patients is more than 26%. Presence or absence of hyposmia/hypogeusia is not a predictor of severity of COVID-19 disease. More than 96% of the patients fully recovered their sense of smell and taste sensation by the end of 5 weeks.

Microbiome and colorectal carcinogenesis: Linked mechanisms and racial differences.

Various studies have shown the interplay between the intestinal microbiome, environmental factors, and genetic changes in colorectal cancer (CRC) development. In this review, we highlight the various gut and oral microbiota associated with CRC and colorectal adenomas, and their proposed molecular mechanisms in relation to the processes of "the hallmarks of cancer", and differences in microbial diversity and abundance between race/ethnicity. Patients with CRC showed increased levels of Bacteroides, Prevotella, Escherichia coli, enterotoxigenic Bacteroides fragilis, Streptococcus gallolyticus, Enterococcus faecalis, Fusobacterium nucleatum (F. nucleatum) and Clostridium difficile. Higher levels of Bacteroides have been found in African American (AA) compared to Caucasian American (CA) patients. Pro-inflammatory bacteria such as F. nucleatum and Enterobacter species were significantly higher in AAs. Also, AA patients have been shown to have decreased microbial diversity compared to CA patients. Some studies have shown that using microbiome profiles in conjunction with certain risk factors such as age, race and body mass index may help predict healthy colon vs one with adenomas or carcinomas. Periodontitis is one of the most common bacterial infections in humans and is more prevalent in Non-Hispanic-Blacks as compared to Non-Hispanic Whites. This condition causes increased systemic inflammation, immune dysregulation, gut microbiota dysbiosis and thereby possibly influencing colorectal carcinogenesis. Periodontal-associated bacteria such as Fusobacterium, Prevotella, Bacteroides and Porphyromonas have been found in CRC tissues and in feces of CRC patients. Therefore, a deeper understanding of the association between oral and gastrointestinal bacterial profile, in addition to identifying prevalent bacteria in patients with CRC and the differences observed in ethnicity/race, may play a pivotal role in predicting incidence, prognosis, and lead to the development of new treatments.

Correlation of Pretransplant Donor-specific Antibody Assay Using Luminex Crossmatch with Graft Outcome in Renal Transplant Patients.

The significance of pretransplant anti-human leukocyte antigen antibody levels that are detectable by more sensitive platforms (including the Luminex platform) yet undetected by complement-dependent cytotoxicity (CDC) assay remains unclear. The aim of this study was to determine the clinical significance of the donor-specific antibody (DSA) assay Luminex crossmatch and its impact on short-term renal graft outcome such as acute rejections, graft survival, and graft function. The results of pretransplant DSA-lymphocyte crossmatching (LCXM) assay in 126 renal allograft recipients whose CDCs crossmatches were negative were retrospectively analyzed for correlation with posttransplant outcomes. Of the 126 recipients, 32 (25.4%) had pretransplant DSA positive. Statistically significant association was found between DSA-LCXM positivity with 14th day estimated glomerular filtration rate (eGFR) (P = 0.05), DSA Class I with 3rd (P = 0.014) and 6th month (P = 0.02) eGFR, DSA Class II with 14th day (P = 0.06) and 1st month (P = 0.10) eGFR, mean fluorescent intensity (MFI) DSA with 7th day (P = 0.08) and 14th day (P = 0.09) eGFR, and maximum MFI DSA with 7th day eGFR (P = 0.09). The posttransplant eGFR was higher at various time intervals in DSA-LCXM-negative patients as compared to DSA-positive patients. However, pretransplant DSA-LCXM results did not predict the rejection episodes, graft loss, and 1-year posttransplant 24 h urine protein. Pretransplant DSA detected by LCXM in patients with a negative CDC does not predict adverse short-term outcomes. However, the difference in posttransplant eGFR supports further investigation in long-term effects.

Blockade of human and porcine myocardial 5-HT4 receptors by SB 203186.

We investigated the blockade of the positive inotropic effects of 5-hydroxytryptamine (5-HT) by SB 203 186 (piperidinoethyl-indole-3-carboxylate hydrochloride) and its affinity for 5-HT4 receptors of human right atrium and piglet left atrium. We also compared the blocking effects of SB 203 186 against 5-HT-evoked tachycardia in anaesthetised adult Yucatan minipigs as well as new-born Camborough piglets. SB 203 186 caused competitive antagonism of the positive inotropic effects of 5-HT in electrically paced atrial preparations of man (pKB = 8.9) and piglet (pKB = 8.5) at concentrations (up to 0.3 micromol/l) which were devoid of depressant or stimulant effects. The affinity of SB 203 186 for atrial 5-HT4 receptors was 30-160 times higher than that of tropisetron. 5-HT caused tachycardia with similar potency and efficacy in Yucatan minipigs and new-born Camborough piglets. SB 203 186 (0.1-3 mg/kg, i.v.) surmountably antagonised 5-HT-evoked tachycardia in anaesthetised Yucatan minipigs or new-born Camborough piglets with similar potency. The blocking potency of SB 203 186 in Yucatan minipigs was 17 times higher than that of tropisetron. Intraduodenally administered SB 203 186 (0.3-3 mg/kg) to new-born Camborough piglets produced blockade of 5-HT-evoked tachycardia which was maximal after 20 min and lasted for more than 3 h with 0.3 mg/kg. The antagonism produced by the SB 203 186 administration in new-born Camborough piglets was dose-related and threefold greater through the intravenous route than through the intraduodenal route. We conclude that SB 203 186 is an antagonist with nanomolar affinity for both human and porcine atrial 5-HT4 receptor. The in vivo results demonstrate that the sinoatrial 5-HT4 receptors function is similar in new-born Camborough piglets and adult Yucatan minipigs. Both porcine breeds are valid models for human atrial 5-HT4 receptors as demonstrated with the antagonist SB 203 186.

Lack of a clinically important pharmacokinetic interaction between sofosbuvir or ledipasvir and hormonal oral contraceptives norgestimate/ethinyl estradiol in HCV-uninfected female subjects.

This study evaluated the potential for a drug-drug interaction between HCV direct-acting antivirals sofosbuvir or ledipasvir and oral hormonal contraceptive (OC) norgestimate/ethinyl estradiol (norgestimate 0.18/0.215/0.25 mg with ethinyl estradiol 25 µg). This was a 112-day, open-label, fixed-sequence pharmacokinetic (PK) study in healthy female subjects that included a lead-in cycle (OC only; N = 21), cycle 1 (OC only; N = 15), cycle 2 (OC + sofosbuvir; N = 15), and cycle 3 (OC + ledipasvir; N = 15). Administration of sofosbuvir with OC did not alter PK of norelgestromin (primary norgestimate metabolite) or ethinyl estradiol. Small increases in norgestrel (secondary norgestimate metabolite) AUC(tau) (19%) and C(tau) (23%) with sofosbuvir were noted. Ledipasvir did not impact PK of norelgestromin or norgestrel but modestly increased ethinyl estradiol C(max) (40%). Sofosbuvir, GS- 331007 (predominant circulating metabolite of SOF), and ledipasvir PK were similar to historical data. Pharmacodynamic markers luteinizing hormone, follicle-stimulating hormone, and progesterone values were generally comparable in all cycles. No loss in contraceptive efficacy is expected upon administration of sofosbuvir or ledipasvir/sofosbuvir with oral contraceptives containing norgestimate and ethinyl estradiol. The use of sofosbuvir or ledipasvir/sofosbuvir FDC with oral contraceptives is permitted.

Vanishing tumor in pregnancy.

A patient with microprolactinoma, who had two successful pregnancies, is described for management issues. First pregnancy was uneventful. During the second pregnancy, the tumor enlarged to macroprolactinoma with headache and blurring of vision which was managed successfully with bromocriptine. Post delivery, complete disappearance of the tumor was documented.

Left atrial strain is reduced in patients with atrial fibrillation, stroke or TIA, and low risk CHADS(2) scores.

BACKGROUND: Left atrial (LA) strain as a marker for discrimination of risk for stroke and transient ischemic attack (TIA) in patients with atrial fibrillation and low-risk CHADS(2) scores (≤1) has yet to be examined. METHODS: Patients with atrial fibrillation, stroke or TIA, and CHADS(2) scores ≤ 1 before their events were identified retrospectively from a large single-center stroke registry and compared with age-matched and gender-matched controls. Antihypertensive use and echocardiographic parameters including chamber volumes and left ventricular mass and LA peak negative and positive strain and strain rate were compared between groups. RESULTS: Fifty-seven patients meeting entry criteria were identified. Patients demonstrated significantly lower left ventricular ejection fractions, larger LA dimensions, and larger LA volume indexes (24.4 ± 11.9 vs 32.3 ± 13.3 mL/m(2), P = .012) compared with controls. Both peak negative LA strain (-3.2 ± 1.2% vs -6.9 ± 4.2%, P < .001) and peak positive LA strain (14 ± 11% vs 25 ± 12%, P < .001) were significantly reduced in patients compared with controls. Peak negative LA strain was significantly associated with stroke by binary logistic regression (odds ratio, 2.15; P < .001). CONCLUSIONS: In patients with low-risk CHADS(2) scores, atrial fibrillation, and stroke or TIA, reduced LA strain is a potentially sensitive maker for increased risk for stroke or TIA. These results suggest that LA strain may have potential as a tool for helping guide the decision for or against oral anticoagulation in this group of patients.