Randomized crossover trial of a modified ketogenic diet in Alzheimer's disease.

BACKGROUND: Brain energy metabolism is impaired in Alzheimer's disease (AD), which may be mitigated by a ketogenic diet. We conducted a randomized crossover trial to determine whether a 12-week modified ketogenic diet improved cognition, daily function, or quality of life in a hospital clinic of AD patients. METHODS: We randomly assigned patients with clinically confirmed diagnoses of AD to a modified ketogenic diet or usual diet supplemented with low-fat healthy-eating guidelines and enrolled them in a single-phase, assessor-blinded, two-period crossover trial (two 12-week treatment periods, separated by a 10-week washout period). Primary outcomes were mean within-individual changes in the Addenbrookes Cognitive Examination - III (ACE-III) scale, AD Cooperative Study - Activities of Daily Living (ADCS-ADL) inventory, and Quality of Life in AD (QOL-AD) questionnaire over 12 weeks. Secondary outcomes considered changes in cardiovascular risk factors and adverse effects. RESULTS: We randomized 26 patients, of whom 21 (81%) completed the ketogenic diet; only one withdrawal was attributed to the ketogenic diet. While on the ketogenic diet, patients achieved sustained physiological ketosis (12-week mean beta-hydroxybutyrate level: 0.95 ± 0.34 mmol/L). Compared with usual diet, patients on the ketogenic diet increased their mean within-individual ADCS-ADL (+ 3.13 ± 5.01 points, P = 0.0067) and QOL-AD (+ 3.37 ± 6.86 points, P = 0.023) scores; the ACE-III also increased, but not significantly (+ 2.12 ± 8.70 points, P = 0.24). Changes in cardiovascular risk factors were mostly favourable, and adverse effects were mild. CONCLUSIONS: This is the first randomized trial to investigate the impact of a ketogenic diet in patients with uniform diagnoses of AD. High rates of retention, adherence, and safety appear to be achievable in applying a 12-week modified ketogenic diet to AD patients. Compared with a usual diet supplemented with low-fat healthy-eating guidelines, patients on the ketogenic diet improved in daily function and quality of life, two factors of great importance to people living with dementia. TRIAL REGISTRATION: This trial is registered on the Australia New Zealand Clinical Trials Registry, number ACTRN12618001450202 . The trial was registered on August 28, 2018.

Antipsychotic-induced priapism in an HIV patient: a cytochrome P450-mediated drug interaction.

BACKGROUND: With upwards of 48% of human immunodeficiency virus (HIV)-infected persons having a probable psychiatric disorder, the possibility of cross-class drug interactions causing adverse effects or fatalities exists. AIMS: This report discusses an emergent case of low-flow priapism caused by an interaction between a previously prescribed combination protease inhibitor (PI) and newly added antipsychotic medications. METHODS: A 50-year-old HIV-positive man on highly active antiretroviral therapy (HAART), including the combination PI, lopinavir/ritonavir (Kaletra((R))), experienced an episode of priapism hours after beginning two new antipsychotic medications. Quetiapine (Seroquel((R))) and perphenazine (Trilafon((R))) were added to treat a diagnosed schizoaffective disorder. RESULTS: The patient presented to the emergency department complaining of a constant, painful erection lasting approximately 42 h. Treatment with intracavernous ephedrine, irrigation, and aspiration helped achieve detumescence. CONCLUSION: This case displays the immediate and detrimental effects due to the addition of antipsychotic medications to previously altered cytochrome P450 (CYP450) enzyme levels. The inhibition of CYP450 enzymes 3A4 and 2D6 by the combination PI, lopinavir/ritonavir, was likely the major culprit in causing greater than expected free levels of perphenazine and quetiapine resulting in priapism.

Acute ischemic stroke update.

Stroke is the third most common cause of death in the United States and is the number one cause of long-term disability. Legislative mandates, largely the result of the American Heart Association, American Stroke Association, and Brain Attack Coalition working cooperatively, have resulted in nationwide standardization of care for patients who experience a stroke. Transport to a skilled facility that can provide optimal care, including immediate treatment to halt or reverse the damage caused by stroke, must occur swiftly. Admission to a certified stroke center is recommended for improving outcomes. Most strokes are ischemic in nature. Acute ischemic stroke is a heterogeneous group of vascular diseases, which makes targeted treatment challenging. To provide a thorough review of the literature since the 2007 acute ischemic stroke guidelines were developed, we performed a search of the MEDLINE database (January 1, 2004-July 1, 2009) for relevant English-language studies. Results (through July 1, 2009) from clinical trials included in the Internet Stroke Center registry were also accessed. Results from several pivotal studies have contributed to our knowledge of stroke. Additional data support the efficacy and safety of intravenous alteplase, the standard of care for acute ischemic stroke since 1995. Due to these study results, the American Stroke Association changed its recommendation to extend the time window for administration of intravenous alteplase from within 3 hours to 4.5 hours of symptom onset; this recommendation enables many more patients to receive the drug. Other findings included clinically useful biomarkers, the role of inflammation and infection, an expanded role for placement of intracranial stents, a reduced role for urgent carotid endarterectomy, alternative treatments for large-vessel disease, identification of nontraditional risk factors, including risk factors for women, and newly published pediatric stroke guidelines. In addition, new devices for thrombolectomy are being developed, and neuroprotective therapies such as the use of magnesium, statins, and induced hypothermia are being explored. As treatment interventions become more clearly defined in special subgroups of patients, outcomes in patients with acute ischemic stroke will likely continue to improve.

Phencyclidine false positive induced by lamotrigine (Lamictal®) on a rapid urine toxicology screen.

BACKGROUND: This report describes two cases with unexplained positive results for phencyclidine (PCP). AIMS: This case will correlate lamotrigine (Lamictal®) use with false-positive results for PCP on a rapid urine toxicology screen. METHODS: Case 1: A 62-year-old male arrived to the emergency department in extreme psychosis. All positive results on the urine drug screen could be accounted for except PCP. A comprehensive drug screen was performed to confirm PCP use, but returned negative. PCP was ruled out as the causative agent. The reason for the PCP false positive remained unknown. Case 2: A 49-year-old female presented to the ED with a history of seizures and depression. Despite positive PCP results on a rapid urine drug screen, PCP use was ruled out due to patient presentation and comprehensive history. RESULTS: The differential diagnosis in case 1 included PCP abuse until PCP was ruled out by a comprehensive drug screen. A literature search failed to explain a reason for false-positive results. The patient in case 2 was not psychotic, but returned a positive urinalysis result for PCP. Case 2's presentation combined with a comprehensive history at the facility ruled out PCP use. Both patients were taking the anti-seizure medication lamotrigine with nothing else in common. CONCLUSION: Lamotrigine has the potential to cause false-positive results for PCP on the Bio-Rad TOX/See urine toxicology screen.

Making a case for acute ischemic stroke.

Stroke is the third leading cause of death in the United States and the number one cause of adult long-term disability. Disability in stroke survivors includes hemiparesis, aphasia, inability to walk without assistance, dependence on others for activities of daily living, depression, and institutionalization. Immediate recognition of acute ischemic stroke (AIS) signs and symptoms is required because many treatment options are time sensitive. Hospital transport via activation of 911 and emergency medical services (EMSs) removes delays to urgent diagnosis and intervention. Intravenous (IV) recombinant tissue plasminogen (rt-PA) is a time-sensitive reperfusion strategy. The American Heart Association (AHA) and American Stroke Association (ASA) recently revised recommendations that the time window for IV rt-PA be expanded from 3 hours to 4.5 hours after symptom onset in patients with mild to moderate stroke. Supportive therapies include crystalloid IV solutions, adequate oxygenation, and normothermia. Best rest is desired along with oxygen supplementation. Avoidance of fever is paramount since fever can contribute to negative outcomes. It is the purpose of this article to review risk factors, stroke symptoms, epidemiology, and current drug therapy of AIS. Standards of care will be reviewed.

Pharmacotherapeutic options for the treatment of preeclampsia.

PURPOSE: Pharmacotherapeutic options for the treatment of preeclampsia are reviewed. SUMMARY: Risk factors for the development of preeclampsia include microvascular diseases, such as diabetes mellitus; vascular and connective tissue disorders; hypertension; antiphospholipid antibody syndrome; and nephropathy. Several pathophysiological factors contribute to the development of the preeclamptic state, including vasospasm onset, coagulation system activation, increased inflammatory response, and ischemia. The specific agents used for the treatment of preeclampsia are dependent on a number of factors including symptom severity, maternal or fetal compromise, the progression to eclampsia, gestational period, and cervical status. The diagnosis of preeclampsia beyond the gestation period of 38 weeks requires delivery. The presence of maternal compromise or eclampsia at gestation greater than 20 weeks also necessitates delivery. In cases of chronic or mild hypertension, oral methyldopa may be administered on an outpatient basis. Intravenous hydralazine is a commonly administered arteriolar vasodilator that is effective for hypertensive emergencies associated with pregnancies. The most common adverse effect of hydralazine administration is unpredictable hypotension. Labetalol decreases heart rate and may be preferred because of a lack of reflex tachycardia, hypotension, or increased intracranial pressure. However, the drug of choice for the prevention and control of maternal seizures in patients with severe preeclampsia or eclampsia during the peripartum period is i.v. magnesium sulfate. Therapeutic serum magnesium levels cause cerebral vasodilation, thereby reversing the ischemia produced by cerebral vasospasm during an eclamptic episode. The results of one study indicated that women receiving magnesium sulfate therapy had a 58% lower risk of eclampsia than placebo. CONCLUSION: Magnesium sulfate remains the drug of choice for the prevention and treatment of preeclampsia. Alternative antihypertensive agents may provide additional benefit in the management of hypertension for preeclamptic patients.