Monday, November 1, 2010

Hospital Admissions for Drug Reactions Double

Hospital admissions for adverse reactions from medications and illegal drugs doubled in between 1997 and 2008, according to a new government report.

The report, released by the Department of Health and Human Services' (HHS) Agency for Healthcare Research and Quality (AHRQ) found that there was a major increase in hospital discharges from effects of both prescription and over-the-counter medications, as well as illegal drugs, among adults ages 45 and older.

"This report reveals a disturbing trend, and we need to find out more about why these admissions are increasing," said AHRQ director Carolyn M. Clancy, MD, in a press release.

Hospital admissions for drug-related conditions grew from about 30,000 per year to more than 65,000 per year -- a 117% increase -- between 1997 and 2008 for people ages 45 to 64, according to the report.

The increase was largely driven by hospitalizations from conditions related to three types of medications and drug-related conditions: drug-induced delirium; "poisoning" or overdose by codeine, meperidine and other opiate-based pain medicines; and withdrawal from narcotic or non-narcotic drugs, according to the press release. "Poisoning" by pain medicines can be caused by accidental overdose or failing to recognize the drug's active ingredient and taking too many pills.

"Substance abuse is rising, and drug abuse of all kinds is exploding as a major public health concern for our country," said Pamela S. Hyde, JD, administrator of HHS' Substance Abuse and Mental Health Services Administration. "The challenge for our healthcare practitioners is to see that patients receive medications when there is medical need but also to help prevent the adverse health consequences from drug use."

Given the explosion in the prescribing of narcotics over the past decade, the trend is not at all a surprise, John Dombrowski, MD, an anesthesiologist at the Washington Pain Center, told MedPage Today.

Dombrowksi, who is a board member of the American Society of Anesthesiologists, explained that in the mid-1990s, there was a push for physicians to measure a new vital sign during office visits -- pain. Dombrowski said the increase in asking patients about their daily pain levels had both positive and negative effects.

On the one hand, many patients divulged malignant pain only after being asked to rate their daily pain on a scale. On the other hand, doctors asking patients about pain led to a huge increase in prescriptions for opioids, oftentimes to treat pain that could be managed better without drugs, according to Dombrowski.

"Unfortunately, Americans are a pill-taking society," Dombrowski said. " 'Sure -- give me a couple percocets and I'll feel better.' But that's not the right way to take care of nonmalignant pain. When you drown the patient in narcotics, they don't do too well."

The AHRQ report detected a similar trend among elderly people. Hospital admissions for drugs grew by 87% among people ages 85 and older.

However, among adults ages 18 to 44, hospitalization for medications and illegal drugs declined by 11% over the study period.

The cost of treating patients with medication and drug-related conditions was $1.1 billion in 2008. Medicare and Medicaid paid 57% of that cost; private insurance covered 24%, and 14% of the costs came from uninsured patients; the remaining 5% were covered by other payers, such as TRICARE.

Dombrowski said he predicts the number of prescriptions for opioid painkillers will decrease as awareness of opioid abuse and misuse grows, and as the Department of Justice continues to focus on the issue.

The FDA recently proposed a plan to prevent inappropriate prescribing, misuse, and abuse of extended-release opioid painkillers. However, an FDA advisory committee voted 25-10 in July to reject the proposal, saying it lacked the teeth to stem the "public health crisis" of opioid addiction, overdose, and death.

The agency's plan to put a risk evaluation and mitigation strategy (REMS) in place would have required drug companies that make extended-release opioids to develop educational programs to guide physicians in patient selection, dosing, and patient monitoring. Prescribers were also to have been trained to counsel their patients on how to safely store and dispose of opioids.

HHS' Substance Abuse and Mental Health Services Administration helped support the analysis of the data in the report on hospital care for mental health and substance abuse disorders.

View the original article here

Sunday, October 31, 2010

Cellular correlates of anxiety in CA1 hippocampal pyramidal cells of 5-HT1A receptor knockout mice

5-HT1A receptor knockout (1AKO) mice have a robust anxiety phenotype. Tissue-specific “rescue” strategies and electrophysiology have implicated a critical role for postsynaptic 5-HT1A receptors, particularly in the CA1 region of the hippocampus. In this study, we evaluated differences in membrane properties and synaptic activity in CA1 hippocampal pyramidal cells between 1AKOs and wild-type (WT) controls to better understand the cellular correlates of anxiety in this mouse model. Whole-cell patch-clamp recordings were conducted in CA1 pyramidal cells in hippocampal brain slices from 1AKOs and WTs that had previously been screened for anxiety with the elevated-plus maze. Spontaneous miniature inhibitory and excitatory postsynaptic currents (IPSCs and EPSCs) and stimulus-evoked eIPSCs and eEPSCs were recorded in addition to the effect of the benzodiazepine agonist diazepam or the inverse agonist FG 7142 on ?-aminobutyric acid (GABA)ergic eIPSCs. Evoked EPSC amplitude was greater in 1AKOs than WTs. When subjects were pooled across genotypes, anxiety measures correlated with eEPSC amplitude, indicating enhanced postsynaptic glutamate synaptic activity under conditions of synaptic activation in anxious subjects. While GABA synaptic activity and sensitivity to diazepam were not affected by genotype or correlated with anxiety, sensitivity to the anxiogenic FG 7142 was smaller in anxious subjects. These data indicate enhanced postsynaptic glutamate receptor sensitivity and decreased GABAergic inhibition by a benzodiazepine inverse agonist in CA1 hippocampal neurons of anxious mice are produced by deletion of the 5-HT1A receptor. These data provide new information about interactions between 5-HT, GABA, and glutamate systems during the expression of chronic anxiety. Keywords  Serotonin - 5-HT1A receptor - Hippocampus - Anxiety - Elevated-plus maze - Electrophysiology

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