CDC report on Opioids

Researchers at the Center for Disease Control (CDC) published an online article in JAMA where they analyzed the trends of opioids’ consumption in the USA during the past decade. Their analysis is based on data from the QuintilesIMS Transactional Data warehouse, which stores the approximate quantity of opioids’ prescriptions by surveying 50,000 US pharmacies; they examined data form 2006 to 2015 at the county, regional and national levels.

“Annual opioid rates increased from 72 to 81.2 per 100 persons from 200 to 2010, were continuous from 2010, were continuous from 2010 to 2012, and then decreased by 13% to 70.6 per 100 persons from 2102 to 2105.” The US consumption of opioids peaked in 2010 with 782 MME (morphine milligram equivalents) per capita and then slid down to 640 MME per capita in 2015.

“The average duration of opioid prescriptions increased, in part because of the continued increase in longer opioid prescriptions (greater or equal to 30 days) through 2012, followed by a stabilization of the rate, and a substantial decrease in shorter prescriptions (less than 30 days) after 2012.” The average prescribed supply increased from 13, 3 days in 2006 to 17.1 days in 2015.

The CDC report found many variations in the geographic distribution of the opiod prescription, which was significantly higher in rural counties with a large population of unemployed whites who also had diabetes and arthritis. At long last the CDC bureaucrats recognized that the dismal economic conditions of certain areas is a critical factor of the raging opioid epidemic; however they also found differing prescription patterns amongst physicians.

They claim that there are approximately 2 million addicted people in the USA, which provoked 33,091 deaths in 2105, half of them involving the use of prescribed drugs; the economic cost was estimated at 78.5 billion dollars.

Even though prescription of opioids is coming down, the number of deaths from drug overdosing keeps rising in the USA, in spite of all the concerted efforts of federal and state authorities to address this Public Health threat.

Perhaps it’s time to consider better care alternatives like Cannabis and its derivatives.

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New focus in Alzheimer’s research

The sustained search for a treatment for Alzheimer’s disease has created many experimental therapies that target the accumulation of a protein called Amyloid Beta in the patient’s brains. On one hand the clinical results with the available treatments have been mixed because the Abeta levels do not correlate well with the severity of symptoms and on the other hand some studies suggest that the loading of this protein begins two or three decades before the patients’ show symptoms, which makes an early prevention impractical.The deterioration of the patients’ clinical picture seems to correlate well with the loss of excitatory neurological synapses that allow connectivity of cells.

Dr. Margolis et al., researchers at the Gladstone Institute of Neurological Disease at the University of California at San Francisco, found in 2010, that a protein called EphB2, which regulates the NMDA function essential for the proper synaptic connectivity, was decreased in the brains of AD patients. The decay of the Ephexin 5 had the collateral of slowing the function of the excitatory synapses, which could explain Autism’s cognitive dysfunction. Recently that fortuitous finding has been used in some new studies.

When the researchers added Amyloid Beta to the brains of healthy mice, there is an increased production of Ephexin 5. The analysis of brain tissues from the autopsy of patients with AD showed increased levels of EphB2. The researchers hypothesized that if they could get rid of EphB2, the process of degeneration of excitatory synapses could be halted or at least slowed.After using genetic engineering techniques to destroy the gene controlling the production of EphN2, they discovered that the animals with severe damage did not lose their excitatory synapses, which spared their memories.

Even though Amyloidosis cannot be ultimately stopped, the preservation of synaptic function might prevent the onset of memory loss in AD patients. If the scientists can determine how the abnormal protein damages the neurons, they can provide therapeutic alternatives to make them “amyloid-resistant.” These preventive measures can be instituted in later stages of the disease, unlike the ones pertaining amyloid that must be started in the 40s or 50s. As there are no drugs that can be safely given for forty years to AD patients, researchers are now focusing on an earlier stage of the disease and the medical therapies that can help patients avoid the ravages of it.

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The need for sex

We can certainly agree that good and frequent sex is a healthy human habit. However when people are asked if having a lot of sex is important for the couple’s sense of well being they will say that it is not the determining factor to consider. A recent study explains the disconnect between these attitudes.

Dr. Lindsey Hicks, a psychological researcher at Florida State University, found that the frequency of sex is not directly related with people’s reporting of their satisfaction in their steady relationships but it does influence their more spontaneous and automatic responses when they are asked about it. As those automatic responses don’t require a conscious vetting, Hicks et al. believed that they might uncover some implicit perceptions and associations.

Initially they studied 216 newlywed-couples with a comprehensive survey that measured the satisfaction in their relationships. The participants rated different qualities of the marriages, their agreement or lack of it with certain statements and their satisfaction with their partners in a marriage setting. After completing the survey, they were tasked with a computer classification of responses to certain words after their partners’ pictures appeared briefly. The response time indicates how firmly two items are linked automatically; the faster the response time, the stronger the association between the two, If, after seeing the picture of their partner, the person responded more slowly to negative words than positive ones, it signified positive implicit attitudes.

Dr. Hicks did not find any direct association between the participants’ frequency of sex and their satisfaction levels, as happened in other studies. But the sexual frequency was directly related to their automatic responses; the more sex they had, the more positive attitudes towards the partners were.

This finding happened in both men and women. Another longitudinal study (extended in time) that studied 112 newlyweds confirmed that sex frequency was related with the participants’ automatic responses to the visual stimuli.

Some people are so profoundly unhappy that they can’t even admit it to themselves.

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Prevention of diabetic neuropathy

Primary care physicians, physiatrists and neurologists deal almost daily with one of the most dangerous complications of diabetes mellitus: chronic neuropathies. Its unchecked progression will eventually produce crippling foot ulcers and a neurogenic arthropathy that may lead to amputations and inability to walk.

A new position statement by the American Diabetes Association written by professionals in North America and Europe updated a consensus statement from the American Diabetes Association published in 2004. As there is an increase in diabetic cases in modern societies and too few specialists to deal with them, the preventive measures take a new Public Health significance.

The clinical exam—outlined in a step-by-step algorithm— performed by primary physicians in the office is the critical step in order to diagnose it and to defer the costly referrals to specialists for electrophysiological studies. The distal symmetric polyneuropathy (DSPN) and autonomic neuropathy are the most common clinical variants seen in the primary care practices.

People in the early stages of the disease process—called pre-diabetes—can develop a neuropathy.  The statement emphasizes that both small and large fiber neuropathy are present in patients with pre-diabetes and new onset of the disease. Close regulation of the blood glucose level can slow the progression of DSPN (distal symmetric polyneuropathy) to a certain degree.

The examination should include a good history and “either temperature or pinprick sensation (small fiber function) and vibration sensation using a 128-Hz tuning fork (large-fiber function) Patients should have a 10-g monofilament test to assess for feet at risk for ulceration and amputation.” Testing for DSPN should start 5 years after diagnosis of type I and patients with type II. Patients where motor involvement is greater than the sensory one, whose symptoms start abruptly or are asymmetric should be referred.

Diabetes is one of the few causes of neuropathy that has treatment options.

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Is endovascular therapy useful in stroke?

Five clinical trials have been designed to establish which is the treatment window and the best method to select patients for the endovascular therapy.There is a consensus that it is effective if it is started within six hours of the episode and the baseline collateral flow predicts the final treatment outcome.But there are still several unanswered questions that have been recently reviewed in a seminal paper that discusses the ongoing clinical trials.

Is thrombectomy useful if it’s implemented at more than 6 hours from onset?

The DEFUSE 3 clinical trial was designed to study the premise that this intervention might be able to salvage the brain tissue 6 hours after the event; the goal is to identify potential candidates by imaging techniques in order to use treatment protocols approved by the Federal Drug Administration (FDA)

The eligible candidates have an occlusion of the Internal Carotid artery or an MI occlusion and a target mismatch profile; those with contraindications for CT or MRI scans and a baseline NIH Stroke Scale (NIHSS) were excluded form the trial. The patients are triaged either for the thrombectomy plus the traditional therapy or that medical therapy alone. The treatment is delivered within 16 hours with a Solitaire device or a Penumbra aspiration system.

Is the Trevo thrombectomy plus medical management better after 90 days?

The DAWN trial will study the outcomes of the endovascular therapy when it is administered 6 to 24 hours after the onset of the event; the participants, randomized in a 1:1 ratio in 50 sites, will be studied at 90 days. Unlike the DEFUSE 3 study some patients will have a clinical-imaging mismatch.

Do stroke patients ineligible for t-PA benefit from the endovascular therapy?

The POSITIVE trial will study those patients that undergo a thrombectomy compared to medical therapy alone at 6 to 12 hours after the event. Patients that do not have in the imaging studies an associated large penumbra—an area that might be functionally compromised—will be excluded from it.

Is thrombectomy better for patients with moderate to good collateral flow?

The MR CLEAN LATE trial will study those eligible patients that undergo the procedure after 6 to 12 hours after the event and will enrol 500 patients. The RACECAT trial in Catalonia will determine which triage method is more effective; after the emergency responders contact the neurologists, the patients will be quickly referred to either a stroke or a thrombectomy unit.

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Is rest necessary after a sports concussion? 

 

At the “Fourth International conference on Concussion in Sport” held in Zurich in November 2012 there was a consensus among the experts that cognitive and physical rest were the pillars of the treatment of concussion. In 2013 the American Academy of Neurology released a report that concurred; those patients are at an increased risk of re-injury in the event’s aftermath.

The prevalent opinion was that people with a sports concussion should have a period of cognitive and physical rest until the post-concussive symptoms like dizziness, fatigue, headache and irritability have disappeared. Once they go back to the sports practice, they must stop it if their symptoms re-appear. However there is a budding dissenting view, which states that long periods of inactivity may lead to loss of physical fitness, anxiety and depression.

In a secondary analysis of the prospective, multicenter “Predicting Persistent postconcussive Problems in Pediatrics” study, Canadian researchers of the “Pediatric Emergency Concussion Team” enrolled 3,063 participants ranging form 5 to 17 year old who had been admitted to the Emergency Department for an acute concussion between August 2013 and June 2015. At the time of admission, data on their medical history, the characteristics of their injury and their physical and cognitive symptomatology were recorded.

At day 7 and also at day 28 the participants were contacted by telephone or email in order to question them (or their parents) based on the questionnaire of the “Zurich Consensus Statement on Concussion” return-to-play steps. Based on those responses, four levels of early physical activity were defined:

  1. No physical activity
  2. Light activity (exercise like walking, swimming, stationary cycling)
  3. Moderate activity (non-contact sports activities)
  4. Full exercise (competitive sports and/or contact sports)

The main measurement for the outcome was the presence of “persistent post-concussive symptoms” (PPCS), which was arbitrarily defined as three new or worsening symptoms on the “Post-Concussion Symptom Injury” scale at day 28 compared with the participants’ status before the concussion event.The clinical signs of PPCS happened in 24% of the participants in the group with early physical activity compared to 43.5% in the no activity-group.

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Are antipsychotics safe for the elderly?

Getting old and marching towards our inevitable passing away have never been easy for humans across the ages, except in some cultures where there is a fatalistic conception of life or a more mature assumption of natural events.In our modern societies the drama is compounded by the radical breakdown of family ties that confine the elderly people to hospitals and nursing homes.

The medical and nursing personnel of assisted living facilities seem all too ready to use antipsychotic drugs to treat the delirium of elderly patients, instead of using preventive measures like the company of someone that provides some attention and comfort to them. Nurses must limit the evening-hour disruptions in sleep, noise and lights while doctors should refrain from prescribing drugs with anticholinergic effects, treat pain and hydrate them.

MR Agar et al. studied the efficacy of risperidone and haloperidol in the treatment of delirium of elderly patients by enrolling 247 patients at 11 inpatient hospice or hospital palliative care in Australia from August 2008 to April 2014. Eighty two patients received risperidone, eighty one received haloperidol and eighty four received a placebo; age-adjusted oral doses were administered every 12 hours for 3 days based on their symptomatology.

After 72 hours the patients receiving antipsychotic drugs had significantly higher symptoms of delirium than those taking the placebo; they also had extrapyramidal effects like acute dyskinesias, dystonic reactions, tardive dyskinesia and Parkinsonism. Patients receiving haloperidol had much more sedation on the “Richmond Agitation Sedation scale” than the placebo. Patients in the haloperidol group had much better survival than the placebo.

Experts in Geriatrics have long criticized the quick fix of administering an antipsychotic drug to the usually frail elderly patients and have advocated the proper training and assignment of critical resources to physicians in the provision of environmental and biopsychosocial interventions to treat them.  Dying is a messy, oftentimes chaotic, process tainted with numerous cultural overtones, which must be understood by caregivers for the elderly patients.

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