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Adding Azithromycin to Seasonal Malaria Chemoprevention: Does the addition of azithromycin to seasonal malaria chemoprevention reduce overall childhood mortality and morbidity? Prevention of Opioid Overdose: When is coprescription of naloxone indicated for a patient receiving opioids?

FEATURED ONLINE HIGHLIGHT CASE CHALLENGE A Woman with Abdominal Pain and Fever A 38-year-old woman with a history of Crohn's disease was admitted to the hospital because of abdominal pain and fever. Despite appropriate medical treatment, she had progressive worsening of clinical symptoms. What is the most likely diagnosis? Vote and comment. Find the answers in the full text of the case, to be published on June 20.

Teaching Topic Adding Azithromycin to Seasonal Malaria Chemoprevention ORIGINAL ARTICLE Effect of Adding Azithromycin to Seasonal Malaria Chemoprevention D. Chandramohan and Others         The frequent contact between children and health care workers that is needed for seasonal malaria chemoprevention provides an opportunity for the delivery of other health interventions. Chandramohan et al. conducted a randomized, double-blind, placebo-controlled trial to determine whether the addition of azithromycin to the monthly sulfadoxine–pyrimethamine plus amodiaquine used for seasonal malaria chemoprevention would reduce mortality and morbidity among African children living in Burkina Faso and Mali. Clinical Pearls   What is the approach to seasonal malaria chemoprevention in the Sahel and sub-Sahel regions of Africa? Malaria transmission is concentrated during a few months of the year in much of the Sahel and sub-Sahel regions of Africa. In these areas, seasonal malaria chemoprevention — the administration of sulfadoxine–pyrimethamine plus amodiaquine to children at monthly intervals three or four times during the malaria-transmission season — has been a highly effective approach to malaria control.   Has mass administration of azithromycin for trachoma control reduced the incidence of other types of infections? Mass administration of azithromycin has been a highly effective approach to trachoma control. Reductions in the incidences of skin, gastrointestinal, and respiratory infections have been recorded after mass administration of azithromycin. Morning Report Questions Q. Does the addition of azithromycin to seasonal malaria chemoprevention reduce overall childhood mortality and morbidity? A. In the trial by Chandramohan et al., among children in Burkina Faso and Mali, the addition of azithromycin to the antimalarial agents used for seasonal malaria chemoprevention did not result in a lower incidence of death or hospital admission that was not due to trauma or surgery than antimalarial agents plus placebo. The authors noted that the incidences of clinic visits for gastrointestinal infections, upper respiratory tract infections, and nonmalarial febrile illnesses, without adjustment for multiple comparisons, were lower among children who received antimalarial agents plus azithromycin than among those who received antimalarial agents plus placebo. Q. Are the findings of Chandramohan et al. similar to those of the MORDOR (Mortality Reduction after Oral Azithromycin) trial? A. The findings of the trial by Chandramohan et al. contrast with those of the MORDOR trial conducted in Malawi, Niger, and Tanzania, in which azithromycin was given to children younger than 5 years of age twice a year for 2 years and then was associated with a 13.5% (95% CI, 6.7 to 19.8) lower overall all-cause mortality than placebo, with the effect being most marked in Niger. There are several possible explanations for the different outcomes of these two trials. One possible explanation is that azithromycin, which has antimalarial activity, contributed to decreased mortality in the MORDOR trial partly through its effect on malaria, and this benefit was lost when an additional, effective antimalarial combination was given at the same time as azithromycin. However, the effect of azithromycin on malaria has been inconsistent when azithromycin has been given in mass drug administration programs. In addition, all the children in the trial by Chandramohan et al. received sulfadoxine–pyrimethamine, which has weak antimicrobial properties, and this may have reduced the potential benefit of adding another antimicrobial to the regimen. Finally, coverage with a pneumococcal conjugate vaccine was high among children in the trial by Chandramohan et al., and this may have reduced the potential benefit of azithromycin in lowering mortality from pneumonia.

Teaching Topic Prevention of Opioid Overdose REVIEW ARTICLE Prevention of Opioid Overdose K.M. Babu, J. Brent, and D.N. Juurlink    All opioid overdoses share a common characteristic: a first opioid exposure. When acute moderate or severe pain necessitates the use of opioids, prescribers should limit the course to the lowest dose and shortest duration possible. Even brief opioid courses have potential long-term consequences. Clinical Pearls   Is there a validated instrument that can estimate the risk of opioid overdose? The revised Risk Index for Overdose or Severe Opioid-Induced Respiratory Depression (RIOSORD) is a validated instrument used to estimate the risk of overdose in opioid-treated patients. The predicted probability of opioid-induced respiratory depression within 6 months after initiation ranges from 1.9% in the lowest-risk group to 83.4% in the highest-risk group. Despite several practical limitations (including the length of the index and a lack of clinician familiarity), the use of RIOSORD can guide risk–benefit decisions and facilitate reassessment of risk over time.   How do prescription drug monitoring programs assist clinicians? Prescription drug monitoring programs (PDMPs) allow the assessment of a patient's prescription opioid history, and a patient-specific query is required before opioid initiation in several states. In areas without a legislative mandate, PDMP inquiries are infrequently completed; recognized obstacles include time, workload, and poor integration into existing electronic medical records. However, PDMPs can identify doctor shopping, concomitant benzodiazepine prescriptions, and evidence of an undisclosed opioid use disorder, such as previous receipt of buprenorphine prescriptions. These signals should prompt clinicians to screen for an opioid use disorder and offer treatment when present. This evaluation can be accomplished through the Rapid Opioid Dependence Screen, which can be administered in under 2 minutes. Morning Report Questions Q. Describe an alternative to gradual opioid tapering as a way to decrease the use of high-dose opioids in patients with chronic pain. A. Clinicians should engage patients receiving high-dose opioids in shared decision making about the merits of gradual dose reduction — specifically, a more favorable balance of benefits versus harms. These discussions are frequently difficult. An alternative to gradual tapering involves transitioning patients from high-dose opioids to buprenorphine, a medication commonly used for the treatment of opioid use disorder. Buprenorphine is a high-affinity partial agonist at mu-opioid receptors that has a ceiling effect on sedation and respiratory depression without a clinically relevant ceiling on analgesia. As is the case with full opioid agonists, buprenorphine causes modest reductions in chronic pain, as compared with placebo, whereas its anxiolytic and antidepressant effects may reflect antagonism at kappa-opioid receptors. Transitioning from full agonists to buprenorphine not only reduces the risk of accidental overdose but frequently imparts subjective improvements in pain, function, sleep, and constipation. Q. When is coprescription of naloxone indicated for a patient receiving opioids? A. Coprescribing of naloxone is increasingly accepted as a valuable tool in patients who are taking opioids for chronic pain. In a large observational study involving patients who were receiving long-term opioid therapy, those who were prescribed naloxone and provided with information on the risk of overdose had 63% fewer emergency department visits at 1 year than those who did not receive such treatment. Naloxone is generally well received by patients and prescribers in the primary care setting. The CDC guideline recommends coprescription of naloxone when patients who have a history of overdose or substance use disorder are prescribed opioids; it is also recommended in patients who are receiving a daily morphine-equivalent dose of more than 50 mg and in those receiving benzodiazepines concurrently.

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QUOTE OF THE WEEK "In this 15-year follow-up study, we found that 5.6 years of intensive glucose lowering that led to a median separation of 1.5 percentage points in the glycated hemoglobin curves did not result in a significantly lower risk of major cardiovascular events than standard therapy." P.D. Reaven and Others, Original Article,  "Intensive Glucose Control in Patients with Type 2 Diabetes — 15 Year Follow-up"

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