Humans

Neutropenia

Author/s: 
Mithoowani, Siraj, Cameron, L., Crowther, M. A.

»Neutropenia is seen in 5%–10% of healthy people
Based on absolute neutrophil count, neutropenia is commonly defined as
mild (1.0–1.5 × 109
/L), moderate (0.5–0.9 × 109
/L) or severe (< 0.5 × 109
/L).1
However, the reference interval is specific to the population. Mild asymptomatic neutropenia per the above definition is common in people of subSaharan African, Arab or West Indian ancestry,2
and is strongly associated
with the Duffy-null phenotype of red blood cells that protects against
Plasmodium vivax malaria.
2 Common causes include medications, infection, nutritional
deficiency, malignant disease and autoimmune disease
Causes include underproduction (e.g., myelodysplastic syndrome),
immune-mediated destruction or redistribution of neutrophils to the
endothelium and reticuloendothelial system. Antithyroid, anti-infective
and psychotropic drugs, as well as chemotherapy, are causes of druginduced neutropenia.3,4 Transient neutropenia may occur after acute
viral infection and typically resolves within 2 weeks. Joint swelling, rash,
bony pain, splenomegaly or lymphadenopathy may suggest malignant or
autoimmune disease.
3Investigation should begin with a repeat complete blood count
and peripheral blood film
Neutropenia is often identified incidentally. Persistent and unexplained
neutropenia requires further work-up for a range of causes, including
chronic viral infection (e.g., hepatitis, HIV) and nutritional deficiency (e.g.,
vitamin B12) (Appendix 1, available at www.cmaj.ca/lookup/doi/10.1503/
cmaj.220499/tab-related-content).
4 Treatment of mild neutropenia should be directed at the
underlying cause
Patients with mild neutropenia are not at substantially increased risk of
infection.5
The neutrophil count should be checked every 3–6 months for
at least 1 year to rule out progression to more severe neutropenia.
5 Patients with moderate-to-severe neutropenia for more than
6 months should be referred to a specialist
Patients with recurrent or severe bacterial infections (e.g., requiring hospital admission or intravenous antibiotics), abnormalities on peripheral blood
films (e.g., circulating blasts, hairy cells, large granular lymphocytes, dysplastic granulocytes) or pancytopenia also warrant referral to a specialist
(e.g., hematologist, internist, pediatrician).1
Febrile neutropenia (absolute
neutrophil count < 0.5 × 109
/L and an oral temperature > 38.0°C sustained
over 1 h) requires immediate treatment with broad-spectrum antibiotics.

Prescribing for common complications of spinal cord injury

Author/s: 
McColl, M. A., Gupta, S., McColl, A., Smith, K.

Objective: To describe prescribing patterns for 3 common complications associated with spinal cord injury (SCI) and to provide family doctors with strategies for optimizing the care of patients with SCI.

Sources of information: Results of a nationwide survey of prescription medication use among people with SCI in Canada and a longitudinal study of secondary complications associated with SCI.

Main message: Altered neurologic and cardiometabolic function in patients with SCI make it difficult for family physicians to predict optimal medication regimens for these patients. Three common problems seen in primary care among patients with SCI that require pharmacologic treatment are pain (treated in 57% of survey respondents), muscle spasms (54%), and recurrent urinary tract infections (43%). Pain management may require multiple medications, depending on the source or nature of the pain. Some prescription medications recommended for treating pain may be underused in this population, such as amitriptyline, while others may be overused in this population, such as antibiotics for urinary tract infections. Spasticity is often related to an underlying problem such as pain, and treatment of concomitant conditions may also reduce spasticity. Short-acting benzodiazepines were found to have been prescribed for spasticity outside the recommended treatment paradigm at a surprisingly high rate. The longitudinal study of secondary complications associated with SCI led to the development of Actionable Nuggets, an innovative knowledge translation tool for primary care providers.

Conclusion: To provide optimal treatment to patients with SCI, family doctors are encouraged to engage in open communication with them about prescription medications, including aspects of cost, polypharmacy, and therapeutic substitutions. Family physicians should also explore interprofessional collaboration with SCI specialists and allied health providers to provide patients with nonpharmacologic strategies tailored to their activity levels and nutritional needs. The Actionable Nuggets mobile app provides family doctors with brief, actionable, evidence-based information on the top 20 health concerns associated with SCI.

Screening for Syphilis Infection in Nonpregnant Adolescents and Adults: US Preventive Services Task Force Reaffirmation Recommendation Statement

Author/s: 
US Preventative Services task Force, Mangione, C. M., Barry, M. J., Nicholson, W. K., Cabana, M., Chelmow, D., Coker, T. R., Davis, E. M., Donahue, K. E., Jaén, C. R., Kubik, M., Li, L., Ogedegbe, G., Pbert, L., Ruiz, J. M., Stevermer, J., Wong, B. J.

Importance: Syphilis is a sexually transmitted infection that can progress through different stages (primary, secondary, latent, and tertiary) and cause serious health problems if left untreated. Reported cases of primary and secondary syphilis in the US increased from a record low of 2.1 cases per 100 000 population in 2000 and 2001 to 11.9 cases per 100 000 population in 2019. Men account for the majority of cases (83% of primary and secondary syphilis cases in 2019), and rates among women nearly tripled from 2015 to 2019.

Objective: To reaffirm its 2016 recommendation, the US Preventive Services Task Force (USPSTF) commissioned a reaffirmation evidence update focusing on targeted key questions evaluating the performance of risk assessment tools and the benefits and harms of screening for syphilis in nonpregnant adolescents and adults.

Population: Asymptomatic, nonpregnant adolescents and adults who have ever been sexually active and are at increased risk for syphilis infection.

Evidence assessment: Using a reaffirmation process, the USPSTF concludes with high certainty that there is a substantial net benefit of screening for syphilis infection in nonpregnant persons who are at increased risk for infection.

Recommendation: The USPSTF recommends screening for syphilis infection in persons who are at increased risk for infection. (A recommendation).

The monkeypox virus

Author/s: 
Halani, S., Mishra, S., Bogoch, I. I.

Monkeypox is a viral infection with person-to-person
transmission through direct contact or fomites
The virus is endemic to West and Central Africa.1
Animal-to-human transmission may initiate outbreaks, and person-to-person transmission
occurs through direct, close contact with a person during their infectious
stage through droplets, contact with infectious bodily fluids or via fomites
(e.g., linens). Airborne transmission is thought to be less common.

Long-Acting Reversible Contraception With Contraceptive Implants and Intrauterine Devices

Author/s: 
Averbach, S., Hofler, L.

Long-acting reversible contraception (LARC), including contraceptive implants and intrauterine devices (IUDs), is highly effective, with typical-use failure rates of less than 1 pregnancy per 100 person-years of use.1 Fertility returns rapidly after discontinuation of LARC.

Cannabis-Based Products for Chronic Pain : A Systematic Review

Author/s: 
McDonah, M. S., Morasco, B. J., Wagner, J., Ahmed, A. Y., Fu, R., Kansagara, D., Chou, R.

Background: Contemporary data are needed about the utility of cannabinoids in chronic pain.

Purpose: To evaluate the benefits and harms of cannabinoids for chronic pain.

Data sources: Ovid MEDLINE, PsycINFO, EMBASE, the Cochrane Library, and Scopus to January 2022.

Study selection: English-language, randomized, placebo-controlled trials and cohort studies (≥1 month duration) of cannabinoids for chronic pain.

Data extraction: Data abstraction, risk of bias, and strength of evidence assessments were dually reviewed. Cannabinoids were categorized by THC-to-CBD ratio (high, comparable, or low) and source (synthetic, extract or purified, or whole plant).

Data synthesis: Eighteen randomized, placebo-controlled trials (n = 1740) and 7 cohort studies (n = 13 095) assessed cannabinoids. Studies were primarily short term (1 to 6 months); 56% enrolled patients with neuropathic pain, with 3% to 89% female patients. Synthetic products with high THC-to-CBD ratios (>98% THC) may be associated with moderate improvement in pain severity and response (≥30% improvement) and an increased risk for sedation and are probably associated with a large increased risk for dizziness. Extracted products with high THC-to-CBD ratios (range, 3:1 to 47:1) may be associated with large increased risk for study withdrawal due to adverse events and dizziness. Sublingual spray with comparable THC-to-CBD ratio (1.1:1) probably is associated with small improvement in pain severity and overall function and may be associated with large increased risk for dizziness and sedation and moderate increased risk for nausea. Evidence for other products and outcomes, including longer-term harms, were not reported or were insufficient.

Limitation: Variation in interventions; lack of study details, including unclear availability in the United States; and inadequate evidence for some products.

Conclusion: Oral, synthetic cannabis products with high THC-to-CBD ratios and sublingual, extracted cannabis products with comparable THC-to-CBD ratios may be associated with short-term improvements in chronic pain and increased risk for dizziness and sedation. Studies are needed on long-term outcomes and further evaluation of product formulation effects.

Palliative care: An update for internists

Author/s: 
Hayver, R. D., Abedini, N., Jayes, R. L., Matti-Orozco, B., Pomerantz, D. H., Ansari, A. A.

All clinicians should maintain basic skills in general palliative care to help address the needs of patients and families. Because keeping up with the information provided by the growing palliative care literature can be challenging, we conducted a detailed search via Medline for palliative care articles published in 2020 in top peer-reviewed medical journals. Using a consensus-driven process of selection, we reviewed and summarized 11 articles to enhance knowledge of the practice-changing palliative care literature for general internists.

Keywords 

Oral Antiviral Medications for COVID-19

Author/s: 
Petty, L. A., Malani, P. N.

Twonewantiviralmedications, ritonavir-boostednirmatrelvir (Paxlovid,
ie, nirmatrelvir-ritonavir) and molnupiravir (Lagevrio), are currently
available in theUS underemergency useauthorization. These 2 drugs
areauthorized for treatmentofpatientswithmild tomoderateCOVID19 who are not currently hospitalized but are at high risk of developingseveredisease.Nirmatrelvir-ritonavirandmolnupiravirareapproved
for use only within 5 days of onset of COVID-19 symptoms.
Nirmatrelvir-ritonavir andmolnupiravir should be considered for
patients with symptoms of COVID-19 who test positive for SARSCoV-2 and either are an older adult (aged 65 years or older) or are
aged 12 years or older with an underlying condition that increases
risk of severe outcomes of COVID-19 (such as cancer, heart disease,
diabetes, and obesity).

Diagnosis and Treatment of Pulmonary Arterial Hypertension: A Review

Author/s: 
Ruopp, N. F., Cockrill, B. A.

Importance: Pulmonary arterial hypertension (PAH) is a subtype of pulmonary hypertension (PH), characterized by pulmonary arterial remodeling. The prevalence of PAH is approximately 10.6 cases per 1 million adults in the US. Untreated, PAH progresses to right heart failure and death.

Observations: Pulmonary hypertension is defined by a mean pulmonary artery pressure greater than 20 mm Hg and is classified into 5 clinical groups based on etiology, pathophysiology, and treatment. Pulmonary arterial hypertension is 1 of the 5 groups of PH and is hemodynamically defined by right heart catheterization demonstrating a mean pulmonary artery pressure greater than 20 mm Hg, a pulmonary artery wedge pressure of 15 mm Hg or lower, and a pulmonary vascular resistance of 3 Wood units or greater. Pulmonary arterial hypertension is further divided into subgroups based on underlying etiology, consisting of idiopathic PAH, heritable PAH, drug- and toxin-associated PAH, pulmonary veno-occlusive disease, PAH in long-term responders to calcium channel blockers, and persistent PH of the newborn, as well as PAH associated with other medical conditions including connective tissue disease, HIV, and congenital heart disease. Early presenting symptoms are nonspecific and typically consist of dyspnea on exertion and fatigue. Currently approved therapy for PAH consists of drugs that enhance the nitric oxide-cyclic guanosine monophosphate biological pathway (sildenafil, tadalafil, or riociguat), prostacyclin pathway agonists (epoprostenol or treprostinil), and endothelin pathway antagonists (bosentan and ambrisentan). With these PAH-specific therapies, 5-year survival has improved from 34% in 1991 to more than 60% in 2015. Current treatment consists of combination drug therapy that targets more than 1 biological pathway, such as the nitric oxide-cyclic guanosine monophosphate and endothelin pathways (eg, ambrisentan and tadalafil), and has shown demonstrable improvement in morbidity and mortality compared with the previous conventional single-pathway targeted monotherapy.

Conclusions and relevance: Pulmonary arterial hypertension affects an estimated 10.6 per 1 million adults in the US and, without treatment, typically progresses to right heart failure and death. First-line therapy with drug combinations that target multiple biological pathways are associated with improved survival.

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