Adult

Geographic Tongue

Author/s: 
Prasanth, V. J., Singh, A.

A 37-year-old woman presented to the outpatient ear, nose and throat department with a 1-year history of intermittent burning and changes in appearance of her tongue. The patient had no history of bleeding, pain or concurrent skin or genital lesions, and she had no dermatologic history. A course of clotrimazole and vitamin B supplementation had been ineffective. On examination, she had well-defined annular lesions with central erythema and a raised white serpentine border involving the dorsal anterior two-thirds of her tongue (Figure 1). There was no fissuring. Based on her history, the appearance of her tongue and an otherwise normal physical examination, we diagnosed geographic tongue. We prescribed topical benzydamine, as required, for symptomatic relief of burning. At 6-month follow-up, she was free of symptoms, with patchy tongue changes.

The effect of high-dose vitamin D supplementation on serum vitamin D levels and milk calcium concentration in lactating women and their infants

Author/s: 
Basile, L. A., Taylor, S. N., Wagner, C. L., Horst, R. L., Hollis, B. W.

Objective: Improve vitamin D status in lactating women and their recipient infants, and measure breast milk calcium concentration [Ca] as a function of vitamin D regimen.

Design/methods: Fully breastfeeding mothers were randomized at 1 month postpartum to 2000 (n = 12) or 4000 (n = 13) IU/day vitamin D for 3 months to achieve optimal vitamin D status [serum 25(OH)D > or =32 ng/mL (80 nmol/L)]. Breast milk [Ca], maternal and infant serum 25(OH)D and serum Ca, and maternal urinary Ca/Cr ratio were measured monthly.

Results: Mothers were similar between groups for age, race, gestation, and birth weight. 25(OH)D increased from 1 to 4 months in both groups (mean +/- SD): +11.5 +/- 2.3 ng/mL for group 2000 (p = 0.002) and +14.4 +/- 3.0 ng/mL for group 4000 (p = 0.0008). The 4000 IU/day regimen was more effective in raising both maternal and infant serum levels and breast milk antirachitic activity than the 2000 IU/day regimen. Breast milk [Ca] fell with continued lactation through 4 months in the 2000 and 4000 IU groups. Decline in breast milk [Ca] was not associated with vitamin D dose (p = 0.73) or maternal 25(OH)D (p = 0.94). No mother or infant experienced vitamin D-related adverse events, and all laboratory parameters remained in the normal range.

Conclusion: High-dose vitamin D was effective in increasing 25(OH)D levels in fully breastfeeding mothers to optimal levels without evidence of toxicity. Breast milk [Ca] and its decline in both groups during 1 to 4 months were independent of maternal vitamin D status and regimen. Both the mother and her infant attained improved vitamin D status and maintained normal [Ca].

Mobile Telemedicine for Buprenorphine Treatment in Rural Populations With Opioid Use Disorder

Author/s: 
Weintraub, E., Seneviratne, C., Anane, J.

Importance
The demand for medications for opioid use disorder (MOUD) in rural US counties far outweighs their availability. Novel approaches to extend treatment capacity include telemedicine (TM) and mobile treatment on demand; however, their combined use has not been reported or evaluated.

Objective
To evaluate the use of a TM mobile treatment unit (TM-MTU) to improve access to MOUD for individuals living in an underserved rural area.

Design, Setting, and Participants
This quality improvement study evaluated data collected from adult outpatients with a diagnosis of OUD enrolled in the TM-MTU initiative from February 2019 (program inception) to June 2020. Program staff traveled to rural areas in a modified recreational vehicle equipped with medical, videoconferencing, and data collection devices. Patients were virtually connected with physicians based more than 70 miles (112 km) away. Data analysis was performed from June to October 2020.

Intervention
Patients received buprenorphine prescriptions after initial teleconsultation and follow-up visits from a study physician specialized in addiction psychiatry and medicine.

Main Outcomes and Measures
The primary outcome was 3-month treatment retention, and the secondary outcome was opioid-positive urine screens. Exploratory outcomes included use of other drugs and patients’ travel distance to treatment.

Results
A total of 118 patients were enrolled in treatment, of whom 94 were seen for follow-up treatment predominantly (at least 2 of 3 visits [>50%]) on the TM-MTU; only those 94 patients’ data are considered in all analyses. The mean (SD) age of patients was 36.53 (9.78) years, 59 (62.77%) were men, 71 (75.53%) identified as White, and 90 (95.74%) were of non-Hispanic ethnicity. Fifty-five patients (58.51%) were retained in treatment by 3 months (90 days) after baseline. Opioid use was reduced by 32.84% at 3 months, compared with baseline, and was negatively associated with treatment duration (F = 12.69; P = .001). In addition, compared with the nearest brick-and-mortar treatment location, TM-MTU treatment was a mean of 6.52 miles (range, 0.10-58.70 miles) (10.43 km; range, 0.16-93.92 km) and a mean of 10 minutes (range, 1-49 minutes) closer for patients.

Conclusions and Relevance
These data demonstrate the feasibility of combining TM with mobile treatment, with outcomes (retention and opioid use) similar to those obtained from office-based TM MOUD programs. By implementing a traveling virtual platform, this clinical paradigm not only helps fill the void of rural MOUD practitioners but also facilitates access to underserved populations who are less likely to reach traditional medical settings, with critical relevance in the context of the COVID-19 pandemic.

Prevention and Control of Seasonal Influenza with Vaccines: Recommendations of the Advisory Committee on Immunization Practices, United States, 2021-22 Influenza Season

Author/s: 
Grohskopf, L. A., Alyanak, E., Ferdinands, J. M., Broder, K. R., Blanton, L. H., Talbot, H. K., Fry, A. M.

This report updates the 2020–21 recommendations of the Advisory Committee on Immunization Practices (ACIP) regarding the use of seasonal influenza vaccines in the United States (MMWR Recomm Rep 2020;69[No. RR-8]). Routine annual influenza vaccination is recommended for all persons aged ≥6 months who do not have contraindications. For each recipient, a licensed and age-appropriate vaccine should be used. ACIP makes no preferential recommendation for a specific vaccine when more than one licensed, recommended, and age-appropriate vaccine is available. During the 2021–22 influenza season, the following types of vaccines are expected to be available: inactivated influenza vaccines (IIV4s), recombinant influenza vaccine (RIV4), and live attenuated influenza vaccine (LAIV4).

The 2021–22 influenza season is expected to coincide with continued circulation of SARS-CoV-2, the virus that causes COVID-19. Influenza vaccination of persons aged ≥6 months to reduce prevalence of illness caused by influenza will reduce symptoms that might be confused with those of COVID-19. Prevention of and reduction in the severity of influenza illness and reduction of outpatient visits, hospitalizations, and intensive care unit admissions through influenza vaccination also could alleviate stress on the U.S. health care system. Guidance for vaccine planning during the pandemic is available at https://www.cdc.gov/vaccines/pandemic-guidance/index.html. Recommendations for the use of COVID-19 vaccines are available at https://www.cdc.gov/vaccines/hcp/acip-recs/vacc-specific/covid-19.html, and additional clinical guidance is available at https://www.cdc.gov/vaccines/covid-19/clinical-considerations/covid-19-v....

Updates described in this report reflect discussions during public meetings of ACIP that were held on October 28, 2020; February 25, 2021; and June 24, 2021. Primary updates to this report include the following six items. First, all seasonal influenza vaccines available in the United States for the 2021–22 season are expected to be quadrivalent. Second, the composition of 2021–22 U.S. influenza vaccines includes updates to the influenza A(H1N1)pdm09 and influenza A(H3N2) components. U.S.-licensed influenza vaccines will contain hemagglutinin derived from an influenza A/Victoria/2570/2019 (H1N1)pdm09-like virus (for egg-based vaccines) or an influenza A/Wisconsin/588/2019 (H1N1)pdm09-like virus (for cell culture–based and recombinant vaccines), an influenza A/Cambodia/e0826360/2020 (H3N2)-like virus, an influenza B/Washington/02/2019 (Victoria lineage)-like virus, and an influenza B/Phuket/3073/2013 (Yamagata lineage)-like virus. Third, the approved age indication for the cell culture–based inactivated influenza vaccine, Flucelvax Quadrivalent (ccIIV4), has been expanded from ages ≥4 years to ages ≥2 years. Fourth, discussion of administration of influenza vaccines with other vaccines includes considerations for coadministration of influenza vaccines and COVID-19 vaccines. Providers should also consult current ACIP COVID-19 vaccine recommendations and CDC guidance concerning coadministration of these vaccines with influenza vaccines. Vaccines that are given at the same time should be administered in separate anatomic sites. Fifth, guidance concerning timing of influenza vaccination now states that vaccination soon after vaccine becomes available can be considered for pregnant women in the third trimester. As previously recommended, children who need 2 doses (children aged 6 months through 8 years who have never received influenza vaccine or who have not previously received a lifetime total of ≥2 doses) should receive their first dose as soon as possible after vaccine becomes available to allow the second dose (which must be administered ≥4 weeks later) to be received by the end of October. For nonpregnant adults, vaccination in July and August should be avoided unless there is concern that later vaccination might not be possible. Sixth, contraindications and precautions to the use of ccIIV4 and RIV4 have been modified, specifically with regard to persons with a history of severe allergic reaction (e.g., anaphylaxis) to an influenza vaccine. A history of a severe allergic reaction to a previous dose of any egg-based IIV, LAIV, or RIV of any valency is a precaution to use of ccIIV4. A history of a severe allergic reaction to a previous dose of any egg-based IIV, ccIIV, or LAIV of any valency is a precaution to use of RIV4. Use of ccIIV4 and RIV4 in such instances should occur in an inpatient or outpatient medical setting under supervision of a provider who can recognize and manage a severe allergic reaction; providers can also consider consulting with an allergist to help identify the vaccine component responsible for the reaction. For ccIIV4, history of a severe allergic reaction (e.g., anaphylaxis) to any ccIIV of any valency or any component of ccIIV4 is a contraindication to future use of ccIIV4. For RIV4, history of a severe allergic reaction (e.g., anaphylaxis) to any RIV of any valency or any component of RIV4 is a contraindication to future use of RIV4.

This report focuses on recommendations for the use of vaccines for the prevention and control of seasonal influenza during the 2021–22 influenza season in the United States. A brief summary of the recommendations and a link to the most recent Background Document containing additional information are available at https://www.cdc.gov/vaccines/hcp/acip-recs/vacc-specific/flu.html. These recommendations apply to U.S.-licensed influenza vaccines used according to Food and Drug Administration–licensed indications. Updates and other information are available from CDC’s influenza website (https://www.cdc.gov/flu); vaccination and health care providers should check this site periodically for additional information.

Screening for Prediabetes and Type 2 Diabetes

Author/s: 
US Preventative Services task Force

IMPORTANCE An estimated 13% of all US adults (18 years or older) have diabetes, and 34.5%
meet criteria for prediabetes. The prevalences of prediabetes and diabetes are higher in older
adults. Estimates of the risk of progression from prediabetes to diabetes vary widely, perhaps
because of differences in the definition of prediabetes or the heterogeneity of prediabetes.
Diabetes is the leading cause of kidney failure and new cases of blindness among adults in the
US. It is also associated with increased risks of cardiovascular disease, nonalcoholic fatty liver
disease, and nonalcoholic steatohepatitis and was estimated to be the seventh leading cause
of death in the US in 2017. Screening asymptomatic adults for prediabetes and type 2
diabetes may allow earlier detection, diagnosis, and treatment, with the ultimate goal of
improving health outcomes.
OBJECTIVE To update its 2015 recommendation, the USPSTF commissioned a systematic
review to evaluate screening for prediabetes and type 2 diabetes in asymptomatic,
nonpregnant adults and preventive interventions for those with prediabetes.
POPULATION Nonpregnant adults aged 35 to 70 years seen in primary care settings who have
overweight or obesity (defined as a body mass index 25 and 30, respectively) and no
symptoms of diabetes.
EVIDENCE ASSESSMENT The USPSTF concludes with moderate certainty that screening for
prediabetes and type 2 diabetes and offering or referring patients with prediabetes to
effective preventive interventions has a moderate net benefit.
CONCLUSIONS AND RECOMMENDATION The USPSTF recommends screening for prediabetes
and type 2 diabetes in adults aged 35 to 70 years who have overweight or obesity. Clinicians
should offer or refer patients with prediabetes to effective preventive interventions.
(B recommendation)

Stress Incontinence in Women

Author/s: 
Wu, J. M.

This Journal feature begins with a case vignette highlighting a common clinical problem. Evidence supporting various strategies is then presented, followed by a review of formal guidelines, when they exist. The article ends with the author’s clinical recommendations.

A 43-year-old woman with a history of obesity (body-mass index [the weight in kilograms divided by the square of the height in meters] of 32.0) reports urinary leakage with coughing, sneezing, and exercise. She first noticed these symptoms after delivering her third child 6 years ago. Since then, her symptoms have worsened, and she now soaks through pads when she runs. She is frustrated by her situation because she would like to exercise to lose weight, but exercise exacerbates her urinary leakage. How should this case be evaluated and managed?

Hematuria as a Marker of Occult Urinary Tract Cancer: Advice for High-Value Care From the American College of Physicians

Author/s: 
Nielsen, Matthew, Qaseem, Amir, High Value Care Task Force of the American College of Physicians

Background: The presence of blood in the urine, or hematuria, is a common finding in clinical practice and can sometimes be a sign of occult cancer. This article describes the clinical epidemiology of hematuria and the current state of practice and science in this context and provides suggestions for clinicians evaluating patients with hematuria.

Methods: A narrative review of available clinical guidelines and other relevant studies on the evaluation of hematuria was conducted, with particular emphasis on considerations for urologic referral.

High-value care advice 1: Clinicians should include gross hematuria in their routine review of systems and specifically ask all patients with microscopic hematuria about any history of gross hematuria.

High-value care advice 2: Clinicians should not use screening urinalysis for cancer detection in asymptomatic adults.

High-value care advice 3: Clinicians should confirm heme-positive results of dipstick testing with microscopic urinalysis that demonstrates 3 or more erythrocytes per high-powered field before initiating further evaluation in all asymptomatic adults.

High-value care advice 4: Clinicians should refer for further urologic evaluation in all adults with gross hematuria, even if self-limited.

High-value care advice 5: Clinicians should consider urology referral for cystoscopy and imaging in adults with microscopically confirmed hematuria in the absence of some demonstrable benign cause.

High-value care advice 6: Clinicians should pursue evaluation of hematuria even if the patient is receiving antiplatelet or anticoagulant therapy.

High-value care advice 7: Clinicians should not obtain urinary cytology or other urine-based molecular markers for bladder cancer detection in the initial evaluation of hematuria.

Mind-Body Therapies for Opioid-Treated Pain: A Systematic Review and Meta-analysis

Author/s: 
Garland, Eric L., Brintz, Carrie E., Hanley, Adam W., Roseen, Eric J., Atchley, Rachel M., Gaylord, Susan A., Faurot, Keturah R., Yaffe, Joanne, Fiander, Michelle, Keefe, Francis J.

Importance: Mind-body therapies (MBTs) are emerging as potential tools for addressing the opioid crisis. Knowing whether mind-body therapies may benefit patients treated with opioids for acute, procedural, and chronic pain conditions may be useful for prescribers, payers, policy makers, and patients.

Objective: To evaluate the association of MBTs with pain and opioid dose reduction in a diverse adult population with clinical pain.

Data sources: For this systematic review and meta-analysis, the MEDLINE, Embase, Emcare, CINAHL, PsycINFO, and Cochrane Library databases were searched for English-language randomized clinical trials and systematic reviews from date of inception to March 2018. Search logic included (pain OR analgesia OR opioids) AND mind-body therapies. The gray literature, ClinicalTrials.gov, and relevant bibliographies were also searched.

Study selection: Randomized clinical trials that evaluated the use of MBTs for symptom management in adults also prescribed opioids for clinical pain.

Data extraction and synthesis: Independent reviewers screened citations, extracted data, and assessed risk of bias. Meta-analyses were conducted using standardized mean differences in pain and opioid dose to obtain aggregate estimates of effect size with 95% CIs.

Main outcomes and measures: The primary outcome was pain intensity. The secondary outcomes were opioid dose, opioid misuse, opioid craving, disability, or function.

Results: Of 4212 citations reviewed, 60 reports with 6404 participants were included in the meta-analysis. Overall, MBTs were associated with pain reduction (Cohen d = -0.51; 95% CI, -0.76 to -0.26) and reduced opioid dose (Cohen d = -0.26; 95% CI, -0.44 to -0.08). Studies tested meditation (n = 5), hypnosis (n = 25), relaxation (n = 14), guided imagery (n = 7), therapeutic suggestion (n = 6), and cognitive behavioral therapy (n = 7) interventions. Moderate to large effect size improvements in pain outcomes were found for meditation (Cohen d = -0.70), hypnosis (Cohen d = -0.54), suggestion (Cohen d = -0.68), and cognitive behavioral therapy (Cohen d = -0.43) but not for other MBTs. Although most meditation (n = 4 [80%]), cognitive-behavioral therapy (n = 4 [57%]), and hypnosis (n = 12 [63%]) studies found improved opioid-related outcomes, fewer studies of suggestion, guided imagery, and relaxation reported such improvements. Most MBT studies used active or placebo controls and were judged to be at low risk of bias.

Conclusions and relevance: The findings suggest that MBTs are associated with moderate improvements in pain and small reductions in opioid dose and may be associated with therapeutic benefits for opioid-related problems, such as opioid craving and misuse. Future studies should carefully quantify opioid dosing variables to determine the association of mind-body therapies with opioid-related outcomes.

Prophylactic antibiotic therapy effective for chronic obstructive pulmonary disease

Author/s: 
Herath, S.

Background

There has been renewal of interest in the use of prophylactic antibiotics to reduce the frequency of exacerbations and improve quality of life in chronic obstructive pulmonary disease (COPD). 

Objectives

To determine whether or not regular (continuous, intermittent or pulsed) treatment of COPD patients with prophylactic antibiotics reduces exacerbations or affects quality of life. 

Search methods

We searched the Cochrane Airways Group Trials Register and bibliographies of relevant studies. The latest literature search was performed on 27 July 2018. 

Selection criteria

Randomised controlled trials (RCTs) that compared prophylactic antibiotics with placebo in patients with COPD. 

Data collection and analysis

We used the standard Cochrane methods. Two independent review authors selected studies for inclusion, extracted data, and assessed risk of bias. We resolved discrepancies by involving a third review author. 

Main results

We included 14 studies involving 3932 participants in this review. We identified two further studies meeting inclusion criteria but both were terminated early without providing results. All studies were published between 2001 and 2015. Nine studies were of continuous macrolide antibiotics, two studies were of intermittent antibiotic prophylaxis (three times per week) and two were of pulsed antibiotic regimens (e.g. five days every eight weeks). The final study included one continuous, one intermittent and one pulsed arm. The antibiotics investigated were azithromycin, erythromycin, clarithromycin, doxycyline, roxithromycin and moxifloxacin. The study duration varied from three months to 36 months and all used intention‐to‐treat analysis. Most of the pooled results were of moderate quality. The risk of bias of the included studies was generally low. 

The studies recruited participants with a mean age between 65 and 72 years and mostly at least moderate‐severity COPD. Five studies only included participants with frequent exacerbations and two studies recruited participants requiring systemic steroids or antibiotics or both, or who were at the end stage of their disease and required oxygen. One study recruited participants with pulmonary hypertension secondary to COPD and a further study was specifically designed to asses whether eradication of Chlamydia pneumoniae reduced exacerbation rates. 

The co‐primary outcomes for this review were the number of exacerbations and quality of life. 

With use of prophylactic antibiotics, the number of participants experiencing one or more exacerbations was reduced (odds ratio (OR) 0.57, 95% CI 0.42 to 0.78; participants = 2716; studies = 8; moderate‐quality evidence). This represented a reduction from 61% of participants in the control group compared to 47% in the treatment group (95% CI 39% to 55%). The number needed to treat for an additional beneficial outcome with prophylactic antibiotics given for three to 12 months to prevent one person from experiencing an exacerbation (NNTB) was 8 (95% CI 5 to 17). The test for subgroup difference suggested that continuous and intermittent antibiotics may be more effective than pulsed antibiotics (P = 0.02, I² = 73.3%). 

The frequency of exacerbations per patient per year was also reduced with prophylactic antibiotic treatment (rate ratio 0.67; 95% CI 0.54 to 0.83; participants = 1384; studies = 5; moderate‐quality evidence). Although we were unable to pool the result, six of the seven studies reporting time to first exacerbation identified an increase (i.e. benefit) with antibiotics, which was reported as statistically significant in four studies. 

There was a statistically significant improvement in quality of life as measured by the St George's Respiratory Questionnaire (SGRQ) with prophylactic antibiotic treatment, but this was smaller than the four unit improvement that is regarded as being clinically significant (mean difference (MD) ‐1.94, 95% CI ‐3.13 to ‐0.75; participants = 2237; studies = 7, high‐quality evidence). 

Prophylactic antibiotics showed no significant effect on the secondary outcomes of frequency of hospital admissions, change in forced expiratory volume in one second (FEV1), serious adverse events or all‐cause mortality (moderate‐quality evidence). There was some evidence of benefit in exercise tolerance, but this was driven by a single study of lower methodological quality. 

The adverse events that were recorded varied among the studies depending on the antibiotics used. Azithromycin was associated with significant hearing loss in the treatment group, which was in many cases reversible or partially reversible. The moxifloxacin pulsed study reported a significantly higher number of adverse events in the treatment arm due to the marked increase in gastrointestinal adverse events (P < 0.001). Some adverse events that led to drug discontinuation, such as development of long QTc or tinnitus, were not significantly more frequent in the treatment group than the placebo group but pose important considerations in clinical practice. 

The development of antibiotic resistance in the community is of major concern. Six studies reported on this, but we were unable to combine results. One study found newly colonised participants to have higher rates of antibiotic resistance. Participants colonised with moxifloxacin‐sensitive pseudomonas at initiation of therapy rapidly became resistant with the quinolone treatment. A further study with three active treatment arms found an increase in the degree of antibiotic resistance of isolates in all three arms after 13 weeks treatment. 

Authors' conclusions

Use of continuous and intermittent prophylactic antibiotics results in a clinically significant benefit in reducing exacerbations in COPD patients. All studies of continuous and intermittent antibiotics used macrolides, hence the noted benefit applies only to the use of macrolide antibiotics prescribed at least three times per week. The impact of pulsed antibiotics remains uncertain and requires further research. 

The studies in this review included mostly participants who were frequent exacerbators with at least moderate‐severity COPD. There were also older individuals with a mean age over 65 years. The results of these studies apply only to the group of participants who were studied in these studies and may not be generalisable to other groups. 

Because of concerns about antibiotic resistance and specific adverse effects, consideration of prophylactic antibiotic use should be mindful of the balance between benefits to individual patients and the potential harms to society created by antibiotic overuse. Monitoring of significant side effects including hearing loss, tinnitus, and long QTc in the community in this elderly patient group may require extra health resources.

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