quality of life

Individualized antidepressant therapy in patients with major depressive disorder: Novel evidence-informed decision support tool

Author/s: 
Chin, T., Huyghebaert, T., Svrcek, C., Oluboka, O.

Objective: To introduce a visual clinical decision support tool to assist with individualizing first-line antidepressant pharmacotherapy for adults with major depressive disorder (MDD) in a Canadian context.

Sources of information: A literature review was conducted with Google Scholar, PubMed, the Cochrane Database of Systematic Reviews, and Trip Pro using the MeSH headings depression, antidepressive agents, primary care, practice patterns, medication adherence, and decision making, shared.

Main message: Major depressive disorder affects about 4.7% of Canadians annually and is a prevalent condition encountered and diagnosed in primary care. Untreated depression is associated with decreased quality of life, increased risk of suicide, and worsening physical health outcomes when depression co-occurs with other chronic medical conditions. In a network meta-analysis, antidepressant medications (such as selective serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors, bupropion, and vortioxetine) reduced depressive symptoms by 50% or more when compared with placebo in acute treatment of adults with moderate to severe MDD. Poor treatment adherence and high discontinuation rates limit MDD treatment success. Factors such as strong therapeutic alliances between patients and prescribers, collaborative care, patient education, and supportive self-management have been shown to enhance treatment adherence. The most recent Canadian Network for Mood and Anxiety Treatments depression treatment guidelines (published in 2016) suggest 15 different first-line antidepressant medication options for the treatment of MDD. There is a need for evidence-informed decision support aids to individualize antidepressant therapy to treat patients diagnosed with MDD.

Conclusion: Recent studies on antidepressants have indicated no single antidepressant is superior to others in treating patients with MDD. This suggests there may be opportunities to enhance treatment adherence and success by tailoring antidepressant therapy to align with each patient's preferences. The Antidepressant Decision Support Tool was developed to help prescribers and adult patients engage in shared decision making to select an individualized and optimal first-line antidepressant for the treatment of acute MDD.

Comparison of Amitriptyline and US Food and Drug Administration–Approved Treatments for Fibromyalgia A Systematic Review and Network Meta-analysis

Author/s: 
Farag, H. M., Yunusa, I., Goswami, H., Sultan, I., Doucette, J. A., Eguale, T.

Importance: Amitriptyline is an established medication used off-label for the treatment of fibromyalgia, but pregabalin, duloxetine, and milnacipran are the only pharmacological agents approved by the US Food and Drug Administration (FDA) to treat fibromyalgia.

Objective: To investigate the comparative effectiveness and acceptability associated with pharmacological treatment options for fibromyalgia.

Data sources: Searches of PubMed/MEDLINE, Cochrane Library, Embase, and Clinicaltrials.gov were conducted on November 20, 2018, and updated on July 29, 2020.

Study selection: Randomized clinical trials (RCTs) comparing amitriptyline or any FDA-approved doses of investigated drugs.

Data extraction and synthesis: This study follows the Preferred Reporting Items for Systematic Reviews and Meta-analyses reporting guideline. Four independent reviewers extracted data using a standardized data extraction sheet and assessed quality of RCTs. A random-effects bayesian network meta-analysis (NMA) was conducted. Data were analyzed from August 2020 to January 2021.

Main outcomes and measures: Comparative effectiveness and acceptability (defined as discontinuation of treatment owing to adverse drug reactions) associated with amitriptyline (off-label), pregabalin, duloxetine, and milnacipran (on-label) in reducing fibromyalgia symptoms. The following doses were compared: 60-mg and 120-mg duloxetine; 150-mg, 300-mg, 450-mg, and 600-mg pregabalin; 100-mg and 200-mg milnacipran; and amitriptyline. Effect sizes are reported as standardized mean differences (SMDs) for continuous outcomes and odds ratios (ORs) for dichotomous outcomes with 95% credible intervals (95% CrIs). Findings were considered statistically significant when the 95% CrI did not include the null value (0 for SMD and 1 for OR). Relative treatment ranking using the surface under the cumulative ranking curve (SUCRA) was also evaluated.

Results: A total of 36 studies (11 930 patients) were included. The mean (SD) age of patients was 48.4 (10.4) years, and 11 261 patients (94.4%) were women. Compared with placebo, amitriptyline was associated with reduced sleep disturbances (SMD, -0.97; 95% CrI, -1.10 to -0.83), fatigue (SMD, -0.64; 95% CrI, -0.75 to -0.53), and improved quality of life (SMD, -0.80; 95% CrI, -0.94 to -0.65). Duloxetine 120 mg was associated with the highest improvement in pain (SMD, -0.33; 95% CrI, -0.36 to -0.30) and depression (SMD, -0.25; 95% CrI, -0.32 to -0.17) vs placebo. All treatments were associated with inferior acceptability (higher dropout rate) than placebo, except amitriptyline (OR, 0.78; 95% CrI, 0.31 to 1.66). According to the SUCRA-based relative ranking of treatments, duloxetine 120 mg was associated with higher efficacy for treating pain and depression, while amitriptyline was associated with higher efficacy for improving sleep, fatigue, and overall quality of life.

Conclusions and relevance: These findings suggest that clinicians should consider how treatments could be tailored to individual symptoms, weighing the benefits and acceptability, when prescribing medications to patients with fibromyalgia.

Olfactory Loss and Beyond: A Practical Review of Chemosensory Dysfunction

Author/s: 
Claus, L. E., Leland, E. M., Tai, K. Y., Schlosser, R. J., Kamath, V., Lane, A. P., Rowan, N. R.

Background: Our ability to smell and taste is dictated by 3 chemosensory systems with distinct physiologic mechanisms - olfaction, gustation, and chemesthesis. Although often overlooked, dysfunction of these special senses may have broad implications on multiple facets of patients' lives -including safety, nutritional status, quality of life, mental health, and even cognitive function. As "loss of smell or taste" emerged as a common symptom of coronavirus disease 2019 (COVID-19), the importance of intact chemosensory function has been thrust into the spotlight. Despite the growing recognition of chemosensory dysfunction, this already highly prevalent condition will increasingly impact a larger and more diverse population, highlighting the need for improved awareness and care of these patients.

Methods: Comtemporary review of chemosensory function and assessments.

Conclusions: Although patient-reported chemosensory function measures highlight the ease of screening of chemosensory dysfunction, self-reported measures underestimate both the prevalence and degree of chemosensory dysfunction and do not adequately distinguish between olfaction, gustation, and chemesthesis. Meanwhile, psychophysical assessment tools provide opportunities for more accurate, thorough assessment of the chemosenses when appropriate. Primary care providers are uniquely situated to identify patients burdened by chemosensory dysfunction and raise patient and provider awareness about the importance of chemosensory dysfunction. Identification of chemosensory dysfunction, particularly olfactory dysfunction, may raise suspicion for many underlying medical conditions, including early detection of neurodegenerative conditions. Furthermore, identification and awareness of patients with chemosensory dysfunction may help primary care providers to identify those who may benefit from additional therapeutic and safety interventions, or consultations with specialists for more detailed evaluations and management.

Diagnosis and management of postural orthostatic tachycardia syndrome

Author/s: 
Raj, S. R., Fedorowski, A., Sheldon, R. S.

Postural orthostatic tachycardia syndrome (POTS) is a chronic multisystem disorder; the cardinal feature is orthostatic tachycardia.

Patients with POTS have symptoms of orthostatic intolerance that improve with recumbence.

Girls and women are more commonly affected with POTS, beginning in puberty and through early adulthood.

Postural orthostatic tachycardia syndrome can lead to marked functional disability, often limiting work or schooling.

Treatments for POTS can improve symptoms and function, and can be initiated in primary care.

The main characteristic of postural orthostatic tachycardia syndrome (POTS) is tachycardia when standing, without a drop in blood pressure. Patients describe lightheadedness and palpitations when upright, particularly when standing, which sometimes leads to syncope. Patients may experience impaired quality of life and functional disability, which can be economically devastating.1–3 The syndrome is more common in girls and young women and has been associated with other disorders, like migraine and Ehlers–Danlos syndrome.4 We discuss the diagnosis of POTS, conditions to consider in the differential diagnosis, associated disorders and the pharmacologic and nonpharmacologic management of patients with POTS, based on original research, narrative reviews and consensus statements

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Essentials of Diagnosis and Management

Author/s: 
Bateman, L., Bested, A., Bonilla, H., Chheda, B., Chu, L,, Curtin, J. M., Dempsey, T. T., Dimmock, M. E., Dowell, T. G., Felsenstein, D., Kaufman, D. L., Klimas, N. G., Komaroff, A. L., Lapp, C. W., Levine, S. M., Montoya, J. G., Natelson, B. H., Peterson, D. L., Podell, R. N., Rey, I. R., Ruhoy, I. S., Vera-Nunez, M. A., Yellman, B. P.

Despite myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) affecting millions of people worldwide, many clinicians lack the knowledge to appropriately diagnose or manage ME/CFS. Unfortunately, clinical guidance has been scarce, obsolete, or potentially harmful. Consequently, up to 91% of patients in the United States remain undiagnosed, and those diagnosed often receive inappropriate treatment. These problems are of increasing importance because after acute COVID-19, a significant percentage of people remain ill for many months with an illness similar to ME/CFS. In 2015, the US National Academy of Medicine published new evidence-based clinical diagnostic criteria that have been adopted by the US Centers for Disease Control and Prevention. Furthermore, the United States and other governments as well as major health care organizations have recently withdrawn graded exercise and cognitive-behavioral therapy as the treatment of choice for patients with ME/CFS. Recently, 21 clinicians specializing in ME/CFS convened to discuss best clinical practices for adults affected by ME/CFS. This article summarizes their top recommendations for generalist and specialist health care providers based on recent scientific progress and decades of clinical experience. There are many steps that clinicians can take to improve the health, function, and quality of life of those with ME/CFS, including those in whom ME/CFS develops after COVID-19. Patients with a lingering illness that follows acute COVID-19 who do not fully meet criteria for ME/CFS may also benefit from these approaches.

Screening and Interventions to Prevent Dental Caries in Children Younger Than 5 Years US Preventive Services Task Force Recommendation Statement

Author/s: 
US Preventative Services task Force

IMPORTANCE Dental caries is the most common chronic disease in children in the US.
According to the 2011-2016 National Health and Nutrition Examination Survey, approximately
23% of children aged 2 to 5 years had dental caries in their primary teeth. Prevalence is higher
in Mexican American children (33%) and non-Hispanic Black children (28%) than in
non-Hispanic White children (18%). Dental caries in early childhood is associated with pain,
loss of teeth, impaired growth, decreased weight gain, negative effects on quality of life, poor
school performance, and future dental caries.
OBJECTIVE To update its 2014 recommendation, the US Preventive Services Task Force
(USPSTF) commissioned a systematic review on screening and interventions to prevent
dental caries in children younger than 5 years.
POPULATION Asymptomatic children younger than 5 years.
EVIDENCE ASSESSMENT The USPSTF concludes with moderate certainty that there is a
moderate net benefit of preventing future dental caries with oral fluoride supplementation at
recommended doses in children 6 months or older whose water supply is deficient in
fluoride. The USPSTF concludes with moderate certainty that there is a moderate net benefit
of preventing future dental caries with fluoride varnish application in all children younger
than 5 years. The USPSTF concludes that the evidence is insufficient on performing routine
oral screening examinations for dental caries by primary care clinicians in children younger
than 5 years and that the balance of benefits and harms of screening cannot be determined.
RECOMMENDATION The USPSTF recommends that primary care clinicians prescribe oral fluoride
supplementation starting at age 6 months for children whose water supply is deficient in
fluoride. (B recommendation) The USPSTF recommends that primary care clinicians apply
fluoride varnish to the primary teeth of all infants and children starting at the age of primary
tooth eruption. (B recommendation) The USPSTF concludes that the current evidence is
insufficient to assess the balance of benefits and harms of routine screening examinations for
dental caries performed by primary care clinicians in children younger than 5 years. (I statement)

Malnutrition in hospitalized adults: A systematic review

Author/s: 
Uhl, S., Siddique, S. M., McKeever, L., Bloschichak, A., D'Anci, K., Leas, B., Mull, N. K, Tsou, A. Y.

Objectives. To review the association between malnutrition and clinical outcomes among hospitalized patients, evaluate effectiveness of measurement tools for malnutrition on clinical outcomes, and assess effectiveness of hospital-initiated interventions for patients diagnosed with malnutrition.

Data sources. We searched electronic databases (Embase®, MEDLINE®, PubMed®, and the Cochrane Library) from January 1, 2000, to June 3, 2021. We hand-searched reference lists of relevant studies and searched for unpublished studies in ClinicalTrials.gov.

Review methods. Using predefined criteria and dual review, we selected (1) existing systematic reviews (SRs) to assess the association between malnutrition and clinical outcomes, (2) randomized and non-randomized studies to evaluate the effectiveness of malnutrition tools on clinical outcomes, and (3) randomized controlled trials (RCTs) to assess effectiveness of hospital-initiated treatments for malnutrition. Clinical outcomes of interest included mortality, length of stay, 30-day readmission, quality of life, functional status, activities of daily living, hospital acquired conditions, wound healing, and discharge disposition. When appropriate, we conducted meta-analysis to quantitatively summarize study findings; otherwise, data were narratively synthesized. When available, we used pooled estimates from existing SRs to determine the association between malnutrition and clinical outcomes, and assessed the strength of evidence.

Results. Six existing SRs (including 43 unique studies) provided evidence on the association between malnutrition and clinical outcomes. Low to moderate strength of evidence (SOE) showed an association between malnutrition and increased hospital mortality and prolonged hospital length of stay. This association was observed across patients hospitalized for an acute medical event requiring intensive care unit care, heart failure, and cirrhosis. Literature searches found no studies that met inclusion criteria and assessed effectiveness of measurement tools. The primary reason studies did not meet inclusion criteria is because they lacked an appropriate control group. Moderate SOE from 11 RCTs found that hospital-initiated malnutrition interventions likely reduce mortality compared with usual care among hospitalized patients diagnosed with malnutrition. Low SOE indicated that hospital-initiated malnutrition interventions may also improve quality of life compared to usual care.

Conclusions. Evidence shows an association between malnutrition and increased mortality and prolonged length of hospital stay among hospitalized patients identified as malnourished. However, the strength of this association varied depending on patient population and tool used to identify malnutrition. Evidence indicates malnutrition-focused hospital-initiated interventions likely reduce mortality and may improve quality of life compared to usual care among patients diagnosed with malnutrition. Research is needed to assess the clinical utility of measurement tools for malnutrition.

Maintenance or Discontinuation of Antidepressants in Primary Care

Author/s: 
Lewis, G., Marston, L., Duffy, L., Freemantle, N., Gilbody, S., Hunter, R., Kendrick, T., Kessler, D., Mangin, D., King, M., Lanham, P., Moore, M.

BACKGROUND
Patients with depression who are treated in primary care practices may receive antidepressants for prolonged periods. Data are limited on the effects of maintaining or discontinuing antidepressant therapy in this setting.

METHODS
We conducted a randomized, double-blind trial involving adults who were being treated in 150 general practices in the United Kingdom. All the patients had a history of at least two depressive episodes or had been taking antidepressants for 2 years or longer and felt well enough to consider stopping antidepressants. Patients who had received citalopram, fluoxetine, sertraline, or mirtazapine were randomly assigned in a 1:1 ratio to maintain their current antidepressant therapy (maintenance group) or to taper and discontinue such therapy with the use of matching placebo (discontinuation group). The primary outcome was the first relapse of depression during the 52-week trial period, as evaluated in a time-to-event analysis. Secondary outcomes were depressive and anxiety symptoms, physical and withdrawal symptoms, quality of life, time to stopping an antidepressant or placebo, and global mood ratings.

RESULTS
A total of 1466 patients underwent screening. Of these patients, 478 were enrolled in the trial (238 in the maintenance group and 240 in the discontinuation group). The average age of the patients was 54 years; 73% were women. Adherence to the trial assignment was 70% in the maintenance group and 52% in the discontinuation group. By 52 weeks, relapse occurred in 92 of 238 patients (39%) in the maintenance group and in 135 of 240 (56%) in the discontinuation group (hazard ratio, 2.06; 95% confidence interval, 1.56 to 2.70; P<0.001). Secondary outcomes were generally in the same direction as the primary outcome. Patients in the discontinuation group had more symptoms of depression, anxiety, and withdrawal than those in the maintenance group.

CONCLUSIONS
Among patients in primary care practices who felt well enough to discontinue antidepressant therapy, those who were assigned to stop their medication had a higher risk of relapse of depression by 52 weeks than those who were assigned to maintain their current therapy. (Funded by the National Institute for Health Research; ANTLER ISRCTN number, ISRCTN15969819.)

Interventional Treatments for Acute and Chronic Pain: Systematic Review

Author/s: 
Chou, R., Fu, R., Dana, T., Pappas, M., Hart, E., Mauer, K. M.

Objective. To evaluate the benefits and harms of selected interventional procedures for acute and chronic pain that are not currently covered by the Centers for Medicare & Medicaid Services (CMS) but are relevant for and have potential utility for use in the Medicare population, or that are covered by CMS but for which there is important uncertainty or controversy regarding use.

Data sources. Electronic databases (Ovid® MEDLINE®, PsycINFO®, the Cochrane Central Register of Controlled Trials, and the Cochrane Database of Systematic Reviews) to April 12, 2021, reference lists, and submissions in response to a Federal Register notice.

Review methods. Using predefined criteria and dual review, we selected randomized controlled trials (RCTs) for 10 interventional procedures and conditions that evaluated pain, function, health status, quality of life, medication use, and harms. Random effects meta-analysis was conducted for vertebral compression fracture; otherwise, outcomes were synthesized qualitatively. Effects were classified as small, moderate, or large using previously defined criteria.

Results. Thirty-seven randomized trials (in 48 publications) were included. Vertebroplasty (13 trials) is probably more effective at reducing pain and improving function in older (>65 years of age) patients, but benefits are small (less than 1 point on a 10-point pain scale). Benefits appear smaller (but still present) in sham-controlled (5 trials) compared with usual care controlled trials (8 trials) and larger in trials of patients with more acute symptoms; however, testing for subgroup effects was limited by imprecision. Vertebroplasty is probably not associated with increased risk of incident vertebral fracture (10 trials). Kyphoplasty (2 trials) is probably more effective than usual care for pain and function in older patients with vertebral compression fracture at up to 1 month (moderate to large benefits) and may be more effective at >1 month to ≥1 year (small to moderate benefits) but has not been compared against sham therapy. Evidence on kyphoplasty and risk of incident fracture was conflicting. In younger (below age for Medicare eligibility) populations, cooled radiofrequency denervation for sacroiliac pain (2 trials) is probably more effective for pain and function versus sham at 1 and 3 months (moderate to large benefits). Cooled radiofrequency for presumed facet joint pain may be similarly effective versus conventional radiofrequency, and piriformis injection with corticosteroid for piriformis syndrome may be more effective than sham injection for pain. For the other interventional procedures and conditions addressed, evidence was too limited to determine benefits and harms.

Conclusions. Vertebroplasty is probably effective at reducing pain and improving function in older patients with vertebral compression fractures; benefits are small but similar to other therapies recommended for pain. Evidence was too limited to separate effects of control type and symptom acuity on effectiveness of vertebroplasty. Kyphoplasty has not been compared against sham but is probably more effective than usual care for vertebral compression fractures in older patients. In younger populations, cooled radiofrequency denervation is probably more effective than sham for sacroiliac pain. Research is needed to determine the benefits and harms of the other interventional procedures and conditions addressed in this review.

Midodrine for the Prevention of Vasovagal Syncope : A Randomized Clinical Trial

Author/s: 
Sheldon, R., Faris, P., Tang, A., Ayala-Paredes, F., Guzman, J., Marquez, M., Morillo, C. A., Krahn, A. D., Kus, T., Ritchie, D., Safdar, S., Maxey, C., Raj, S. R.

Background: Recurrent vasovagal syncope is common, responds poorly to treatment, and causes physical trauma and poor quality of life. Midodrine prevents hypotension and syncope during tilt tests in patients with vasovagal syncope.

Objective: To determine whether midodrine can prevent vasovagal syncope in usual clinical conditions.

Design: Randomized, double-blind, placebo-controlled clinical trial. (ClinicalTrials.gov: NCT01456481).

Setting: 25 university hospitals in Canada, the United States, Mexico, and the United Kingdom.

Patients: Patients with recurrent vasovagal syncope and no serious comorbid conditions.

Intervention: Patients were randomly assigned 1:1 to placebo or midodrine and followed for 12 months.

Measurements: The primary outcome measure was the proportion of patients with at least 1 syncope episode during follow-up.

Results: The study included 133 patients who had had a median of 6 syncope episodes in the prior year (median age, 32 years; 73% female). Compared with patients receiving placebo, fewer patients receiving midodrine had at least 1 syncope episode (28 of 66 [42%] vs. 41 of 67 [61%]). The relative risk was 0.69 (95% CI, 0.49 to 0.97; P = 0.035). The absolute risk reduction was 19 percentage points (CI, 2 to 36 percentage points), and the number needed to treat to prevent 1 patient from having syncope was 5.3 (CI, 2.8 to 47.6). The time to first syncope was longer with midodrine (hazard ratio, 0.59 [CI, 0.37 to 0.96]; P = 0.035; log-rank P = 0.031). Adverse effects were similar in both groups.

Limitation: Small study size, young and healthy patients, relatively short observation period, and high proportion of patients from 1 center.

Conclusion: Midodrine can reduce the recurrence of syncope in healthy, younger patients with a high syncope burden."

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