Howard Libman, MD, FACP
Judith A Melin, MA, MD, FACP
Daniel J Sullivan, MD, MPH
H Nancy Sokol, MD
Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed by vetting through a multi-level review process, and through requirements for references to be provided to support the content. Appropriately referenced content is required of all authors and must conform to UpToDate standards of evidence.
The following represent additions to UpToDate from the past six months that were considered by the editors and authors to be of particular interest. The most recent What's New entries are at the top of each subsection.
Methylphenidate for apathy in patients with Alzheimer disease (October 2017)
Apathy is a common and understudied symptom of dementia that can emerge early in the disease course and contribute to functional impairment and caregiver burden. In a randomized trial of 77 patients with mild Alzheimer disease (AD), methylphenidate improved apathy scores compared with placebo over a 12-week treatment period . Adverse effects were similar between groups. These results add support to low-dose methylphenidate as an option in patients with persistent and distressing apathy despite a cholinesterase inhibitor and treatment of depression. (See "Management of neuropsychiatric symptoms of dementia", section on 'Apathy'.)
PPI use and mortality (July 2017)
It is unclear if proton pump inhibitor (PPI) use is associated with an increase in risk of death. In an observational cohort study, the incident death rate among 275,977 new PPI users was higher than among 73,335 new histamine-2 receptor antagonist (H2RA) users over a median follow-up of 5.7 years (4.5 versus 3.3 per 100 person-years) . After adjusting for potential confounders, PPI use was associated with increased all-cause mortality compared with H2RA use (HR 1.25); the risk of death increased with the duration of PPI use. Limitations of the study include its generalizability as the study cohort primarily consisted of older white males and lack of data on the cause of mortality. The underlying basis for this apparent increased risk of death with PPI use is not known, and further studies are needed to evaluate whether the association is due to unmeasured confounding. However, we continue to recommend that PPIs be prescribed at the lowest dose for the shortest duration appropriate for the condition being treated. (See "Proton pump inhibitors: Overview of use and adverse effects in the treatment of acid related disorders", section on 'Mortality'.)
GERIATRIC INFECTIOUS DISEASES
Low effectiveness of the influenza vaccine in Australia (December 2017)
During the 2017 influenza season in the southern hemisphere, Australia reported very high numbers of influenza cases, multiple institutional outbreaks, and increased numbers of hospitalizations and deaths . Influenza A H3N2, which usually causes more severe disease than other strains, predominated. The overall adjusted vaccine effectiveness in Australia was estimated to be 33 percent, but only 10 percent for H3N2. Since the vaccine for the 2017-2018 influenza season in the northern hemisphere has the same composition as the vaccine used in the southern hemisphere during the 2017 season, there is concern that regions in the northern hemisphere could experience a severe influenza season, particularly if influenza A H3N2 virus circulates widely . (See "Seasonal influenza vaccination in adults", section on 'Low effectiveness in the Southern Hemisphere during the 2017 season'.)
Inactivated zoster vaccine in the United States (October 2017)
To date, only a live zoster vaccine has been available to prevent herpes zoster and postherpetic neuralgia; it is contraindicated in highly immunocompromised patients, and its efficacy is reduced in patients ≥70 years old. In October 2017, the US Food and Drug Administration approved an inactivated recombinant zoster vaccine that reduces the risk of herpes zoster by ≥90 percent, even among older individuals . The Advisory Committee on Immunization Practices has recommended the recombinant (administered in two doses) rather than the live attenuated vaccine for all adults ≥50 years old, although not all committee members agreed given the lack of data in minority groups and on the long-term vaccine safety and effectiveness in real-world settings . The optimal use of the inactivated vaccine continues to be assessed. Recommendations by the Centers for Disease Control and Prevention are forthcoming. (See "Vaccination for the prevention of shingles (herpes zoster)", section on 'Vaccine formulations'.)
2017-2018 influenza immunization recommendations for the United States (September 2017)
The Advisory Committee on Immunization Practices (ACIP) and the American Academy of Pediatrics (AAP) have released recommendations for influenza immunization for the 2017-2018 season in the United States [7,8]. Routine influenza immunization with a licensed, age-appropriate vaccine (table 1) is recommended for all persons ≥6 months of age. Live attenuated influenza vaccine is not recommended for the 2017-2018 season. Pregnant women and persons with egg allergy of any severity can receive any licensed, age-appropriate inactivated influenza vaccine with standard immunization precautions. Although neither the ACIP nor the AAP provide a preference for a particular formulation, we favor a quadrivalent vaccine when available for adults <65 years and we recommend the high-dose vaccine for those ≥65 years. (See "Seasonal influenza in children: Prevention with vaccines", section on 'Types of vaccine' and "Seasonal influenza vaccination in adults", section on 'Choice of vaccine formulation' and "Influenza and pregnancy", section on 'Vaccination' and "Influenza vaccination in individuals with egg allergy", section on 'Safety of vaccines in patients with egg allergy'.)
Recombinant hemagglutinin influenza vaccine in older adults (June 2017)
Recombinant hemagglutinin influenza vaccines (Flublok and Flublok Quadrivalent) are produced using recombinant DNA technology and a baculovirus expression system rather than the traditional egg-based methods. In a randomized trial that included adults ≥50 years of age, Flublok Quadrivalent was more effective than the quadrivalent standard-dose inactivated vaccine for preventing influenza . Flublok Quadrivalent has not been compared directly with the high-dose inactivated vaccine, which has been found to be more effective than the standard dose inactivated vaccine in older adults (including a mortality benefit). Flublok Quadrivalent is a reasonable alternative to the high-dose vaccine for older adults. (See "Seasonal influenza vaccination in adults", section on 'Recombinant hemagglutinin vaccine'.)
Treatment of nonpurulent cellulitis (June 2017)
Empiric antibiotic therapy for nonpurulent cellulitis (ie, with no purulent drainage and no associated abscess) should be active against beta-hemolytic streptococci and methicillin-susceptible Staphylococcus aureus (MSSA) but not necessarily methicillin-resistant S. aureus (MRSA). This approach is supported by a randomized trial of nearly 500 patients with nonpurulent cellulitis, in which cephalexin plus placebo (active against beta-hemolytic streptococci and MSSA) and cephalexin plus trimethoprim-sulfamethoxazole (TMP-SMX, which adds activity against MRSA) resulted in statistically similar clinical cure rates (69 versus 76 percent) . Although there was a trend toward higher cure rates with the addition of TMP-SMX, the results were likely skewed by a relatively large number of patients who did not complete the full course of therapy. (See "Cellulitis and skin abscess in adults: Treatment", section on 'Cellulitis'.)
GERIATRIC NEPHROLOGY AND HYPERTENSION
Prevalence of high blood pressure in United States adults under the 2017 revised definition of hypertension (November 2017)
The 2017 American College of Cardiology/American Heart Association (ACC/AHA) guidelines changed the definition of hypertension in adults (now defined as a systolic pressure ≥130 mmHg and/or a diastolic pressure ≥80 mmHg). This has substantially changed the prevalence of hypertension among adults in the United States. According to NHANES data from 2011 to 2014, 46 percent of adults 18 years and older had hypertension . Based upon the size of the adult population, this translates into 103 million adults in the United States with hypertension. (See "The prevalence and control of hypertension in adults", section on 'Prevalence of hypertension'.)
New criteria for hypertension in the 2017 American College of Cardiology/American Heart Association (ACC/AHA) guidelines (November 2017)
The 2017 American College of Cardiology/American Heart Association (ACC/AHA) guidelines, with input from the American Society of Hypertension (ASH) as well as geriatrics, pharmacist, and nursing organizations, provide guidance for the prevention, detection, evaluation, and management of hypertension in adults . Major changes from prior recommendations include a lower threshold for the diagnosis of hypertension based upon office blood pressure readings (hypertension now defined as a blood pressure ≥130 mmHg systolic or ≥80 mmHg diastolic), and a lower blood pressure goal (<130/<80 mmHg). Pharmacologic therapy is recommended for all hypertensive patients with a higher cardiovascular risk, and for lower-risk patients who have a blood pressure ≥140 mmHg systolic or ≥90 mmHg diastolic. Recommendations in UpToDate are broadly consistent with these guidelines. (See "What is goal blood pressure in the treatment of hypertension?" and "Overview of hypertension in adults" and "Blood pressure measurement in the diagnosis and management of hypertension in adults" and "The prevalence and control of hypertension in adults".)
Gender differences in risk of Alzheimer disease conferred by APOE e4 (November 2017)
The apolipoprotein E epsilon 4 (APOE e4) allele is a well-recognized risk factor for late-onset Alzheimer disease (AD), and most studies have found that its effect is greater in women than men. Now, a global meta-analysis of observational studies in more than 57,000 adults has found that the differential effect in women may be age-dependent and limited to ages 55 to 70 years for the development of mild cognitive impairment (MCI) and ages 65 to 75 years for the development of AD . The mechanisms underlying this vulnerability are not well understood but could provide important insights into gender-specific strategies for AD prevention. (See "Genetics of Alzheimer disease", section on 'Strength of association'.)
Dementia risk factors and prevention (September 2017)
Two major reports released by a Lancet Commission in the United Kingdom and the Agency for Healthcare Research and Quality in the United States review the literature on risk factors for dementia and the impact of risk factor modification on dementia incidence [14,15]. The Lancet Commission estimates that approximately one-third of dementia cases are attributable to a combination of nine potentially modifiable risk factors: low educational attainment, midlife hypertension, midlife obesity, hearing loss, late-life depression, diabetes, physical inactivity, smoking, and social isolation . While the overall evidence is generally of low quality and does not support any single intervention, there is optimism that intensive risk factor modification, especially during midlife, has the potential to delay or prevent dementia. (See "Risk factors for cognitive decline and dementia" and "Prevention of dementia".)
EULAR recommendations on the use of imaging for osteoarthritis (September 2017)
The European League Against Rheumatism (EULAR) has published evidence-based recommendations for the use of imaging for the management of symptomatic peripheral joint osteoarthritis (OA) . Among the recommendations are guidance to avoid diagnostic imaging in patients with typical symptoms and to use conventional radiography as the first-choice imaging modality in most patients. Our approach to imaging for peripheral joint OA is generally consistent with these guidelines. (See "Clinical manifestations and diagnosis of osteoarthritis", section on 'Imaging'.)
GERIATRIC UROLOGY AND UROGYNECOLOGY
Electroacupuncture for stress urinary incontinence in women (August 2017)
Treatment options for stress urinary incontinence (SUI) in women include lifestyle modifications, bladder training, medications, devices, and surgery. The use of electroacupuncture for SUI has been reported in a multicenter randomized trial in China . Compared with sham treatments, electroacupuncture reduced the volume of urine leaked and number of leakage episodes. Availability of this therapy may limit this option. Additionally, confirmation of these results in other trial settings is needed before its general use can be widely recommended. (See "Treatment of urinary incontinence in women", section on 'Other specialty treatments'.)
Comprehensive geriatric assessment before elective vascular surgery (June 2017)
Older adults undergoing vascular surgery have a high incidence of medical co-morbidities that increase the risk for perioperative morbidity and mortality. In a trial that compared comprehensive geriatric versus standard preoperative assessment in patients at least 65 years old undergoing major elective vascular surgical procedures, comprehensive geriatric assessment reduced postoperative complications and length of stay, with a trend toward fewer discharges to a higher level of dependency . This trial underscores the need to accurately assess medical risk prior to undertaking elective vascular surgery in older adults. (See "Overview of lower extremity peripheral artery disease", section on 'Revascularization'.)
- Padala PR, Padala KP, Lensing SY, et al. Methylphenidate for Apathy in Community-Dwelling Older Veterans With Mild Alzheimer's Disease: A Double-Blind, Randomized, Placebo-Controlled Trial. Am J Psychiatry 2017; :appiajp201717030316.
- Xie Y, Bowe B, Li T, et al. Risk of death among users of Proton Pump Inhibitors: a longitudinal observational cohort study of United States veterans. BMJ Open 2017; 7:e015735.
- Sullivan SG, Chilver MB, Carville KS, et al. Low interim influenza vaccine effectiveness, Australia, 1 May to 24 September 2017. Euro Surveill 2017; 22.
- Paules CI, Sullivan SG, Subbarao K, Fauci AS. Chasing Seasonal Influenza - The Need for a Universal Influenza Vaccine. N Engl J Med 2017.
- Shingrix approved in the US for prevention of shingles in adults aged 50 and over. Press release available at https://www.gsk.com/en-gb/media/press-releases/shingrix-approved-in-the-us-for-prevention-of-shingles-in-adults-aged-50-and-over/ (Accessed on October 27, 2017).
- CDC Advisers Recommend New Herpes Zoster Vaccine over Zostavax. http://www.jwatch.org/fw113469/2017/10/26/cdc-advisers-recommend-new-herpes-zoster-vaccine-over (Accessed on October 27, 2017).
- Grohskopf LA, Sokolow LZ, Broder KR, et al. Prevention and Control of Seasonal Influenza with Vaccines: Recommendations of the Advisory Committee on Immunization Practices - United States, 2017-18 Influenza Season. MMWR Recomm Rep 2017; 66:1.
- COMMITTEE ON INFECTIOUS DISEASES. Recommendations for Prevention and Control of Influenza in Children, 2017 - 2018. Pediatrics 2017; 140.
- Dunkle LM, Izikson R, Patriarca P, et al. Efficacy of Recombinant Influenza Vaccine in Adults 50 Years of Age or Older. N Engl J Med 2017; 376:2427.
- Moran GJ, Krishnadasan A, Mower WR, et al. Effect of Cephalexin Plus Trimethoprim-Sulfamethoxazole vs Cephalexin Alone on Clinical Cure of Uncomplicated Cellulitis: A Randomized Clinical Trial. JAMA 2017; 317:2088.
- Muntner P, Carey RM, Gidding S, et al. Potential U.S. Population Impact of the 2017 American College of Cardiology/American Heart Association High Blood Pressure Guideline. Circulation 2017.
- Whelton PK, Carey RM, Aronow WS, et al. 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Hypertension 2017.
- Neu SC, Pa J, Kukull W, et al. Apolipoprotein E Genotype and Sex Risk Factors for Alzheimer Disease: A Meta-analysis. JAMA Neurol 2017; 74:1178.
- Livingston G, Sommerlad A, Orgeta V, et al. Dementia prevention, intervention, and care. Lancet 2017.
- Kane RL, Bulter M, Fink HA, et al. Interventions to prevent age-related cognitive decline, mild cognitive impairment, and clinical Alzheimer's-type dementia: Comparative effectiveness review No. 188. AHRQ Pub. No. 17-EHC008-EF, Agency for Healthcare Research and Quality, Rockville, MD 2017.
- Sakellariou G, Conaghan PG, Zhang W, et al. EULAR recommendations for the use of imaging in the clinical management of peripheral joint osteoarthritis. Ann Rheum Dis 2017; 76:1484.
- Liu Z, Liu Y, Xu H, et al. Effect of Electroacupuncture on Urinary Leakage Among Women With Stress Urinary Incontinence: A Randomized Clinical Trial. JAMA 2017; 317:2493.
- Partridge JS, Harari D, Martin FC, et al. Randomized clinical trial of comprehensive geriatric assessment and optimization in vascular surgery. Br J Surg 2017; 104:679.