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Practice Changing UpDates
Official reprint from UpToDate® ©2017 UpToDate, Inc. and/or its affiliates. All Rights Reserved.
The content on the UpToDate website is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. The use of this website is governed by the UpToDate Terms of Use ©2017 UpToDate, Inc.
Practice Changing UpDates
All topics are updated as new evidence becomes available and our peer review process is complete.
Literature review current through: Nov 2017. | This topic last updated: Dec 14, 2017.

INTRODUCTION — This section highlights selected specific new recommendations and/or updates that we anticipate may change usual clinical practice. Practice Changing UpDates focus on changes that may have significant and broad impact on practice, and therefore do not represent all updates that affect practice. These Practice Changing UpDates, reflecting important changes to UpToDate over the past year, are presented chronologically, and are discussed in greater detail in the identified topic reviews.


Elvitegravir-cobicistat use during pregnancy

For HIV-infected women who become pregnant while on an elvitegravir-cobicistat-containing regimen, we suggest switching to a different regimen (Grade 2C).

Preferred antiretroviral regimens for pregnant women differ somewhat from those for the general HIV-infected adult population, in part because of altered pharmacokinetics during pregnancy. Recently updated Department of Health and Human Services perinatal guidelines now state that elvitegravir-cobicistat should not be selected as part of an initial antiretroviral regimen for treatment-naïve pregnant women because of emerging data suggesting decreased drug levels during pregnancy and an associated risk of loss of virologic suppression [1,2]. Furthermore, if an HIV-infected woman is already receiving a suppressive elvitegravir-cobicistat-containing regimen when she becomes pregnant, we suggest switching to a different regimen; if elvitegravir-cobicistat is continued, the potential risks and need for close viral monitoring should be discussed. (See "Antiretroviral and intrapartum management of pregnant HIV-infected women and their infants in resource-rich settings", section on 'On ART with viral suppression'.)


Acetylcysteine does not prevent contrast nephropathy

For patients undergoing angiography who are at increased risk for contrast nephropathy, we suggest that acetylcysteine not be given, either orally or intravenously (Grade 2B).

Radiocontrast media may cause acute kidney injury (AKI) among high-risk patients. Earlier studies have been inconsistent but indicated that the administration of oral acetylcysteine may decrease the risk of AKI, and led to our previous suggestion to administer acetylcysteine before and the day of angiography to patients at risk of contrast nephropathy. A recent randomized trial in over 5000 patients at increased risk for nephropathy who were undergoing scheduled angiography found that oral acetylcysteine, compared with placebo, did not prevent death, need for dialysis, or decline in kidney function [3]. The trial was a 2 by 2 factorial design and also compared intravenous sodium bicarbonate with isotonic saline, finding no benefit for sodium bicarbonate. UpToDate recommends giving isotonic saline rather than sodium bicarbonate and now suggests not giving acetylcysteine prior to angiography. (See "Prevention of contrast nephropathy associated with angiography", section on 'Acetylcysteine'.)

HEMATOLOGY (November 2017)

Frequency for dosing of oral iron

For individuals with iron deficiency who are treated with oral iron, we suggest that the dose be taken every other day rather than every day (Grade 2C).

For many years, iron deficiency has been treated with oral iron given at least once per day, despite significant gastrointestinal side effects in the majority of individuals. A small, unblinded randomized trial has now demonstrated that giving oral iron every other day rather than every day resulted in greater iron absorption and fewer gastrointestinal side effects [4]. Alternate-day dosing is also supported by mechanistic studies that showed favorable effects on hepcidin, a negative regulator of intestinal iron absorption and iron release from macrophages. We now suggest that patients treated with oral iron for iron deficiency take the iron every other day rather than daily. (See "Treatment of iron deficiency anemia in adults", section on 'Dosing and administration (oral iron)'.)


Revised recommendations for endoscopy in the evaluation of dyspepsia

Patients ≥60 years of age with new onset dyspepsia should undergo an upper endoscopy. For patients <60 years, upper endoscopy is reserved for those with clinically significant weight loss, overt gastrointestinal bleeding, more than one alarm feature, or rapidly progressive alarm features. Patients <60 years of age should be tested and treated for H. pylori infection.

The American College of Gastroenterology (ACG) and Canadian Association of Gastroenterology (CAG) have published guidelines on the evaluation and management of dyspepsia [5]. The recommended age threshold for routine upper endoscopy in patients with dyspepsia, to exclude upper gastrointestinal neoplasia, has been raised to ≥60 years, in contrast to earlier guidelines advising ≥55 years. The new guidelines also recommend that patients <60 years with dyspepsia be tested for Helicobacter pylori and treated if positive. For patients <60 years, upper endoscopy is reserved for those with significant weight loss, overt gastrointestinal bleeding, more than one alarm feature (table 1), or rapid progression of one or more alarm features. The rationale for these revised recommendations is the low risk of gastric cancer in younger patients, the low positive predictive value of any single alarm feature in detecting gastrointestinal neoplasia, and the inherent risk and cost of performing upper endoscopy. Our management approach is generally consistent with these guidelines (algorithm 1). (See "Approach to the adult with dyspepsia", section on 'Diagnostic strategies and initial management'.)

HEMATOLOGY (November 2017)

Cross-sectional imaging for suspected multiple myeloma

For patients with suspected multiple myeloma, we prefer cross-sectional imaging (low-dose CT, PET/CT, or MRI scan), rather than a skeletal survey, as the imaging modality to detect bone involvement.

Imaging is a key part of the evaluation of all patients with suspected multiple myeloma (MM). Until recently, a skeletal survey using plain radiographs had been the preferred modality for detecting bone lesions that would trigger the institution of therapy. Low-dose computerized tomography (CT), FDG positron emission tomography (PET)/CT, and magnetic resonance imaging (MRI) are all more sensitive than plain radiographs for the detection of most skeletal lesions in myeloma. Accumulating data suggest that patients who previously would have met criteria for smoldering myeloma based on negative skeletal surveys, but who have lesions detected by one of these modalities, have a shorter time to progression than similar patients with negative cross-sectional imaging [6]. We now prefer cross-sectional imaging with one of these modalities for patients with suspected MM. The preferred modality depends upon availability, cost, institutional preference, and clinical features. (See "Clinical features, laboratory manifestations, and diagnosis of multiple myeloma", section on 'Choice of modality' and "Clinical features, laboratory manifestations, and diagnosis of multiple myeloma", section on 'CT, MRI, and PET'.)

NEUROLOGY (October 2017)

Patent foramen ovale (PFO) device closure for prevention of recurrent ischemic stroke

For patients age ≤60 years with an embolic-appearing cryptogenic ischemic stroke who have a patent foramen ovale (PFO) with a right-to-left shunt detected by bubble study, we suggest percutaneous PFO closure in addition to antiplatelet therapy, rather than antiplatelet therapy alone (Grade 2B).

Treatment for patients with a cryptogenic stroke who have a patent foramen ovale (PFO) has been controversial. In earlier randomized controlled trials, point estimates suggested that percutaneous device closure of a PFO in patients ≤60 years of age was more effective than antiplatelet therapy for reducing recurrent stroke, but the findings did not reach statistical significance. However, the results of three recent randomized trials, RESPECT extended follow-up [7], REDUCE [8], and CLOSE [9], provide stronger evidence that device closure of a PFO plus antiplatelet therapy is more effective than antiplatelet therapy alone for preventing recurrent ischemic stroke in such patients, with absolute risk reductions ranging from 2.2 to 6 percent. Based upon these results, we now suggest percutaneous PFO closure in addition to antiplatelet therapy for patients who meet all of the following criteria: age ≤60 years, embolic-appearing cryptogenic ischemic stroke (ie, no evident source of stroke despite a comprehensive evaluation), and a PFO with a right-to-left interatrial shunt detected by bubble study. (See "Treatment of atrial septal abnormalities (PFO, ASD, and ASA) for prevention of stroke in adults", section on 'Percutaneous closure of PFO'.)

ONCOLOGY (October 2017)

Anti-EGFR therapy and primary tumor location in metastatic colorectal cancer

For patients with RAS/BRAF wild-type (wt) metastatic colorectal cancer (mCRC) and a left-sided primary tumor, we suggest treatment with an antibody targeting the epidermal growth factor receptor (EGFR), rather than bevacizumab, when a biologic agent is chosen as a component of first-line therapy (Grade 2A). For most patients with RAS/BRAF wt mCRC and a right-sided primary tumor, we suggest bevacizumab rather than an anti-EGFR antibody in conjunction with first-line chemotherapy (Grade 2C).

Accumulating data suggest that the site of the primary tumor influences the effectiveness of first-line treatments for metastatic colorectal cancer (mCRC) that target the epidermal growth factor receptor (EGFR). In a meta-analysis of trials comparing anti-EGFR with anti-vascular endothelial growth factor (VEGF) agents when added to standard first-line chemotherapy, patients with RAS wild-type (wt) mCRC and a left-sided primary tumor had longer survival with anti-EGFR treatment, while there was a trend toward longer survival in patients with right-sided tumors who received bevacizumab [10]. Given these data, when a biologic agent is chosen as a component of first-line therapy, we suggest treatment with an anti-EGFR antibody rather than bevacizumab for patients with RAS/BRAF wt mCRC and a left-sided primary tumor. For most patients with RAS/BRAF wt mCRC and a right-sided primary tumor, we suggest bevacizumab rather than an anti-EGFR antibody in conjunction with first-line chemotherapy, although anti-EGFR agents could be used for later lines of therapy. (See "Systemic chemotherapy for nonoperable metastatic colorectal cancer: Treatment recommendations", section on 'Anti-EGFR agent versus bevacizumab with first-line chemotherapy'.)


Management of treatment resistant depression in adults

For patients with mild to moderate treatment resistant major depression, we suggest augmenting the initial antidepressant with a second drug and/or psychotherapy, rather than other strategies such as switching antidepressants or switching from pharmacotherapy to psychotherapy (Grade 2C).

For patients with treatment resistant depression, there has been little comparative evidence to guide the choice between add-on therapy (augmentation) and switching to a different antidepressant drug. In an open label trial, more than 1500 patients with treatment resistant depression were randomly assigned to one of three treatment strategies: augment the current antidepressant with aripiprazole, augment with bupropion sustained release, or switch to bupropion [11]. At 12 weeks, remission was more likely in the augment-aripiprazole group than the switch group, but the clinical difference was small (29 versus 22 percent). Akathisia, somnolence, weight gain, and laboratory abnormalities were more common with aripiprazole, and anxiety occurred more often in the other groups. Based on these results, we now favor augmentation for managing treatment resistant depression; however, switching remains a reasonable alternative, especially for patients who want to avoid medication side effects. (See "Unipolar depression in adults: Treatment of resistant depression", section on 'Efficacy of augmentation compared with switching'.)


Glecaprevir-pibrentasvir and sofosbuvir-velpatasvir-voxilaprevir for chronic HCV infection

For patients with chronic HCV genotype 1 infection who have not been previously treated with sofosbuvir or an NS5A inhibitor, we suggest ledipasvir-sofosbuvir, sofosbuvir-velpatasvir, or glecaprevir-pibrentasvir (Grade 2B).

For patients with chronic HCV genotype 2 or 3 infection who have not been previously treated with a DAA regimen, we suggest sofosbuvir-velpatasvir or glecaprevir-pibrentasvir (Grade 2B).

Treatment options for patients with chronic hepatitis C virus (HCV) continue to grow. Two new combination therapies, glecaprevir-pibrentasvir and sofosbuvir-velpatasvir-voxilaprevir, were recently approved by the Food and Drug Administration in the United States and are expected to be approved in Europe this year. Glecaprevir-pibrentasvir is highly effective for patients with genotypes 1 through 6 infection, offers the possibility of an eight-week regimen for most patients without cirrhosis, and can be used in patients with renal impairment (including those on dialysis) [12-15]. It is now one of our preferred regimens for all genotypes; regimen duration depends on the genotype, the presence of cirrhosis, and the treatment history (algorithm 2 and algorithm 3 and algorithm 4 and algorithm 5). Sofosbuvir-velpatasvir-voxilaprevir is highly effective in patients with genotypes 1 through 6 infection who have failed a prior direct acting antiviral (DAA) regimen and is now the main treatment option for those who have failed an NS5A inhibitor-containing regimen [16]. Like other contemporary DAA regimens, these new combinations are well tolerated, with common but mild side effects. (See "Treatment regimens for chronic hepatitis C virus genotype 1 infection in adults", section on 'Selection of treatment regimens' and "Treatment regimens for chronic hepatitis C virus genotypes 2 and 3 infection in adults", section on 'Selection of treatment regimen' and "Treatment regimens for chronic hepatitis C virus genotypes 4, 5, and 6 infection in adults", section on 'Selection of treatment regimens'.)


Midostaurin for advanced systemic mastocytosis

For patients with advanced systemic mastocytosis, we suggest midostaurin for initial systemic therapy rather than imatinib or other cytoreductive therapies (Grade 2B).

Cytoreductive treatment of advanced systemic mastocytosis (SM) can mitigate organ dysfunction, improve quality of life, and limit disease progression until a suitable donor for allogeneic hematopoietic cell transplant is identified. Midostaurin is a multikinase inhibitor that is effective against SM with wild type or mutant KIT (eg, KIT D816V). A recent phase II study found that midostaurin was associated with improved measures of organ damage (eg, cytopenias, liver function studies) in two-thirds of patients with advanced SM, with median overall survival >3 years [17], confirming similar findings from an earlier trial [18]. The drug was well tolerated, with primarily grade 1 to 2 nausea/vomiting or modest cytopenias. The US Food and Drug Administration approved midostaurin for treatment of advanced SM earlier this year. We now suggest midostaurin for initial systemic therapy of advanced SM. (See "Systemic mastocytosis: Management and prognosis", section on 'Choice of therapy'.)

HEMATOLOGY (August 2017)

Rituximab in acquired TTP

For patients with a presumptive diagnosis of acquired TTP, we suggest administration of rituximab as a component of initial therapy (Grade 2C).

Acquired thrombotic thrombocytopenic purpura (TTP) is a potentially life-threatening condition; standard treatment includes plasma exchange (PEX) and glucocorticoids. The role of additional up-front rituximab in acquired TTP is evolving, as evidence continues to accumulate suggesting that rituximab may reduce the risk of relapse and refractory disease and may hasten initial response. The latest evidence comes from a retrospective study from the United Kingdom TTP Registry, which found low rates of relapse in patients treated with rituximab as part of initial therapy, although patients were only observed for a median of 15 months [19]. Based on this and other studies, we now use rituximab as a component of initial therapy for acquired TTP. Some experts may reasonably omit rituximab due to concerns about toxicity, pending additional data. Other considerations for rituximab use In TTP include the optimal dose, timing relative to PEX, and risk of hepatitis B reactivation. (See "Acquired TTP: Initial treatment", section on 'Rituximab'.)

ONCOLOGY (June 2017)

Management of a positive sentinel lymph node biopsy in patients with cutaneous melanoma

For patients with cutaneous melanoma and a positive sentinel lymph node biopsy, we suggest clinical observation and ultrasound surveillance of the positive nodal basin rather than immediate completion lymph node dissection (Grade 2B).

Historically, completion dissection of all involved nodal basins was considered the standard treatment approach for patients with cutaneous melanoma and a positive sentinel lymph node biopsy (SLNB). In the phase III Multicenter Selective Lymphadenectomy Trial II (MSLT II), patients with a positive SLNB were randomly assigned to either completion lymph node dissection or observation that included ultrasound evaluation of the appropriate lymph node basins at each follow-up visit [20]. Melanoma-specific survival at three years was the same for both groups, although the incidence of recurrence in regional lymph nodes was higher in patients managed with observation and ultrasound surveillance. The incidence of lymphedema was higher in patients who underwent immediate lymph node dissection. For patients with a positive SLNB, we suggest clinical observation coupled with ultrasound surveillance of the positive nodal basin. Completion lymph node dissection is indicated if, in the absence of distant metastases, there is evidence of regional lymph node recurrence. (See "Evaluation and treatment of regional lymph nodes in melanoma", section on 'Multicenter Selective Lymphadenectomy Trial II'.)

ONCOLOGY (June 2017)

Next-generation ALK-inhibitors in crizotinib-naive ALK-positive NSCLC

For patients with newly diagnosed ALK-positive NSCLC, we recommend alectinib as first-line treatment (Grade 1B). For those without access to alectinib, appropriate alternatives include crizotinib or ceritinib.

For patients with advanced anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC), crizotinib has been administered as frontline therapy. However, newer agents have shown promising efficacy in advanced ALK-positive NSCLC:

In a global trial of 303 patients randomly assigned to frontline crizotinib versus the next-generation inhibitor alectinib (ALEX), those receiving alectinib experienced a longer progression-free survival (PFS, not reached versus 11.1 months), with fewer toxicities, at a median follow-up of approximately 18 months [21]. These results are consistent with an earlier Japanese trial [22].

In a phase III trial of 376 patients comparing ceritinib, another next-generation ALK inhibitor, with pemetrexed and a platinum agent, ceritinib improved progression-free survival (17 versus 8 months) [23]. Ceritinib has not been compared with crizotinib in the frontline setting.

For patients with newly diagnosed, ALK-positive NSCLC, we now recommend frontline therapy with alectinib. For those without access to alectinib, appropriate alternatives include crizotinib or ceritinib. (See "Anaplastic lymphoma kinase (ALK) fusion oncogene positive non-small cell lung cancer".)


Revised follow-up for a solitary pulmonary nodule

For patients with an asymptomatic solid or subsolid (pure ground glass or part-solid) solitary pulmonary nodule (SPN) <6 mm, no routine follow-up is required. For patients with solid SPNs that have been stable on serial CT over a two year period, or with subsolid SPNs that have been stable over a five year period, we suggest no further diagnostic testing.

Fleischner Society guidelines have been updated to reflect the accumulating data on the malignancy risk of incidental pulmonary nodules and growth rates of lung cancer [24]. Important changes include guidance on identifying benign nodules with minimal follow-up imaging. For patients with a solid or subsolid (ground glass or part-solid) solitary pulmonary nodule measuring <6 mm, follow-up computed tomography (CT) is optional, but no longer required. A solitary pulmonary nodule that is solid and unchanged on serial CT over a two-year period, or subsolid and unchanged over a five-year period, is likely benign and does not need further diagnostic evaluation. Recommendations in UpToDate have been revised to reflect these new guidelines. (See "Diagnostic evaluation of the incidental pulmonary nodule", section on 'Management' and "Diagnostic evaluation of the incidental pulmonary nodule", section on 'Solid nodule ≤8 mm'.)


Tranexamic acid for management of postpartum hemorrhage

For women with postpartum hemorrhage diagnosed within three hours of delivery, we recommend administration of tranexamic acid as a component of overall treatment (Grade 1B). When more than three hours have elapsed since delivery, we still suggest tranexamic acid (Grade 2C), but the benefit of treatment is less clear.

Tranexamic acid, an antifibrinolytic drug, reduces bleeding in surgical and trauma patients. In a pragmatic randomized trial involving over 20,000 women with postpartum hemorrhage in over 20 countries (the World Maternal Antifibrinolytic Randomized Trial [WOMAN]), tranexamic acid, compared with placebo, reduced the relative risk of death due to bleeding by 20 to 30 percent, reduced the incidence of laparotomy to control bleeding, and was not associated with an increase in adverse effects [25]. Overall mortality was not reduced. We now recommend administration of tranexamic acid as a component of the treatment for postpartum hemorrhage. (See "Postpartum hemorrhage: Medical and minimally invasive management", section on 'Administer tranexamic acid'.)

NEUROLOGY (May 2017)

Edaravone for amyotrophic lateral sclerosis

For patients with ALS who have a disease duration of two years or less, are living independently, and have an FVC ≥80 percent, we suggest treatment with edaravone (Grade 2B). We also suggest edaravone for patients with more advanced ALS (Grade 2C).

Edaravone is a free radical scavenger that is thought to reduce oxidative stress, which has been implicated in the pathogenesis of amyotrophic lateral sclerosis (ALS). Edaravone may slow functional deterioration in some patients with ALS. An earlier trial found no benefit for edaravone compared with placebo, but a post-hoc analysis showed a possible treatment effect in a subgroup of individuals with early-stage ALS. A subsequent trial enrolled 137 Japanese patients within two years of ALS diagnosis who were living independently and had a forced vital capacity (FVC) of ≥80 percent [26]. Compared with placebo, functional decline at 24 weeks was smaller in the edaravone group, and the difference was considered clinically meaningful. Edaravone was approved in 2015 for the treatment of ALS in Japan and Korea and has now received regulatory approval to treat patients with ALS in the United States [27]. We now suggest edaravone for patients with early-stage disease as well as for those with more advanced disease, although the data are less compelling for the latter group. (See "Disease modifying treatment of amyotrophic lateral sclerosis", section on 'Edaravone'.)


Eltrombopag for adults with acquired severe aplastic anemia unable to undergo HCT

For adults with acquired severe aplastic anemia who are not candidates for allogeneic hematopoietic cell transplantation, we suggest eltrombopag plus standard immunosuppressive therapy (IST) rather than IST alone (Grade 2C).

Acquired aplastic anemia (AA) has a high morbidity, and allogeneic hematopoietic cell transplantation (HCT) is suggested as therapy for patients healthy enough to tolerate HCT who have a suitable donor. Immunosuppressive therapy (IST) is offered to those for whom HCT is not an option but is often ineffective in improving outcomes over the long term. A prospective cohort study in adults with acquired severe AA evaluated the effectiveness of IST plus eltrombopag, a thrombopoietin receptor agonist that acts on platelet precursors and hematopoietic stem cells [28]. Eltrombopag plus IST produced higher rates of overall hematologic response at six months compared with responses in a historical cohort (80 to 94 percent versus 66 percent for the historical group). Based on these findings, we now suggest administration of eltrombopag plus IST for individuals with acquired severe AA who are not candidates for allogeneic HCT. (See "Treatment of aplastic anemia in adults", section on 'Evidence for efficacy'.)

NEUROLOGY (April 2017)

Ocrelizumab for primary progressive multiple sclerosis

For patients with primary progressive multiple sclerosis, we suggest treatment with ocrelizumab (Grade 2B).

Ocrelizumab is the first drug to reduce the risk of disability progression among patients with primary progressive multiple sclerosis (PPMS), as shown by the multicenter ORATORIO randomized trial [29]. Compared with placebo, ocrelizumab modestly reduced the proportion of patients with disability progression at 24 weeks (30 versus 36 percent). In addition, ocrelizumab slowed deterioration from baseline to week 120 on the timed 25-foot walk and led to improvements on other endpoints. While the long-term risks of infection and neoplasm with ocrelizumab are uncertain, there are no other disease-modifying therapies for PPMS. Therefore, we suggest treatment with ocrelizumab for most patients with PPMS. Ocrelizumab has also been approved by the US Food and Drug Administration for use in relapsing-remitting MS (RRMS), although its role in the early treatment of this form of the disease remains to be determined. (See "Treatment of progressive multiple sclerosis in adults", section on 'Ocrelizumab'.)

ONCOLOGY (March 2017)

Scalp hypothermia to prevent chemotherapy-induced alopecia

For women with breast cancer who are receiving chemotherapy that is expected to result in significant alopecia, and who place a high value on avoiding chemotherapy-induced alopecia, we suggest the use of a scalp cooling device (Grade 2A). Scalp hypothermia could also be discussed as a potential option for patients with other solid tumors who are receiving chemotherapy that is expected to result in significant alopecia, although the evidence base is less robust.

Two prospective studies have evaluated the efficacy of two different automated scalp cooling devices in women with early stage breast cancer [30,31]:

In an interim analysis of a randomized trial comparing the Paxman Scalp Cooling device and no scalp hypothermia for women with breast cancer receiving adjuvant chemotherapy (one-third anthracycline-based, the remainder taxane-based), one-half of the hypothermia group had limited hair loss (to less than 50 percent, not requiring a wig) compared with none in the control group [30]. Adverse events were all grade 1 and 2, including primarily headache and feeling cold. The success rate was higher with taxane-containing regimens.

In a multicenter prospective cohort study, 101 patients receiving non-anthracycline taxane-based chemotherapy and who used the DigniCap Scalp Cooling device were compared with 16 concurrently treated controls who did not use the device [31]. Two-thirds of the intervention group, compared with none of the control group, had limited hair loss (to less than 50 percent) one month after the end of chemotherapy. At a median follow-up of 2.5 years, no patient developed scalp metastases.

These results confirm prior studies on the efficacy and safety of scalp hypothermia to reduce chemotherapy-related hair loss. The FDA approved one device (DigniCap) for patients with breast cancer in December 2015 and expanded the approval to cover all solid tumors in July 2017. (See "Chemotherapy-induced alopecia", section on 'Efficacy and safety'.)


Immunotherapy for stinging insect hypersensitivity in adults

We suggest not giving venom immunotherapy (VIT) to patients with reactions to stinging insects limited to cutaneous systemic symptoms and not involving other organ systems (Grade 2C). However, VIT is effective in reducing the severity of future reactions and may still be offered in selected situations.

Venom immunotherapy (VIT) for the treatment of patients with anaphylactic reactions to stings of Hymenoptera insects (eg, bees, yellow jackets, wasps, hornets, and fire ants) is highly effective in preventing future anaphylactic reactions. However, in an updated practice parameter from the American Joint Task Force, VIT is no longer suggested for adults with systemic reactions limited to the skin (ie, generalized erythema, pruritus, urticaria, or angioedema) as studies suggest these patients are at low risk for serious future systemic reactions [32]. This change brings the American approach into closer alignment with guidelines of other countries and is similar to the existing recommendation for children. Despite this revision, VIT may be appropriate for certain adults with cutaneous systemic reactions (eg, those with underlying medical conditions or medications that could affect the outcome of a systemic reaction, frequent unavoidable exposure to Hymenoptera, or impaired quality of life due to fear of future stings). (See "Hymenoptera venom immunotherapy: Efficacy, indications, and mechanism of action", section on 'Patients with past cutaneous systemic reactions'.)


Tenofovir alafenamide for the treatment of chronic hepatitis B virus infection

For most patients with chronic HBV infection who initiate therapy with tenofovir, we recommend tenofovir alafenamide rather than tenofovir disoproxil fumarate (tenofovir DF) (Grade 1B). We also suggest that those initially started on tenofovir DF switch to tenofovir alafenamide (Grade 2B).

Tenofovir disoproxil fumarate is a first-line therapy for chronic hepatitis B virus (HBV) infection. A newer formulation of tenofovir, tenofovir alafenamide, was approved by the US Food and Drug Administration in November 2016 for the treatment of chronic HBV in patients with compensated liver disease [33]. In two large randomized noninferiority trials among patients with chronic HBV infection (both treatment-naive and experienced, and including patients positive or negative for HBV e antigen), tenofovir alafenamide resulted in similar rates of HBV suppression and fewer adverse effects on renal function and bone density at 48 weeks compared with tenofovir disoproxil fumarate [34,35]. Given these findings, tenofovir alafenamide is our preferred formulation for patients with chronic HBV who initiate therapy with tenofovir. We also favor switching those initially started on tenofovir disoproxil fumarate to tenofovir alafenamide. Given limited available safety data, we do not currently use tenofovir alafenamide in pregnant women. (See "Hepatitis B virus: Overview of management", section on 'Nucleos(t)ide analogues'.)

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