NEJM This Week - February 14, 2019

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Welcome. This is the New England Journal of medicine. I'm Dr Michael beer this week February fourteenth two thousand nineteen. We feature articles on trust us MAB 'em Tensing in residual breast cancer e cigarettes versus nicotine replacement therapy outpatient, Mersa decolonization notch and liver fibrosis and divided. We fall a review article on aspirated pneumonia. A case report of a woman with delusional thinking and Paris, usua- and perspective articles on Brazil's fight against hepatitis C. Under a stray Elliot's approach to hepatitis C on reducing unfair out of network billing and on developing drugs for high risk early breast cancer. Trust user, MAB 'em Tensing for residual invasive her two positive breast cancer by Gunter on mink, bits from the German breast group, nor Eason book Germany patients who have residual invasive breast cancer after receiving Neo adjutant chemotherapy, plus her two targeted therapy. Have a worse prognosis than those who have no residual cancer the Katherine trial compared agile entrust us album Tensing T DM one with trust us map alone. In one thousand four hundred eighty six patients who had her two positive early breast cancer and residual invasive cancer at surgery after completion of Neo Adua chemotherapy, plus her two targeted therapy at the interim analysis invasive disease or death had occurred in twelve point two percent of patients in the T DM one group and in twenty two point two percent. Of patients in the trustee map group. The estimated percentage of patients who were free of invasive disease at three years was eighty eight point three percent in the T DM one group and seventy seven percent in the trust using map group T DM one resulted in a fifty percent lower risk of recurrence of invasive disease or death distant recurrence as the first invasive disease event occurred in ten point five percent of patients in the T DM one group and fifteen point nine percent of those in the trust. Using math group. The safety. Data were consistent with the known safety profile of T DM one with more adverse events associated with T DM one than with trust user, MAB alone. Among patients with her two positive early breast cancer who had residual invasive disease after completion of Neo Adua in therapy. The risk of recurrence of invasive, breast cancer or death was fifty percent lower. Lower with education tedium one than with trust user, mob alone in an editorial Daniel Hayes from the university of Michigan Rogle cancer center and Arbor writes that the trial by on mink Vitz and colleagues is a game changer. It suggests that Neo edge of chemotherapy with trust us you MAB with or without per Tuesday. Mab is the standard of care for patients with newly diagnosed her two positive breast cancer, especially those with stage two or three disease. This approach has the ability to reduce the extent of local treatment more important it will guide post operative systemic therapy. If patients do not have a pathological complete response with such a regimen post operative treatment with T DM one offers a major opportunity to improve long term outcomes, caveat, emptor, doctors and patient. Need to be aware that the side effects of this regimen are more common than with trust us, some abolone and occasional severe toxic effects need to be considered therefore T DM one should not be used in patients with a pathological complete response or in those with stage one disease. These patients have a very favorable outcome with agile unpack la- Taxol and trust us him AB alone. Nonetheless, this trial is one more step toward personalized medicine and reduced mortality among patients with early stage, breast cancer. Residual disease after Neo edge of in therapy. Developing drugs for high risk early breast cancer, a perspective article by touch on prowl from the food and Drug administration, Silver, Spring, Maryland registration trials have drugs for early breast cancer have historically involved administration of standard systemic therapy with or without a new drug after breast surgery such trials typically enroll thousands of patients and require lengthy follow up because the majority of patients will not have a recurrence, and there can be an interval of years between early stage, breast, cancer and development of metastatic disease, this research model delays regulatory approval of potentially curative agents for use in early stage cancer by a decade or more in the Katherine trial patients received standard systemic therapy before surgery and the new agent was. Tested, only in those found to have residual invasive cancer in the breast or lymph nodes at the time of surgery. These patients are at higher risk for future metastatic disease than patients without residual cancer. In two thousand twelve these authors from the FDA proposed using the pathological complete response rate as a new regulatory end point to expedite development of drugs for high risk early breast cancer despite ongoing questions about whether pathological complete response. Rates can identify beneficial agents in early breast cancer trials are underway. The Katherine trial should prompt study of other strategies for introducing new agents into breast cancer treatment. A randomized trial of e cigarettes versus nicotine replacement therapy by Peter hey, Jack from Queen Mary university of London in this study, eight hundred eighty six adults attending UK national health service. Stop smoking services were randomly assigned to receive either nicotine replacement products of their choice, including product combinations provided for up to three months or an e cigarette starter pack a second generation refillable e cigarette with one bottle of nicotine illiquid with a recommendation to purchase further illiquid of the flavor and strength of their choice. Treatment included weekly behavioral support for at least four weeks the one year abstinence rate was eighteen percent in the e cigarette group as compared with nine point nine percent in the nicotine replacement group among participants with one year abstinence. Once those in the e cigarette group were more likely than those in the nicotine replacement group to use their assigned product at fifty two weeks eighty percent versus nine percent. Overall throat or mouth irritation was reported more frequently in the e cigarette group sixty five point three percent versus fifty one point two percent. In the nicotine replacement group and nausea more frequently in the nicotine replacement group thirty seven point nine percent versus thirty one point three percent. In the cigarette group the cigarette group reported greater declines in the incidence of cough and phlegm production. There were no significant between group differences in the incidence of wheezing or shortness of breath. E cigarettes were more effective for smoking cessation than nicotine replacement therapy. When both products were accompanied by behavioral support. Bill Linda Borrelli from Boston University writes in an editorial that the evidence of effectiveness in this trial must be balanced against the short term and long term safety of e cigarettes. A key finding is that among participants with sustained abstinence at one year eighty percent in the cigarette group or still using e cigarettes, whereas only nine percent in the nicotine replacement group or still using nicotine replacement this differential pattern of long term. Use raises concerns about the health consequences of long-term e cigarette. Use e cigarette vapour contains many toxins and exerts potentially adverse biologic effects on human cells in vitro or in animal models, although toxin levels and biologic effects are generally lower than those of tobacco smoke. An additional societal consideration is the effect of adult e cigarette use on children and young. Bolts a consensus has emerged that e cigarettes are safer than traditional combustible cigarettes. But it remains controversial whether e cigarettes should be recommended as a first line treatment to assist smoking cessation alongside FDA approved treatments. The appropriate duration of e cigarette quote treatment for smokers trying to quit is also uncertain. The editorial lists recommend that e cigarettes used only when FDA approved treatments combined with behavioral counseling fail. That patients. Be advised to use the lowest dose needed to manage their cravings. And that there be a clear timeline and off ramp for us use of e cigarettes should be monitored by healthcare providers further research on the health consequences of long-term e cigarette. Use is needed. In an editorial. Jeffrey driven writes that nicotine is amazingly addictive. Electronic cigarettes are nicotine delivery devices for humans since smoking is not a natural behavior like eating or drinking. The manufacturers of these devices commonly add flavoring to the liquid from which the nicotine aerosol is generated to make the initial exposures more pleasurable the flavoring enhances the appeal to first time users, especially teenagers flavored e cigarettes have been successful in the marketplace. The rates of vaping among teenagers are increasing at an alarming rate. The creation of a large cohort of nicotine addicted adults has consequences beyond the adverse physiological effects of nicotine, Scott Gottlieb. The Commissioner of the FDA has been admirably outspoken on this issue in his taken strong action. The FDA. A will soon be banning the sale of flavored products other than mint menthol and tobacco at most convenience stores and gas stations and will be halting online sales until websites have heightened age verification standards. We think the FDA should simply ban the sale of flavored nicotine products for use in e cigarettes. The public health problem that e cigarettes can help solve by helping people who are users of combustible tobacco products, stopped smoking by switching to vaping is adequately. Addressed by liquids that are not flavored to appeal to adolescence we urge the FDA to use it. Statutory powers in regulating nicotine delivery devices to take the bold step of removing these flavored products from the market. Decolonisation to reduce post discharge infection risk among Mercer carriers by Susan Wong from the university of California Irvine school of medicine hospitalized. Patients who are colonized with methicillin resistant staff aureus Mersa are at high risk for infection after discharge this trial evaluated whether after hospital discharge decolonisation with topical Chlor heck sitting and MU Perote's in monthly for six months. Plus hygiene education was superior to educational alone in reducing the likelihood of Mersa infection in patients colonized with Mercer carriers in the per protocol population, Mercer infection occurred in nine point two percent of participants in the education group and in six point three percent in the decolonization group. Eighty four point eight percent of the Mersa infections lead to hospitalization infection from any cause. Occurred in twenty three point seven percent of the participants in the education group and nineteen point six percent of those in the decolonization group. Eighty five point eight percent of the infections lead to hospitalization. The hazard of Mersa infection was significantly lower in the decolonization group than in the education group hazard ratio zero point seven this lower hazard, led to a lower risk of hospitalization due to Mersa infection has ratio zero point seven one in as treated analyses. Participants in the decolonization group who adhered fully to the regimen had forty four percent fewer Merce infections than the education group and had forty percent. Fewer infections from any cause post discharge Mersa decolonisation with Chlor heck sitting and Mupa Rousson led to a thirty percent lower risk of Mersa infection than education alone. Aspiration pneumonia. A review article by Lionel Mandel from McMaster University Hamilton, Ontario, Canada, aspiration pneumonia is best considered. Not as a distinct entity. But as part of a continuum that also includes community and hospital acquired pneumonias, it is estimated that aspiration pneumonia accounts for five to fifteen percent of cases of community acquired pneumonia, large volume. Aspiration? Macro aspiration of colonized aura fringe or upper gastrointestinal contents is the scenic Kwan, none of aspiration pneumonia. This review focuses on aspirin involving the lung Parang, comma, primarily aspirated pneumonia and chemical Newman Itis challenges remain in distinguishing aspiration pneumonia from chemical Newman. Itis aspiration pneumonia is an infection caused by specific microorganisms, whereas chemical Newman is. This is an inflammatory reaction to irritative gastric contents. The diagnosis of aspirated pneumonia depends on a characteristic clinical history witnessed macro aspirin risk factors and compatible findings on chest radiography. These radiographic findings include infiltrates in gravity dependent lung segments superior lower lobe or post earier upper lobe segments. If the patient is in a supine position during the event or basil segments of the lower lobe if the patient is upright during the event, the causative agents in aspirin pneumonia have shifted from anaerobic to Arabic bacteria treatment, and prevention strategies are discussed. A forty eight year old woman with delusional thinking and parasitism of the right hand a case record of the Massachusetts General Hospital by Charlotte, HOGAN and colleagues a forty eight year old woman presented to an emergency department with tingling of the right hand and was found to have disorganized and delusional thinking one hour earlier the patient felt in acute prick Ling and tingling sensation diffusely on the right palm, the tingling resolved before examination. The patient stated that she had recently traveled to Boston from New York City to visit museums and she requested accommodations from medical personnel in Boston because she did not have a place to stay on examination. The patient was described as having a lay bio affect with rapid and tangential speech. The patient was discharged the list of local shelters and hotels, five hours. After discharge the patient felt recurrent. Ruling on the right palm primarily along the radio nerve distribution. And she again presented to the emergency department. She reported that she had been unable to find a shelter and that she feared hotel staff would perform unwanted sleep. Studies or gas her examination revealed inconsistent thought processes and delusions of persecution laboratory evaluation revealed normal Siddiq anemia and an elevated proacting level MRI of the head was normal. Vitamin b twelve deficiency was most likely to cause the symptoms that were seen in this patient vitamin b twelve deficiency can cause a range of neuropsychiatric symptoms, including psychosis personality, changes and affective symptoms. In addition to cognitive impairment. Divided. We fall a medicine and society article by Lisa Rosenbaum, though medicine can inure us to the extraordinary on a Saturday night about a year ago. Doctor Rosenbaum witnessed something striking a group of doctors on call for Brigham and women's hospitals. Shock team got on the phone to talk to each other. The team had been created for patients just like the one they were discussing critically ill with multi organ involvement in need of urgent decision. Making the doctors tried to piece together the man's story. Who was he before had his condition? Decline over a day or a month would mechanical cardiac support or extra Correal membrane opposite Genego offer a chance of meaningful recovery or merely satisfied the urge to do something. What would the patient want? And who if anyone could tell us after about. Twenty minutes with decisions and contingencies in place. The call ended Dr Rosenbaum's first impression what a remarkable interaction was followed closely by her second. It shouldn't be yet opportunities to collaborate. So seamlessly are rare. Indeed, the next morning consulting on a patient with critical Eric's to noses and an obstructing Billy airy duct stone. Dr Rosenbaum participated in a more typical chain of communication. Everyone was talking about how best to care for the patient. But at no point where they all talking to each other. Why when there are so many easy ways to communicate is fragmentation of patient care more common than a streamlined collaboration among clinicians. What are the barriers to better collaboration that could improve care? This essay is the first innings three parts series. Notch and non alcoholic fatty liver and fibrosis a clinical implications of basic research article by Stephanos Romeo from the university of Goldenberg Sweden. Non alcoholic fatty liver disease is a complex condition involving the progression from simple status to inflammation, non alcoholic statal hepatitis and then to severe fibrosis and Pata cellular carcinoma, which are the major predictors of death in patients with this disease in parallel with the recent rise in obesity, the incidence of non alcoholic fatty liver disease is increasing however at present there is no approved drug treatment that specifically targets non alcoholic Seattle hepatitis notch. Proteins are a family of receptors involved in cell differentiation during embryo Genesis notch. Proteins have also been implicated in metabolism. A recent study investigated the inhibition of notch signaling as therapeutic strategy against fibrosis caused by non alcoholic fatty liver disease. Although under normal circumstances notch signaling is abolished in Pata sites. After differentiation, the authors found an up regulation of this signaling in the livers of persons with non alcoholic fatty liver disease, and in mice fed a diet that induce non alcoholic statal, hepatitis importantly, down regulation and ablation of notch signaling in these mice resulted in an amelioration of liver fibrosis down regulation of notch signaling represents a candidate therapeutic target against fibrosis in patients with non alcoholic fatty liver disease. Brazil's fight against hepatitis C universalism. Local production and patents at perspective. Article. By a Lisa different Seca from Sao Paulo business school Brazil, the emergence of new direct acting antiviral drugs has revolutionized the treatment of hepatitis c virus h see these more thanksgiv- and better tolerated drugs allow for curates exceeding ninety percent. The price of these new therapies, however is prohibitive in many countries, so creative strategies are needed for ensuring access. Brazil a pioneer in the fight against HIV. Aids is now at the forefront in addressing h see an estimated seven hundred thousand people in Brazil are living with hepatitis c in two thousand seventeen in keeping with the World Health Organization goal of eliminating h c by twenty thirty the Brazilian ministry of. Health ensured that fifty thousand patients were treated the decision to follow the most current treatment protocol available was made possible by innovative approaches to cost containment the ministry of health has adopted an incremental strategy for h see the programs started with patients with severe liver fibrosis and co-infections and expanded over time to encompass the entire patient population. When preparing to purchase substantial quantities of h c medicines to expand treatment the ministry of health. Demanded that commercial prices be lower than international market prices. Brazil has also made substantial efforts to enable local production of generic versions of Safafa, vir. And more recently declared is fear. However, the ministry of health ability to take advantage of this supply source is complicated by ongoing conflicts over. Masud ical patents. Universal medicine access through lump sum. Remuneration Australia's approach to hepatitis C, a perspective article by swear moon from the Graduate Institute of international and development. Studies Geneva Australia's approach to providing direct acting antivirals for patients with HCC suggests that under certain conditions. Innovative approaches to payment can remove price as a barrier to access in Australia. Medicines on the national formularies are largely paid for by the government in two thousand fifteen the authorities negotiated an agreement to spend approximately one billion Australian dollars seven hundred sixty six million dollars US over five years in exchange for an unlimited volume of direct acting antivirals for H CV from suppliers. This approach has been called. The subscription or Netflix model and the state of Louisiana announced in January that it was pursuing a similar approach for H CV is this unconventional approach. A good deal for Australians these authors used publicly available data including data from Medicare Australia to find out even in the more pessimistic estimate. Prices still fall far below those paid in similar countries. The lower per patient prices are a central benefit of the Australian approach, but they are not the only ones payers benefit because Australia can offer universal access to direct acting antivirals with certainty about the cost to the public purse the benefit to patients and the public is that all who need the medicines can receive them lump sum. Remuneration for innovation may be an effective underused strategy for achieving universal access. Reducing unfair out of network. Billing integrated approaches to protecting patients a perspective article by Mark hall from Wake Forest school of medicine. Winston Salem, North Carolina. The emergence of health plans with narrower provider networks has been hailed by some observers as a positive development arising in part from more competitive market conditions. Brought about by the Affordable Care Act, but the inclusion of fewer contracting providers makes out of network treatment more common which exposes patients to substantially higher out of pocket. Costs a health plan might offer. Either no coverage outside its contracted network or coverage that is subject to higher deductibles, and for only those charges that the plan deems reasonable the ACA mandated caps on out of pocket spending. Don't apply to out of network charges. So the resulting costs for patients can be financially ruinous. However, high charges for out of network care are demonstrably unfair. When health plans have inadequate networks. And when patients are treated by providers. They don't choose there is widespread agreement that patients deserve protection from out of network billing in these circumstances, but state and federal regulators and private accreditation groups that set network adequacy requirements have found it challenging to protect patients without squelching desirable market dynamics, the pin is streamlined dispute resolution. This approach requires health plans and providers to submit to binding arbitration, the determination of whether out of network bills are reasonable. Our images in clinical medicine features a three year old girl who presented to the emergency department after she had ingested a metal pendant. She had not vomited and had no pain in her chest. An x Ray of the chest confirmed a heart shaped foreign body in the proximal veracity Qasaf Agha's ingestion of foreign bodies are most commonly reported in children one to three years of age ingested items that warrant immediate and discuss removal from the Asaf Agha's include sharp, objects button, batteries and foreign bodies that have been present for longer than twenty four hours. Asymmetric children who have ingested items that do not have potentially dangerous features may be observed without intervention to allow the foreign body to pass spontaneously in this patient, the position of the foreign body appeared to be unchanged on repeat radio of the chest. The patient was taken to the operating room to undergo rigid and ask. Skippy and a gold heart shaped pendant was removed. Reinspection of the Asaf Agha's showed minor abrasions of the Asaf ajilon Muchota after the procedure the patient recovered. Well, and was discharged home. A sixty four year old man presented to the emergency department with a two week history of worsening shortness of breath. He had been in good health previously and had not undergone recent surgeries or had periods of prolonged immobilization the oxygen. Saturation was eighty four percent while he was breathing ambient air and the blood pressure was one hundred fifty six over one hundred three millimeters of mercury. A physical examination was notable for swelling of the right calf and electrocardiogram showed extreme right axis deviation and t wave inversions in the lateral leads CT of the chest showed thrombosis in both the right and left pulmonary arteries as well as a linear density in the right ventricle trans the Rasic echocardiographic confirmed the presence of a six centimeter thrombosis in the right ventricle. See the video at any J M dot org. Duplex ultra. Geography showed extensive deep venous thrombosis in the right leg the patient underwent surgical from back me, which resulted in reduction of an extensive caught burden. He did well post operative Lii and was treated with a pixel van at a follow up. Visit one month after surgery his oxygen saturation was ninety four percent while he was breathing ambient air, and he had improving exercise capacity. This concludes our summary. Let us know what you think about our audio summaries, and he comments or suggestions may be sent to audio at n e j m dot org. Thank you for listening.

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