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education

You can gain CPD points from your reading by recording what you have read in your appraisal folder. You should try to link your reading back to a learning need and also consider how you plan to improve your practice as a result of your learning. http://learning.bmj.com

EDUCATION INTO PRACTICE Ideas for quality improvement, audit, or changing your practice. COPD and inhaler techniqueRegular review of inhaler technique could reduce emergency admissions and hospital bed days due to COPD, leading to an improved quality of life and a reduction in the £600m (€830m; $925m) that COPD related medical admissions are estimated to cost the NHS every year.1

How could you build regular inhaler checks into your everyday practice?To develop this idea further as a quality improvement project, visit BMJ Quality quality.bmj.com/The reference can be viewed on bmj.com (BMJ 2015;351:h5670)

THE ART OF MEDICINE

The medical selfieCan doctors learn anything from the latest craze of “selfies”—photographs taken of oneself with a smartphone or a webcam?

The average smartphone is far better than archaic (and elusive) hospital cameras, yet data protection means that doctors mustn’t just take a quick snap of an interesting patient.

Selfies should therefore be celebrated within clinical medicine because patients’ own photographs do not fall under the strict data protection rules that hospital acquired photographs do.

We have been encouraging patients to take selfies to track their progress for review to great effect. Several patients with burns have used medical selfies so that they can take “ownership” of their condition. Most injuries are treated conservatively with regular dressing changes. Patients often worry that dressings applied in the community are not of the same standard as those done in our unit, and it is not always feasible for patients to attend regularly to have them changed. We have therefore started encouraging patients to take their own photos of dressings being applied so that they can “educate” their local nursing staff. The benefits include ensuring consistency in management and allowing some control after a traumatic event. This concept is beautifully simple. The photographs are retained by the patients who can then choose to show them to whomsoever they wish, thereby avoiding any legal or ethical pitfalls.Arunava Ray, Annabel Diane Scott, Dariush Nikkhah, Baljit S Dheansa Queen Victoria Hospital, East Grinstead, UK arunray@doctors.org.ukWe welcome contributions to this column. Please email samuel.parker@bmj.com.Cite this as: BMJ 2015;351:h5802

CLINICAL UPDATESCoeliac diseaseAnyone with persistent unexplained abdominal or gastrointestinal symptoms, prolonged fatigue, or unexpected weight loss should be offered serological testing for coeliac disease, the National Institute for Health and Care Excellence (NICE) has said. The advice is included in NICE’s new guideline on the recognition, assessment, and management of coeliac disease in children, young people, and adults. The guideline also says that serological testing should be offered to first degree relatives of people with coeliac disease.www.nice.org.uk/guidance/ng20

Mid-life health improvementProviders of NHS services should help people identify and address the personal barriers that prevent them from making changes to improve their health, NICE has said. In this guidance on mid-life approaches to delaying or preventing the onset of dementia, disability, and frailty in later life, NICE says that health service providers need to help people to maintain healthy behaviours throughout life.www.nice.org.uk/guidance/ng16

Resuscitation updateThe Resuscitation Council has updated its guidelines for 2015. The guidelines, which were previously updated in 2010, contain detailed information about basic and advanced life support for adults, children, and the newborn. Also included are guidelines on the use of automated external defibrillators and other related topics. The council’s quality standards for cardiopulmonary resuscitation practice and training are designed to help with the implementation of the updated guidelines.www.resus.org.uk/resuscitation-guidelines Cite this as: BMJ 2015;351:h5800

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WHAT YOU NEED TO KNOW

•  Patellofemoral pain often presents as gradual onset of knee pain behind or around the patella

•  It is usually unrelated to trauma, but is associated with greater frequency or duration of patellofemoral loaded activities (squatting, climbing stairs, hiking, running)

•  Imaging is rarely indicated

•  Conservative therapies (physiotherapist-led, targeted exercises, foot orthoses) are effective

•  Accurate diagnosis and explanation of the condition and rehabilitation programmes can improve the outcome

PRACTICE POINTER

Patellofemoral painKay M Crossley,1 Michael J Callaghan,2 Robbart van Linschoten3

Patellofemoral pain is pain behind or around the patella (also known as patellofemoral pain syndrome, anterior knee pain, runner’s knee, and, formerly, chondromalacia patellae). It is common, and, though not invariably, typically affects physically active people aged <40 years.1 2 It can be diagnosed clinically, and evidence based treatments can help patients maintain a physically active lifestyle.

How do patients present?Patients commonly describe a gradual onset of anterior knee pain, usually unrelated to trauma, but associated with greater frequency or duration of patellofemoral loaded activities (squatting, climbing stairs, hiking, running, rising from chairs). Pain is rarely present when the patellofemoral joint is not loaded (during sleeping, standing, resting). Patients often also describe patellofemoral crepitus, knee stiffness, difficulty with activities of daily living, and poor quality of life. Symptoms can persist for up to 20 years.7

Patients may curtail physical activity, leading to weight gain, more patellofemoral joint loading and pain, and a vicious cycle that discourages further activity.

1School of Allied Health, La Trobe University, Melbourne, Vic3086, Australia2Centre for Musculoskeletal Research, Institute for Inflammation and Repair, University of Manchester, UK3Aspetar, Qatar Orthopaedic and Sports Medicine Hospital, Doha, QatarCorrespondence to: K M Crossley k.crossley@latrobe.edu.au 0.5 CREDITS

Patellofemoral pain may also present after patellar dislocation or subluxation, or less often, acute trauma (such as a direct blow to the patella) or other knee injury, such as a meniscal tear or ruptured anterior cruciate ligament.

Patellofemoral pain most often affects younger adults. In adolescents, it occurs especially during periods of rapid growth.6 People aged >40 years may have radiographic signs of degenerative change in the patellofemoral joint.8 9

How is it diagnosed?This is a clinical diagnosis, mainly based on symptoms of anterior knee pain aggravated by patellofemoral loaded activities. There is no definitive clinical diagnostic test.10 The best available test is anterior knee pain elicited during squatting (80% of those with a positive test will have patellofemoral pain).10 Patellofemoral pain is evident in 71-75% of people with tenderness at the patellar edges,10 but patellar grinding and apprehension tests have limited diagnostic accuracy.10 Examination usually reveals a full range of knee motion and no effusion.

Patellofemoral pain with radiographic evidence of degenerative changes (osteophytes or joint space narrowing) in the patellofemoral joint indicates patellofemoral osteoarthritis.

Is imaging warranted?Imaging is usually not required. It may occasionally have a role in patients:•  With a history of patellar dislocation or repeated

subluxations, direct trauma, or persistent swelling and pain (when osteochondral lesion of the knee is suspected)—radiography (including a skyline and tunnel view) may identify bony causes of pain such as avulsions, fracture, or osteochondral lesions.

•  With inferior patellar pain with activities such as jumping and landing—ultrasound scans can show patellar tendinopathy.

•  Aged >40 years with persistent pain—radiography (including a skyline view) can show signs of osteoarthritis.

HOW PATIENTS WERE INVOLVED IN THE CREATION OF THIS ARTICLETwo patients with patellofemoral pain gave feedback on the article, including whether the issues discussed were relevant to them. We altered the section “How do patients present?” to highlight the presence of associated knee stiffness, difficulty with activities of daily living, restricted physical activity and poor quality of life, and the impact of patellofemoral pain on activity cessation and weight gain.

P

RED FLAGS FOR SPECIALIST REFERRALAll patients—Fever, significant knee swelling, heat over the knee joint, or night pain suggest septic arthritis, septic bursitis, osteomyelitis, or a tumour.

Children and adolescents—A limp, leg length discrepancy, or painful, reduced hip movement (see videos cited above) suggest Perthes disease (disruption of the blood supply to the hip, which may lead to avascular necrosis) or a slipped femoral capital epiphysis. Mild knee effusion and a locking sensation in children may indicate osteochondritis dissecans (degeneration or necrosis of small areas of bone and cartilage within the joint).

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Fig 2 | Patellar taping is a useful addition to physiotherapy-led exercise, although ineffective alone.5 16 Tape is applied to the lateral aspect of the patella. Skin medial to the patella is brought towards the patella, and the tape attached onto the medial knee region. Reproduced with permission from Brukner and Khan’s Clinical Sports Medicine, McGHill

DIFFERENTIAL DIAGNOSIS Examine the knee and hip (especially in children and adolescents), to exclude other causes of anterior knee symptoms (see videos at https://www.youtube.com/playlist?list=PLAD99E958AC0F43B1 ).Inferior patellar pole tenderness suggests patellar tendinopathy, seen in adults involved in jumping sports, or known as Sinding Larssen disease in children. Localised tenderness and swelling around the tibial tuberosity in adolescents points to Osgood Schlatter disease (overuse syndrome with patellar tendon traction). Acute knee trauma and swelling (with or without knee locking) suggest ligament sprains or ruptures, patellar dislocations, or acute meniscal tears. Sensations of the patella “moving,” “slipping,” or “popping out” suggest patellar subluxation or instability, especially when rotating (such as, twisting or changing direction), or, with hypermobility, shallower femoral trochlea or a small, high riding patella. Prolonged morning stiffness >30 minutes, multiple joint or tendon involvement, and joint swelling may indicate systemic joint disease requiring rheumatologist referral.

WHAT PATIENTS SHOULD KNOW • Patellofemoral pain is a

common knee condition that starts gradually. How you move your hip, knee, or foot, the alignment of your kneecap (patella) in the groove of the thigh bone, and the strength of certain muscles will affect the load on your kneecap and can cause pain (see fig 1).

• Physiotherapist-led exercise and foot orthotics can reduce pain and improve physical function.

• Most people improve 6-12 weeks after starting physiotherapy. However, people who have had pain for longer may need more time to respond.

• Patients who regularly do their exercises respond better to treatment. • If you don’t notice improvement with the first therapy you try (such as

supervised exercise), you can substitute or add other therapies (such as foot orthotics, patellar taping (figure 2), or kneecap mobilisation)

• Imaging (radiographs, MRI scans) is rarely needed.

Hamstrings

Femur (thigh bone)

Ligament

Meniscus

Tibia

Ligament

Patella

Quadriceps

Fig 1 | Lateral view of knee. Patellofemoral pain may be associated with patellar malalignment and quadriceps weakness.3

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SEBA

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N K

AULI

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/SPL

CLAU

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There is no role for MRI to diagnose patellofemoral pain because of limited diagnostic accuracy for low grade cartilage lesions,11 and poor association between articular cartilage lesions and patellofemoral pain symptoms.11 12

How is it managed?Physiotherapy and foot orthotics: Refer for physiotherapy (for quadriceps or hip exercises, possibly with patellar taping (see figure) and mobilisation), or shoe orthotics.5 These options are similarly effective in improving symptoms, so the choice should include patient preference and clinical findings.12 13 The best results are obtained with targeted exercises, augmented where appropriate by foot orthotics. A simplified exercise intervention that is part of a patient’s regular routine may improve long term adherence and speed of recovery.6 Benefits can be expected 6-12 weeks after starting physiotherapy.

Refer to physiotherapy or for rehabilitation as early as possible. Greater severity and longer duration of patellofemoral pain have a poorer prognosis.14 However, there is insufficient evidence to predict which patients are most likely to respond to treatment.4 Weight management may be necessary to manage symptoms.

Best results and patient adherence require accurate diagnosis, with a clear explanation to the patient of the condition, the rationale for the coordinated physiotherapy programme, and likely prognosis (see box).

Other physical agents: Ice or cold, ultrasound, phonophoresis, iontophoresis, neuromuscular electrical stimulation, electrical stimulation for pain control, electromyographic biofeedback, and laser do not reduce pain or improve function, in a recent systematic review.17

Patellofemoral osteoarthritis: People with patellofemoral osteoarthritis have similar impairments to those with patellofemoral pain (such as patellar malalignment, quadriceps and hip muscle weakness), and a randomised controlled trial found that similar interventions resulted in more people reporting improvement after 12 weeks.19

What if patients do not respond to physical and exercise therapy?For some patients, recovery is protracted despite adherence to the rehabilitation approach.6 They may wish to consider adjunctive therapies, such as acupuncture,5 non-steroidal anti-inflammatory drugs,20 or movement retraining programmes (such as running retraining),6 although there is limited evidence for their use.

In patients with persistent, non-specific and inconsistent, pain with a non-mechanical pattern (that is, pain not related to activities expected to load the joint), consider central sensitisation or psychosocial factors. Few studies have investigated these in people with patellofemoral pain.3 Consider referring such patients to a physician or physiotherapist with expertise in pain management.

Surgery cannot be recommended, given its inherent invasiveness and risks, and the lack of randomised controlled data to show it reduces patellofemoral pain.Cite this as: BMJ 2015;351:h3939

WHAT YOUR PATIENT IS THINKING

How to talk to someone with an “untreatable” lifelong conditionNick Wood suggests ways to help people with conditions that have no obvious treatment

WHAT YOU NEED TO KNOW

•  You should be open about the limits of your knowledge, but you can make a huge difference by checking for relevant guidelines, making referrals, and helping us to find external support. I was helped most by referral for chronic pain and mood management, potential sexual therapy for sexual dysfunction difficulties, and finding online groups for patient peer support

•  Even when you cannot cure us, your continuing support is crucially important to patient morale and engagement, especially during multiple investigations that are potentially confusing and traumatic

I live with a painful condition that no one wants to talk about and relatively few seem to research. It is also a condition that took a long time to diagnose, which resulted in many months of fear and turmoil as to whether I might have the dreaded prostate cancer.

There was little relief though in finally being told, after months of invasive investigations, that I had chronic prostatitis or chronic pelvic pain syndrome (CP/CPPS), because when I asked about treatment options I was told (with a shrug): “Not much is truly effective with your condition currently I’m afraid.”

“What’s the usual course of illness then? How can I get better?” I asked desperately.

The urology registrar replied: “Well, it might burn itself out, anywhere from four years to . . . perhaps never.” He shrugged again on that last word and the consultation ended.

A life sentence of suffering I left that appointment in tears, clutching some out of date printouts from the web. I had already had many months of incessant pelvic pain and urinary difficulties with limited sleep. Although I had avoided crying in front of the registrar, I found myself (usually a very private and contained person) weeping helplessly as I collected

the bmj | 7 November 2015 33

WHAT YOUR PATIENT IS THINKING

The belief that the evidence is evolving is somewhat reassuring

• Link to this article online for CPD/CME credits

ROSE

LLO

YD

a pain prescription from the pharmacy. It was as if I had been given a life sentence of suffering, with a lack of empathy and dismissal that made me feel very alone.

As time went on I often felt I was a “heartsink” patient. No general practitioner seemed to want to listen to my story, and a few perhaps even doubted my experiences. (I also had the sense that they felt that little else could be done, so what was the point of my “complaining” or even continuing to attend medical appointments?)

A turning pointBut there were things they could have done, as I realised over time. I finally found a urologist who had been through a bout of acute prostatitis. It was a huge relief when he told me about his own experience and how hard it was for him to accept there was little he could do to help me. Having contact with a medical professional who acknowledged my suffering, but who respected me and made time to listen to me, was a turning point. I have also since found a sympathetic GP who has no personal experience of the illness but a listening ear and a non-dismissive attitude. He has referred me to a specialist pain clinic with some hope I can get a handle of sorts on this condition.

At diagnosis, then, how might the doctor of my dreams have answered my questions?

“What’s the usual course of illness then? How can I get better?”

“Well, I’m afraid we don’t really know; prognosis varies greatly. There are some evolving guidelines you can look at here; once you’ve had a chance to read them we can discuss them if it would help. What other support do you have to manage this terrible condition? And what else can I do to help you with this?’

There is something strangely reassuring about doctors who admit to limits of knowledge—it makes them more human and present in the moment. Being pointed towards developing guidelines would have alerted me to the fact that the doctor was keeping up to date with this condition. The belief that the evidence is evolving is somewhat reassuring. Finally, being invited back would have reassured me that I was not being abandoned to manage an “incurable” condition.

I am one of an estimated 15% of men with this difficult and painful condition. There’s some truth in the stereotype that men don’t talk enough—we need to talk more and raise awareness, galvanising further research to combat this debilitating illness. Many men, and perhaps some doctors, may feel embarrassed about the symptoms of CP/CPPS, but we need to take the lid off this condition. And all we ask from our doctors is honesty, care, and support—so if in doubt about how your patient feels, ask (and it’s up to us male patients to tell).

For series information contact Rosamund Snow, patient editor, rsnow@bmj.com.

Cite this as: BMJ 2015;351:h5037

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Diagnosis and initial evaluationThe serologic indicators for HBV infection include HBsAg, hepatitis B surface antibody (anti-HBs), hepatitis B e antigen (HBeAg), hepatitis B e antibody (anti-HBe), and hepatitis B core antibody (IgM and IgG; (anti-HBc) ) (box). Serum HBsAg is the primary marker of infection. Once the diagnosis of HBV has been made on the basis of positive HBsAg, further evaluation should be performed by measuring alanine aminotransferase (ALT), HBV DNA, and anti-HBc IgG, as well as assessing HBeAg status and liver fibrosis.10 14 15 Screening for coinfection with HIV and hepatitis C virus is also recommended.14

HBeAg negative chronic HBV: After HBeAg seroconversion, a subset of patients may enter a disease state of viral reactivation, known as HBeAg negative chronic HBV. Similar to the inactive carrier phase, this condition is also denoted by the absence of HBeAg.

Occult HBV infection: This is defined as the presence of HBV DNA in the liver and the absence of detectable HBsAg using currently available assays, with or without the presence of HBV DNA in the serum.24 Occult HBV infection is more common in patients with hepatitis C virus (HCV) infection. In these patients it is associated with a greater risk of progression to cirrhosis and development of HCC, as well as a shorter survival time.25  26

Assessment of liver fibrosisBecause treatment is indicated for those with stage 2 fibrosis or greater, it is often necessary to stage the degree of hepatic fibrosis. Non-invasive evaluation of liver fibrosis can be considered as an alternative to biopsy.

Among serologic biomarkers of liver fibrosis, the aspartate aminotransferase-to-platelet ratio index (APRI) and fibrosis index based on the four factors (FIB-4) have been most widely studied in patients with HBV. Transient elastography uses

WHAT YOU NEED TO KNOW

•  About 30% of patients with chronic HBV develop liver cirrhosis, and nearly 23% of these decompensate within five years.

•  Patients with decompensated cirrhosis should be treated with nucleos(t)ide analogs, regardless of HBV DNA or ALT level.

•  In people without cirrhosis, in the immune tolerant phase, observation and monitoring of ALT and HBV DNA values every three to six months is appropriate.

•  When both HIV and HBV infections need to be treated, antiretroviral therapy using the combination of tenofovir and emtricitabine or lamivudine is preferred.

•  The safety of nucleos(t)ide analogs during pregnancy has not been established; however use of these medications in the third trimester is safe and can reduce neonatal transmission in women with a high HBV viral load.

STATE OF THE ART REVIEW HIGHLIGHTS

Management of chronic hepatitis B infectionVinay Sundaram,1 Kris V. Kowdley2

1Department of Medicine and Comprehensive Transplant Center, Cedars-Sinai Medical Center, Los Angeles, CA, USA2Liver Care Network, Swedish Medical Center, Seattle, USA Kris.Kowdley@swedish.orgThis is an edited version of the state of the art review. The full version is on thebmj.com.

Fig 1 | Natural course of hepatitis B virus (HBV) disease progression

SUMMARYHepatitis B virus (HBV) is a global health problem that can lead to cirrhosis and hepatocellular carcinoma (HCC). Although HBV vaccination has reduced the prevalence of HBV infection, the burden of disease remains high. Treatment with antiviral drugs reduces the risk of liver disease and the development of HCC, and can even reverse liver fibrosis. However, challenges remain regarding optimal timing, as well as the modality and duration of treatment. Currently approved drugs include pegylated interferon and nucleos(t)ide analogs. Nucleos(t)ide analogs are better tolerated and provide excellent viral suppression with a low risk of antiviral resistance, but pegylated interferon offers the benefit of a finite duration of treatment. Monitoring of hepatitis B surface antigen (HBsAg) levels may help to predict the likelihood of response to treatment, particularly for pegylated interferon. Prolonged treatment is usually needed with oral antiviral agents, and relapse is common if treatment is discontinued. New treatments that result in sustained clearance of HBV DNA and the clearance of HBsAg are needed.

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ultrasound elastography to assess the amount of liver stiffness as a surrogate of hepatic fibrosis.35 The outcome is measured in kPa and ranges from 2.5 kPa to 75 kPa, with 5 kPa often designated as normal and 13.4 kPa or more as cirrhosis.36-38

When to start treatmentThe decision to begin treatment is based on the goals of treatment, including suppression of HBV DNA levels, normalization of alanine aminotransferase (ALT), and HBeAg seroconversion in HBeAg positive patients as well as patient characteristics, including the presence or absence of cirrhosis and hepatitis B inactive carrier state.

People with cirrhosis Guidelines agree that those with decompensated cirrhosis should be treated with a nucleos(t)ide analogs, regardless of HBV DNA or ALT level.10  14  15 However, the approach to the treatment of patients with compensated cirrhosis differs between guidelines.

People without cirrhosisRecommendations from guidelines and from a panel of experts suggest that for those in the immune tolerant phase, observation and monitoring of ALT and HBV DNA values every three to six months is appropriate, given the lack of data showing a benefit of treatment and the potential for antiviral resistance.10  14  15  42

People in the inactive carrier stateThe same guidelines also recommend that close monitoring rather than treatment is appropriate for people in the inactive carrier state.10  14  15

Other patientsIn the remainder of patients the decision to start therapy should be based on a variety of factors including HBeAg status, ALT concentration, HBV viral load, age (<40 v >40 years), and stage of liver fibrosis. Table 1 shows recommendations from the AASLD, EASL, and APASL guidelines on when to start HBV therapy.

Predictors of treatment outcomeEvidence has consistently shown that the most important outcome of treatment is suppression of HBV

1 CREDIT

viral load because this parameter strongly correlates with the risk of progression to cirrhosis and development of HCC.47

Currently available treatmentsTwo therapeutic approaches are available for both HBeAg positive and HBeAg negative patients: finite therapy and long term suppressive therapy.

Finite therapyThis strategy uses treatment with pegylated interferon for 48 weeks. Because pegylated interferon is associated with multiple toxicities, including fatigue, a flu-like reaction, anemia, pancytopenia, and depression (in 20-30% of patients),51 it is important to determine which patients will respond to this drug before starting treatment. Characteristics indicating a favorable response include low HBV DNA levels, high levels of ALT and HBV, presence of the HBV genotype A or B, and lack of advanced liver disease.52  53

Because interferon seems to be successful in only a third of patients, studies have assessed how to improve the efficacy of interferon based therapy, including combination therapy with nucleos(t)ide analogs. However, regimens involving interferon combined with nucleos(t)ide analogs or ribavirin did not improve the response in HBeAg positive and HBeAg negative patients with HBV.55-57

Long term suppressive therapyThe second approach aims to obtain rapid and long term viral suppression with the use of oral nucleos(t)ide analogs, although the duration of treatment may be indefinite. Several nucleos(t)ide analogs are available for the treatment of HBV including lamivudine, adefovir, telbivudine, entecavir, and tenofovir disoproxil fumarate. However, international guidelines recommend only entecavir and tenofovir as first line therapy for nucleos(t)ide analog naive patients with HBV.10  14  15 Both of these drugs are well tolerated overall with minimal adverse effects.

Studies of combination therapy with two nucleos(t)ide analogs have found marginal benefit over monotherapy overall. Additional studies have shown that tenofovir monotherapy has comparable efficacy to tenofovir combined with emtricitabine (Truvada) in both naive and lamivudine experienced patients.43  72

Fig 2 | Phases of HBV infection. The immune tolerance phase occurs in patients who acquire HBV infection perinatally or in childhood and may last for 20-30 years. During this phase, the virus is not cytopathic and minimal hepatic inflammation occurs. In the immune clearance phase, the host immune system attempts to eliminate infected hepatocytes. Subsequently ALT levels rise above normal, HBV DNA levels fluctuate, and hepatic inflammation occurs. The inactive carrier state occurs after the immune clearance phase and is characterized by the presence of HBsAg in serum.

the bmj | 7 November 2015 41

answ

ers

We welcome contributions that would help doctors with postgraduate examinations. We also welcome submissions relevant to primary care. See thebmj.com/endgames

A 60 year old male non-smoker was referred to the ear, nose, and throat clinic with suspected lymphoma owing to enlarging bilateral neck masses. On examination the masses were pulsatile and expansile. A computed tomogram showed these to be bilateral aneurysms of the subclavian arteries (figure; the arrows mark the communication between the right supraclavicular mass and the right subclavian artery).

He was referred to the vascular surgeons and investigations identified popliteal and femoral aneurysms. Systemic diseases including Behçet’s disease, connective tissue disease, and

autoimmune disease were all excluded. The patient underwent repair of the subclavian aneurysms. Learning points:• Vascular lesions can present as neck

lumps, and subclavian aneurysms represent less than 1% of all peripheral aneurysms

• If a subclavian aneurysm is suspected, examination of the entire vascular system should be carried out.

Submitted by Sonia Kumar, Gaurav Chawdhary, and Ram MoorthyPatient consent obtained.Cite this as: BMJ 2015;351:h4678

CASE REVIEWImpending airway obstruction after dental extractions1 Signs and symptoms suggest a fulminating infection of the neck. Elevation of the floor of the mouth

and hot potato speech suggest involvement of deeper fascial spaces. The diagnosis is Ludwig’s angina.

2 Computed tomography in the acute setting if deep neck infection is suspected, with airway assessment by a specialist anaesthetist before scanning is performed.

3 Stridor, dysphonia, drooling, raised tongue, swollen floor of the mouth, bilateral neck swelling, dropping oxygen saturations, and increased respiratory rate.

4 Mainstay of treatment is incision and drainage of the neck spaces affected in a patient with a protected airway. Multidisciplinary management involves surgeons, anaesthetists, and radiologists.

A 22 year old man presented to the department of oral and maxillofacial surgery with a five day history of sore throat, pain on swallowing, and low grade fever. He was previously fit and well with no medical history of note. His lower wisdom teeth had been extracted seven days before presentation. He was a non-smoker and non-drinker.

On examination, he looked unwell with tachycardia (120 beats/min) and a temperature of 37.2ºC. He was normotensive and mildly tachypnoeic (22 breaths/min).

Oropharyngeal examination was difficult owing to marked trismus, but a raised floor of the mouth was noted. He had a tender

swelling in his upper neck extending to bilateral submandibular regions and a “hot potato” voice.

Initial investigations showed a raised white cell count of 29.9×109/L (reference range 4.5-11) and a C reactive protein of 4343 nmol/L (0.76-28.5). Urgent contrast enhanced computed tomography of his head and neck was performed (figure).1 What is the likely diagnosis?2 What imaging modality should be used to

investigate this patient?3 What are the red flags for impending

airway obstruction?4 How should this patient be managed?

CASE SCENARIOBilateral neck lumps

CASE REVIEWImpending airway obstruction after dental extractions

ENDGAMES For long answers go to the Education channel on thebmj.com @BMJEndgames

Submitted by Kemal Tekeli, Guven Kaya, Samuel Grant, Michael Williams, and David Howlett

Patient consent obtained.Cite this as: BMJ 2015;351:h5277

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Treatment of antiviral resistance involves selection of an agent without cross resistance to the mutation, thereby reducing the risk of selecting viral strains with mutations that lead to multidrug resistance. This is best accomplished by switching to a drug with a high barrier to resistance instead of adding extra drugs (table 2).14  15

Monitoring surface antigen levelHBsAg has traditionally been used to diagnose HBV infection and two commercially available assays for measuring HBsAg—the Architect HBsAg assay (Abbott Diagnostics)76 and the Elecsys HBsAg II quant assay (Roche Diagnostics)77—have recently been developed. Recent studies suggest that the measurement of HBsAg titers may also be useful for predicting the course of HBV infection and assessing treatment response.78

HBsAg levels may also help distinguish between inactive carriers and chronic active HBeAg negative infection. With regard to HBsAg and treatment response, data suggest that lower pretreatment HBsAg values are associated with a greater response to pegylated interferon, and that HBsAg titers may be used as an on-treatment marker for sustained treatment response to this drug.82

Treatment withdrawalEvidence from a randomized controlled trial of 548 patients supports the notion that pegylated interferon should be stopped in any of the following scenarios: absence of a decline in HBV DNA level to 20 000 IU/mL or less, lack of a reduction of HBsAg to less than 1500 U/mL at week 12 or 24,58 and completion of 48 weeks of treatment.10

Withdrawal of nucleos(t)ide analogs can be considered six to 12 months after anti-HBe seroconversion in patients who are HBeAg positive before they start treatment, and after HBsAg loss in those who are HBeAg negative at the start of treatment.10  14  15 However, published findings suggest that relapse rates may be high after withdrawal of treatment.

Table 1 | Guideline recommendations on treatment initiation in patients with hepatitis B virus (HBV) infectionPatient characteristics AASLD (2009) EASL (2012) APASL (2012)HBeAg statusPositive HBV DNA >20 000 IU/mL and ALT >2× upper limit of normal HBV DNA > 2000 IU/mL with ALT > upper limit of normal or

biopsy with moderate fibrosis or inflammationHBV DNA >20 000 IU/mL and ALT >2× upper limit of normal

Negative HBV DNA >2000 IU/mL and ALT > upper limit of normal or stage 2 fibrosis

HBV DNA >2000 IU/mL with ALT > upper limit of normal or biopsy with moderate fibrosis or inflammation

HBV DNA >2000 IU/mL and ALT > upper limit of normal or stage 2 fibrosis

CirrhosisCompensated HBV DNA >2000 IU/mL All patients regardless of decompensation or HBV DNA level HBV DNA >2000 IU/mLDecompensated All patients All patients regardless of decompensation or HBV DNA level All patientsAASLD=American Association for Study of Liver Diseases; ALT=alanine aminotransferase; APASL=Asian Pacific Association for Study of the Liver; EASL=European Association for the Study of the Liver; HBeAg=hepatitis B e antigen.

Table 2 | Guideline recommendations for management of antiviral resistance in patients with hepatitis B virus infectionDrug AASLD (2009) EASL (2012)Lamivudine Add adefovir or tenofovir Switch to tenofovir or add adefovir if tenofovir not availableTelbivudine Add adefovir or tenofovir;

switch to emtricitabine Switch to or add tenofovir

Adefovir Add lamivudine; switch to or add entecavir; switch to or add tenofovir

Switch to entecavir or tenofovir if naive to lamivudine; switch to tenofovir and add nucleoside analogue if has been exposed to lamivudine

Entecavir Switch to tenofovir or tenofovir + emtricitabine

Switch to or add tenofovir

AASLD=American Association for Study of Liver Diseases; EASL=European Association for the Study of the Liver.

Outcomes of long term treatmentLong term treatment with third generation nucleos(t)ide analogs may lead to improvement in liver fibrosis and potentially reversal of cirrhosis. With regard to the effect of HBV treatment on the progression of liver disease and development of HCC, a landmark study in patients with advanced fibrosis from East Asia and the Pacific showed that a response to lamivudine delays progression of HBV related liver disease in terms of hepatic decompensation, liver related mortality, and development of HCC.92

Evidence on the effectiveness of entecavir and tenofovir in preventing complications of HBV has come primarily from observational studies.

HIV coinfection When both HIV and HBV infections need to be treated, antiretroviral therapy using the combination of tenofovir and emtricitabine or lamivudine is preferred.14  15 A retrospective study of 65 HBV and HIV coinfected patients showed that tenofovir was effective in patients with wild-type and lamivudine resistant HBV infection, indicating that tenofovir can be used as a component of HIV therapy even in those exposed to lamivudine.103

Treatment in pregnancy and women of childbearing age In women of childbearing age, treatment aims to reduce HBV transmission to the infant because the risk of developing chronic HBV infection is high in those exposed during birth.109 Active-passive immunoprophylaxis reduces mother to child transmission rates by 95%.110

In women who are pregnant or planning pregnancy in the near future, nucleos(t)ide analogs should be used with caution because of the risk of mitochondrial toxicity.10 However, in women with advanced fibrosis or cirrhosis it has been suggested that treatment should be initiated and continued throughout pregnancy.109

Women without advanced fibrosis and with HBV DNA levels greater than 107 IU/mL can be considered for treatment in the third trimester to prevent fetal transmission. Interferon should be avoided because animal studies suggest that it may lead to fetal abortion and data from humans are not available.113 If nucleos(t)ide analogs are used, telbivudine and tenofovir are pregnancy category B drugs. It has been shown that administration of either of these drugs to highly viremic mothers leads to 0% HBV transmission to the fetus, compared with about 8% transmission in controls.114-116

If antiviral therapy is started during pregnancy it should be discontinued postpartum in mothers who intend to breast feed. Cite this as: BMJ 2015;351:h4263

the bmj | 7 November 2015 PB42 7 November 2015 | the bmj

Info-epidemiology and the bed bugWhat bugs America, bugs Google. Since the well publicised return of bed bugs to US hotels, Americans have done increasing numbers of Google searches about them. A study (J Med Entomol 2015, doi:10.1093/jme/tjv158 tjv158) using Google Trends found a massive spike in searches in 2011, followed by seasonal waves over the next years, which show little sign of abating. There has been a decrease in searches using terms like “hotel” but an increase in terms like “exterminator”, so the authors conclude that there continues to be an epidemic of bites from Cimex lectularius.

Altitude and Alzheimer’sThe mountain life is traditionally associated with wisdom and health, and this is confirmed by a study of the association between death from Alzheimer’s dementia and altitude in California (JAMA Psychiatry 2015, doi:10.1001/jamapsychiatry.2015.1852). The numbers were small and the scatter was wide, but the plot shows a clear trend towards higher mortality from Alzheimer’s disease at lower altitudes. The authors wonder if air pollution might play a part. What—in California?

Does eating frequency matter?Is it the kind of food you eat that makes you fat or how much you eat? The third factor, often ignored, is how often. The evidence is hard to unpack. Using recall data from 18 696 US adults, all measures of eating frequency, meal frequency, and snack frequency showed inverse or null associations with overweight and

detected in CD68+ macrophages in both lymphoma and lymphadenitis tissues but localisation in CD123+ plasmacytoid dendritic cells was found only in lymphoma tissues. Do pay attention, Bond, I won’t be showing this again.

Brain musicRather rarely, the brain makes its own music. A fascinating review of 393 patients with musical hallucinations in the Mayo Clinic registry reports that those with an underlying neurodegenerative disorder or isolated hearing impairment tended to hear fairly persistent music, which was often religious and patriotic. Those with a structural lesion heard more modern music, and music was mood-congruent in those with psychiatric disorders (Brain 2015, doi:10.1093/brain/awv286).

Patient information? Whatever next?In a Bateman cartoon-like show of indignation, The BMJ ran a series of four editorials refuting the suggestion by a young upstart that patients should be given information leaflets about their conditions. The year was 1949, and the upstart was Dr Charles Fletcher, who advocated for patient knowledge throughout his career. He was proud of being one himself and would inject himself with insulin publicly on ward rounds. The BMJ made amends with an editorial subtitled “Happy birthday—and sorry” on his 80th birthday in 1991 (www.bmj.com/content/303/6793/6), and Max Blythe has completed a biography of this flamboyant pioneer, which is due to appear just in time for Christmas.Cite this as: BMJ 2015;351:h5773

central obesity (J Nutr 2015, doi:10.3945/jn.115.219808). But when adjusted for estimated energy requirement, the association with central obesity became positive.

Seek and ye shall find asthmaResearchers who received a grant from Asthma UK report how difficult they are finding it to investigate the epidemiology, healthcare utilisation, and costs of asthma care for the UK as a whole and its member nations (J R Soc Med 2015, doi:10.1177/0141076815600909). We’re told that they are among the highest in the world, but just how high? As they explain, it depends on which database and questionnaire you use, and these differ between most of the British countries.

Q fever: pay attention BondThe human infection caused by Coxiella burnetii is known as Q fever: why Q is disputed, although it definitely has nothing to do with 007. But cunning devices worthy of Q himself have been used to trace a connection between this infection and diffuse large B cell lymphoma and follicular lymphoma (Blood 2015, doi:10.1182/blood-2015-04-639617). The presence of C burnetii was tested by immunofluorescence and fluorescence in situ hybridisation using a specific 16S rRNA probe and genomic DNA probe. C burnetii was

A 71 year old woman presented with a persistent facial rash consisting of several papulo-nodular erythematous lesions. Clinical examination showed bilateral cervical, axillary, and inguinal lymphadenopathy. Imaging showed diffuse lymphadenopathy and hepatosplenomegaly. Skin and lymph node biopsy were consistent with a diagnosis of secondary cutaneous low grade follicular lymphoma. This rare condition is commonly misdiagnosed as granulomatous rosacea, lupus miliaris disseminatus faciei, persistent arthropod bite reaction, or other

inflammatory skin conditions. Accurate diagnosis can usually be made through microscopic examination on biopsy. Primary cutaneous follicular lymphoma, which is more common, can be ruled out if there is systemic nodal involvement.Samer Tabchi (tabchi@hotmail.com), haematology-oncology fellow, Tarek Assi, haematology-oncology fellow, Joseph Kattan, chairman and professor, Haematology and Oncology Department, Faculty of Medicine, Saint Joseph University, Beirut, Lebanon

Patient consent obtained.Cite this as: BMJ 2015;351:h5449

Follicular lymphoma infiltrating the skin

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