education education FROM THE JOURNALS Edited highlights of Richard Lehman’s blog on http://bmj.co/Lehman

Uselessness: a key outcome The authors are fond of eosinophils for diabetes drugs as the current fashionable marker, I’m an old man and I have long but I’m not so sure. The point is that since said all I want to about drugs we keep flexibility in our diagnostic for diabetes. I’ll just commend to thinking, and don’t go too far up your attention two of the latest any one mechanistic byway. abstract summaries from the ̻̻Lancet doi:10.1016/S0140- world’s most prestigious journal: 6736(17)30879-6 “Among patients with type 1 diabetes who were receiving Removing axillary nodes in insulin, the proportion of early breast cancer surgery patients who achieved a glycated Here’s a 10 year survival study of haemoglobin level lower than 7.0% women who underwent localised with no severe hypoglycaemia or resection and radiotherapy diabetic ketoacidosis was larger in for T1-2 breast cancer. If 1-2 the group that received sotagliflozin metastases were found in the than in the placebo group. However, sentinel nodes, they were the rate of diabetic ketoacidosis was randomised either to sentinel higher in the sotagliflozin group.” node resection only or to complete Q: In that case, why would you use axillary node resection. Got sotagliflozin in type 1 diabetes? that? It took me a couple of goes. Next: “Among patients with Return of reflux Survival was actually slightly type 2 diabetes with or without “Laparoscopic anti-reflux better in the women who had previous cardiovascular disease, surgery was associated with a sentinel node removal alone. the incidence of major adverse relatively high rate of recurrent They also presumably had a cardiovascular events did not differ gastroesophageal reflux disease lower incidence of lymphoedema, significantly between patients who requiring treatment, diminishing though disappointingly I can’t see received exenatide and those who some of the benefits of the any mention of that in the paper. received placebo.” Q: Why not give operation.” What’s your idea of ̻̻JAMA doi:10.1001/jama.2017.11470 them placebo then? a “relatively high rate” in this ̻̻New Engl J Med doi:10.1056/ situation? Relative to what? Diagnostic reasoning: NEJMoa1708337 Actually, in this Swedish follow-up an endangered skill? ̻̻New Engl J Med doi:10.1056/ study lasting a mean of 5.6 years, If you’re interested in lifelong NEJMoa1612917 recurrence of symptoms only learning and being a good occurred in 17.7% of patients, diagnostician, do try to get hold of Reconsidering respiratory and the majority of these opted this article. If you’re not interested labels for medical treatment, therefore in lifelong learning and being a One key to progress in medicine the overall proportion of the total good diagnostician, consider a is to reconsider diagnostic cohort who underwent further different career. And yet we do so labels. “” used to mean surgery was less than 3%. little as a profession to encourage breathlessness generally, crudely ̻̻JAMA doi:10.1001/jama.2017.10981 a deep exchange of skills across divided into cardiac asthma and a lifetime in medical practice. pulmonary asthma. Nowadays for asthma and to acknowledge Arabella Simpkin’s snapshot of we just cling to the latter, but isn’t the assumptions associated with how diagnostic thinking is taught it time to let go? I’m glad to see them. Airways diseases should be to junior residents at Massachusetts an article on the Lancet website deconstructed into traits that can General Hospital is inspiring, but arguing for just that. be measured and, in some cases, only hints at what should be going “We suggest that the only way modified (ie, treatable traits), and on from entry into medical school we can make progress in the future which are set in the context of social up to the point where we hang up is to be much more clear about and environmental factors and our stethoscopes. the meaning of the labels used extrapulmonary comorbidities.” ̻̻Ann Intern Med doi:10.7326/M17-0163 the bmj | 23 September 2017 451 RAPID RECOMMENDATIONS for Bert Aertgeerts,1 2 Thomas Agoritsas,3 4 Reed A C Siemieniuk,3 5 Jako Burgers,6 7 Geertruida E Bekkering,1 2 Arnaud Merglen,8 Mieke van Driel,9 Mieke Vermandere,1 Dominique Bullens,10 11 Patrick Mbah Okwen,12 Ricardo Niño,13 Ann van den Bruel,14 15 Lyubov Lytvyn,16 Carla Berg-Nelson,17 18 Shunjie Chua,19 Jack Leahy,20 Jennifer Raven,21 Michael Weinberg,22 Behnam Sadeghirad,3 23 Per O Vandvik,15 24 Romina Brignardello-Petersen2 25

1 Academic Centre for General Practice, Department of Public Health and Primary HOW THE RECOMMENDATION WAS CREATED Care, KU Leuven, Belgium READING Our international panel—including general practitioners, Correspondence to: B Aertgeerts [email protected] general internists, paediatricians, an otorhinolaryngologist, Full author details can be found on bmj.com. 0.5 HOURS epidemiologists, methodologists, statisticians, and people This BMJ Rapid Recommendation article is one of a series that provides with lived experience of sore throat—decided the scope clinicians with trustworthy recommendations for potentially practice changing evidence. of the recommendation and the outcomes that are most important to patients. After a systematic review on the benefits and harms of corticosteroids,16 and a systematic What is the role of a single dose of oral corticosteroids search for evidence about patients’ values and preferences for those with acute sore throat? In this article an (appendix 1 on bmj.com), the panel met to formulate expert panel makes a weak recommendation in favour a recommendation. No person had financial conflicts of use, using the GRADE framework of interest; intellectual and professional conflicts were according to the BMJ Rapid Recommendation process. minimised and managed (appendix 2 on bmj.com). The panel followed the BMJ Rapid Recommendations These recommendations are based on a linked procedures for creating a trustworthy recommendation,26 27 systematic review (see p 437) triggered by a large including using the GRADE approach to critically appraise randomised trial published in April 2017. This trial the evidence and create recommendations (appendix 3 on reported that corticosteroids increased the proportion bmj.com).28 of patients with complete resolution of pain at 48 hours.

Acute sore throat is defined as pain in the throat for less than with sore throat will have a mononucleosis caused 14 days. Acute sore throat could be caused by , by an Epstein-Barr virus, which could prolong the duration nasopharyngitis, , peritonsillar , or of symptoms.8 . Some patients with sore throat Some patients experience unacceptable morbidity and also experience headache, , muscle stiffness, cough, inconvenience, and miss school or work due to recurrent and general . sore throat.9 Pain is a common reason for work or school Acute sore throat is common, but only a minority of absence. Complications of sore throat are rare: about patients will visit their general practitioner.1 0.2% of patients with tonsillitis will develop a peritonsillar Acute sore throat is a self limiting disease and typically abscess.10 resolves after 7-10 days in adults and 2-7 days in children.7 The diagnosis of an acute sore throat is based on signs Most are of viral origin; only a few are caused by a and symptoms. bacterial infection. About 2% of patients initially presenting Most guidelines recommend paracetamol or ibuprofen as the first choice treatment.13 The use of corticosteroids is WHAT YOU NEED TO KNOW mentioned in few, and is generally discouraged. are probably not helpful for pain relief in an episode of acute International guidance varies about whether to use corticosteroids • sore throat caused by viruses, but may help those with a to treat acute sore throat, but a trial published in April 2017 bacterial infection.14 15 suggested that costicosteroids might be effective We make a weak recommendation to use a single dose of oral • The evidence corticosteroids in those presenting with acute sore throat after The linked systematic review (page 437) reports the effects performing a systematic review of the new evidence in this rapid of corticosteroids when added to standard care in patients recommendation with acute sore throat.16 Figure 1 (overleaf) gives an The recommendation is weak because corticosteroids did not help • overview of the trials included. all patient reported outcomes and patients’ preferences varied The panel identified eight patient-important outcomes substantially needed to inform the recommendation: complete resolution Steroids somewhat reduced the severity and duration of pain by • of pain, time to onset of pain relief, pain severity, need for one day, but time off school or work was unchanged. Harm seems antibiotics, days missed from school or work, recurrence of unlikely with one steroid dose.The treatment is inexpensive and likely to be offered in the context of a consultation that would symptoms, duration of bad or non-tolerable symptoms, and have taken place anyway adverse effects. The included studies reported on all patient- important outcomes, except for duration of bad or

452 23 September 2017 | the bmj the bmj | 23 September 2017 453 Population

This recommendation applies to almost all patients with sore throat: Children 5 years and older and all adults Severe and not severe sore throat Emergency and Patients with a viral primary care settings or bacterial sore throat Patients who receive immediate or deferred antibiotics

However the recommendation is not applicable to patients with: Infectious Immunocompromising mononucleosis conditions Sore throat following surgery or intubation Children under 5 years old

Comparison

Short course Adults: Children: No steroids of steroids 10 mg 0.6 mg Standard clinical 1-2 doses of oral per kg care, which Standard care Dexamethasone + or typically includes (or equivalent Standard care analgesics, and + dose of alternative may include corticosteroid) + Analgesics antibiotics +/- Antibiotics + standard care +/- Antibiotics

Favours steroids Favours no steroids

Strong Weak Weak Strong

We suggest a course of steroids. Discuss with patients in shared decision making.

Comparison of benefits and harms

Favours steroids No important difference Favours no steroids

Events per 1000 people Evidence quality Complete pain resolution (24h) 224 124 more 100 Moderate Complete pain resolution (48h) 608 183 more 425 High

Mean time to resolution (hours) Complete pain resolution 33.0 11.1 fewer 44.0 Low

Events per 1000 people Symptom recurrence or relapse 34 No important difference 65 Moderate Antibiotics prescription 468 96 fewer 564 Low

Preferences and values Serious adverse events Multiple doses

The panel believes that there is One-dose administration Risks may outweigh benefits when a great variability on how much of steroids is not likely to cause cumulative doses of steroids are reduction in pain severity or time serious adverse events. Very given for multiple episodes of sore to complete pain resolution each low quality evidence exists for throat. To mitigate this issue, patient would consider important. extremely rare but serious adverse clinicians could administer the Shared decision making may help effects following higher doses medication in the office if possible, establish what matters most to each or longer courses of steroids or prescribe only one dose patient. (up to 30 days). per visit.

Disclaimer: This infographic is not a clinical decision aid. This information is provided without any representations, conditions or warranties that it is accurate or up to date. BMJ and its licensors assume no responsibility for any aspect of treatment administered with the aid of this information. Any reliance placed on this information is strictly at the user's own risk. For the full disclaimer wording see BMJ's terms and conditions: http://www.bmj.com/company/legal-information/

452 23 September 2017 | the bmj the bmj | 23 September 2017 453 DATA SOURCES Use this information to gauge how similar your patients’ conditions are to those of people studied in the trials

NUMBER OF TRIALS 10 NUMBER OF PATIENTS 14 26

TRIAL CHARACTERISTICS PATIENT CHARACTERISTICS Drugs studied in trials MEAN NUMBER OF SEX PRESCRIPTION Dexamethasone Prednisone Betamethasone PATIENTS ENROLLED % women % of patients

Max 8 1255 1 79 1 92 Min Mean Min Mean Max Min Mean Max 58 153 576 37 57 75 40 78 100

Oral 5 delivery 1044 0 200 400 600 0 20 40 60 80 100 0 20 40 60 80 100

Intramuscular MEAN AGE POSITIVE USE 3 delivery 211 at baseline % of patients % of patients

Min Mean Max Min Mean Max Min Mean Max 10 26 34 15 51 100 38 83 100 Trials conducted in emergency 8 771 departments

010203040 0 20 40 60 80 100 0 20 40 60 80 100 Trials conducted in primary 2 655 care practices The proportion of Streptococcus positive people across all trials was 37%

NDIN PART FU G T NE N R IE S T H

A I 80% of trials did not report the source of funding P No trials involved patients

P and 20% of trials reported non-industry funding in design or conduct

Fig 1 | Characteristics of patients and trials included in systematic review of effects of corticosteroids on acute sore throat non-tolerable symptoms. Regarding pain, the panel or bacterial sore throat, and patients who seek care in appraised the likelihood of complete resolution of pain at 24 the emergency department as well as those who attend hours and 48 hours, as well as the mean time to complete primary care. resolution of pain and the mean time to onset of pain relief. Although most of the studies (80%) were conducted in Absolute benefits and harms emergency departments, they accounted for 54% of all Although the evidence indicates that the treatment patients enrolled across studies. The remaining 46% were works on average, it did not reduce the severity of pain enrolled in the studies conducted in primary care settings, dramatically and failed to improve several other patient- and the panel was therefore confident that the evidence was important outcomes. applicable to them as well. Most of the studies focused on Considering the evidence and its certainty, the panel adults only (60%). The studies that focused only on children was confident that: (three studies, 2% of all the patients enrolled in the studies) • Corticosteroids increase the chance of complete did not include children younger than 5 years old, and thus EDUCATION IN resolution of pain at 24 and 48 hours, reduce the the recommendation does not apply to younger ages. PRACTICE severity of pain, and shorten the time to onset of pain Since the randomised controlled trials focused on • How do you relief (GRADE high to moderate quality evidence) patients who did not have recurrent episodes of sore currently • Corticosteroids are unlikely to reduce recurrence or throat, the panel was less confident of the applicability of approach giving relapse of symptoms or days missed from school or advice for those the evidence to such patients, and the recommendation work (GRADE moderate quality evidence) with acute sore therefore does not apply to them. Similarly, the panel did A single dose of corticosteroids is unlikely to cause throat? Do you • not consider patients with sore throat after surgery or consider offering serious adverse events intubation, nor immunocompromised patients. corticosteroids? –– The randomised trials did not report any major event • The attributable to single dose corticosteroids (GRADE Understanding the recommendation recommendation moderate quality evidence) The recommendation for using corticosteroids made by for corticosteroid –– The panel also considered evidence from the panel was weak because of the modest reduction of use is weak. observational studies that used higher doses symptoms and the large variability in patient preferences. What information of steroids. A cohort study of private insurance The panel is confident that the recommendation applies could you share claims assessed adverse events in 327 452 to almost all patients with acute sore throat: children 5 with your patient adults who received an outpatient prescription years and older and adults, severe and not severe sore to help reach of corticosteroids.18 There was a small a decision throat, patients who receive immediate antibiotics and absolute increase in the rate of , venous together? those who receive deferred antibiotics, patients with a viral thromboembolism, and fracture in the first 30 days

454 23 September 2017 | the bmj the bmj | 23 September 2017 455 PRACTICAL ISSUES • It is unlikely that new information will change interpretation for outcomes that are high to moderate Steroids No steroids quality of evidence.

One (or two) dose of steroids, taken The panel was less confident about whether: as pill(s) or intramuscular injection(s) • Corticosteroids reduced antibiotic use, due to a lack of improvement or worsening of symptoms in patients not MEDICATION May require concomitant antibiotics, and/or prescribed antibiotics immediately when consulting the ROUTINE over-the- counter pain relievers physician (GRADE low quality evidence) • Corticosteroids reduced the average time to complete May need additional visits if symptoms do not resolve or resolution of pain (GRADE low quality evidence). worsen TESTS & VISITS Values and preferences The weak recommendation for corticosteroids reflects a Serious adverse events are unlikely with one-dose steroids. There may be high value on a modest reduction of symptom severity risks with repeated doses across and the time that it takes to achieve such improvement, multiple episodes of sore throat, or and a substantial and important increase in the chance of ADVERSE through self medication complete resolution of pain at 48 hours. EFFECTS The panel, including the patient representatives, felt May require concomitant antibiotics, and or over-the-counter pain relievers that the values and preferences are likely to vary greatly across patients, which justifies a weak recommendation. For example, achieving complete pain resolution 12 hours May cause transient sleep disturbance earlier may be of little importance for patients who feel and excitability, although infrequently less busy in their daily life, have higher tolerance to pain, EMOTIONAL with one-dose steroids WELL-BEING or whose symptoms are not so severe. The weak recommendation for corticosteroids also Dexamethasone crosses the placenta, reflects the concerns that the panel had with acceptability. and is generally avoided during Specifically, how acceptable is it to treat a condition that PREGNANCY & pregnancy. There is, however, is usually not severe and is self limiting with a drug that probably no risk of malformation NURSING many patients, practitioners, and other stakeholders know is almost always used for more severe diseases. A systematic search identified two studies with relevant Inexpensive, available by prescription information on patients’ values and preferences (see COSTS & ACCESS appendix 1 on bmj.com). Neither of the studies provided additional data that had not been raised by the panel May increase appetite, particularly members: the panel had identified appropriate patient- in children important outcomes and considered the variability in FOOD & DRINK patient values and preferences regarding sore throat management. Fig 2 | Practical issues about use of corticosteroids to treat acute sore throat

Practical issues, costs, and resources (GRADE low quality evidence). The panel agreed that Figure 2 outlines the key practical issues for patients and such events seemed unlikely with single dose steroids clinicians discussing adjunct steroids for sore throat, which –– Similarly, among paediatric populations, indirect are also accessible along with the evidence as decision aids evidence from a meta-analysis of 44 randomised trials to support shared decision making in MAGICapp. Steroids did not report any major adverse events in patients with are typically given as 10 mg dexamethasone (or adapted to conditions requiring a short course of corticosteroids weight for children: 0.6 mg/kg, up to a maximum dose of (such as asthma, , , wheeze, and 10 mg), typically taken as pill or intramuscular injection. pharyngitis or tonsillitis)20 The risks may outweigh the benefits when larger • There are no differences in the relative effects of cumulative doses of corticosteroids are given to patients corticosteroids (when compared with usual care) between who experience multiple episodes of sore throat. primary care settings and emergency departments The treatment is inexpensive and likely to be offered in P the context of a consultation that would have taken place HOW PATIENTS WERE INVOLVED IN THE CREATION OF THIS ARTICLE anyway. Nevertheless, it remains uncertain whether it may Five people with lived experience of sore throat were full panel members. These increase the proportion of patients visiting a doctor to get a panel members identified important outcomes, and led the discussion on values prescription of corticosteroids. and preferences. They agreed that while small reductions in pain severity and Competing interests: See bmj.com. time to complete pain resolution were important to them, these values may not Cite this as: BMJ 2017;358:j4090 be shared by all patients; they expected moderate to great variability in how much Find the full version with references at http://dx.doi.org/10.1136/bmj.j4090 importance other patients would place in small reductions in pain. ЖЖRESEARCH, p 437

454 23 September 2017 | the bmj the bmj | 23 September 2017 455 UNCERTAINTIES Is gabapentin effective for women with unexplained chronic pelvic pain? Andrew W Horne,1 Katy Vincent,2 Roman Cregg,3 Jane Daniels4

1MRC Centre for Reproductive Health, University of Edinburgh, Edinburgh, UK 2 WHAT YOU NEED TO KNOW Nuffield Department of Obstetrics and Gynaecology, University of Oxford, READING Oxford, UK Up to half of all women with chronic pelvic 3 • Pain Management Centre, National Hospital for Neurology and Neurosurgery, pain in secondary care have no obvious University College London Hospitals NHS Foundation Trust, London, UK 0.5 HOURS 4 underlying pathology Nottingham Clinical Trial Unit, University of Nottingham, Nottingham, UK Correspondence to: AW Horne [email protected] • For pain relief, a combination of drugs, physiotherapy, and cognitive behavioural Chronic pelvic pain in women is a common therapy can be tried presentation in primary care. Pain persists • There is no strong direct evidence to support or recurs over at least six months1 and can be the use of gabapentin for women with chronic distressing, affecting physical function, quality of pelvic pain, and uncertainty remains regarding 2 its safety, and clinical and cost effectiveness life, and productivity. Nearly 38 per 1000 women are affected annually in the UK. Global estimates range from 2.1% to 24% of the female population.3 4 secondary care appear to have no obvious underlying Endometriosis, adenomyosis, adhesions, pelvic pathology based on clinical history, examination, inflammatory disease, irritable bowel syndrome, and investigations.4 6 Management of this group of bladder pain syndrome, nerve entrapment, and women is challenging and there are few established musculoskeletal pain are among the common gynaecological treatments. The Royal College of causes.4 5 These are often identified by screening Obstetricians and Gynaecologists recommends a for pelvic infection (eg, Chlamydia trachomatis), combination of pharmacological interventions, pelvic imaging (eg, , magnetic resonance physiotherapy, and cognitive behavioural therapy.1 imaging), and diagnostic laparoscopy.1 Some Often women try several methods sequentially or 40%-55% of women with chronic pelvic pain in in combination.4‑8 The figure presents a common

Primary care Referred to other Treatment started Referred to other Secondary care specialty eg oral contraceptive No response specialty eg gastroenterology pill, antibiotics, to treatment eg gastroenterology Primary and/or secondary care or urology dietary advice or urology

Investigations No cause Referred back to Chronic History and eg abdo/pelvic/renal Referred to Diagnostic identified general practice pelvic pain examination USS, pelvic MRI, gynaecology laparoscopy presentation GUM swabs Cause identified Referred to chronic (eg endometriosis) pain clinic and surgically Treatment started treated or medical eg oral contraceptive treatment started Physiotherapy pill, antibiotics, No response to dietary advice treatment Cognitive behavioural therapy

Pharmacological 4 – 12 weeks interventions (monotherapy, 6 weeks – 6 months combination therapy) 12 – 18 weeks Flow diagram showing the possible “treatment journey” (and timelines) for a woman who presents to primary care with chronic pelvic pain (adapted from guidance from the Royal College of Obstetricians and Gynaecologists) 4 – 18 weeks

456 23 September 2017 | the bmj the bmj | 23 September 2017 457 SEARCH STRATEGY We searched PubMed, Embase, the Centre for Reviews and Dissemination database, and the Cochrane Library from their inception to 20 December 2016 for published studies on effectiveness of gabapentin for treatment of women with chronic pelvic pain.

diagnostic and treatment approach that women with chronic pelvic pain might be off ered. One option is the prescription of neuromodulators, including gabapentin, which can help address some of the potential pain generating/maintaining mechanisms that could be responsible. Neuromodulators primarily aff ect modulation of pain by the central nervous system, in contrast with non-steroidal anti-infl ammatory drugs, for example, which act on peripheral mediators of infl ammation. Neuroimaging studies have shown gabapentinoids to aff ect brain function in models of central sensitisation and in patients with chronic pain.9 10 Like most neuromodulators, gabapentin and pregabalin are only licensed for peripheral neuropathic pain 11 and their use in chronic pelvic pain is off licence. There is uncertainty around the eff ectiveness and safety of gabapentin in women with chronic pelvic pain.

Primary care Referred to other Treatment started Referred to other Secondary care specialty eg oral contraceptive No response specialty eg gastroenterology pill, antibiotics, to treatment eg gastroenterology Primary and/or secondary care or urology dietary advice or urology

Investigations No cause Referred back to Chronic History and eg abdo/pelvic/renal Referred to Diagnostic identified general practice pelvic pain examination USS, pelvic MRI, gynaecology laparoscopy presentation GUM swabs P Cause identified Referred to chronic HOW PATIENTS WERE INVOLVED IN THE CREATION (eg endometriosis) pain clinic OF THIS ARTICLE and surgically A patient representative kindly agreed to review this paper. Treatment started treated or medical She asked to clarify the criteria for chronic pelvic pain. eg oral contraceptive treatment started Physiotherapy pill, antibiotics, No response to We have now used the definition from the International dietary advice treatment Association for the Study of Pain, although consensus Cognitive on criteria for defining chronic pelvic pain is lacking. The behavioural therapy patient also stressed that clinicians must be vigilant in the assumption that no treatable pathology exists. We Pharmacological have clarified the importance of history, examination, and 4 – 12 weeks interventions investigations to identify any pathology. We also include the (monotherapy, estimated proportion of patients based on earlier studies in 6 weeks – 6 months combination therapy) whom no pathology might be detected. 12 – 18 weeks

4 – 18 weeks

456 23 September 2017 | the bmj the bmj | 23 September 2017 457 What is the evidence of uncertainty? COMMENTARY There are very sparse data from trials of the use of gabapentin in women with chronic What should we do in light pelvic pain. We found one randomised controlled trial comparing gabapentin and of the uncertainty? amitriptyline for chronic pelvic pain in women with a range of pelvic pathologies,12 Treatment of women These can limit and our own recently published pilot trial with chronic pelvic compliance but are often (GaPP1) comparing gabapentin with placebo pain is directed towards tolerated.8 An increased in women with chronic pelvic pain and achievement of higher risk of suicidal thoughts no identifiable pelvic pathology.13 In both function with some pain and behaviour has been studies, gabapentin was shown to improve rather than a cure.4 At observed with use of pain scores compared with the control arm; the initial consultation, gabapentin. Ask patients however, neither study has sufficient power to explore and document or carers to report any guide practice. the severity of pain, and changes in moods or Data on harms from trials in women with its effect on lifestyle, behaviour. Gabapentin chronic pelvic pain are lacking, although daily activities, including is not recommended side effects such as drowsiness have been sleep disturbance, and in pregnant women. reported. participation.5 Reassure Treatment is directed Caution is advised in the patient that no towards achievement patients with renal Is ongoing research likely to treatable pathology of higher function impairment as it is provide relevant evidence? has been identified on with some pain rather exclusively excreted by We searched the World Health Organization investigation. Explain than a cure the kidneys.10 trials portal, ClinicalTrials.gov, and the that this is not unusual Arrange a follow-up ISRCTN registry, for ongoing randomised and some approaches might be tried to visit to assess dosage titration, controlled trials in women with chronic relieve the pain. tolerability, adverse effects, and pelvic pain comparing gabapentin with no Guidelines from the Royal College continued need for treatment.5 If treatment or a control treatment or placebo to of Obstetricians and Gynaecologists the overall benefit is limited by side alleviate pain. Our search identified our own recommend initial pain management effects, the lowest effective dose trial, GaPP2. with non-steroidal anti-inflammatory should be found by downtitration. If Although this study will likely provide drugs with or without paracetamol.6 7 side effects are not tolerated or if there evidence on whether gabapentin Compound analgesics such as is no benefit, gabapentin should be (monotherapy) is beneficial in the co-dydramol can also be considered.7 withdrawn. management of women with unexplained Encourage the woman to monitor A treatment approach embedded chronic pelvic pain, further research is and record pain, its impact on daily within a multidisciplinary care required to determine the effectiveness of activities, and treatment side effects. model, which takes into account the gabapentin in women with chronic pelvic Ask her to report if the pain worsens or individual needs and preferences of pain with endometriosis,15 or other pain she develops other symptoms, which women with chronic pelvic pain, can conditions, and how it compares with other might warrant repeat investigations for reduce the disruption to the woman’s treatments. a suspected pathology. life and avoid an endless succession Competing interests: We have read and understood the BMJ If pain relief is insufficient, consider of referrals, investigations, and policy on declaration of interests and declare the following referral to a pain management team or operations.7 interests: AWH reports collaborating with Roche on a project a specialist pelvic pain clinic. These can James M N Duffy, Balliol College, University of to identify a biomarker for endometriosis. KV reports advising Oxford [email protected] Grunenthal on a set of documents regarding conditions deliver a multidisciplinary care model, associated with chronic pelvic pain and receiving a grant including components of physical Competing interests: None declared. from Bayer Healthcare to investigate pain mechanisms treatment, cognitive behavioural Cite this as: BMJ 2017;358:j3624 in endometriosis. KV also received payment from Bayer Find the full version with references at Pharmaceuticals on chronic pelvic pain. RC consulted Allergen therapy, complementary therapies, http://dx.doi.org/10.1136/bmj.j3624 on the mechanism of botox to treat chronic pelvic pain. transcutaneous nerve stimulation, Cite this as: BMJ 2017;358:j3520 and other medical disciplines, such as Find the full version with references at anaesthesia and gynaecology.4‑8 EDUCATION INTO PRACTICE http://dx.doi.org/10.1136/bmj.j3520 Gabapentin is currently • Recollect a woman you have seen at recommended only in a specialist your practice with unexplained chronic CORRECTION setting for women with suspected pelvic pain. neuropathic pain. Explain the • How did you manage her pain? An image accompanying an article on uncertainty in evidence of benefit and • What would you do differently in penicillin allergy that appeared in the potential side effects of gabapentin explaining about her pain and the 5 August print edition of The BMJ p246 within the context of chronic pelvic treatment options? showed dropper containers with the label pain. Warn about common side • Do you routinely document the severity ‘penicillum.’ The picture should have shown effects, including dizziness, fatigue, of pain and impact on functioning and instead containers with the label ‘penicillin.’ quality of life? drowsiness, and peripheral oedema.9 10

458 23 September 2017 | the bmj ENDGAMES For long answers go to the Education channel on bmj.com @bmj_latest

CASE REVIEW Sudden onset headache in a 50 year old woman A 50 year old a 50 pack year department (below). woman presented smoking history. 1 What is the to the emergency She was afebrile, diagnosis based department several alert (Glasgow coma on the history and CASE REVIEW An older woman with hours after the scale 15), and had CT scan? spontaneous bruising sudden onset of a no focal neurological 2 What are the risk severe headache signs. Blood tests factors for this An 85 year old woman attended the Prothrombin time was normal, with associated were unremarkable, condition? emergency department with large however, and fibrinogen assay stiffness, in particular her 3 What is the bruises on her right forearm and was within normal limits photophobia, white blood cell and left leg, which had appeared four (3.8 g/L, reference range 1.5 to treatment for this and vomiting. She neutrophil counts condition? days earlier. She had not sustained 4.0 g/L). Mixing studies with 1 part reported having were within the Submitted by Divyansh any injuries to account for the of patient’s plasma and 1 part of a dental abscess, normal range. A non- bruising. There was no pooled normal plasma showed no Gulati, Michael William and was taking contrast computed Shea, and James Ray from any other site. Her only correction of elevated activated norethisterone tomography (CT) medical history was hypertension. partial thromboplastin time. Factor Patient consent regularly for scan of the head obtained. Her medications included assays revealed very low level of persistent vaginal was obtained in Cite this as: BMJ amlodipine. On examination there factor VIII (<1 IU/dL, reference range bleeding. She had the emergency 2017;358:j4016 were extensive subcutaneous 50-150 IU/dL), and factors IX, XI, haematomas on the right forearm and XII were within normal ranges. extending up to the upper arm and 1 What is the most likely on the left leg extending up to the diagnosis? thigh. Initial investigations showed 2 How is this condition diagnosed? low haemoglobin of 95 g/L with a 9 3 What is the management for this normal platelet count (369 × 10 /L). condition? Coagulation assays showed Submitted by Muhajir Mohamed and Ajay markedly elevated activated partial Prakash thromboplastin time of 74 seconds Patient consent obtained.

(reference range 25 to 35 seconds). Cite this as: BMJ 2017;358:j3863

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Sudden onset headache in a 50 year old woman old year 50 a in headache onset Sudden CASE REVIEW REVIEW CASE CASE REVIEW CASE answers

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0.5 HOURS the bmj | 23 September 2017 459 MINERVA A wry look at the world of research

An unusual palmar eruption A 21 year old woman presented with episodic DF508) but also occurs in carriers; palmar itching, stinging, and skin peeling after referral to specialist genetics services for testing is brief exposure to water. Palmar water immersion therefore essential. Aquagenic palmar wrinkling can in the dermatology clinic resulted in multiple be induced by medication or, as in our patient, can be whitish papules and exaggerated wrinkling after idiopathic. Treatments include topical antiperspirants seven minutes, consistent with aquagenic palmar and iontophoresis. wrinkling (right). Aquagenic palmar wrinkling is a Rachel Fisher ([email protected]); Penelope Pratsou, clinical diagnosis demonstrated by reproducible Department of dermatology, Royal Berkshire Hospital, signs on water immersion. Its pathogenesis has Reading, UK been attributed to sweat electrolyte dysfunction. It Patient consent obtained. is common in cystic fibrosis (especially homozygous Cite this as: BMJ 2017;358:j3852

Statins in the elderly Mortality among children with practice of matching older donors to older In the UK in the early type 1 diabetes recipients isn’t in the best interests of older 2000s, the prevalence Paediatricians in Wales have candidates for transplants? of statin use in been tracking new cases of type 1 people over 80 was diabetes in children under 15 since Bone marrow biopsies around 10%. By 1995 (Arch Dis Child doi:10.1136/ The likelihood of getting a reliable 2015, it had risen archdischild-2016-312581). What diagnosis from a bone marrow biopsy to almost 50%, they’ve found is rather disappointing: depends on the length of the biopsy core largely because mortality rates are about three times available for examination. As is so often people who had higher than in the general population the case with routine investigations, started taking statins and, despite developments in clinical there’s not much research into the best in their 60s and 70s had got care, showed no signs of decreasing over way to get an adequate specimen. The older (Age Ageing doi:10.1093/ time. Ketoacidosis remains the most traditional approach is to bore the needle ageing/afx100). Cardiovascular common cause of death before straight down from the posterior superior risk increases with age, of age 30. Chronic complications of iliac spine, in a direction perpendicular course, so this level of use might diabetes were not a cause of mortality to the back. A trial in the Journal of be appropriate. However, in the in this age group. Clinical Pathology finds that substantially absence of clinical trial evidence longer biopsies can be obtained by showing that cholesterol Using pen and paper to aiming the needle in the direction of the lowering treatment reduces diagnose the cause of tremor anterior superior iliac spine (Clin Pathol mortality in elderly people, Tremor is a presenting feature of several doi:10.1136/jclinpath-2017-204686). no one can be sure that it’s a neurological diseases, and an article in sensible idea. Practical Neurology explains how simple Alcohol, health education, and tests with pen and paper can be used to the public in 1970s Britain Syncope and postural tell them apart (Pract Neurol doi:10.1136/ Articles in Social History of Medicine hypotension practneurol-2017-001719). Watching a tend to be long and thoughtful, and they A longitudinal study from patient’s upper limb as they write a short rarely come to anything as vulgar as a Sweden finds that middle aged sentence can reveal bradykinesia and conclusion. Although it’s impossible to people admitted to hospital dystonic posturing. Asking them to draw distil its message into a short paragraph, after an episode of loss of a spiral and a straight line records the Minerva recommends an essay on consciousness, and discharged frequency, amplitude, and consistency of attempts at alcohol health education with a diagnosis of syncope the tremor. in Britain in the 1970s (Soc Hist Med or postural hypotension, are doi:10.1093/shm/hkw094). It’s critical subsequently at increased Survival after heart transplant of a clumsy advertising campaign that risk of cardiovascular A systematic review of observational targeted problem diseases (Heart doi:10.1136/ studies of recipients of heart transplants drinkers, and heartjnl-2017-311857). A identifies several variables associated the failure to diagnosis of unexplained with higher mortality at one year (Heart engage with syncope was associated doi:10.1136/heartjnl-2017-311435). the social and with coronary events, They include increasing age, congenital environmental cardiovascular death, and aetiology of heart disease, age of the factors that aortic stenosis. Orthostatic donor heart, and donation from a female encouraged hypotension, by contrast, was to a male recipient. These findings raise drinking. more strongly associated with questions about optimum selection of Cite this as: stroke and heart failure. donors and recipients. Perhaps the current BMJ 2017;358:j4269

460 23 September 2017 | the bmj