This is part of a series of occasional articles on common problems in primary care. The BMJ welcomes contributions from GPs.A 72 year old woman, who had been diagnosed as having recurrent deep vein thrombosis six weeks earlier, attends the practice's phlebotomy clinic for an international normalised ratio (INR) check. Her INR is greater than 8.0 (target INR range: 2.0-3.0). During the consultation, you look through her previous INR readings and notice they have been supra-therapeutic over the past two weeks despite a reduction in the dose of warfarin. What you should cover• Screen for "red flag" symptoms and signs of active, non-resolving bleeding: -Use a thorough systems review; in particular look for any evidence of gastrointestinal bleeding, such as vomiting blood and passing altered or fresh rectal blood. If ongoing gastrointestinal bleeding is suspected, inpatient warfarin reversal and an oesophagogastroduodenoscopy are indicated -Any evidence of intracranial bleeding? Ask about recent head trauma with an episode of amnesia, loss of consciousness, or more than one episode of vomiting. Examine for a reduced Glasgow coma score as well as focal neurological signs. If any of these features are present, an urgent computed tomography head scan is needed 1 -Check pulse and sitting and standing blood pressure for evidence of haemodynamic compromise.• Clarify the doses of warfarin the patient has been taking because some patients may overmedicate by mistake. If this is the case, ask how often the patient takes warfarin and at what dose. Provide appropriate written information if necessary. A dossette box might help her comply with the prescribed dose.• Is there an important medical problem, such as liver disease or cancer, that might result in impaired synthesis of clotting factors? Patients with underlying cancer are at a higher risk of haemorrhage with warfarin than with low molecular weight heparin. They are also more likely to experience polypharmacy, hepatic dysfunction, and poor nutrition, which can influence their INR control. In these patients, consider using low molecular weight heparin instead. 2• Take a thorough drug history. Ask about prescribed drugs, over the counter drugs, and herbal supplements. The cytochrome P450 enzyme metabolises warfarin, so P450 inhibitors can cause the INR to rise. Common inhibitors of warfarin metabolism include clarithromycin, erythromycin, and amiodarone-for a comprehensive list see: www.medicinescomplete.com/mc/bnf/current/bnf_ int222-warfarin.htm. Check the INR three to five days later after starting any drug that interacts with warfarin that will be taken for longer than seven days because the dose of warfarin may need adjusting. 3

The combination of panobinostat, bortezomib and dexamethasone (PanBorDex) is available as a treatment option for relapsed refractory multiple myeloma (RRMM) based on the PANORAMA-1 trial which investigated this triplet in early relapse. In routine clinical care, PanBorDex is used primarily in later relapses and is commonly administered in attenuated dosing schedules to mitigate the treatment-related toxicity. We set out to evaluate efficacy and safety outcomes with PanBorDex later in the disease course and evaluate the role of attenuated dosing schedules. This was a retrospective evaluation of patients treated in routine clinical practice between 2016–2019 across seven heamatology centres in the UK; patients who received at least one dose of PanBorDex were eligible for inclusion. The dosing schedule of panobinostat (10mg, 15mg or 20mg, twice or three times a week) and bortezomib (0.7mg/m2, 1mg/m2 or 1.3mg/m2 once or twice weekly) was as per treating physician choice. Patients received treatment until disease progression or unacceptable toxicity. The primary outcome is response rates according to IMWG criteria. Key secondary endpoints include progression-free survival (PFS) and overall survival (OS). Other secondary endpoints include rates of adverse events according to CTCAE criteria. In total, 61 patients were eligible for inclusion and received PanBorDex primarily as ≥5th line of treatment. One third of patients received PanBorDex at full dose, for the remaining two thirds, treatment was given in reduced dose intensities. The overall response rate was 44.2%, including 14.7% very good partial response (VGPR) rates; 68.8% of patients derived clinical benefit with stable disease or better. The median PFS was 3.4 months; non-refractory patients and those who achieved VGPR benefited from prolonged PFS of 11.4 months and 17.7 months, respectively. The median OS was 9.5 months. The triplet was associated with 45% and 18% incidence of grade 3–4 thrombocytopenia and diarrhea, respectively.

SummaryAn elderly woman, two months after chemotherapy for diffuse large B-cell lymphoma, presented with left-sided otalgia, discharge and facial nerve palsy. MRI showed an active left mastoid infection with an ear canal lesion, likely to be a cholesteatoma. However, a biopsy of the mass showed recurrent high-grade lymphoma. Following diagnosis, the patient opted for palliative care within the community and consequently passed away a few weeks later. BACKGROUND