Off-label prescribing

To the Editor: Off-label prescribing is a complex paradigm, with important clinical, safety, ethical, legal and financial dimensions. The articles by Seale,1 Hickie,2 and Harris and Naylor3 highlight some associated controversies and the need for a rigorous approach.

The Council of Australian Therapeutic Advisory Groups (CATAG) has recently developed national guiding principles that provide a structured framework to support judicious, appropriate, safe, effective and cost-effective off-label use of medicines.4 This framework will facilitate a more rigorous and consistent approach to decision making by health professionals, consumers, and drug and therapeutics committees in their evaluation and use of medicines that are prescribed off label. CATAG’s guidance provides an important expansion and update on previous Australian recommendations.5

There are seven overarching guiding principles, including a core principle of systematic evaluation of the evidence base and risk–benefit ratio for proposed off-label uses. Comprehensive advice for involving patients and carers in shared decision making and systematic outcomes evaluation is also provided. Applying these principles in routine practice will help address the clinical, safety and ethical concerns that have recently been highlighted. CATAG anticipates undertaking future work to support wider implementation of the guiding principles.

Crusted scabies in remote Australia, a new way forward: lessons and outcomes from the East Arnhem Scabies Control Program

Case record

An 8-year-old girl had received treatment for scabies at a health centre in a remote Northern Territory Arnhem Land community on 32 occasions since her birth. Seventeen of these occasions required treatment with parenteral antibiotics for secondary infection. Many episodes were noted to involve the “whole body” and on two occasions she had required hospitalisation. During this time, she was also found to have a low body mass index and failure to thrive.

The girl was often found crying from pain and itch and had been excluded from school for extended periods because of her infectivity. Her family reported that she was bullied by her peers because of the disfigurement of her skin. Her frequent bouts of disfiguring scabies, skin sores and weight loss had led to referrals to child and family services over concerns of parental neglect.

The girl was brought to the attention of East Arnhem Scabies Control Program staff in 2011. Contact tracing was initiated, and a senior member of the family, with whom the girl shared a room, was found to have Grade 2 (moderate) crusted scabies. Clinical audits showed that the senior family member had repeatedly presented with crusted scabies since 1996. After a hospital admission in 2006, she had avoided contact with health services, even though her skin condition deteriorated, reportedly due to fear of the treatment regimen involving extended isolation in hospital and the use of creams that caused a burning skin sensation.

The senior family member was subsequently treated for crusted scabies and the girl and other household members were treated for simple scabies. The woman was then enrolled in a pilot program to prevent recurrent disease. During 19 months of follow-up with the preventive regimen in place for the woman, the girl’s skin condition improved and required no further specific management other than treatment for scabies on one occasion.

Crusted scabies is a highly infectious, debilitating and disfiguring condition (Box 1) that develops when scabies mite proliferation is not controlled by the host immune system. It is characterised by hyperkeratotic skin crusts and mite loads of a million or more on affected individuals (up to 4700 mites per gram of skin), compared with a total of 10–15 mites in simple scabies.2 Crusted scabies is generally seen in immunocompromised patients3 and historically had a 5-year mortality rate of up to 50%.4 However, a multidose regimen of ivermectin, benzyl benzoate and keratolytic agents introduced in 1996 at the Northern Territory’s Royal Darwin Hospital has led to a significant decrease in the annual mortality rate, to 1.6%.4 Unmanaged crusted scabies is known to cause outbreaks of simple scabies and contributes to the hyperendemic rates seen in many remote communities.4,5

While rare in urban settings, rates of crusted scabies reported in remote Aboriginal communities of northern Australia are the highest in the world.4,6 A review of 78 patients admitted to hospital for crusted scabies in northern Australia over 10 years found nearly all (97%) were Aboriginal people from remote communities, and in nearly half of these patients no underlying immune defect was found.4 From its inception in early 2011 to April 2014, active case finding by the East Arnhem Scabies Control Program (EASCP) across 11 remote communities of northern Australia and their homelands had confirmed 20 cases (1.8 cases per 1000 population).

There is currently no register or follow-up of people living in scabies-endemic areas who are at risk of developing recurrent crusted scabies. Recurrences are only detected if patients self-present to health services and are seen by a clinician familiar with the condition. Current protocols treat the condition acutely. The EASCP postulated that the lack of follow-up surveillance and chemoprophylaxis was inadequate for patients returning to endemic areas.

Here, we present results of routine monitoring and evaluation of the EASCP between August 2011 and June 2013, from the three remote East Arnhem communities in the NT where we had data sharing agreements to access clinical records and the operational capacity to deploy a preventive program. Individual consent was obtained to publish case history details. Publication of EASCP monitoring data was approved by the board of Miwatj Health Aboriginal Corporation and the Human Research Ethics Committee of the NT Department of Health and Menzies School of Health Research (approval number 2013-2055).

The East Arnhem Scabies Control Program

The EASCP was established in early 2011 and is a joint initiative of One Disease, Miwatj Health Aboriginal Corporation and the NT Government Department of Health. The consultancy EveryVoiceCounts was contracted to design the program and guide implementation. More information on the EveryVoiceCounts learning partnership model used to design the program is available at http://www.everyvoicecounts.org/scabies-partnership. For more on the EASCP, see https://1disease.org.

The EASCP was developed to enhance regional efforts to reduce the impact of scabies as a public health problem in remote communities of Arnhem Land and is a service delivery program integrated into existing health services. The program’s first goal was to reduce the burden of crusted scabies on affected individuals and households in participating East Arnhem communities. This goal was the result of consultations and baseline clinical audits that indicated a significant burden of illness and ongoing disruption to quality of life arising from unmanaged crusted scabies. Patients we encountered in remote communities in 2011 suffered similar stigma and disfigurement to those described in a case report of crusted scabies published more than 60 years earlier (Box 1).1 The EASCP also recognised that better management of these “core transmitters” was a foundation of broader scabies control efforts.

In late 2011, the EASCP convened a medical working group to update the scabies and crusted scabies guidelines in the Central Australian Rural Practitioners Association (CARPA) Standard treatment manual. Drawing on experience with a patient who had successfully used short-term treatment creams in a preventive fashion, as well as a preventive model proposed in 2004,7 the working group approved a provisional protocol to prevent recurrences of crusted scabies, which the EASCP then trialled.

EASCP crusted scabies case management protocol

The EASCP used active case finding to identify people with crusted scabies. When cases were confirmed in one of the three communities where EASCP had operations, the patients were first treated (in hospital or, when this was declined, in the community) using a protocol developed by the Royal Darwin Hospital.8,9 Patients were then enrolled in the new preventive care regimen, which involved:

regular (every 1–4 weeks) skin checks looking for signs of recurrent crusted scabies;
frequent use of a keratolytic cream (to limit the build-up of keratin crusts, where mites live and multiply in crusted scabies) combined with a moisturiser; and
regular (every 2–4 weeks) use of a scabies (acaricide) cream. The frequency depended on the likely level of recurrent exposure to mites (eg, in a household with many young children, fortnightly applications were used). Benzyl benzoate was selected because of the limited risk of resistance developing with this agent. An initial test application of benzyl benzoate ruled out the side effect of transient burning sensation on the skin.

This clinical protocol was implemented by the EASCP through a long-term household case management approach, focused on developing therapeutic rapport with patients and senior members of households. The EASCP’s early consultations with care providers and patients highlighted significant fear and stigma associated with the disease and a reluctance to engage with health services. Given the chronicity of the disease, the long-term goal was adherence to the treatment regimen and ultimately self-management of the condition. We aimed to achieve this through consistency of staff, regular supply of the preventive creams needed for self-management, and reinforcing the household costs of disease recurrence.

Active case finding and EASCP inclusion criteria

Cases

From August 2011, the EASCP investigated patients identified by health centres as having recurrent scabies or crusted scabies. The EASCP also examined the NT hospital database and related discharge summaries to find patients from participating communities who had been treated for crusted scabies. An experienced EASCP clinician then examined the patient and confirmed or excluded the diagnosis of crusted scabies, and this was verified by visiting dermatologists and infectious disease specialists.

Sentinel contacts

EASCP monitoring paired each confirmed case with a household child contact. The contacts served as sentinels of recurrent disease in the cases and to track their infectivity, as our baseline data showed that most patients with active disease did not present to health services. Contacts were confirmed to have the same primary residence as the cases with whom they were paired. Crusted scabies was excluded in the contacts. Sentinel contacts often had a history of recurrent simple scabies and had been referred to the EASCP for management. Due to capacity constraints, where multiple contacts were known to the EASCP, the contact with the most extensive history of presentation for scabies was selected as the sentinel.

Evaluation of EASCP case management protocol

Between August 2011 and June 2013, seven patients in the three communities under evaluation were confirmed as having crusted scabies and were enrolled in preventive case management. These seven patients and their seven sentinel contacts are included in this review.

EASCP monitoring data consisted of EASCP, health centre and hospital clinical records before and after the preventive care protocol was introduced. The outcome measures examined were the number of presentations involving recurrences of crusted scabies in cases and recurrent simple scabies in contacts. To avoid double counting, each new presentation was recorded as one episode (follow-up visits for multidose treatments were counted only once), and only one episode was recorded if presentations led to referrals to hospital or the health centre for management. Search parameters for the outcome measures were consistent for the intervention (during preventive case management) and control (before preventive case management) periods. However, screening of cases for recurrence was active (1–4-weekly skin checks) during the intervention period, but passive (self-presentation) during the control period. This is likely to significantly bias results towards the null.

The duration of case management was from the time of case identification and consent to June 2013. We examined the change in the number of outcome events during the intervention period compared with those during a pre-intervention control period of the same duration for each case and contact. The Wilcoxon signed-rank test was used to determine statistical significance, and P values < 0.05 were considered significant. Data were analysed using Stata version 11 (StataCorp).

Detailed baseline data and monitoring methods can be found in the Appendix.

Baseline findings

We audited a combined 57 years of clinical records for the seven cases (26 years) and seven contacts (31 years). Among cases, one patient was aged 20–39 years and six were aged 40–59 years. Among contacts, three were aged 0–4 years, three were aged 5–9 years and one was aged 10–14 years.

No immune defect was recorded in the seven cases, apart from one patient who had crusting in a neuropathic limb. Six of the seven patients had active crusting of moderate to severe grade (ie, high infectivity) at the time of first review by the EASCP. Of these six, four had not presented to health services despite having recurrent disease and were only identified through active surveillance. Most (4/6) declined hospitalisation.

Cases presented with recurrent disease a median of five times per year (range, 1–9) during the 26 years of record review. Paired sentinel contacts presented with simple scabies (with or without skin sores) a median of five times per year (range, 0.4–11) during 31 years of record review. Combined case–contact pairs presented a median of 12 times per year (range, 4–16) with presentations related to simple or crusted scabies during the combined 57 years of audited records.

Child contacts had a median of 10 presentations (range, 5–11) for simple scabies and sores in their first year of life, and most contacts had multiple episodes of scabies described as “extensive/whole body”. Nearly all of the paired child contacts had suffered periods of recurrent scabies and sores associated with weight loss and failure to thrive. Five of these children had been referred to child and family services over concerns of parental neglect, where recurrent scabies and sores featured in the referral.

EASCP case management findings

From August 2011 to June 2013, a cumulative total of 99 months of preventive case management was undertaken in the seven cases (mean duration of enrolment in care, 14 months; range, 3–20 months). Clinical records from a matching 99-month control period immediately before preventive case management were also reviewed, making a cumulative total of 198 months before and during the intervention. Clinical records for the corresponding 198 months were examined for paired contacts.

During the 99-month intervention period, cases were reviewed at 1–4-weekly intervals. For the seven cases, a total of 245 skin checks were performed in the community (every 1.6 weeks on average). The EASCP recorded no reports of adverse effects from the preventive treatment regimen.

For the seven cases, we detected a significant 44% reduction in clinically diagnosed episodes of recurrence of crusting (from 36 to 20; P = 0.025) during the intervention period, compared with the control period (Box 2). We also detected a 56% reduction in episodes of hospitalisation (from 9 to 4; P = 0.09) and an 80% reduction in days spent in hospital as a result of recurrence of crusted scabies (from 173 to 35; P = 0.09), compared with the control period. However, these changes were not significant and are due to the number of cases that had not recorded a hospitalisation and, in light of our baseline data, are likely to indicate non-presenters.

For the seven paired contacts, we detected a statistically significant 75% decrease in the combined number of hospital admissions and presentations to local health centres with scabies and skin sores (from 28 to 7; P = 0.017) during the intervention period, compared with the control period (Box 2). We also detected a significant 58% reduction in paired case–contact presentations (from 64 to 27; P = 0.016).

Limitations of the evaluation

The nature of the analysis (involving audit of program monitoring records) and the small sample size limit the generalisability of our findings. The routine nature of data collection means there is interoperator variability, and diagnoses made on clinical grounds allow for false-positive results. For cases, this is likely to be low because recurrences were based on detection of characteristic skin lesions in patients who had a hospital- or specialist-confirmed history of crusted scabies. Importantly, the criteria were consistent during the intervention and control periods. We believe our method of analysis is conservative, with the dominant bias being towards the null, as surveillance for recurrences was active during the intervention period, compared with passive surveillance during the control period. The use of a primary contact to track disease transmission also limits generalisability of the study. However, the contacts act as useful sentinels of recurrent disease and infectivity of cases. EASCP monitoring is ongoing, and subsequent analyses will improve the generalisability of findings as the duration of follow-up and number of managed cases increases.

Lessons

EASCP’s program monitoring and evaluation findings offer important lessons for the control of crusted and simple scabies in Australia.

Lesson 1: Current passive surveillance for recurrences leads to likely underdetection of crusted scabies in scabies-endemic areas.

Lesson 2: Combined presentations of cases and sentinel contacts suggest significant scabies transmission from cases to household contacts, increasing the risk of complications from chronic renal and rheumatic heart disease. Repeated episodes of scabies and skin sores are likely to significantly impair household quality of life,10 and to increase the risk of repeated exposure to group A streptococcus isolates, which has been associated with increased risk of chronic renal and rheumatic heart disease.11,12

Lesson 3: Skin disfigurement and weight loss associated with recurrent scabies and skin sore infections may have led to child contacts being misdiagnosed as victims of parental neglect. Recurrent infections can lead to weight loss as a result of altered metabolism, nutrient loss and decreased appetite. Malnutrition in turn lowers immunity and susceptibility to infections.13–15 Thus, in contacts of patients with crusted scabies, weight loss and skin disfigurement associated with severe recurrent scabies and skin sores are likely to signify ongoing disease transmission from infected patients, rather than parental neglect.

Lesson 4: EASCP case management appears to reduce the burden of illness in patients with crusted scabies. Due to the differential screening methods used in the intervention (active) versus control (passive) periods, the actual reduction in recurrences during EASCP preventive care (and duration of time patients remained disease-free, compared with time spent with active crusting) is likely to be significantly greater than the 44% decrease we observed.

Lesson 5: EASCP case management reduces simple scabies presentations in sentinel contacts. The decrease we detected in presentations of contacts is likely to signify less time spent unwell from recurrent scabies and sores and thus less suffering, disfigurement and stigmatisation. EASCP case management thus provides a way to reduce the long-term disruption to quality of life for these households.10 At the community level, our findings suggest the improved control of an important driver of scabies endemicity.3–5,11 The reduced infectivity of cases can be explained by two novel features of the EASCP preventive care regimen: ongoing skin checks, allowing early detection of recurrences; and regular use of keratolytic and scabicide agents, both of which inhibit mite hyperinfestation.

Recommendations

Based on the EASCP’s preliminary findings, and in light of the disruption caused by the condition to affected households, we recommend that patients with crusted scabies living in scabies-endemic areas be offered this preventive care regimen. The crusted scabies guidelines in the forthcoming 6th edition of the CARPA Standard treatment manual have been revised to feature this model of care, and our recommendations to facilitate its wider adoption are shown in Box 3.

1 The disfiguring plaques of crusted scabies

A: Photograph of crusted scabies reproduced from a 1948 case report.1 B: Crusted scabies of the elbow. C: Crusted scabies of the foot (partially treated).

2 Review of cases of crusted scabies and paired contacts before and during East Arnhem Scabies Control Program (EASCP) household preventive case management

	Control (pre-intervention) period	Intervention period	Change	P

Cases (n = 7)
Months audited	99	99	—
Hospital admissions for recurrences	9	4	− 56%	0.09
Days in hospital	173	35	− 80%	0.09
EASCP or health centre-diagnosed recurrences	27	16	− 41%	0.04
Total recurrences (rate per year)	36 (4.4)	20 (2.4)	− 44%	0.025
Contacts (n = 7)
Months audited	99	99	—
Hospital admissions for severe infected scabies	3	0	− 100%	0.16
Days in hospital	13	0	− 100%	0.16
Health centre presentations for scabies skin sores	25	7	− 72%	0.017
Total scabies-related presentations (rate per year)	28 (3.4)	7 (0.8)	− 75%	0.017
Paired case–contact presentations	64	27	− 58%	0.016

3 Recommendations for implementing the preventive care regimen of the East Arnhem Scabies Control Program (EASCP)

Wider adoption of the preventive regimen for patients with crusted scabies living in scabies-endemic areas will require:

Ongoing program monitoring and operational research to refine preventive case management protocols and document the transferability of programs
Active surveillance for recurrences and a chronic disease case management approach to crusted scabies care — a long-term therapeutic approach is more likely to lead to better outcomes than an acute-outbreak approach and to overcome the fear, stigma and avoidance of health services evident in most patients’ clinical histories
Support from regional disease control and chronic disease programs for health centres to adopt this new model of care in communities
A regional register to facilitate continuity of care when patients move between communities — for this, a diagnostic criterion for “recurrent” crusted scabies must be developed, and we recommend adopting Grades 2–3 of the Royal Darwin Hospital grading scale as a criterion for inclusion in ongoing preventive care9
Investigation of the household to exclude contact with crusted scabies in situations where recurrent scabies, skin sores and weight loss are seen in a child; in households where crusted scabies is present, a diagnosis of parental neglect due to recurrent scabies and weight loss in children should be made with extreme caution
Urgent research and development to bring easier-to-use and more effective crusted scabies (and simple scabies) therapies, including immunotherapies, to the market

Guidelines fall short on bariatric surgery

To the Editor: I am writing in relation to the concerns raised by Dixon in his critique of the Clinical practice guidelines for the management of overweight and obesity from the National Health and Medical Research Council (NHMRC).1

When developing guidelines, the NHMRC always includes a consultation phase and Dixon did not raise his concerns during this phase. When his concerns were subsequently brought to NHMRC’s attention — just as the guidelines were in the process of being published — the guideline committee agreed to remove examples of nutritional complications as they were open to misinterpretation.

The revised guidelines were issued in October 2013 and Dixon was informed of the amendment. Hence the version of the guidelines cited in Dixon’s article does not contain the text with which he took issue in the Journal.

Further, the guidelines are not intended for bariatric surgeons and their teams, as Dixon suggests. The guidelines are specifically targeted at primary care management of overweight and obesity. As such they note that “Individual monitoring and follow-up protocols should be determined by the appropriate specialist team or surgeon, in consultation with the primary care health professionals involved”.

The evidence base for the guidelines is documented in the accompanying 656-page systematic review, available on the NHMRC website.2

The NHMRC develops guidelines against a rigorous set of standards that include governance by an expert multidisciplinary committee, a documented evidence review process, strict conflict of interest management, and independent expert and methodological review.

An integral element is a transparent public consultation process, and the NHMRC urges all clinicians to review guidelines at this stage and respond as appropriate.

With great power comes great responsibility

To the Editor: In October 2013, the Australian Broadcasting Corporation television program Catalyst featured a two-part documentary series entitled Heart of the matter. The first episode questioned the role of dietary saturated fat in the development of heart disease, and the second debated the use of
3-hydroxy-3-methylglutaryl coenzyme
A (HMG-CoA) reductase inhibitors (statins) as a suitable treatment for hypercholesterolaemia.1

Justin Coleman, a general practitioner and senior lecturer in medicine at Griffith University, provided an excellent summary of the two episodes, highlighting the bias of several of the medical experts featured in the program.2 Coleman drew particular attention to their undisclosed conflicts of interest, describing one expert as having his own commercial line of alternative treatments for heart disease. The views portrayed in the program could not have been published in any reputable medical journal without adequate disclosure of the experts’ conflicts of interest. So why should this be allowed on television, when the audience is potentially so much larger and more impressionable?

Perhaps the worst of the views aired was from an expert who suggested that starting statins means weighing up the risk of getting diabetes as a trade-off
for preventing a cardiovascular event. Such an opinion shows ignorance of international standards for scientific evidence — pitting the weak observational data suggesting a slight increase in risk of diabetes among statin users3 against the overwhelmingly strong evidence from multiple randomised controlled trials demonstrating the benefits of statins when used for secondary prevention after an acute coronary syndrome.4 Why are television stations allowed
to broadcast material on so-called scientific programs that includes
such misleading statements?

This program significantly hinders progress in tackling problems such as non-adherence with evidence-based medicines after acute coronary syndromes. It has been demonstrated that patients who stop taking their medications after myocardial infarction have a 10% higher chance of dying within 1 year.5 Resolving this problem requires patient education and empowerment, and a strong doctor–patient relationship — a relationship that is, unfortunately, often tested
by skewed views from the media.

Impact of drug interactions when medications are stopped: the often forgotten risks

Clinical record

An 82-year-old man sustained an unwitnessed mechanical fall within his residential care facility, after which he developed lower back pain and intermittent dizziness. On review by his general practitioner 3 days later, he was found to have extensive bruising of his back, buttocks and thighs. Pathology tests 6 days after the fall showed a haemoglobin level of 69 g/L (reference interval [RI], 122–170 g/L). On arrival at the Alfred Hospital emergency department, he had mild abdominal pain, appeared lethargic and displayed clinical signs of anaemia.

Initial investigations revealed a haemoglobin level of 57 g/L,
an international normalised ratio (INR) of > 20 (RI, 0.9–1.3), a prothrombin time of > 200 s (RI, 10.6–15.3 s), and an activated partial thromboplastin time of 95.4 s (RI, 26.0–38.0 s). He also had acute kidney injury, with an estimated glomerular filtration rate of 28 mL/min/1.73 m2 (RI, > 90 mL/min/1.73 m2; baseline, 40 mL/min/1.73 m2).

His medical history included chronic kidney disease, type 2 diabetes mellitus, atrial fibrillation, pulmonary embolism with associated cardiac arrest, colon cancer and tuberculosis. Tuberculosis
was diagnosed 11 months before the current admission on bronchoscopically collected sputum specimens. The treatment regimen was rifampicin, isoniazid, pyrazinamide and ethambutol for 2 months, and rifampicin and isoniazid for a further 7 months. He was on chronic warfarin prophylaxis (target INR, 2–3) in the setting of atrial fibrillation. The warfarin therapy was managed by his GP, and all his medications were managed using a dose administration aid. While taking rifampicin, INR monitoring occurred on a 2–4-weekly basis via his usual private pathology service.

He was admitted to hospital and given intravenous phytomenadione 5 mg and Prothrombinex-VF (CSL Biotherapies) 2500 IU, with rapid effect. Subsequently, he was transfused with 5 units of packed red blood cells, with restoration of haemoglobin to 98 g/L 2 days later. Computed tomography imaging showed an intramuscular haematoma
in the right gluteal region. There was no clinical evidence of blood loss in any other body compartment, and computed tomography imaging of the brain was unremarkable.

The treating team of doctors and pharmacists reviewed the possible contributing factors to the extreme supratherapeutic anticoagulation, and determined that a drug interaction between rifampicin and warfarin was most plausible. There were no other changes to the patient’s medications, health status (such as cardiac or liver failure) or diet, and no concerns about medication preparation or adherence.

Throughout the 9 months of antimycobacterial therapy, his anticoagulation was largely stable on a warfarin dose of 12 mg daily. Before commencing antimycobacterial therapy, his usual warfarin dose was 4 mg daily. His antimycobacterial regimen was ceased by the treating specialist 7 weeks before the current admission.

Five days after admission, warfarin was safely recommenced at 4 mg daily. As a consequence of this case, an education process was instigated by the Pharmacy Department at Alfred Health, to heighten knowledge among clinicians about the clinical implications of the rifampicin–warfarin interaction, especially around the time of rifampicin withdrawal.

The use of rifampicin to treat tuberculosis and methicillin-resistant Staphylococcus aureus infections is increasing in Australia, yet it remains a specialised medication that is mostly prescribed by infectious diseases physicians. In contrast, warfarin is widely used — monitored by general practitioners, haematologists, cardiologists or pathology providers — but there are not necessarily mechanisms to reliably notify clinicians of medication changes.1

Rifampicin is a potent inducer of the hepatic and intestinal cytochrome P450 (CYP) enzyme system and the P-glycoprotein transport system, resulting in the potential for a broad range of clinically significant drug interactions.2 The effect of rifampicin on the pharmacokinetics of warfarin has been established since the 1970s,3 but may not be well known to all clinicians engaged in the management of warfarin. The proposed mechanism for the rifampicin–warfarin interaction involves the induction of CYP2C9, CYP3A4, CYP1A2 and CYP2C19.4

Following the commencement of rifampicin, our patient’s warfarin dose changed from 4 mg daily to 12 mg daily. This demonstrates that the magnitude of the effect of rifampicin on warfarin requirements can be profound — well beyond the effect of the myriad other medications that interact with warfarin. In most cases, the introduction of rifampicin heralds the need to progressively escalate the warfarin dose. As rifampicin therapy is usually continued over several months, patients often become stabilised on a new warfarin dose, and the presence of the rifampicin–warfarin interaction recedes in prominence. Therefore, when the end of the rifampicin treatment course is reached, clinicians often overlook the likely need for reducing the warfarin dose and monitoring the international normalised ratio (INR) more frequently.

After rifampicin is discontinued, the induced CYP enzymes decline in activity over a period of time. This means that the intensive INR monitoring needs to be maintained until it is certain that the drug interaction is no longer relevant. Our patient was hospitalised 7 weeks after rifampicin was withdrawn. Previous case reports have shown that the interaction may persist for over 4 weeks after rifampicin cessation.5,6

Lessons from practice

Important drug interactions must be considered when commencing a new medication and when discontinuing a medication.
Different prescribers contributing to a patient’s care must ensure reliable communication when high-risk medications are used.
The primary care practitioner, with the aid of prescribing software, remains the central figure in maintaining quality use of medicines.
Keeping consumers informed and educated about their medications may be a safeguard against adverse outcomes.

This case illustrates the importance of promoting awareness of the rifampicin–warfarin interaction. In addition, improved strategies must be developed to ensure that communication is accurate and timely between physicians who are managing antimicrobial therapy and those managing anticoagulant therapy. The challenges posed to the management of warfarinisation by the fragmented nature of medical care have previously been described.1 In relation to warfarin dosing, this is compounded by the use of subcontracted pathology services, which lack dynamic access to patients’ complete health information.

Automated alerts in GP prescribing software and pharmacy dispensing systems are designed to moderate the potential adverse outcomes from drug interactions at the time of medication initiation. However, these aids do not safeguard against adverse outcomes from drug interactions occurring at the time of medication cessation. Educating patients at the point of initiation about interacting drugs and the extra vigilance required when the drug is later ceased may be a useful strategy in appropriate circumstances.

The novel anticoagulants, such as dabigatran, may also interact with rifampicin; however, there are no laboratory testing methods available to monitor such an interaction.7

Serious adverse events may occur if monitoring of warfarin is inadequate on discontinuation of rifampicin therapy. The key elements to avoiding these outcomes include increasing the level of understanding about this interaction among clinicians, improving interclinician communication, creating alert systems at the point of care for doctors and pharmacists, and ensuring that patients are informed about the safe use of medicines.

Taking the inferior out of inferior vena cava filter follow-up

To the Editor: Follow-up of inferior vena cava (IVC) filters after insertion is a task that is variably successful. This was highlighted
by a recent article describing poor removal rates of IVC filters at our institution between 2007 and 2009.1 Since that time, the interventional radiology (IR) department has established a filter database and clinic with the aim of improving IVC filter monitoring and removal. This radiology-driven initiative has been integrated into the standard interventional procedures and has proven extremely effective. Based
on the success of this program, we advocate strongly that IVC filter follow-up should be the responsibility of those who provide the insertion service.

Between 2011 and 2013, all 87 IVC filters inserted by IR at St Vincent’s Hospital Melbourne have been accounted for; 44 have been removed, 33 were planned not for removal (eg, patients with a poor prognosis or contraindications), and 10 are awaiting removal or review in our IR clinic. The average indwelling time for IVC filters inserted between 2011 and 2013 was 23 weeks (range, 1–130 weeks), with 71/87 filters remaining in situ for less than 6 months. The average time in situ fell from 35 weeks in 2011 to 14 weeks
in 2013. These results contrast with 2008–2010 data from our institution, where only 16/68 IVC filters were removed or planned for removal,
19/68 were planned not for removal or the patient was deceased, and
33/68 were lost to follow-up (Box).

Concerns about inadequate IVC filter removal and follow-up have been reported in the literature, particularly as the use of filters has increased.2,3 Potential complications associated with “forgotten” IVC filters include thrombogenesis, caval perforation, and filter fracture and migration. However, the important role of IR in tracking and removing lost filters is becoming widely recognised, with a number of studies outlining improvements in IVC filter follow-up that have resulted from radiology-led initiatives.4,5 Our data support the conclusion that IR departments, through easily implemented strategies, can and should take responsibility for tracking and removing all IVC filters they insert.

Inferior vena cava filter outcomes at St Vincent’s Hospital Melbourne

Here

there is something comforting about sitting here with my hand on Robert’s breast

he says, here, steady yourself against me here, he says, after a pause, he is thinking how best

to fit me, he says it must have been bad but you’re here, you’re with us

the surroundings burst with surgical fittings

it all looks very Weimar, very neue Sach

i expect fishnets, a crossed leg, a trail of cigar smoke somewhere

but there is only Robert and me and all the boxes

and Robert saying again, here, steady yourself against me here

Peter Thomson MB BS, FFARACS

Peter Thomson was born on 12 June 1940 in Esher, near London. His mother May was a highly trained registered nurse. His Australian-born father, George Macdonald Thomson, was a medical graduate from the University of Sydney who qualified and practised as a surgeon in England in the 1930s until he was conscripted into the British Army in World War II. Peter and the rest of the family spent the war in a heavily blitzed London. Many were the tales that May told of near misses from doodlebugs (German V-1 flying bombs). After the war, they left the United Kingdom to join George in Sydney in 1947, where he had been demobilised. George subsequently became a general practitioner and surgeon in Newtown.

Peter attended Burwood Public School and Fort Street Boys’ High School. He entered medicine at the University of Sydney in 1957, graduating in 1963. After a year’s residency at Royal Prince Alfred Hospital, he was a resident medical officer for 2 years at Royal Newcastle Hospital, developing an interest in anaesthetics, which he would maintain for the rest of his life.

While working at Lidcombe Hospital, Peter passed the first part of his Fellowship of the Faculty of Anaesthetists of the Royal Australasian College of Surgeons in 1967 and was awarded the Renton Prize. In 1969, he passed the second part of his Fellowship.

From 1968 to 1970, Peter worked at St Vincent’s Hospital, Darlinghurst, where he was the anaesthetic registrar involved in the first heart transplant in Australia in 1968. He completed his training at Royal Alexandra Hospital for Children in Camperdown and went into private practice in 1970.

Peter was a visiting medical officer at Liverpool and Auburn Hospitals, and then Concord Repatriation General Hospital. He also worked at many private hospitals, including Strathfield, Holroyd and Ashfield. He was a very skilled and devoted anaesthetist, highly respected by his surgeons and patients. He retired from active practice in 2007.

Besides medicine, Peter had many interests. He kept extremely fit by running, walking and cycling. He was a keen birdwatcher and photographer, and greatly enjoyed his Probus club activities.

Peter retired from anaesthetics in 2007 and died on 21 June 2013. He is survived by his wife Sandra, daughters Lynda, Karen and Jenny, and stepdaughter Tammy.

A difficult conversation

Investigation results are a false crutch for breaking bad news to patients

Several years out of medical school, I was working my first general medical registrar job as the night cover in a rural hospital. An elderly gentleman, unconscious and intubated, was brought in by ambulance to our emergency department. A computed tomography (CT) scan of his brain showed massive bilateral haemorrhages. I phoned my consultant, discussed the case, and agreed that a “not for resuscitation” order was appropriate.

An urgent family meeting was arranged.

At 2 am I entered the relatives’ room, expecting one or two people. There were 15. They were crowded in the room, some standing, some in pyjamas, all white-faced and anxious.

None of them knew that this man, so special to them, was now lying unconscious in the next room, breathing through a tube, irreversibly damaged. I introduced myself, and thanked them for coming. I looked at the expectant faces. They already knew of the unconscious collapse. What “warning shot” could I give, to help steel them for the bad news? I thought about the only new information I had: the cerebral CT results. These were so clearly bad; surely they’d allude to the dismal outlook?

“The brain scan was very abnormal. There were large blood clots on both sides of the brain. So big, they had compressed the ventricles.”

I paused, the warning shot duly delivered.

Fifteen bewildered faces looked back at me.

Then: “Will he be okay?”

Only one person was shocked. It was me.

What was I doing? I know the importance of not speaking jargon. But here I was, hoping some test results would do the hard yards, would explain the tragic event, would hint at the sad prognosis. A man’s life was at an end, an eventful life, a life he had shared with all the people in this room. And I had tried to describe an axial slice of his brain to people with no medical background.

Of course, mishandling the breaking of bad news does not happen infrequently. Medical schools supply us with a framework; verbal and non-verbal tools. But it is hard to recreate those leisurely afternoons in sun-filled tute rooms. Everyone is your age, speaks English, knows the drill, and — this is most important — is not actually about to be bereaved. Nothing prepares you for the real thing. I had asked a mentor once if it ever got easier. “No. But you get better at it.”

Breaking bad news is a necessary, never-ending challenge for doctors. Each situation is unique, each tear-stained face exacts its emotional toll, each condolence is accompanied by a bitter feeling of inadequacy; inability to save every life, inability to ease loved ones’ pain. I wonder how many of my colleagues use investigation results as a means of deflecting or avoiding these issues.

Why do we resort to this?

Maybe it is easier to “clinicalise” the truth, talk about reports and numbers, rather than about the imminent death of the person in front of us. But conversations like this are not fair to people who deserve an honest and sensitive discussion. The medical profession deals in difficult decisions and difficult conversations in the service of the patients and their families.

That night in the relatives’ room was hard. I started again, and I watched as my carefully selected, layman-friendly words tore the world apart for 15 people. It was the first time I had to say the real words — the words I had tried to imply by relating a test result, the words that the family needed to hear. “I’m very sorry, but he is dying . . . he will die.”

Months afterwards, I asked myself: if I had not said it, would it have been less real? I thought back . . . I watched as my words took hold. I explained how their loved one was not responsive, had a tube in his throat, and that this would be distressing to see. All were determined to see him one last time. I escorted the family into the resuscitation area, watched them take it in turns to hold his hand. I watched, as the last goodbye was said, as the patient was extubated, and as he slipped away. I watched, as 15 tear-stained faces left. And I had my answer: it was real for the patient, it was real for his family and friends, and it deserved the real conversation that we eventually had.

Hubert (Hugh) Roy Harris MB BS

Hubert (Hugh) Harris was a country doctor who earned the respect and affection of all who knew him.

Hugh was born in Stockton, New South Wales, in 1919 to Dr Hubert and Emily Harris. He was educated at Armidale and studied medicine at the University of Sydney.

On graduating in 1943, Hugh was appointed a resident medical officer at Grafton Base Hospital. In 1944, he enlisted in the Royal Australian Air Force, serving as a Flight Lieutenant.

After the war, Hugh returned to Grafton Base Hospital and, in 1947, he joined a large group medical practice in Grafton and pursued his interest in surgery.

In 1948, he married Shirley Holland in Christ Church Cathedral, Grafton, leading to a lifelong and wonderful partnership of 65 years.

Hugh was adept at emergency surgery and trauma work but, in later years, he turned more to obstetrics and gynaecology. Hugh’s prime focus was always the patient needing help, no matter the hour or day of the week. He unstintingly gave his time and expertise, often to his own detriment. He also served on the boards of Grafton Base Hospital and ambulance service, and lectured nurses at the hospital training school.

Hugh enjoyed fishing at Yamba. He was a skilled woodworker who loved to work with North Coast cedar and built a beautiful dining table for his home.

His later years were marred by increasing deafness and macular degeneration, which he bore without complaint. Shirley lovingly cared for him at home until he needed full-time nursing care.

Hugh passed away peacefully on 9 July 2013 and is survived by Shirley and children John, Richard and Anne.