Western Infirmary Research Articles

Should substitution monotherapy or combination therapy be used after failure of the first antiseizure medication? Observations from a 30-year cohort study.

To assess the temporal trends in the use of second antiseizure (ASM) regimens and compare the efficacy of substitution monotherapy and combination therapy after failure of initial monotherapy in people with epilepsy. This was a longitudinal observational cohort study conducted at the Epilepsy Unit of the Western Infirmary in Glasgow, Scotland. We included patients who were newly treated for epilepsy with ASMs between July 1982, and October 2012. All patients were followed up for a minimum of 2 years. Seizure freedom was defined as no seizure for at least 1 year on unchanged medication at the last follow up. During the study period, 498 patients were treated with a second ASM regimen after failure of the initial ASM monotherapy, of whom 346 (69%) were prescribed combination therapy and 152 (31%) were given substitution monotherapy. The proportion of patients receiving second regimen as combination therapy increased during the study period from 46% in first epoch (1985 to 1994) to 78% in the last (2005 to 2015) (RR=1.66, 95% CI: 1.17-2.36, corrected-p=0.010). Overall, 21% (104/498) of the patients achieved seizure freedom on the second ASM regimen, which was less than half of the seizure-free rate on the initial ASM monotherapy (45%, p<0.001). Patients who received substitution monotherapy had similar seizure-free rate compared with those who received combination therapy (RR=1.17, 95% CI: 0.81-1.69, p=0.41). Individual ASMs used, either alone or in combination, had similar efficacy. However, the subgroup analysis was limited by small sample sizes. The choice of second regimen used based on clinical judgement was not associated with treatment outcome in patients whose initial monotherapy failed due to poor seizure control. Alternative approaches such as machine learning should be explored to aid individualized selection of the second ASM regimen.

The relationship between the Glasgow Microenvironment Score and markers of epithelial-mesenchymal transition in TNM II-III colorectal cancer

Recently published work on the Glasgow Microenvironment Score (GMS) demonstrated its relevance as a biomarker in TNM II-III colorectal cancer (CRC). Epithelial-mesenchymal transition (EMT) markers in CRC have also shown promise as prognostic biomarkers. This study aimed to assess the relationship between GMS and markers of EMT in stage II-III CRC. A previously constructed tissue microarray of CRC tumors resected between 2000 and 2007 from the Western Infirmary, Stobhill, and Gartnavel General Hospitals in Glasgow was used. Immunohistochemistry was performed for 5 markers of EMT: E-cadherin, β-catenin, Fascin, Snail, and Zeb1. Two-hundred and thirty-eight TNM II-III CRC with valid scores for all EMT markers and GMS were assessed. The prognostic significance of markers of EMT in this cohort and relationships between GMS and markers of EMT were determined. High cytoplasmic and nuclear β-catenin and membrane Zeb-1 were significant for worse cancer-specific survival (hazard ratio [HR] 1.67, 95% confidence interval [CI] 1.01-2.76, P<.05; HR 2.22, 95% CI 1.24-3.97, P<.01; and HR 2.00, 95% CI 1.07-3.77, P=.03, respectively). GMS 0 was associated with low membrane Fascin (P=.03), whereas membrane and cytoplasmic Fascin were observed to be highest in GMS 1, but lower in GMS 2. Nuclear β-catenin was lowest in GMS 0, but highest in GMS 2 (P=.03), in keeping with its role in facilitating EMT. Novel associations were demonstrated between GMS categories and markers of EMT, particularly β-catenin and Fascin, which require further investigation in independent cohorts.

Progress Toward Obtaining Seizure Freedom With New Medications in Older Adults.

Characteristics and Treatment Outcomes of Newly Diagnosed Epilepsy in Older People: A 30-Year Longitudinal Cohort Study Alsfouk BAA, Hakeem H, Chen Z, Walters M, Brodie MJ, Kwan P. Epilepsia. 2020;61(12):2720-2728. doi:10.1111/epi.16721Objectives:To describe the clinical characteristics and evaluate the long-term treatment outcomes in older people with newly diagnosed epilepsy over the past 30 years. Methods: We included patients newly diagnosed with epilepsy and commenced on anti-seizure medications (ASMs) at age 65 years or older between July 1982 and October 2012 at the Western infirmary in Glasgow, Scotland. They were followed up until April 2016 or death. Seizure freedom was defined as no seizure for at least 1 year on unchanged medication at the last follow-up. Results: A total of 201 patients (median age 73 years, 59% male) were included. The median duration from initial seizure to starting treatment was 8 months (interquartile range: 3.0-24.0 months); 42.2% (85/201) patients had more than 5 seizures before commencing treatment. Brain imaging showed potentially epileptogenic lesions in 19.7% (38/193) of patients and other abnormalities in 56.5% (109/193); 78.6% patients (158/201) were seizure-free at the last follow-up, of whom 94.9% were taking monotherapy. Concomitant aspirin use (n = 80) was associated with a lower probability of being seizure-free (relative risk 0.82, 95% confidence interval 0.70-0.97; P = .02). The use of second-generation ASMs as the initial monotherapy increased from 31.5% (23/73) before 2000 to 70.3% (90/128, P < .001) from 2000 onward. However, the seizure freedom rates (67.1% vs 55.5%; P = .35) and intolerable adverse-effect rates (16.4% vs 19.5%; P = .45) did not show any significant difference. Significance: There was often a long interval between seizure onset and the initiation of treatment in older people with new-onset epilepsy, although the majority responded well to ASM treatment. Brain imaging showed a high rate of abnormalities. Despite the increased use of second-generation ASMs, treatment outcomes in later-onset epilepsy have not improved over time. The possible effect of aspirin on treatment response warrants further investigation.

Characteristics and treatment outcomes of newly diagnosed epilepsy in older people: A 30-year longitudinal cohort study.

To describe the clinical characteristics and evaluate the long-term treatment outcomes in older people with newly diagnosed epilepsy over the past 30years. We included patients newly diagnosed with epilepsy and commenced on antiseizure medications (ASMs) at age 65years or older between July 1982 and October 2012 at the Western infirmary in Glasgow, Scotland. They were followed up until April 2016 or death. Seizure freedom was defined as no seizure for at least 1year on unchanged medication at the last follow-up. A total of 201 patients (median age 73years, 59% male) were included. The median duration from initial seizure to starting treatment was 8 months (interquartile range: 3.0-24.0 months); 42.2% (85/201) patients had more than five seizures before commencing treatment. Brain imaging showed potentially epileptogenic lesions in 19.7% (38/193) of patients and other abnormalities in 56.5% (109/193); 78.6% patients (158/201) were seizure-free at the last follow-up, of whom 94.9% were taking monotherapy. Concomitant aspirin use (n=80) was associated with a lower probability of being seizure-free (relative risk 0.82, 95% confidence interval 0.70-0.97; P=.02). The use of second-generation ASMs as the initial monotherapy increased from 31.5% (23/73) before 2000 to 70.3% (90/128, P<.001) from 2000 onward. However, the seizure freedom rates (67.1% vs 55.5%; P=.35) and intolerable adverse-effect rates (16.4% vs 19.5%; P=.45) did not show any significant difference. There was often a long interval between seizure onset and the initiation of treatment in older people with new-onset epilepsy, although the majority responded well to ASM treatment. Brain imaging showed a high rate of abnormalities. Despite the increased use of second-generation ASMs, treatment outcomes in later-onset epilepsy have not improved over time. The possible effect of aspirin on treatment response warrants further investigation.

Shantakumar Dnyaneshwar Bhandarkar

Shantakumar Dnyaneshwar Bhandarkar was a pioneer endocrinologist, devoted physician, inquisitive scientist-researcher, and a passionate teacher. He had a long and distinguished scholastic career at the Seth Gordhandas Sunderdas Medical College...

Maria de Sousa, (1939-2020).

Maria de Sousa, (1939-2020).

James Hume Adams

James Hume Adams, retired professor of neuropathology, died peacefully in Clarkston House, Glasgow, on Sunday 12 April 2020, in his 91st year. Hume—the name by which he was always known—was...

Ian James Burns

Ian James Burns was born in Glasgow to parents James Aloysius Burns and Mabel Thomson Dick of Rutherglen. He attended Burnside Primary School and St Aloysius College, Glasgow, before gaining...

Pharmacological outcomes in teenagers with newly diagnosed epilepsy: A 30-year cohort study.

To evaluate the long-term pharmacological outcomes in teenagers with different epilepsies. This study included teenagers aged 13-19years at treatment initiation who were newly treated with antiepileptic drugs (AEDs) at the epilepsy unit of the Western Infirmary in Glasgow, Scotland, between 1 September 1982 and 30 September 2012. Patients were prospectively followed until 30 April 2016, or death, with at least a 2-year follow-up. A total of 332 adolescent patients (53% female; median age 16years; 54% with generalized epilepsy) were included. At the end of the study, 221 patients (67%) were seizure-free. A higher seizure-free rate was observed in those with generalized compared to focal epilepsy (72% versus 60%, P=0.01). During the study, 108 patients had relapses after periods of being seizure-free, most commonly due to poor adherence to AEDs (49%, n=53/108). AED withdrawal was associated with a high risk of seizure recurrence (70%, n=26/37), but 56% (n=61/108) of relapsed patients became seizure-free again by the end of the study, with only 9% (n=31/332) meeting the International League Against Epilepsy (ILAE) definition of pharmacoresistance during follow-up. Of the 221 seizure-free patients, 83% achieved this on monotherapy. There was no significant difference in efficacy rate between new and standard AED monotherapy (74% versus 77%, P=0.66). The overall poor tolerability rate of AEDs was 21% (n=69/332). Among the different new and standard AEDs used as initial monotherapy, lamotrigine was associated with the lowest rate of adverse effects (12%, n=15/124), while topiramate was associated with the highest rate (56%, n=5/9). Teenagers with epilepsy showed good seizure control, particularly those with generalized epilepsy. However, relapse was common and there was high risk of seizure recurrence after treatment withdrawal. Most patients were controlled on monotherapy. As the efficacy of AEDs was comparable, tolerability can be a primary consideration for AED selection in this population.

Alasdair Iain Macdougall

Alasdair Iain Macdougall was a consultant physician and nephrologist at Stobhill Hospital, Glasgow. Except for national service in the Royal Navy, his early posts were at the Western Infirmary, …

Brian James Ross Junor

Brian James Ross Junor was a consultant nephrologist at Glasgow’s Western Infirmary. He trained in nephrology in Aberdeen and Melbourne and started in Glasgow in 1979. A considerate and skilled...

Verification and Extension of the Glasgow Western Infirmary based Theory of Limited Acute Appendicitis using a Nigerian Hospital

Verification and Extension of the Glasgow Western Infirmary based Theory of Limited Acute Appendicitis using a Nigerian Hospital

Treatment Outcomes in Patients With Newly Diagnosed Epilepsy Treated With Established and New Antiepileptic Drugs

A study published in 2000 showed that more than one-third of adults with epilepsy have inadequate control of seizures with antiepileptic drugs (AEDs). This study evaluates overall treatment outcomes in light of the introduction of more than 1 dozen new AEDs in the past 2 decades. To assess long-term treatment outcome in patients with newly diagnosed and treated epilepsy. This longitudinal observational cohort study was conducted at the Epilepsy Unit of the Western Infirmary in Glasgow, Scotland. A total of 1795 individuals who were newly treated for epilepsy with AEDs between July 1, 1982, and October 31, 2012, were included in this analysis. All patients were followed up for a minimum of 2 years (until October 31, 2014) or until death, whichever came sooner. Data analysis was completed between March 2015 and May 2016. Treatment with antiepileptic drugs for patients newly diagnosed with epilepsy. Seizure control was assessed at the end of the study period. Probability of achieving 1-year seizure freedom was estimated for each AED regimen prescribed. Multivariable models assessed the associations between risk factors and AED treatment outcome after adjustments were made for demographic and clinical characteristics. Of the 1795 included patients, 964 (53.7%) were male; the median age was 33 years (range, 9-93 years). At the end of the study period, 1144 patients (63.7%) had been seizure free for the previous year or longer. Among those achieving 1-year seizure freedom, 993 (86.8%) were taking monotherapy and 1028 (89.9%) had achieved seizure control with the first or second AED regimens. Of the total patient pool, 906 (50.5%) remained seizure free for 1 year or longer with the initial AED. If this AED failed, the second and third regimens provided an additional 11.6% and 4.4% likelihoods of seizure freedom, respectively. Only 2.12% of patients attained optimal seizure control with subsequent AEDs. Epilepsy that was not successfully controlled with the first AED had 1.73 times greater odds of not responding to treatment for each subsequent medication regimen (odds ratio, 1.73; 95% CI, 1.56-1.91; P < .001). Despite the availability of many new AEDs with differing mechanisms of action, overall outcomes in newly diagnosed epilepsy have not improved. Most patients who attain control do so with the first or second AED. The probability of achieving seizure freedom diminishes substantially with each subsequent AED regimen tried. More than one-third of patients experience epilepsy that remains uncontrolled.

2017 Lucian Award: John McMurray.

The 2017 Louis and Artur Lucian award for research in circulatory disease, established by a bequest to McGill University in 1965, has been awarded to John J.J.V. McMurray, MD, of the University of Glasgow. McMurray has dedicated much of his career to heart failure, with more than 900 publications ranging from basic research and epidemiology to the design and completion of numerous clinical trials that have altered our understanding of the condition and its treatment and prognosis. > “He’s done a tremendous amount that is clinically relevant and has resulted in new medications for heart failure. He was head and shoulders above the other applicants this year, with an incredible track record and extensive publications,” says James Martin, MD, chair of the McGill University department of medicine and chair of the Lucian Committee . As McMurray was completing medical school, American and European investigators were beginning to understand the disease mechanisms of heart failure and to identify targets for treatment other than digoxin and diuretics. At that time, there was no way to directly influence the weakness in cardiac contraction underlying heart failure, but inappropriate and sustained activation of the renin–angiotensin–aldosterone system (RAAS) helped explain why the function of blood vessels, kidneys, and heart muscle deteriorated over time. Shortly after the introduction of the angiotensin-converting enzyme (ACE) inhibitor captopril, McMurray witnessed the Lazarus-like recovery and discharge from the hospital of an extremely ill woman with heart failure after she was given the new drug—spurring a career-long interest in heart failure. After 2 years of residency training, McMurray obtained a cardiovascular research fellowship in Dundee, Scotland, where physician scientist Allan Struthers was studying cardiac natriuretic peptides, newly described hormones produced by the heart, which helped that organ protect itself and the whole body from volume and pressure overload by, among other things, …

James Graham Pinney Hutchison

James Graham Pinney Hutchison entered the Royal Army Medical Corps and was posted to Trinidad in 1947. As a civilian he embraced pathology and trained at the Royal Victoria Infirmary...

In-patient hospital mortality patterns by day of the week: an analysis of admissions to a regional renal unit.

Higher mortality rates have been reported for patients admitted at a weekend compared to a weekday. Our aim was to assess in-patient mortality patterns by day of the week, in a tertiary renal unit. Mortality related to day of admission and day of death was analysed over a two-year period at Glasgow Western Infirmary renal unit. Typical caseload was also assessed over two random four-week periods. As a proportion of admissions, 30-day mortality was 46/540 (8.5%) on a weekend day compared with a weekday 107/2013 (5.3%) (RR1.60, p = 0.005). Thirty-day mortality rate was 46/208 = 0.22 deaths/weekend day of admission compared with 107/523 = 0.20 deaths/weekday of admission (incident rate ratio = 1.08, p = 0.67). There was no significant increased risk of death on a weekend day compared to a weekday (RR1.23, p = 0.23). A higher proportion of weekend admissions were from other hospitals. Acute kidney injury and haemodialysis patients formed a higher percentage of admissions. Admission day mortality expressed as a death rate/day does not differ between weekend/weekday admissions. Admission day mortality expressed as a proportion of total admissions was significantly higher at weekends. This suggests admission case-mix/workload differs at weekends with fewer 'well' patients admitted. In-patient mortality patterns are complex and any conclusions made should take into account case mix and workload.

Oncological Outcomes and Complications After Volume Replacement Oncoplastic Breast Conservations-The Glasgow Experience.

INTRODUCTIONOncoplastic breast conservation surgery (OBCS) combines the principles of surgical oncology and plastic surgery. OBCS has now become a growing option for the treatment of breast cancer and forms a part of breast-conserving therapy (BCT). We sought to investigate and report our experience in two breast units in Glasgow (Victoria Infirmary and Western Infirmary) on volume replacement OBCS.MATERIALS AND METHODSDetails of patients treated with volume replacement OBCS were identified from a prospectively recorded database from November 2010 to October 2015. The clinical records included in the oncoplastic dataset were analyzed for demographics, tumor, treatment characteristics, and recurrences. The data were analyzed for follow-up to determine the pattern and timing of recurrence up to April 2016. The primary outcome of this study was tumor-free margin resection rates, and the secondary outcomes were locoregional and distant recurrence rates as these correlate with the overall oncological safety of volume replacement oncoplastic breast surgery (OPBS).RESULTSA total of 30 volume replacement oncoplastic breast conservation procedures have been carried out in this time period. The mean age of the former group was 51 years. Twice as many patients presented symptomatically than had tumors detected on screening. The mean preoperative tumor size on radiology was 25.4 mm. Patients underwent 13 thoracoepigastric flaps, 5 lateral intercostal artery perforator (LICAP) flaps, 2 thoracodorsal artery perforator (TDAP) flaps, 1 lateral thoracic artery perforator (LTAP) flap, 1 crescent flap volume replacement surgery, and 8 matrix rotations. Two patients had neoadjuvant chemotherapy. Fourteen patients had adjuvant chemotherapy, and all patients were treated with adjuvant radiotherapy. Twenty-two patients were treated with hormonal therapy and four patients were treated with Herceptin. The rate of incomplete excision was 10%. Median follow-up time was 48.5 months. Only one regional recurrence was detected. Eight patients encountered some form of complication.CONCLUSIONThis study continues to show the relative oncological safety of volume replacement oncoplastic conservations as an option for reconstruction in breast cancer patients. Further research is urgently needed to build robust evidence supporting the long-term oncological safety.

A Woman With Treatment-Resistant Hypertension.

Although this is not a particularly unusual or rare case of hypertension, it highlights the challenges we have as clinicians in managing such patients. The patient, a 60 year-old woman, was referred to the tertiary blood pressure clinic at Glasgow’s Western Infirmary 5 years ago by a consultant cardiologist for management of resistant hypertension. This lady has a vasculopathy with ongoing intermittent claudication and had previous bilateral superficial femoral artery occlusions on a background of hypercholesterolemia and a significant smoking history. The patient has problematic underlying ischemic heart disease, having had angina since 2001, numerous percutaneous interventions, and a 2-vessel coronary artery bypass graft. Despite this, she had a non–ST-segment–elevation myocardial infarction (MI) 2 years before presentation. Blood pressure at first visit to the clinic was 182/106 mm Hg despite numerous antihypertensive medications, including an angiotensin-converting enzyme inhibitor, calcium channel blocker, 2 different diuretics, α-blocker, and β-blocker in addition to her antianginal and secondary preventative medications (Table). Review of case notes and previous clinic documentation revealed that clinic blood pressure was elevated for at least 10 years with systolic readings ranging from 150 to 200 and diastolic between 90 and 100 mm Hg. View this table: Table. Total Daily Dose of Antihypertensive Medications: An Overview of Antihypertensive Medication at the Time of Referral to the Clinic (2010), Before RDN (2012) and Immediately After RDN (2012), and in 2015 The patient was admitted to the investigation ward for a week of workup. During this time, routine biochemistry showed normal renal function and electrolytes. Urine albumin/creatinine ratio was within the microalbuminuric range at 4.2 mg/mmol. Cardiac and mediastinal contours seemed normal on chest x-ray, and neither ECG nor echocardiogram showed significant left ventricular hypertrophy (LVH). No biochemical evidence to suggest pheochromocytoma or primary aldosteronism was found. Renal ultrasound exhibited 2 normal sized nonobstructed kidneys with no …

Ronald John Leslie Davidson

Ronald John Leslie Davidson (“Ron”) did his house posts in the professorial units of Dundee Royal Infirmary. After two years’ national service in the military hospital in Penang, Malaya, he...

Pharmacological outcomes in juvenile myoclonic epilepsy: Support for sodium valproate

PurposeJuvenile myoclonic epilepsy (JME) is one of the most frequently diagnosed of the idiopathic generalised epilepsy syndromes, but long term outcome data still remain sparse. MethodsA retrospective audit was undertaken in 186 patients (male: n=78; female: n=108) diagnosed with JME at the Epilepsy Unit at the Western Infirmary in Glasgow, Scotland between July 1981 and July 2012. Median age at treatment start was 16 years (range 13–44), with median follow-up of 14 years (range 2–32). ResultsOverall, 171 patients (92%) achieved remission with antiepileptic drug (AED) treatment (median 9.5 years; range 1–31). After discontinuing treatment in 28 patients, only 11 remained seizure-free off medication. Fifteen patients (8%) continued to have seizures despite having tried up to 8 AED regimens: (5 male, 10 female), 7 of whom had psychiatric comorbidities. AEDs most commonly prescribed included sodium valproate (VPA; n=142), lamotrigine (LTG; n=66) and levetiracetam (LEV; n=22). More male patients than female attained remission with their first or second AED schedule (88% versus 56%). More male patients (44%) received VPA than female (31%) overall. Fewer male patients than female received LTG (26% versus 74%) and LEV (22% versus 78%). Of the monotherapies, remission was achieved using VPA (n=74; 52%), LTG (n=21; 32%) and LEV (n=12, 55%). A total of 76 (25%) of AED schedules resulted in intolerable side-effects, including 29 with VPA, 12 with LTG and 4 with LEV. ConclusionOverall, JME showed a high rate of seizure freedom with AED treatment. VPA appeared to be the most effective AED. Women tended to have a worse outcome than men, since they were increasingly less likely to receive VPA. Patients with psychiatric comorbidities also had a poorer prognosis.