Multimorbidity in bullous pemphigoid: a case-control analysis of bullous pemphigoid patients with age- and gender-matched controls.

BACKGROUND: Bullous pemphigoid (BP) is the most common autoimmune blistering disease in the elderly and is associated with increased mortality. The extent of multimorbidity in patients with BP and its impact on survival are unclear. OBJECTIVES: To describe the extent and spectrum of multimorbidity in patients with BP and to ascertain its impact on survival. METHODOLOGY: This was a case-control study conducted in the setting of an academic medical centre. Cases defined as newly diagnosed BP patients referred to the inpatient dermatology service between 2005 and 2014. For every case, three age- and gender-matched controls were randomly selected. Retrospective review of medical records was performed. Univariate and multivariate comparisons of cases and controls were performed using conditional logistic regression. RESULTS: A total of 105 cases and 315 controls were included in this study. Eighty-eight cases (84%) were multimorbid (≥2 chronic diseases) as compared to 205 controls (65%) (P < 0.001), while the mean number of comorbid conditions was 3.2 ± 1.6 in cases compared to 2.4 ± 1.6 in controls (P < 0.001). 43% of cases had ≥4 comorbidities compared to 27% in controls (P = 0.003). On multivariate analysis (adjusting for age, gender and comorbidities), neurological disease (OR 10.93; CI: 5.74, 20.79) and hypertension (OR 2.38; CI: 1.18, 4.77) were positively associated with BP. Charlson comorbidity index was 6.0 ± 2.5 in cases compared to 5.0 ± 2.1 in controls (P = 0.002), and the 1-year mortality of cases and controls was 32.4% and 17.8%, respectively. CONCLUSION: Our study has shown that a significant proportion of patients with BP are multimorbid and individually have a higher number of comorbidities compared to matched controls. Disease burden and multimorbidity may well impact the prognosis of patients with BP.

A systematic review of factors that influence treatment adherence in paediatric oncology patients.

WHAT IS KNOWN AND OBJECTIVE: Treatment adherence is an essential component in ensuring best outcomes in the management of paediatric cancers. Compared to the adult population, treatment adherence in the paediatric population is a more complex subject which involves unique dimensions. In this study, we aimed to systematically review the literature to identify factors associated with treatment adherence in the paediatric oncology population. METHODS: A literature search was carried out using related keywords on electronic databases. RESULTS AND DISCUSSION: A total of 1036 articles were reviewed, and 39 articles were found to be relevant. A comprehensive review of these articles identified 17 factors that influence adherence. These factors were classified into five major categories: patient-/caregiver-related factors; therapy-related factors; condition-related factors; health system-related factors; and social/economic factors. A baby bear model was proposed to better visualize these five categories that affect treatment adherence, and a framework of questions was designed to help clinicians identify those at risk of non-adherence for early intervention. WHAT IS NEW AND CONCLUSION: Seventeen factors reviewed were categorized into five main categories, namely patient-/caregiver-related factors, therapy-related factors, condition-related factors, health system factors and social/economic factors, as causes for poor medication adherence in the paediatric oncology population. Clinicians need to be aware that these factors can interact to influence treatment adherence and that some factors may be more relevant in specific contexts (e.g. third world countries, minority groups). The baby bear model is presented to help understand the issues affecting adherence in the paediatric oncology population, and a framework of questions is proposed to help clinicians identify patients at risk of non-adherence.

Building pharmacogenetics into a pharmacovigilance program in Singapore: using serious skin rash as a pilot study.

To study the possible genetic associations with adverse drug reactions (ADR), the Singapore Health Sciences Authority (HSA) has piloted a program to collect DNA and phenotype data of ADR cases as part of its pharmacovigilance program. Between 2009 and 2012, HSA screened 158 cases of Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). To assess the association between HLA-B*1502 and carbamazepine (CBZ)-induced SJS/TEN, 13 cases and 26 drug-tolerant controls were analyzed. All 13 CBZ-SJS/TEN cases and 3/26 controls were HLA-B*1502 positive (odds ratio 181, 95% confidence interval: 8.7-3785, P=6.9 × 10(-8)). Discussions of the finding with the Ministry of Health and an expert panel led to the decision to make HLA-B*1502 testing the standard of care prior to first use of CBZ in Asians and to subsidize the genotyping test at public hospitals. This program illustrates the role of a regulatory authority in advancing the use of pharmacogenetics for drug safety.

Clinical outcomes of bacteraemia in cellulitis of the leg.

BACKGROUND: Infections of the blood are associated with high mortality and morbidity. In cellulitis, the utility of blood cultures remains controversial because of their relatively low bacterial yield. However, some important but less well studied aspects include risk factors for bacteraemia, the effects of bacteraemia on the length of hospitalization and on morbidity and mortality rates. AIM: To determine the incidence of bacteraemia in cellulitis in an inpatient cohort; to identify risk factors for bacteraemia in cellulitis; and to assess length of hospitalization stay, rate of recurrence of cellulitis, and mortality in patients with cellulitis and bacteraemia. METHODS: Records of 214 patients diagnosed with cellulitis were reviewed. Blood cultures, length of hospitalization stay, rate of recurrence of cellulitis, mortality, coexistent dermatoses and local factors predisposing to cellulitis and comorbidities were analyzed. RESULTS: The incidence of bacteraemia was 10.8%. Mean duration of hospitalization was longer (P < 0.01) and recurrence (P < 0.01) was higher in patients with bacteraemia. There was no difference in mortality between patients with and patients without bacteraemia (P = 0.47). Risk factors for bacteraemia included lymphoedema (P < 0.01), presence of an ipsilateral orthopaedic implant (P < 0.01), total white blood cell (WBC) count > 13.5 × 10(6) µL (P < 0.01, liver cirrhosis (P = 0.02) and chronic kidney disease (P = 0.04). CONCLUSIONS: Blood cultures should be performed for patients with cellulitis who have factors increasing the risk of bacteraemia, such as presence of lymphoedema, ipsilateral orthopaedic device implantation, leucocytosis of > 13.5 × 10(6) µL, liver cirrhosis or chronic kidney disease, and other forms of immunosuppression. Bacteraemia in cases of cellulitis of the leg is a prognostic factor for increased length of hospitalization stay and recurrence of cellulitis.

The role of intravenous immunoglobulin in toxic epidermal necrolysis: a retrospective analysis of 64 patients managed in a specialized centre.

BACKGROUND: Toxic epidermal necrolysis (TEN) is a severe cutaneous adverse drug reaction with a mortality of 40%. Intravenous immunoglobulin (IVIg) is widely used as a specific treatment for this reaction, although evidence of its benefit is conflicting. OBJECTIVES: We sought to evaluate whether the use of IVIg improved mortality in patients with Stevens-Johnson syndrome (SJS)/TEN overlap and TEN. METHODS: We retrospectively analysed data for 64 patients with SJS/TEN overlap and TEN who were treated with IVIg at a single referral centre. The primary outcome analysed was in-hospital mortality. Predicted mortality was calculated based on severity-of-illness score for TEN (SCORTEN) values. Secondary analyses of survival based on IVIg dosages and prior corticosteroid exposure were also performed. RESULTS: There were 28 cases of SJS/TEN overlap and 36 cases of TEN, with a mean SCORTEN value of 2·6. The mean dose of IVIg given was 2·4 g kg(-1) and the mean delay from the onset of epidermal detachment to administration of IVIg was 3·2 days. There were 20 deaths (31%) in our cohort. The standardized mortality rate was 1·10 (95% confidence interval 0·62-1·58). Subgroup analysis comparing survivors and nonsurvivors showed a higher SCORTEN in nonsurvivors (3·4 vs. 2·2). There were no differences with regard to the dosage, delay and duration of IVIg administration. When stratified according to dosage, there was no mortality difference between patients who receive high-dose (≥ 3 g kg(-1) ) vs. low-dose (< 3 g kg(-1) ) IVIg. CONCLUSIONS: This study shows that the use of IVIg does not yield survival benefits in SJS/TEN overlap and TEN, even when corrected for IVIg dosages.

Systemic lupus erythematosus presenting as Stevens-Johnson syndrome and toxic epidermal necrolysis: a report of three cases.

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are life-threatening dermatological conditions that are characterized by mucositis, epidermal detachment and erosions. The underlying etiology in SJS and TEN is almost invariably secondary to drugs. Rarely, other causes such as systemic lupus erythematosus (SLE), infections and vaccinations have been implicated. This report describes three patients with SLE who presented with manifestations of SJS/TEN without a clear drug causality. All three patients presented with photodistributed macular exanthema, which evolved to target lesions, bullae, erosions or sheet-like detachment. This was associated with oral mucositis and conjunctivitis. The onset of the rash was insidious with a protracted clinical course. Ultraviolet exposure and steroid tapering appear to be precipitating factors. In two of the patients, SJS and TEN were the initial presentation of lupus. Although SJS and TEN are almost invariably due to medications, they may, rarely, be an initial presentation of lupus, particularly when associated with an initial photodistribution, absence of genital involvement and a prolonged clinical course.

Dermatology referrals in an East Asian tertiary hospital: a need for inpatient medical dermatology.

BACKGROUND: Within hospitals, there is a need for dermatological expertise, as hospitalized patients have a wider spectrum of severe and serious dermatological conditions, associated with significant morbidity. AIM: To characterize the patient profile and referral pattern of inpatient dermatology consultations, and to evaluate the diagnostic accuracy of non-dermatologists. METHODS: This was a retrospective study reviewing all inpatient referrals for dermatology consultations during a 1-year period from July 2005 to June 2006 (inclusive), at the largest multi-disciplinary tertiary hospital in Singapore. RESULTS: Of the 731 referrals made for dermatology consultations, 26.9% of patients had ≥ 3 important underlying comorbidities. Eczema/dermatitis (33.1%; n = 242) and cutaneous infections (23.4%; n = 171) accounted for over half of the dermatological consultations, followed by cutaneous adverse drug reactions (12.3%; n = 90). The provisional diagnoses of the referring doctors agreed with the final diagnoses confirmed by dermatologists in only 30.2% of all referrals; incorrect diagnoses were made in 35.2% of cases, and no provisional diagnoses were made in the remaining 34.6% of cases. Most misdiagnosed skin diseases were in fact common dermatoses (such as eczemas, cutaneous infections, drug rash) that required only standard treatment. CONCLUSION: Our study reiterates the importance of inpatient medical dermatology in terms of both service and education. There should be continual efforts to ensure that dermatologists have the highest level of training and experience in medical dermatology, to provide collaborative optimum care for hospitalized patients with dermatological diseases.

Unprofessional behaviour of junior doctors: a retrospective analysis of outcomes by the Singapore Medical Council disciplinary tribunals.

INTRODUCTION: This is a retrospective analysis of outcomes by Singapore Medical Council (SMC) disciplinary tribunals in cases involving junior doctors. We aimed to classify the types of unprofessional behaviour and consider appropriate measures for remediation and prevention. METHODS: SMC's annual reports from 1979 to 2017 and published grounds of decision from 2008 to 2017 were examined using two screening levels to identify cases involving junior doctors. Cases were sorted into five outcome categories: (a) professional misconduct; (b) fraud and dishonesty; (c) defect in character; (d) disrepute to the profession; and (e) acquitted. RESULTS: A total of 317 cases were identified, of which 13 (4.1%) involved junior doctors: 4 (30.8%) cases involved professional misconduct, 4 (30.8%) cases involved fraud and dishonesty, 3 (23.1%) cases saw an acquittal, and one case each involved defect in character and disrepute to the profession. The four cases of professional misconduct highlight the need to differentiate medical errors due to systems factors from those due to individual culpability, by applying analytical tools such as root cause analysis and Unsafe Act Algorithms. Disciplining the individual alone does not help prevent the recurrence of similar medical errors. We found that fraud and dishonesty was an important category of unprofessional behaviour among junior doctors. CONCLUSION: While the frequency of unprofessional behaviour among junior doctors, as determined by the SMC disciplinary tribunal, is low (4.1%), this study highlights that complaints against medical doctors often involve systems issues and individual factors. Unprofessional behaviours related to fraud and dishonesty need special attention in medical school.

Legal medicine: assessing mental capacity and writing medical reports for deputy applications.

Medical reports are required to support court applications to appoint a deputy to make decisions on behalf of a person who has lost mental capacity. The doctor writing such a medical report needs to be able to systematically assess the mental capacity of the person in question, in order to gather the necessary evidence for the court to make a decision. If the medical report is not adequate, the application will be rejected and the appointment of the deputy delayed. This article sets out best practices for performing the assessment and writing the medical report, common errors, and issues of concern.

Serious cutaneous adverse reactions to traditional Chinese medicines.

INTRODUCTION: Serious cutaneous adverse reactions to traditional medicines are not well described or reported in the literature, despite growing use of these medicines. METHODS: This is a case series of four patients who were found to have various serious cutaneous adverse reactions to the traditional Chinese medicines that they had taken. RESULTS: In this series, there was a patient with toxic epidermal necrolysis from traditional Chinese medicine, another with acute generalised exanthematous pustulosis from piroxicam and salicylate-contaminated traditional Chinese medicine, and two patients with drug hypersensitivity syndrome--one from traditional Chinese medicine and the other from phenylbutazone-adulterated traditional Chinese medicine. CONCLUSION: The series illustrates that serious cutaneous adverse reactions do occur with traditional medicines and emphasises the importance of being aware of such reactions.

Chemoprophylaxis and gonococcal infections in prostitutes.

The influence of chemoprophylaxis on gonorrhoea has not been reported recently. 777 prostitutes were interviewed and checked for evidence of chemoprophylaxis. The study showed that chemoprophylaxis does reduce the risk of gonococcal infections and that those who took penicillin chemoprophylaxis had a higher risk of Penicillinase producing Neisseria gonorrhoeae (PPNG) infections compared to those who took non-penicillin chemoprophylaxis and those who did not take any prophylaxis.

Clinical and laboratory study of first episode genital herpes in Singapore.

A prospective study of the epidemiology, clinical aspects and laboratory features of first episode genital herpes was carried out in Middle Road Hospital, Singapore between June 1986 and December 1987. A total of 68 patients were studied. There were more women than men in the study population with a female to male ratio of 7.5 to 1. The peak incidence of first episode genital herpes was between 20 and 29 years of age. Specimens from 63 patients yielded positive culture for herpes simplex virus (HSV). HSV-1 was isolated from 21 patients (30.9%), HSV-2 from 41 patients (60.3%) and untyped HSV from one patient (1.5%). True primary genital herpes was diagnosed in 43 patients (68.3%) using a test for complement fixing antibodies to HSV. HSV-1 was found to be the causative agent in 18 (41.9%) of the true primary infections, HSV-2 in 24 (55.8%) and untyped HSV in one (2.3%). In comparison, HSV-1 was isolated in only 2 (10%) of the 20 patients with non-primary first episode genital herpes; HSV-2 was found in 13 patients (65%) and the culture was negative in 5 (25%).

PIP: A prospective study of the epidemiology, clinical aspects, and laboratory features of 1st episode genital herpes was conducted in Middle Road Hospital, Singapore between June 1986-December 1987. A total of 68 patients were studied and there were more women than men in the study population; the ratio of females:males was 7.5:1. The peak incidence of 1st episode genital herpes was between 20-29 years of age. Specimens from 63 patients yielded positive culture for herpes simplex virus (HSV). HSV-1 was isolated from 21 patients (30.9%), HSV-2 from 41 patients (60.3%), and untyped HSV from 1 patient (1.5%). True primary genital herpes was diagnosed in 43 patients (68.3%) using a test for complement fixing antibodies to HSV. HSV-1 was found to be the causative agent in 18 (41.9%) of the true primary infection, HSV-2 in 24 (55.8%), and untyped HSV in 1 (2.3%). In comparison, HSV-1 was isolated in only 2 (10%) of the 20 patients with nonprimary 1st episode genital herpes; HSV-2 was found in 13 patients (65%), and the culture was negative in 5 (25%).

Evidence of HTLV-I infection in Singapore prostitutes.

Sera obtained in 1987 from 63 male and 632 female Singapore prostitutes were screened for antibody to human T-cell leukaemia virus (HTLV)-I with a particle agglutination test. Of the 3 males and 4 females who were positive one had antibody to HTLV-I core and envelope antigen on Western Blot. Two subjects had presumptive antibody to HTLV-I core antigen and a third subject had such antibody on a repeat specimen in 1989. These sera were negative for HIV-1 antibody. There is evidence of infection with HTLV-I or a variant virus in this population. The infection is likely to have been sexually transmitted.

The changing patterns of scabies among in-patients in Singapore (1982-1989).

One hundred and fourteen patients with scabies admitted to a dermatological ward between 1982 and 1989 were studied retrospectively. There was a change in the epidemiological pattern over the eight-year period. We noticed an increase of two to three fold in the incidence of in-patients with scabies. At the beginning of the decade the majority of the patients were below 20 years but towards the end of the decade the same proportion of patients were above 50 years. There was also a change in the racial distribution of scabies from a Malay predominance to a Chinese predominance. We also noticed a change in the residential status of these patients; more patients admitted towards the end of the decade came from institutional homes. The changing epidemiological pattern brought with it new problems both in diagnosis and in the prevention of scabies.