Trends in the epidemiology of head and neck cancer in London.

BACKGROUND: Head and neck cancers [HNCs] are biologically heterogeneous tumours. The objectives of this study were to describe trends in incidence of HNCs amongst London residents by sex, age, anatomical site, deprivation and ethnicity. METHODS: Annual age-standardised incidence rates [ASRs] were calculated on HNC registration data, overall and for specific cancer sites, by sex and morphology (1985-2010) and area-based socio-economic deprivation score (2006-2010). Age-standardised incidence rate ratios [IRRs] for the main ethnic groups were calculated by cancer site, using White males and females as the reference groups (1998-2009). RESULTS: The ASR of HNC in males increased by 40% from 17.3 [95% CI: 15.8-18.6] to 24.2 [95% CI: 22.5-25.8] per 100 000 and in females by 87% from 7.0 [95% CI: 6.2-7.8] to 13.1 [95% CI: 11.9-14.2] per 100 000. Seventy-three per cent of cases spanned four cancer sites: larynx, thyroid, oral and oropharynx. Larynx was most common (23%), and had the highest male: female ratio (6 : 1); ASRs decreased significantly over time, most notably in males [P < 0.001]. Oral cavity was the second most common (21%), with a male: female ratio of 2 : 1, and increasing ASRs in both sexes [P < 0.001]. The majority of cases were male (64%) and from deprived areas (59%). Deprivation was associated with a significantly higher incidence for larynx (males), oropharynx (males and females) and oral cavity (females) [P < 0.05]. The age-specific rate for middle-aged adults (45-64 years) was high for oropharyngeal cancer. The incidence of thyroid cancers increased significantly in both sexes [P < 0.001], and this was the only site more common in females. One in five cases with known ethnicity was from a non-White group (20%). Compared with their White counterparts, Bangladeshi females had a higher incidence of oral, laryngeal and thyroid cancers; Chinese males and females had a higher incidence of nasopharyngeal cancer; and Pakistani and Indian females and Indian males also had higher incidence of oral cancer. CONCLUSIONS: HNCs are increasing in London males and females with significant variation by cancer site over time; oral and oropharyngeal cancers show the most significant rise, with implications for public health action and service provision.

Challenges in pediatric drug use: A pharmacist point of view.

The pediatric population is an enormously diverse segment of population varying both in size and age. The diversity caused pharmacists face various challenges primarily related to procuring, provision as well as use of drugs in this group of patients. Pediatric dose calculation is particularly a concern for pharmacists. Another challenge faced by pharmacists is unavailability of suitable formulations for pediatric use. This has also led many pharmacists to prepare extemporaneous liquid preparations, even though stability data on such preparations are scarce. Some extemporaneous preparations contain excipients which are potentially harmful in children. Besides that, inadequate labeling and drug information for pediatric drug use had not only challenged pharmacists in recommending and optimizing drug use in children, but also inadvertently caused many drugs used outside the approved terms of the product license (off-label use). Pharmacists are striving to stay connected to overcome the common and comparable challenges faced in their day to day duties and strive to maximize the safe and effective use of medicines for children.

Awareness, knowledge and views of off-label prescribing in children: a systematic review.

AIM: The aim of this review was to provide an updated overview of awareness, knowledge and views of off-label prescribing in children. METHOD: A literature search using electronic databases including PubMed, Medline, Scopus, Science Direct, Springer Link, Proquest, Ebsco Host and Google Scholar was conducted. Additional articles were identified by reviewing the bibliography of retrieved articles. The articles were searched with any of the following medical subject headings (MeSH) terms in the title: attitude, awareness, knowledge, experience, view, off-label, pediatric, paediatric and children. The inclusion criteria were full text articles published in English between January 2004 and February 2015 and reported outcome related to awareness, knowledge and views regarding off-label prescribing in children. Editorials, reviews, notes, conference proceedings, letters and studies reporting prevalence of off-label prescribing were excluded. The articles were scrutinized using thematic analysis. RESULTS: Eleven studies conducted among doctors, community pharmacists, paediatric nurses, parents and children met the inclusion criteria. Nine themes were developed through document analysis which included main domains such as knowledge, awareness and views on off-label drug use in children, choice of information sources, reasons and suggestions to reduce off-label prescribing, concern regarding obtaining consent and participation in clinical trials. CONCLUSION: The studies reviewed reported that the majority of doctors and community pharmacists were familiar with the term off-label prescribing but knowledge among parents was low. Awareness on off-label prescribing in children remains low among all study participants. There is a mismatch between views on off-label prescribing in children of study participants and the finding of previous studies.

Risk of bleeding after thyroid surgery: matched pairs analysis.

OBJECTIVE: To identify those patients most at risk of developing a compressive post-operative haematoma following thyroid surgery. METHOD: Retrospective analysis of patients undergoing thyroid surgery. Factors associated with the group of patients who developed a post-operative haematoma were examined using a matched pairs, case-control design. RESULTS: Following 355 thyroid operations, seven patients developed a post-operative haematoma requiring return to the operating theatre for bleeding control. A post-operative systolic blood pressure of greater than 150 mmHg, in the post-anaesthetic care unit, was the major significant factor identified by regression analysis (p = 0.002). Current smoking status was also a significant factor (p = 0.04). CONCLUSION: In our facility, a post-anaesthetic systolic blood pressure in excess of 150 mmHg was associated with an increased risk of haemorrhage following thyroid surgery.

Herb-drug interactions: methods to identify potential influence of genetic variations in genes encoding drug metabolizing enzymes and drug transporters.

Herbal supplements are often used concomitantly with conventional medications resulting in considerable potential for herb-drug interactions. These interactions, which are generally through interfering with pharmacokinetic and/or pharmacodynamic pathways, may result in beneficial effects or more often adverse reactions such as toxicity or treatment failure and may be influenced by multiple environmental and/or genetic factors. The pharmacogenetic approach may help to identify some interactions which may be more pronounced or only occur in specific groups of subjects although the complex nature of the herbal medicines may limit the discovery of such an interaction. Preclinical studies such as gene expression profiling in rodent liver may help to define metabolic pathways influenced by herbal medicines and facilitate more accurate targeting of human in vivo studies. This review discusses the mechanisms of herb-drugs interaction and the potential influence of genetic variation on herb-drug interactions based on available clinical evidence.

Variation, precision and validity of 1-year survival estimates for lung, breast, colon and prostate cancer in South East England primary care trusts.

BACKGROUND: English cancer policy has encouraged primary care trusts (PCTs) to consider their 1-year cancer survival estimates. This study quantifies variation in these estimates across 39 PCTs in the London and South East Coast strategic health authorities, and explores their precision, possible confounding by age and bias due to death certificate only (DCO) registrations. STUDY DESIGN: Retrospective observational study. METHODS: One-year relative survival estimates and data on DCO registrations for patients diagnosed with lung, colorectal, breast and prostate cancers between 2002 and 2006 were extracted from the UK Cancer Information Service. Direct age standardization was performed with weightings derived from the standard cancer patient population for Europe. Pearson correlation coefficients between survival estimates and DCO proportions were calculated. RESULTS: Mean 1-year PCT survival estimates ranged from 6.9 to 19.4 percentage points, and the precision of individual estimates ranged from ±0.9 to ±6.5 percentage points (at 95% confidence level). Age standardization significantly changed the estimates of nine PCTs for breast cancer, five PCTs for lung cancer and three PCTs for colorectal cancer. None of the prostate cancer estimates were affected significantly. DCO proportions were positively associated with lung cancer survival and negatively associated with colorectal and breast cancer survival. CONCLUSIONS: PCT 1-year cancer survival estimates may be informative, but caveats relating to data quality and hence the validity of the estimates means that they require careful investigation before naïve use, as random variation, confounding due to age and bias due to DCO registrations may be significant.

A synopsis of current care of thalassaemia major patients in Hong Kong.

OBJECTIVE: To provide a synopsis of current thalassaemia major patient care in Hong Kong. DESIGN: Retrospective study. SETTING: All haematology units of the Hospital Authority in Hong Kong. PATIENTS: All patients with thalassaemia major with regular transfusion. RESULTS: To date, there were 363 thalassaemia major patients under the care of the Hospital Authority. Prenatal diagnosis has helped to reduce the number of indigenous new cases, but in recent years immigrant cases are appearing. The patients have a mean age of 23 (range, 1-52) years, and 78% of them are adults. In 2009, they received 18 782 units of blood. This accounted for 9.5% of all blood consumption from the Hong Kong Red Cross. In the past, cardiac iron overload was the major cause of death (65%) and few patients survived beyond the age of 45 years. The availability of cardiac iron assessment by magnetic resonance imaging (T2 MRI) to direct the use of oral deferiprone chelation has reduced the prevalence of heart failure and cardiac haemosiderosis, which should reduce mortality and improve life expectancy. CONCLUSION: The future for thalassaemia care in Hong Kong is bright. With better transfusion and chelation, it should be possible to avoid growth and endocrine deficiencies in younger patients.

Simvastatin-induced myopathy, the role of interaction with diltiazem and genetic predisposition.

WHAT IS KNOWN AND OBJECTIVE: Diltiazem shows a pharmacokinetic interaction with statins that are CYP3A substrates but this may not result in myopathy unless additional genetic or clinical factors are present. Subsequent changes in treatment or underlying disease may result in a delayed onset of this adverse affect. Our objective is to report on two cases of statin-induced myopathy associated with concomitant use of diltiazem and other contributing factors, and to briefly review the related literature. COMMENT: A 63-year-old Chinese woman with hypertension and familial hypercholesterolaemia (FH) taking diltiazem 90 mg twice daily had elevation of creatine kinase (CK) to 4016 U/L and alanine aminotransferase (ALT) to 165 IU/L 4 weeks after increasing the dose of simvastatin from 40 to 80 mg daily. Another 80-year-old Chinese woman with FH, mild vascular dementia and hypertension was hospitalized with bilateral lower limb weakness associated with raised CK (8869 IU/L), lactate dehydrogenase (1384 IU/L) and ALT (288 IU/L) after taking diltiazem 60 mg twice daily with simvastatin 40 mg for 11 months. Statin-associated myopathy was suspected and simvastatin was stopped in both cases, and symptoms resolved and all laboratory parameters returned to normal in 2 weeks. The myopathy in both cases is likely to have resulted from an interaction of higher doses of simvastatin with diltiazem through inhibition of CYP3A enzymes and drug transporters. The strength of simvastatin-diltiazem interactions in the two cases estimated by the Drug Interaction Probability Scale (DIPS) indicated a possible association. WHAT IS NEW AND CONCLUSION: The two cases reported here and the brief literature review emphasize the potential interaction between two drugs frequently coadministered, simvastatin and diltiazem and we suggest that diltiazem should not be used with higher doses of those statins metabolized by CYP3A such as simvastatin or atorvastatin and even with lower doses caution should be exercised in patients who may have cause for impaired metabolism.

The effect of economic deprivation on oesophageal and gastric cancer in a UK cancer network.

AIMS: The National Health Service (NHS) Cancer Plan aims to eliminate economic inequalities in healthcare provision and cancer outcomes. This study examined the influence of economic status upon the incidence, access to treatment and survival from oesophageal and gastric cancer in a single UK cancer network. METHODOLOGY: A total of 3619 patients diagnosed with either oesophageal or gastric cancer in a London Cancer Network (population = 1.48 million) were identified from the Thames Cancer Registry (1993-2002). Patients were ranked into economic quintiles using the income domain of the Multiple Index of Deprivation. Statistical analysis was performed using a chi(2) test. Survival analysis was performed using a Cox's proportional hazards model. RESULTS: Between 1993-1995 and 2000-2002, the incidence of oesophageal cancer in the most affluent males rose by 51% compared with a 2% rise in the least affluent males. The incidence of gastric cancer in most affluent males between 1993-1995 and 2000-2002 fell by 32% compared with a 7% fall in the least affluent males. These changes were less marked in females. Economic deprivation had no effect on the proportion of patients undergoing either resectional surgery or chemotherapy; the least affluent oesophageal cancer patients with a higher incidence of squamous cell carcinoma received significantly more radiotherapy. Economic deprivation had no effect upon survival for either oesophageal or gastric cancer. CONCLUSIONS: There has been an increase in oesophageal cancer and a decrease in gastric cancer incidence among more affluent males in the last 10 years. Economic status did not appear to influence access to treatment or survival.

The epidemiology and treatment of mesothelioma in South East England 1985-2002.

OBJECTIVES: To describe trends in the incidence of mesothelioma for men and women in South East England and the geographical variation at the level of primary care trust. To describe treatment patterns by cancer network of residence, and relative survival by cancer network, disease stage and treatment modality. METHODS: 5753 cases were extracted from the Thames Cancer Registry database. We calculated age standardised incidence rates for each year, age specific incidence rates in 10 year age groups, and we used linear regression to compute the average annual percentage change in age standardised incidence. We used Poisson regression to analyse generational trends in incidence. RESULTS: Men had five times higher incidence of mesothelioma than women. In men, there was an overall 4% increase per year between 1985 and 2002. Over the same period, the overall increase in incidence for women was 5% per year. The incidence was highest in men aged over 70 years, and men aged over 80 years had the highest increase of 8% per year. The incidence rate ratio increased for men born between 1892 and 1942 and started to slow for those born from 1947 onwards. Areas along the Thames and its estuary had the highest incidence. There was some variation by cancer network in the proportion of patients receiving cancer surgery, radiotherapy and chemotherapy. There were no discernable differences in relative survival by cancer network of residence or disease stage but those receiving combined treatment had higher 5 year survival. CONCLUSIONS: Mesothelioma incidence has increased in South East England, particularly for men aged over 70 years. The highest incidence occurs along the Thames and its estuary, reflecting areas of asbestos use in shipbuilding and industry in the past. More research is needed to understand the interrelationships of prognostic factors, treatment choices and survival, and to determine the best care and support for these patients and their families.

Does deprivation of area of residence influence the incidence, tumour site or T stage of cutaneous malignant melanoma? A population-based and clinical database study.

This study aimed to document the incidence of malignant melanoma at specific subsites in men and women, stratified by deprivation of area of residence in southeast England, and to explore the association between deprivation and tumour thickness at diagnosis. Data were extracted on 6468 cases from the Thames Cancer Registry for the years 1998 to 2002, and data on, and 508 cases were extracted from the clinical database of the Skin Tumour Unit, St Thomas' Hospital, for the years 1996 to 2004. The postcode of residence was used to assign quintiles of deprivation based on the income domain stated in the Indices of Deprivation 2000. For both males and females, the incidence was higher for those living in the most affluent areas. The trunk was the most common site in males and the lower limbs in females. All sites showed an affluence gradient, although this was least pronounced for head and neck tumours. Distribution of T stage at diagnosis did not differ by deprivation of area of residence.

Incidence of cancer in a cohort of patients with primary Sjogren's syndrome.

OBJECTIVE: To compare the incidence of subsequent cancers in a cohort of patients with primary Sjögren's syndrome (pSS) with that of the general population in the same region of England. METHODS: A retrospective analysis was carried out on 112 patients who had attended the out-patients department at University College Hospital, London, from 1979 onwards. Patients were followed up from diagnosis of pSS to diagnosis of first subsequent cancer, death, loss to follow-up or 31 December 2003 (the censoring date) to determine the person-years at risk for each individual. The expected numbers of subsequent cancers were calculated from sex-/age-/period-specific rates for the general population of southeast England, derived from registrations at the Thames Cancer Registry. Standardized incidence ratios (SIRs) were then calculated as the ratio of observed to expected numbers of cancers, along with 95% confidence intervals (CIs). Separate analyses were performed for all malignant cancers combined, lymphomas and non-lymphoid cancers. RESULTS: Among the 112 patients with pSS, 25 developed cancer (either before or after development of pSS), with lymphoma occurring in 11 cases. Nine patients had two cancers. There was a significantly elevated incidence of lymphomas in pSS patients compared with the general population (SIR 37.5, 95% CI 20.7-67.6). For non-lymphoid cancer, the observed increase in incidence was small and not statistically significant (SIR 1.5, 95% CI 0.9-2.6). CONCLUSION: This study confirms that there is an increased incidence of lymphoma in patients with pSS. An increase in the incidence of other cancers was not proven but the observation that some patients developed more than one cancer raises the possibility that there may be a subgroup of patients who are at greater risk of developing cancer.

Catalase-like and superoxide dismutase-like activities in human seminal plasma.

Human spermatozoa are highly susceptible to oxidative injury but are naturally protected from such injury by the antioxidant properties of seminal plasma. We measured catalase-like and superoxide dismutase (SOD)-like activities in the seminal plasma of fertile and vasectomized men in order to gain insight into the potential source(s) and function(s) of these antioxidants in semen. Semen samples were obtained from fertile men ( n=11) and men post-vasectomy ( n=16). Catalase-like activity was measured by the decrease in hydrogen peroxide concentration after incubation with seminal plasma. SOD-like activity was measured as the inhibition of nitroblue tetrazolium reduction due to superoxide anion generation by xanthine plus xanthine oxidase. Mean seminal catalase-like activity (+/-1SD) in the fertile group was not significantly different from that of the post-vasectomy group (389+/-163 and 325+/-119 U/ml, respectively). Similarly, mean seminal SOD-like activity in the fertile group was not significantly different from that of the post-vasectomy group (37+/-10 and 36+/-10 U/ml, respectively). Our data suggest that the testis and epididymis are not an important source of catalase-like and SOD-like activities in semen. These findings indicate that antioxidants in semen are primarily of post-testicular origin and probably serve to protect ejaculated spermatozoa from oxidative stress such as that which occurs in the female reproductive tract.