Teratogenesis, Perinatal, and Neurodevelopmental Outcomes After In Utero Exposure to Antiseizure Medication: Practice Guideline From the AAN, AES, and SMFM.

This practice guideline provides updated evidence-based conclusions and recommendations regarding the effects of antiseizure medications (ASMs) and folic acid supplementation on the prevalence of major congenital malformations (MCMs), adverse perinatal outcomes, and neurodevelopmental outcomes in children born to people with epilepsy of childbearing potential (PWECP). A multidisciplinary panel conducted a systematic review and developed practice recommendations following the process outlined in the 2017 edition of the American Academy of Neurology Clinical Practice Guideline Process Manual. The systematic review includes studies through August 2022. Recommendations are supported by structured rationales that integrate evidence from the systematic review, related evidence, principles of care, and inferences from evidence. The following are some of the major recommendations. When treating PWECP, clinicians should recommend ASMs and doses that optimize both seizure control and fetal outcomes should pregnancy occur, at the earliest possible opportunity preconceptionally. Clinicians must minimize the occurrence of convulsive seizures in PWECP during pregnancy to minimize potential risks to the birth parent and to the fetus. Once a PWECP is already pregnant, clinicians should exercise caution in attempting to remove or replace an ASM that is effective in controlling generalized tonic-clonic or focal-to-bilateral tonic-clonic seizures. Clinicians must consider using lamotrigine, levetiracetam, or oxcarbazepine in PWECP when appropriate based on the patient's epilepsy syndrome, likelihood of achieving seizure control, and comorbidities, to minimize the risk of MCMs. Clinicians must avoid the use of valproic acid in PWECP to minimize the risk of MCMs or neural tube defects (NTDs), if clinically feasible. Clinicians should avoid the use of valproic acid or topiramate in PWECP to minimize the risk of offspring being born small for gestational age, if clinically feasible. To reduce the risk of poor neurodevelopmental outcomes, including autism spectrum disorder and lower IQ, in children born to PWECP, clinicians must avoid the use of valproic acid in PWECP, if clinically feasible. Clinicians should prescribe at least 0.4 mg of folic acid supplementation daily preconceptionally and during pregnancy to any PWECP treated with an ASM to decrease the risk of NTDs and possibly improve neurodevelopmental outcomes in the offspring.

Stroke Prevention in Symptomatic Large Artery Intracranial Atherosclerosis Practice Advisory: Report of the AAN Guideline Subcommittee.

BACKGROUND AND OBJECTIVES: To review treatments for reducing the risk of recurrent stroke or death in patients with symptomatic intracranial atherosclerotic arterial stenosis (sICAS). METHODS: The development of this practice advisory followed the process outlined in the American Academy of Neurology Clinical Practice Guideline Process Manual, 2011 Edition, as amended. The systematic review included studies through November 2020. Recommendations were based on evidence, related evidence, principles of care, and inferences. MAJOR RECOMMENDATIONS: Clinicians should recommend aspirin 325 mg/d for long-term prevention of stroke and death and should recommend adding clopidogrel 75 mg/d to aspirin for up to 90 days to further reduce stroke risk in patients with severe (70%-99%) sICAS who have low risk of hemorrhagic transformation. Clinicians should recommend high-intensity statin therapy to achieve a goal low-density lipoprotein cholesterol level <70 mg/dL, a long-term blood pressure target of <140/90 mm Hg, at least moderate physical activity, and treatment of other modifiable vascular risk factors for patients with sICAS. Clinicians should not recommend percutaneous transluminal angioplasty and stenting for stroke prevention in patients with moderate (50%-69%) sICAS or as the initial treatment for stroke prevention in patients with severe sICAS. Clinicians should not routinely recommend angioplasty alone or indirect bypass for stroke prevention in patients with sICAS outside clinical trials. Clinicians should not recommend direct bypass for stroke prevention in patients with sICAS. Clinicians should counsel patients about the risks of percutaneous transluminal angioplasty and stenting and alternative treatments if one of these procedures is being contemplated.

Telemedicine in neurology: Telemedicine Work Group of the American Academy of Neurology update.

PURPOSE: While there is strong evidence supporting the importance of telemedicine in stroke, its role in other areas of neurology is not as clear. The goal of this review is to provide an overview of evidence-based data on the role of teleneurology in the care of patients with neurologic disorders other than stroke. RECENT FINDINGS: Studies across multiple specialties report noninferiority of evaluations by telemedicine compared with traditional, in-person evaluations in terms of patient and caregiver satisfaction. Evidence reports benefits in expediting care, increasing access, reducing cost, and improving diagnostic accuracy and health outcomes. However, many studies are limited, and gaps in knowledge remain. SUMMARY: Telemedicine use is expanding across the vast array of neurologic disorders. More studies are needed to validate and support its use.

Beta-blocker usage after malignant melanoma diagnosis and survival: a population-based nested case-control study.

BACKGROUND: Beta-blockers have potential antiangiogenic and antimigratory activity. Studies have demonstrated a survival benefit in patients with malignant melanoma treated with beta-blockers. OBJECTIVES: To investigate the association between postdiagnostic beta-blocker usage and risk of melanoma-specific mortality in a population-based cohort of patients with malignant melanoma. METHODS: Patients with incident malignant melanoma diagnosed between 1998 and 2010 were identified within the U.K. Clinical Practice Research Datalink and confirmed using cancer registry data. Patients with malignant melanoma with a melanoma-specific death (cases) recorded by the Office of National Statistics were matched on year of diagnosis, age and sex to four malignant melanoma controls (who lived at least as long after diagnosis as their matched case). A nested case-control approach was used to investigate the association between postdiagnostic beta-blocker usage and melanoma-specific death and all-cause mortality. Conditional logistic regression was applied to generate odds ratios (ORs) and 95% confidence intervals (CIs) for beta-blocker use determined from general practitioner prescribing. RESULTS: Beta-blocker medications were prescribed after malignant melanoma diagnosis to 20·2% of 242 patients who died from malignant melanoma (cases) and 20·3% of 886 matched controls. Consequently, there was no association between beta-blocker use postdiagnosis and cancer-specific death (OR 0·99, 95% CI 0·68-1·42), which did not markedly alter after adjustment for confounders including stage (OR 0·87, 95% CI 0·56-1·34). No significant associations were detected for individual beta-blocker types, by defined daily doses of use or for all-cause mortality. CONCLUSIONS: Contrary to some previous studies, beta-blocker use after malignant melanoma diagnosis was not associated with reduced risk of death from melanoma in this U.K. population-based study.

Second primary cancers in patients with skin cancer: a population-based study in Northern Ireland.

Among all 14,500 incident cases of basal cell carcinoma (BCC), 6405 squamous cell carcinomas (SCC) and 1839 melanomas reported to the Northern Ireland Cancer Registry between 1993 and 2002, compared with the general population, risk of new primaries after BCC or SCC was increased by 9 and 57%, respectively. The subsequent risk of cancer, overall, was more than double after melanoma.

Reliability testing of a sun exposure questionnaire for the Northern Ireland population.

BACKGROUND: Sunbathing and other types of exposure to ultraviolet radiation are the major preventable risk factors for skin cancer. Due to the continued increase in incidence of melanoma in Northern Ireland, we have conducted a questionnaire survey in an attempt to gather information about sunbathing habits and other forms of ultraviolet light exposure amongst the Northern Ireland population. AIM: The aim of this study was to examine the test-retest reliability of a questionnaire used in a large-scale cross-sectional population survey pertaining to sunbathing habits, use of sun screen, skin types, and frequencies of sunburn and to assess the responses given by the subjects to determine the nature of their sun-related behaviour. METHODS: Thirty control subjects were randomly selected from a population control sample participating in a large case-control study investigating melanoma in the Northern Ireland population. All participants completed the interview questionnaire on two occasions, with a median of 15 days (range, 12-42 days) between interviews. We randomly chose control subjects who had been visited by the same research nurse, thus ruling out interobserver bias in the analyses. We used the test-retest method. Kappa statistics were used to calculate the association between test and retest scores of all the individual items. If the items contained within the questionnaire are reliable, then repeated measurement after a fairly short period of time should result in high within-subject repeatability. RESULTS: Questions pertaining to hours spent in the sun and sun bed usage showed high reliability (kappa > 0.7). Questions about sunscreen usage showed moderately high reliability (kappa > 0.6) in all but one of the 10-year age bands and complete agreement (kappa = 1) in one age category (>50 years). CONCLUSION: This questionnaire is a reliable method of assessing sun-associated behaviour identifying high-risk sun-related behaviour and misconceptions about tanning, which can be targeted for improvement in public health.

Skin cancer trends in Northern Ireland and consequences for provision of dermatology services.

BACKGROUND: The incidence of skin cancer, both melanoma and nonmelanoma skin cancer (NMSC), is rising throughout the world. The evaluation of trends in skin cancer will allow better planning of the future development of skin cancer services. OBJECTIVES: Using data collected from the Northern Ireland Cancer Registry (NICR), the incidence of the three major cutaneous cancers, basal cell carcinoma (BCC), squamous cell carcinoma (SCC) and malignant melanoma (MM), was determined and the workload associated with their management assessed. METHODS: The records of patients with a first diagnosis of BCC, SCC or MM occurring between 1993 and 2002 were retrieved from the NICR database. The annual age- and sex-adjusted incidence rates of all three skin cancers were computed per 100 000 person-years by direct standardization according to the European Standard Population. Trends in incidence were estimated by calculating the estimated annual percentage change using Microsoft Excel. For patients registered with the NICR as having BCC, SCC or MM, the number of pathological reports where malignant samples had been examined was counted and then summed to provide the number of specimens examined each year between 1993 and 2004. RESULTS: For all three cancers the age-specific rates for both males and females increased with age, except for MM in men aged 75 years and over, where the rates were seen to decrease. Over the 12-year period there was a 62% increase in the overall number of skin cancer samples processed by local pathology laboratories and a 20% increase in the number of patients. These data highlight the fact that many patients will have more than one skin cancer, which reinforces the benefit in collecting data for both patient and sample numbers in order to obtain a true reflection of the workload. The data have also shown that more affluent men and women have higher rates of BCC and MM than their less affluent counterparts. CONCLUSIONS: In view of the data presented it is clear that management of NMSC and MM will impose significant demands on services in the years ahead. This will impact on the entire multidisciplinary team. Future planning, in terms of manpower and resources, will prove essential if we are to remain in a position to manage our patients with these malignant tumours appropriately.

Follow-up of basal cell carcinomas: an audit of current practice.

BACKGROUND: Follow-up of patients after treatment of basal cell carcinoma (BCC) allows for monitoring of recurrence and detection of new tumours, but adds a significant burden to outpatient clinics. At the skin tumour clinic in the dermatology department, the Royal Hospitals, Belfast, all patients are reviewed for 2 years after surgical excision of a low-risk primary BCC. OBJECTIVES: An audit was undertaken to determine the quality of data set recorded relating to prognostic factors for BCCs to determine the rate of recurrence and number of new primary tumours detected and to determine the completeness of follow-up by patients. METHOD: Patients who had primary BCCs treated by excision were identified from a database held at the clinic. Medical charts were reviewed to determine data recorded about lesions, the number of recurrent BCCs and new tumours detected, and the number of patients completing follow-up. RESULTS: Between January 1999 and December 2000, 114 patients had 121 primary BCCs excised. BCC location and size were recorded in 100% and 35% of cases, respectively. Histological type was stated for morphoeic or multifocal lesions. Two years of follow-up was completed by 53% of patients and 1 year by 78% of patients. The rate of recurrence was low, with 2 BCC recurring within 2 years of excision. The risk of developing a new BCC was 11.6% in the first year and 6.3% in the second year. CONCLUSIONS: Follow-up of patients after excision of a low-risk BCC at the clinic has been reduced to 1 year. A proforma has been developed to encourage documentation of prognostic factors.

Improved survival for melanoma in Northern Ireland: a comparison of two 5-year periods (1984-88 and 1994-98).

BACKGROUND: The incidence of cutaneous malignant melanoma has been rising steadily in Caucasian populations for several decades, with a doubling time of 10-14 years. An increase in incidence of about 5% per year has been reported in most Caucasian populations since the early 1960s. OBJECTIVES: This study was designed to determine the changing incidence of primary cutaneous malignant melanoma in Northern Ireland and to examine changes in survival rates from cutaneous malignant melanoma in two 5-year periods, 1984-88 and 1994-98. METHODS: One thousand three hundred and twenty-six patients with invasive primary cutaneous melanoma were included in the study. RESULTS: The age standardized rate of melanoma rose from 4.3 per 100,000 population per year in men and 8.6 per 100,000 population per year in women to 7.7 and 11.8, respectively, per 100,000 population per year in the 1994-98 period. Overall, the absolute 5-year survival for the 1984-88 period was 71.0% [95% confidence interval (CI) 66.9-75.1%] and 77.4% (95% CI 73.4-81.4%) for the 1994-98 period. Women consistently showed better survival at all ages and within almost all categories of thickness of primary tumour. Younger patients of both sexes showed better survival rates. CONCLUSIONS: When survival rates between the 1984-88 and 1994-98 periods were compared using multivariate analysis, we found that patients diagnosed in the second period had a one-third lower risk of dying than those in the earlier period. Much of this reduction was explained by changes in the number of melanomas of thin Breslow depth and ulcerated melanomas.

Knowledge, attitudes and behaviour in the sun: the barriers to behavioural change in Northern Ireland.

To inform future health promotion programmes, we studied the knowledge, attitudes and behaviour of the Northern Ireland population to sun care. An interviewer-administered questionnaire was applied to one adult per household from a random sample of 1242 addresses. Lower levels of knowledge were found among respondents who were male, aged under 25 years or over 65 years, in a manual occupation or living in the west where health promotion activity on this topic was less active than in the east. Younger adults, females and professional groups were more likely to indicate that a suntan was important, healthy or attractive. Use of high factor sunscreen was inversely proportional to perceived importance of a suntan. Sunburn was more common in younger adults but more men reported multiple episodes of burning. Regular skin checks were uncommon and self-assessment of skin type was unrealistic indicating that sun care advice based on self assessment should be avoided in this population. Future campaigns should target appropriate messages at specific population subgroups. The study highlights the importance of collecting baseline information before implementing health promotion programmes and suggests that repeat monitoring is essential to ensure that key messages remain relevant. This study also indicates that Care in the Sun campaigns here impacted on general awareness in the population even with limited resources. There is, therefore, potential for greater impact with high funding levels.

Association between long-term acitretin therapy and osteoporosis: no evidence of increased risk.

Osteoporosis has been observed with chronic hypervitaminosis A, leading some authors to hypothesize that systemic retinoids may have an effect on bone mineral density. Two previous small studies identified osteoporosis in patients who received long-term therapy with etretinate. Etretinate has now been superceeded by acitretin in clinical use. We hypothesized that bone mineral density is lower in patients taking long-term acitretin than control cases who had never taken acitretin. Thirty Caucasian patients receiving acitretin for a median of 3.6 years for a variety of dermatoses were studied. Bone mineral density measurements were determined using DEXA scanning at two standard sites, the lumbar spine and Ward's triangle. We did not find an association between daily dose of acitretin, total dose administered or overall duration of treatment and risk of osteopenia or osteoporosis. Acitretin appears to be safe for long-term use in patients with chronic dermatoses.

Transcriptional regulation and structural organization of the human cytosolic phospholipase A(2) gene.

Cytokines are established regulators of the arachidonic acid cascade in lung cells. The levels of various arachidonic metabolites distinguish the normal and pathogenic states of the human lung. Arachidonyl-selective cytosolic phospholipase A(2) (cPLA(2)) is ubiquitously present in human lung and is most likely the rate-limiting step in eicosanoid generation. We therefore studied the regulation of this pivotal gene in human lung fibroblasts and epithelial cells by proinflammatory cytokines. We demonstrate a dose- and time-dependent induction of human cPLA(2) mRNA by interleukin-1beta, tumor necrosis factor-alpha, and interferon-gamma as well as the abrogation of this induction by glucocorticoids. Nuclear runoff studies demonstrate that de novo transcription of the cPLA(2) gene is required for cytokine induction. We have characterized the human cPLA(2) gene, which is encoded by 18 exons and spans in excess of 137 kb. Deletion analysis of a 3.4-kb fragment of the human promoter identified two regions responsible for basal expression of the cPLA(2) gene. Conversely, a CA-dinucleotide repeat in the proximal promoter appears to repress overall promoter activity. Understanding the molecular mechanisms associated with cytokine-dependent expression of the cPLA(2) gene should provide further insight into regulating the level of proinflammatory mediators in pulmonary diseases.