TREATMENT OF INSOMNIA WITH ZALEPLON,A NOVEL SLEEP MEDICATION

Insomnia is a highly prevalent sleep problem that often results in poor daily functioning of the affected patient. Unfortunately, sedative hypnotic agents prescribed in the past often resulted in residual sedation, as well as impairment of cognitive and psychomotor performance, throughout the day after use. Newer agents with relatively rapid elimination require administration regularly each night before bedtime if symptoms of insomnia are to be prevented and next-day sedation is to be avoided. The availability of zaleplon challenges these standards of practice. The rapid elimination of zaleplon, combined with its unique receptor binding affinity, permits 10 mg of zaleplon to be taken at bedtime or later in the night with minimal concern for next-day residual effects. Clinical studies of zaleplon also identified the low risk of withdrawal syndrome or rebound insomnia after the discontinuation of nightly use. If used only on the nights when symptoms actually occur, the occurrence of such problems with zaleplon will be minimal.     

Models predicting non-sentinel node involvement also predict for regional recurrence in breast cancer patients without axillary treatment

Background

Non-SN prediction models are frequently used in clinical decision making to identify patients that may not need axillary treatment, but these models still need to be validated by follow-up data. Our purpose was the validation of non-sentinel node (SN) prediction models in predicting regional recurrences in patients without axillary treatment.

Methods

We followed a cohort of 486 women with favorable primary tumor characteristics and pN0(i+)(sn) or pN1mi(sn) for median 4.5 years. None of the patients underwent axillary treatment. Based on four published non-SN prediction models, the threshold allowing separation into low versus high-risk on non-SN involvement was set at 10%.

Results

Overall 5-year regional recurrence rate was 3.0% (SE, ±0.1%). Using the Tenon scoring system, 438 low-risk patients had a 5-year regional recurrence rate of 2.3% (±0.8%), and 48 high-risk patients a recurrence rate of 10.1% (±0.4%). The MSKCC nomogram identified 300 low-risk patients with a recurrence rate of 2.8% (±1.1%), versus 166 high-risk patients with a rate of 3.4% (±0.5%) (20 patients not assessable). The Stanford nomogram identified 21 high-risk patients without recurrence, and 465 low-risk patients with a 3.2% (±0.9%) recurrence rate. A Dutch model discriminated between 384 low-risk patients with a recurrence rate of 2.2% (±0.8%) and 102 high-risk patients with a rate of 6.3% (±2.9%).

Conclusion

The Tenon scoring system outperformed the other models as it identified the largest subgroup of patients with low recurrence rate. In patients resembling our cohort we would recommend axillary treatment if they had a Tenon score above 3.5.     

The implementation of CDK 4/6 inhibitors and its impact on treatment choices in HR+/HER2− advanced breast cancer patients: A study of the Dutch SONABRE Registry

In August 2017, cyclin-dependent kinase 4/6 (CDK4/6) inhibitors combined with endocrine therapy have been reimbursed in the Netherlands for patients with hormone receptor positive (HR+), HER2 negative (HER2?) advanced breast cancer (ABC). This study evaluates the implementation of CDK4/6 inhibitors and changes in treatment choices in the Netherlands. All patients diagnosed with HR+/HER2? ABC in 2009 to 2018 in seven hospitals were selected from the Southeast Netherlands Advanced Breast cancer (SONABRE) registry. The 2-year cumulative use of CDK4/6 inhibitors since reimbursement date (August 2017) was assessed using competing-risk methodology in two cohorts. The first cohort included patients with ABC diagnosis between August 2017 and December 2018. The second cohort included patients with ABC diagnosis between 2009 and August 2017, and still alive on August 1, 2017. In addition, treatment choices in the first three lines of therapy in calendar years 2009 to 2018 were evaluated for the total study population. Among patients diagnosed since August 2017 (n = 214), 50% (95% confidence interval [CI] = 43-57) received CDK4/6 inhibitors within 2 years beyond diagnosis. Of eligible patients diagnosed before August 2017 (n = 417), 31% (95% CI = 27-36) received CDK4/6 inhibitors within 2 years following reimbursement. Another 20% of both cohorts are still CDK4/6 inhibitor naïve and on first-line therapy. The use of chemotherapy decreased in first two lines of therapy between 2009 and 2018 (first-line: 29%-13%; second-line: 26%-19%). The implementation rate of CDK4/6 inhibitors since reimbursement is currently 50% within 2 years beyond diagnosis and is expected to increase further. The implementation of targeted therapy decreased the use of chemotherapy as first-line therapy.     

Safety of avoiding routine use of axillary dissection in early stage breast cancer: a systematic review

Physicians are moving away from routine axillary lymph node dissection (ALND) in clinically node-negative breast cancer. We conducted a systemic review on the safety of this policy. Pubmed and Cochrane library were searched for. Sixty-eight studies were included: studies of clinically node-negative patients in the pre-sentinel node (SN) era; observational studies of SN-negative patients, without ALND; comparative studies of SN-negative patients, with a non-ALND and an ALND group; SN-positive studies, of patients without ALND. Primary endpoint was the pooled axillary recurrence rate (ARR) of each category; secondary endpoint was overall survival (OS) rate. In pre-SN studies, with larger tumors and less systemic therapy, ARR without ALND after 5–10 years follow-up was 12–18%, with 5% reduced OS. In the observational SN-negative studies, with median follow-up of 36 months, the pooled ARR was 0.6% (95% CI 0.6–0.8). In the comparative SN-negative studies, pooled ARR was 0.4% (95% CI 0.2–0.6) without ALND versus 0.3% (95% CI 0.1–0.6) with ALND at 31 and 47 months, respectively, and no survival disadvantage. In SN-positive studies, ARR was up to 1.7% (95% CI 1.0–2.7) at 30 months. For patients with an H&E positive SN the ARR without ALND was 5% after 23 months, which may imply rates as high as 13 and 18% after 5 and 8 years. In conclusion, this systematic review confirms the safety of omitting ALND in SN-negative patients. There is a potential role for avoiding ALND in selected SN-positive patients, but eligibility criteria and the role of systemic therapy need further to be elucidated.     

Sclerosing peritonitis: an unusual cause of ascites in a patient with systemic lupus erythematosus

Sclerosing peritonitis is a rare condition characterised by fibrosis and adhesion of the peritoneum to loops of the small intestine. It is generally associated with continuous peritoneal dialysis, peritoneo-venous shunts or &beta-adrenergic blocking agents. In this case we report a female patient with idiopathic sclerosing peritonitis and systemic lupus erythematosus.     

Follicular flushing at oocyte retrieval: a reappraisal

A survey of Australian assisted reproduction technique (ART) units revealed many (> 50%) use flushing of the follicle in addition to direct aspiration of the fluid during oocyte retrieval. The rationale is that flushing offers an advantage to the patient, with a larger number of oocytes being collected and thus a higher potential for pregnancy Following a complication in a patient, the medical staff determined that flushing might have been implicated. While this was later shown to be unfounded, the unit changed the method of oocyte collection, thus providing an opportunity historically to evaluate the differences between aspiration of follicular fluid alone or with additional flushing of each follicle. Thus the aim of this analysis was to test the hypothesis that aspiration alone does not effect the outcomes of ART with respect to oocyte numbers collected, their quality and subsequent fertilisation, or ultimate pregnancy rate in a large patient group (n = 2378). During the review period (1991-1993) the manufacturer of the aspiration needles; the pump and pressure used for aspiration; the staff involved in all procedures; and the premises, equipment and media used for oocyte collection and culture remained constant. Similarly the two patient groups did not differ in their demographics and physical characteristics. There was no difference (p > 0.5) in the number of oocytes collected, the number of embryos created or the pregnancy rate for that treatment cycle. There was also no significant difference between the two groups in fertilisation rates, irrespective of the type of treatment being used in vitro fertilisation (IVF), gamete intrafallopian transfer (GIFT) or intracytoplasmic sperm injection (ICSI)). The data presented in this paper are not prospective. They use historical comparison and are confounded by minor changes in ovarian stimulation protocols, but the conclusions are still valid. These data suggest there is no difference in the outcome of ART (from oocyte collection through to pregnancy rate) whether or not aspiration of follicles is accompanied by flushing. First principles of surgery advocate the shortest possible operating time, the simplest procedure and minimum amount of tissue handling as maxims for reducing complication. Therefore, as a routine, flushing would seem superfluous in ART.     

Headache in systemic lupus erythematosus: a controlled study

Intractable headaches, the so-called 'lupus headaches', have been long thought of as a common and characteristic manifestation of systemic lupus erythematosus (SLE). Seventy-eight patients with SLE, including 10 patients with definite central nervous system (CNS) involvement, and 89 healthy individuals matched for age, sex and socioeconomic status, were studied by a specific questionnaire addressing the characteristics and type of headache. Clinical features of SLE, neurological manifestations and treatment, disease severity and autoantibody profiles were correlated to the presence of headache. One year prevalence of headache was similar between patients (32%) and otherwise healthy individuals (30%). No significant differences regarding frequency, family history of headache and need for analgesic medication were observed. Headache refractory to analgesic treatment, but responsive to corticosteroid regimen, was recorded in only one patient. Clinical and serological features of SLE, including Raynaud's phenomenon and the presence of anticardiolipin antibodies, were not significantly different between headache sufferers and non-sufferers. In the majority of patients reporting headache, anxiety and/or depression co-existed. Episodic tension headache was the most frequent type, while migraine was traced in a quarter of headache sufferers. Neither the presence nor the clinical type of headache was related to, or predictive of, the development of seizures or psychosis. These results indicate that headache is not specifically related to SLE expression or severity, and suggest that accepting the presence even of a severe headache as a neurological manifestation of SLE in the absence of seizures or overt psychosis may result in overestimation of the disease status.