MIDA boronate allylation – synthesis of ibuprofen

MIDA boronates are among the most useful reagents for the Suzuki–Miyaura reaction. This chemistry typically generates new bonds between two aromatic rings, thereby restricting access to important areas of chemical space. Here we demonstrate the coupling of MIDA boronates to allylic electrophiles, including a new synthesis of the well-known COX inhibitor ibuprofen.

Here we demonstrate the coupling of MIDA boronates to allylic electrophiles, including a new synthesis of the well-known COX inhibitor ibuprofen.     

The quality of care under a managed-care program for dual eligibles

PURPOSE: Our objective in this study was to compare the quality of care provided under the Minnesota Senior Health Options (MSHO), a special program designed to serve dually eligible older persons, to care provided to controls who received fee-for-service Medicare and Medicaid managed care. DESIGN AND METHODS: Two control groups were used; one was drawn from nonenrollees living in the same area (Control-In) and another from comparable individuals living in another urban area where the program was not available (Control-Out). Cohorts living in the community and in nursing homes were included. Quality measures for both groups included mortality rates, preventable hospital admissions, and preventable emergency room (ER) visits. For the community group, nursing home admission rates were also tracked. For nursing home residents, quality measures included quality indicators derived from the Minimum Data Set. RESULTS: There were no differences in mortality rates for either cohort. MSHO had fewer short-stay nursing home admissions but no difference for stays 90 days or longer. MSHO community and nursing home residents had fewer preventable hospital and ER visits compared to Control-In. There were no major differences in nursing home quality indicator rates. IMPLICATIONS: The cost of changing the model of care for dual eligibles from a mixture of fee-for-service and managed care to a merged managed-care approach cannot be readily justified by the improvements in quality observed.     

Characterization, mapping, and expression of the human ceruloplasmin gene.

Ceruloplasmin (CP) is a copper-binding protein in vertebrate plasma. It is the product of an intragenic triplication and is composed of three homologous domains. Oligonucleotide probes constructed according to published amino acid sequences were used to identify cDNA clones encoding human CP. Two clones, CP-1 and CP-2, differed from each other by the presence or absence, respectively, of a deduced sequence of four amino acids. The two clones provided 81% of the sequence encoding CP. Comparison of the nucleotides of the three domains of the CP coding sequence revealed internal domain homology with identity of sequences ranging from 50.1% to 56%. The nucleotide sequence of CP-2 cDNa was compared to that of a homologous human protein, clotting factor VIII, and was found to be 48% identical overall. The CP gene was mapped to human chromosome 3 by somatic-cell-hybrid analysis and to 3q25 by in situ hybridization; however, sites of hybridization to DNA on other chromosomal sites suggested additional CP-like DNA sequences in the human genome. A DNA polymorphism was detected with CP cDNA after endonuclease digestion of human DNA by Pst I. CP mRNA was detected in human liver, macrophages, and lymphocytes by in situ histohybridization.     

Ministry of Health Clinical Practice Guidelines: Anxiety Disorders

The Ministry of Health (MOH) has developed the clinical practice guidelines on Anxiety Disorders to provide doctors and patients in Singapore with evidence-based treatment for anxiety disorders. This article reproduces the introduction and executive summary (with recommendations from the guidelines) from the MOH clinical practice guidelines on anxiety disorders, for the information of SMJ readers. Chapters and page numbers mentioned in the reproduced extract refer to the full text of the guidelines, which are available from the Ministry of Health website: http://www.moh.gov.sg/content/moh_web/healthprofessionalsportal/doctors/guidelines/cpg_medical.html. The recommendations should be used with reference to the full text of the guidelines. Following this article are multiple choice questions based on the full text of the guidelines.

1.1 Background information

Anxiety disorders are known to be one of the most prevalent of psychiatric conditions, yet they often remain under-diagnosed and under-treated. Their chronic, disabling symptoms cause considerable burden not only to sufferers but also to their families, and contribute to poorer quality of life and considerable economic burden on society.In many instances, there is a delay in seeking treatment and in some cases such delay may stretch up to nearly ten years. This may result from ignorance of the condition, fear of taking medications, and the stigma of receiving a psychiatric diagnosis, and or having to accept psychiatric treatment.The anxiety disorders include panic disorder with or without agoraphobia, social anxiety disorder, specific phobia, obsessive-compulsive disorder, generalised anxiety disorder, acute stress disorder and post-traumatic stress disorder. In the clinical evaluation of anxiety disorders, it is important to ascertain the type of anxiety disorder present. This would allow treatment to be targeted at the specific type of disorder.These guidelines are developed to provide practical, evidence-based recommendations to primary care physicians and specialists in psychiatry for the diagnosis and management of the anxiety disorders.The first edition of the guidelines was published in 2003. In this edition, we present data from newer research as well as older data not previously reported in the earlier guidelines.For example, we examine the efficacy of combining medications with psychological therapy over medications alone, or psychological therapy alone. In view of the majority of anxiety sufferers being female we have made recommendations for pharmacotherapy during pregnancy and breastfeeding. As these guidelines are intended for use in the Singapore context, we have omitted treatments that are currently not available in Singapore.

1.2 Aim

These guidelines are developed to facilitate the diagnosis and assessment of the anxiety disorders, and to ensure that their management is appropriate and effective.

1.3 Scope

These guidelines will cover the management of anxiety disorders in adults and address the issues of medication use during pregnancy and breastfeeding.

1.4 Target group

The content of the guidelines will be useful for all doctors treating patients with anxiety disorders. Efforts have been made to ensure that the guidelines are particularly useful for primary care physicians and specialists in psychiatry, including all those involved in the assessment and management of patients with anxiety disorders in the community. The doctor treating the patient is ultimately responsible for clinical decisions made after reviewing the individual patient’s history, clinical presentation and treatment options available.

1.5 Development of guidelines

These guidelines have been produced by a committee of psychiatrists, a clinical psychologist, pharmacist, patient representative, and family practitioners appointed by the Ministry of Health. They were developed by revising the existing guidelines, reviewing relevant literature, including overseas clinical practice guidelines, and by expert clinical consensus of professionals with experience in treating patients in the local setting.The following principles underlie the development of these guidelines:

• Treatment recommendations are supported by scientific evidence whenever possible (randomised controlled clinical trials represent the highest level of evidence) and expert clinical consensus is used when such data are lacking.
• Treatment should maximise therapeutic benefits and minimise side effects.

1.6 What’s new in the revised guidelines

This edition of the guidelines contains updated recommendations based on latest evidence, as well as detailed discussions and recommendations on the management of anxiety disorders in adult populations.The following represent changes to the revised guidelines

• An extensive review of the literature, including new evidence. This involved the re-writing and extensive revision of the chapters.
• Length of treatment, which provides answers to a pertinent question.
• Use of medications during pregnancy and breastfeeding. Given that females are more likely to be at risk of being diagnosed with anxiety disorders, this is an important subject.

We are aware that the Diagnostic and Statistical Manual of Mental Disorders-5 (DSM-5) was released in 2013. In DSM-5, post-traumatic stress disorder and obsessive-compulsive disorder have been removed and classified separately from the rest of the anxiety disorders. If we were to adhere strictly to DSM-5, this would entail omitting discussion on post-traumatic stress disorder and obsessive-compulsive disorder. As it is our aim to provide an update on the 2003 guidelines, post-traumatic stress disorder and obsessive-compulsive disorder have been included in this edition of the guidelines.In addition, anxiety conditions in children are included in DSM-5. Since the present guidelines are meant to address only adult anxiety disorders, guidelines on children’s anxiety conditions are not included here.Hence, for purposes of these guidelines, we will continue to use classifications based on the International Classification of Diseases-10 (ICD-10) and DSM-IV-TR criteria.

1.7 Review of guidelines

Evidence-based clinical practice guidelines are only as current as the evidence that supports them. Users must keep in mind that new evidence could supersede recommendations in these guidelines. The workgroup advises that these guidelines be scheduled for review five years after publication, or when new evidence appears that requires substantive changes to the present recommendations.     

Revisiting the Free Nipple Graft: An Opportunity for Nipple Sparing Mastectomy in Women with Breast Ptosis

Objective

Nipple areolar complex (NAC) sparing mastectomy improves the cosmetic outcome of patients with breast cancer. However, women with significant breast ptosis are not candidates for this technique due toexcessive skin flap length and ensuing risk of NAC ischemia.1 ^– 3 We report a novel technique using free nipple graft during skin sparing mastectomy for patients with significant ptosis while concurrently maintaining oncologic integrity.

Design

Case series.

Setting

Community and tertiary care hospital practices.

Patients

Women with breast cancer desiring NAC preservation who are otherwise candidates for nipple sparing mastectomy, but with significant breast ptosis that precludes NAC viability. All women underwent immediate, autologous breast reconstruction.

Interventions

Bilateral and unilateral free nipple grafts were harvested, placed on ice during skin sparing mastectomy and free flap reconstruction, grafted at the conclusion of the case and secured with a bolster.

Outcome Measures

Full or partial NAC preservation, ischemia time, local wound complications at NAC grafting site, pathologic outcomes.

Results

A total of three patients underwent free nipple grafting at the time of skin sparing mastectomy and free or pedicled flap for breast cancer between March and September 2012. Of five total nipple grafts, one had partial NAC loss but did not require operative debridement. Pathologic review of areolar tissue removed during intraoperative defatting of free nipple graft demonstrated residual duct epithelium.

Conclusions

Women with significant breast ptosis that would preclude them from NAC sparing mastectomy can successfully preserve their NAC using a free nipple graft. Duct epithelium present in defatted tissue during preparation of the free nipple graft suggests that oncologic integrity can also be maintained.