Upgrading and upstaging of low-risk prostate cancer among Korean patients: a multicenter study

Only 54% of prostate cancer cases in Korea are localized compared with 82% of cases in the US. Furthermore, half of Korean patients are upgraded after radical prostatectomy (41.6%–50.6%). We investigated the risk factors for upgrading and/or upstaging of low-risk prostate cancer after radical prostatectomy. We retrospectively reviewed the medical records of 1159 patients who underwent radical prostatectomy at five hospitals in Honam Province. Preoperative data on standard clinicopathological parameters were collected. The radical prostatectomy specimens were graded and staged and we defined a “worsening prognosis” as a Gleason score ≥ 7 or upstaging to ≥ pT3. Multivariate logistic regression models were used to assess factors associated with postoperative pathological upstaging. Among the 1159 patients, 324 were classified into the clinically low-risk group, and 154 (47.5%) patients were either upgraded or upstaged. The multivariable analysis revealed that the preoperative serum prostate-specific antigen level (odds ratio [OR], 1.131; 95% confidence interval [CI], 1.007–1.271; P= 0.037), percent positive biopsy core (OR: 1.018; 95% CI: 1.002–1.035; P= 0.032), and small prostate volume (≤30 ml) (OR: 2.280; 95% CI: 1.351–3.848; P= 0.002) were predictive of a worsening prognosis. Overall, 47.5% of patients with low-risk disease were upstaged postoperatively. The current risk stratification criteria may be too relaxed for our study cohort.     

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.     

Japanese Cedar (Cryptomeria japonica) Pollinosis in Jeju,Korea: Is It Increasing?

Jeju is an island in South Korea located in a temperate climate zone. The Japanese cedar tree (JC) has become the dominant tree species while used widely to provide a windbreak for the tangerine orchard industry. An increase in pollen counts precedes atopic sensitization to pollen and pollinosis, but JC pollinosis in Jeju has never been studied. We investigated JC pollen counts, sensitization to JC pollen, and JC pollinosis. Participants were recruited among schoolchildren residing in Jeju City, the northern region (NR) and Seogwipo City, the southern region (SR) of the island. The JC pollen counts were monitored. Sensitization rates to common aeroallergens were evaluated by skin prick tests. Symptoms of pollinosis were surveyed. Among 1,225 schoolchildren (49.6% boys, median age 13 years), 566 (46.2%) were atopic. The rate of sensitization to Dermatophagoides pteronyssinus (35.8%) was highest, followed by D. farinae (26.2%), and JC pollen (17.6%). In the SR, 156 children (23.8%) were sensitized to JC pollen; this rate was significantly higher than that in the NR (59 children, 10.4%, P<0.001). A significant increment in the sensitization rate for JC pollen with increasing school level was observed only in the SR. JC pollen season in the SR started earlier and lasted longer than that in the NR. JC pollen season in Jeju was defined as extending from late January to mid-April. The prevalence of JC pollinosis was estimated to be 8.5%. The prevalence differed significantly between the NR and SR (5.3% vs 11.3%, P<0.001), mainly due to the difference in sensitization rates. JC pollen is the major outdoor allergen for early spring pollinosis in Jeju. JC pollen season is from late January to mid-April. Warmer weather during the flowering season scatters more JC pollen in the atmosphere, resulting in a higher sensitization rate in atopic individuals and, consequently, making JC pollinosis more prevalent.     

Priming the Surface of Orthopedic Implants for Osteoblast Attachment in Bone Tissue Engineering

The development of better orthopedic implants is incessant. While current implants can function reliably in the human body for a long period of time, there are still a significant number of cases for which the implants can fail prematurely due to poor osseointegration of the implant with native bone. Increasingly, it is recognized that it is extremely important to facilitate the attachment of osteoblasts on the implant so that a proper foundation of extracellular matrix (ECM) can be laid down for the growth of new bone tissue. In order to facilitate the osseointegration of the implant, both the physical nanotopography and chemical functionalization of the implant surface have to be optimized. In this short review, however, we explore how simple chemistry procedures can be used to functionalize the surfaces of three major classes of orthopedic implants, i.e. ceramics, metals, and polymers, so that the attachment of osteoblasts on implants can be facilitated in order to promote implant osseointegration.     

Rescuing the physician-scientist workforce: the time for action is now

The 2014 NIH Physician-Scientist Workforce (PSW) Working Group report identified distressing trends among the small proportion of physicians who consider research to be their primary occupation. If unchecked, these trends will lead to a steep decline in the size of the workforce. They include high rates of attrition among young investigators, failure to maintain a robust and diverse pipeline, and a marked increase in the average age of physician-scientists, as older investigators have chosen to continue working and too few younger investigators have entered the workforce to replace them when they eventually retire. While the policy debates continue, here we propose four actions that can be implemented now. These include applying lessons from the MD-PhD training experience to postgraduate training, shortening the time to independence by at least 5 years, achieving greater diversity and numbers in training programs, and establishing Physician-Scientist Career Development offices at medical centers and universities. Rather than waiting for the federal government to solve our problems, we urge the academic community to address these goals by partnering with the NIH and national clinical specialty and medical organizations.In June 2014, the NIH Physician-Scientist Workforce (PSW) Working Group completed a year of data collection and deliberation, and released a report about the status of the PSW (1). The report is a combination of good news and bad news. The good news is that, despite the decline in the NIH budget, the size of the PSW has remained relatively stable. The bad news is that the current demographics, diversity, and career progression of this workforce raise concerns about the future. For a start, although apparently stable in size, the PSW is even smaller than many of us realized, and the apparent stability has hidden important demographic trends. In American Medical Association surveys of the nearly 1 million (and rising) MD physicians in the United States, only 14,000 (1.5%) consider research to be their primary focus (1). Even fewer have NIH grant support; only 8,200 physicians are principal investigators on NIH grants, split evenly between MDs and MD-PhDs (1). The number of extramural NIH-funded physician-scientists with research program (R series) awards has been essentially constant for the past 20 years, while the number of nonphysician (PhD) NIH-funded investigators has increased by half over the same period, reaching 19,400 in 2012 (1). As a result, the percentage of NIH awardees who are physicians has fallen to 30%. Although public policies have encouraged an increase in the number of medical schools and medical students in the US, and medical school admission policies have placed value on undergraduate research, the percentage of physicians focused on research has fallen.At the same time that the PSW has remained stable in size, data in the report show that the average age of the workforce is rising, as older investigators remain employed and younger investigators have not emerged in sufficient numbers. The average age at which a physician-scientist received his or her first NIH R01 grant in 2011 was 44 years for MD-PhDs and 45 years for MDs: approximately 10 years older than in 1980 (2). R01-funded investigators (physicians and nonphysicians) younger than 37 years have all but disappeared, and the time from graduating medical school to obtaining a first faculty position has increased to over 10 years for MD-PhDs and even longer for MDs without a PhD. Women and minorities are underrepresented, having opted not to enter or remain in the workforce. Thus, gathering places for physician-scientists look mostly like clubs for older white men. Without corrective action, the PSW appears headed for a population crash as older investigators retire. We recognize that younger physician-scientists have not entirely disappeared; they just take longer to obtain faculty appointments and independent NIH grants. This situation creates an extended waiting period that we call the holding zone, which contributes to the disturbing demographics (Figure 1).Open in a separate windowFigure 1The physician-scientist pipeline: long and leaky.The figure highlights a number of issues, including career attrition at every stage and the existence of a protracted period when well-trained physicians in their 30s are serving in subordinate positions awaiting the next step in their career progression. To draw attention to their plight, we call this period the holding zone. The illustration is based on the experience of MD-PhD program graduates, but many of the issues reflect the obstacles for any would-be physician-scientist. Attrition rates from MD-PhD programs are low, with most of those who withdraw completing medical school or graduate school. Very few MD-PhD program graduates (5% or fewer) choose to forego postgraduate clinical training as residents and fellows. In our experience, career attrition takes many forms and becomes cumulative at each stage, reflecting the proportion of individuals who either never return to research, opt for full-time clinical practice outside of academia, join academia as an assistant professor but spend their time caring for patients, or are appointed to the tenure track but end up devoting minimal time to research (1). A declaration of success depends in part on the definition of success. Outcome data show that approximately 80% of MD-PhD program graduates are working in academia, industry, or research institutes — including the NIH — but not all are doing research (3). Data on NIH award rates, conversions from K grants to R grants, and the proportion of individuals appointed to MSTP T32 grants can be found in the PSW report (1). The NIH continues to track principal investigators on grants but is just starting to track physician-scientists who play essential roles as other key personnel.