Medical Tribune November 2008 SFXII
David Brill
Scientists in Singapore have developed a simple battery-operated device that could be used to detect pathogens in remote medical clinics and war zones.
The palm-sized system, measuring around 10 cm in diameter, can detect a wide range of proteins and other molecules and does not need to be connected to a computer to function.
The researchers hope to make the device commercially available in the near future, estimating that it would cost around S$500 per unit once mass production was underway.
Dr. Pavel Neuzil, who led the project, said that the sensor took around 2 years to develop. He suggested that it could be used to detect diseases such as cancer or Alzheimer’s disease, or to identify toxins used in bioterrorism.
“This whole effort, lab-on-a-chip, is meant for simple tools which can be very economical and can go to places where people who don’t have electricity can do very simple things,” he said.
Neuzil and his colleague Dr. Julien Reboud, who are based at Singapore’s Institute of Microelectronics, reported their work last month in the journal Analytical Chemistry. [2008 Aug 1;80(15):6100-3]
The system employs a technique called localized surface plasmon resonance to measure the intensity of light reflected from the surface of the test molecule. Although the guiding principles are not new, the device is greatly simplified compared to its predecessors, Neuzil said.
He added that the ability to operate without a computer was a major advantage of the system, which was initially developed for performing polymerase chain reactions and for use in tackling avian influenza.
“At the beginning somebody told me you should power it from USB because everybody has a computer around. And I told him ‘you are very funny because if you want to talk about avian flu it would be for Indonesia, places where they don’t even have electricity,’” he said.
Wednesday, February 18, 2009
Quick, accurate HPV test for developing countries
Medical Tribune November 2008 SFXIX
Seah Yee Mey and David Brill
A new rapid screening test for the human papilloma virus (HPV), created specifically for use in developing countries, is 90 percent accurate in detecting precancerous cervical disease, a study has shown.
careHPV is a signal-amplification assay adapted from the hybrid capture test, which is widely regarded as the gold standard in HPV DNA screening. Fourteen high-risk types of carcinogenic HPV can be detected using careHPV in about 2.5 hours.
The test takes up only a small area of clean bench-top space, with no need for mains electricity or running water supply. The short assay time allows for testing and clinical follow-up the same day.
careHPV can be operated by non-technical support staff with just 1 or 2 days of training.
The prototype was tested on 2,530 women aged 30 to 54 years in Shanxi province, eastern China, with complete data available for 2,388 women. careHPV correctly indentified precancerous cells in 90 percent of cervical specimens, while 84.2 percent of those without precancerous disease were identified as negative.
The recent publication of the findings online in The Lancet Oncology represents the culmination of a 5-year collaboration between the Program for Appropriate Technology in Health (PATH), a US-based nonprofit organization, and QIAGEN, who manufacture the test.
PATH, who receive funding for the project from the Bill and Melinda Gates Foundation, will now oversee a further 5 years of operational research in public health clinics in India, Uganda and Nicaragua.
The test still needs to be commercialized and undergo registration studies before it will be widely available, said Professor John Sellors, corresponding author of the study.
It is hoped that the 3 test countries will serve as examples for their respective regions, he added, noting that the generation of operational data will enable PATH to work alongside policy makers in other countries and help them to implement their own projects in future.
“From these results in China, careHPV looks very promising as a test that will allow the rapid and highly accurate screening of women in developing regions for cervical cancer,” said Sellors, a professor of family medicine at McMaster University in Canada.
“If women 30 years and older could be screened at least once in their lifetimes with such a test, and appropriate treatment administered at the same visit, public health programmes would be affordable and deaths from cervical cancer would be reduced by a third.”
The cost of careHPV is yet to be confirmed and will be negotiated on an individual basis with each government or organization.
careHPV was designed by Attila Lorincz, professor of molecular epidemiology at Barts and the London School of Medicine and Dentistry, UK. The prototype study in China was led by Professor You-Lin Qiao of the Cancer Institute, Chinese Academy of Medical Sciences, Beijing.
Cervical cancer is the second most common cancer in women, with some 500,000 new cases and 300,000 deaths worldwide every year. Carcinogenic HPV causes almost 100 percent of the cancers.
Seah Yee Mey and David Brill
A new rapid screening test for the human papilloma virus (HPV), created specifically for use in developing countries, is 90 percent accurate in detecting precancerous cervical disease, a study has shown.
careHPV is a signal-amplification assay adapted from the hybrid capture test, which is widely regarded as the gold standard in HPV DNA screening. Fourteen high-risk types of carcinogenic HPV can be detected using careHPV in about 2.5 hours.
The test takes up only a small area of clean bench-top space, with no need for mains electricity or running water supply. The short assay time allows for testing and clinical follow-up the same day.
careHPV can be operated by non-technical support staff with just 1 or 2 days of training.
The prototype was tested on 2,530 women aged 30 to 54 years in Shanxi province, eastern China, with complete data available for 2,388 women. careHPV correctly indentified precancerous cells in 90 percent of cervical specimens, while 84.2 percent of those without precancerous disease were identified as negative.
The recent publication of the findings online in The Lancet Oncology represents the culmination of a 5-year collaboration between the Program for Appropriate Technology in Health (PATH), a US-based nonprofit organization, and QIAGEN, who manufacture the test.
PATH, who receive funding for the project from the Bill and Melinda Gates Foundation, will now oversee a further 5 years of operational research in public health clinics in India, Uganda and Nicaragua.
The test still needs to be commercialized and undergo registration studies before it will be widely available, said Professor John Sellors, corresponding author of the study.
It is hoped that the 3 test countries will serve as examples for their respective regions, he added, noting that the generation of operational data will enable PATH to work alongside policy makers in other countries and help them to implement their own projects in future.
“From these results in China, careHPV looks very promising as a test that will allow the rapid and highly accurate screening of women in developing regions for cervical cancer,” said Sellors, a professor of family medicine at McMaster University in Canada.
“If women 30 years and older could be screened at least once in their lifetimes with such a test, and appropriate treatment administered at the same visit, public health programmes would be affordable and deaths from cervical cancer would be reduced by a third.”
The cost of careHPV is yet to be confirmed and will be negotiated on an individual basis with each government or organization.
careHPV was designed by Attila Lorincz, professor of molecular epidemiology at Barts and the London School of Medicine and Dentistry, UK. The prototype study in China was led by Professor You-Lin Qiao of the Cancer Institute, Chinese Academy of Medical Sciences, Beijing.
Cervical cancer is the second most common cancer in women, with some 500,000 new cases and 300,000 deaths worldwide every year. Carcinogenic HPV causes almost 100 percent of the cancers.
Paracetamol in infancy raises childhood asthma risk
Medical Tribune November 2008 SFXX
David Brill
Exposure to paracetamol during infancy could increase the subsequent risk of developing asthma, new research suggests.
Children aged 6 to 7 had a 46 percent increased risk of having asthma symptoms if they had received paracetamol for fever during their first year of life, data from the International Study of Asthma and Allergies in Childhood showed.
Use of the drug in infancy was also associated with an increased risk of rhinoconjunctivitis and eczema (odds ratios 1.48 and 1.35, respectively).
The authors of the Lancet study reviewed questionnaires completed by the parents or guardians of 205,487 children in 31 countries. [372(9643):1039-48]
“Because it was an epidemiological study we were unable to determine whether the relationship was causal … but when you put it together with all the other evidence we have it does suggest that paracetamol might be an important risk factor for the development of asthma,” said lead researcher Professor Richard Beasley, Medical Research Institute of New Zealand, Wellington.
Paracetamol should remain the preferred drug for relief of fever and pain in infancy but should be used sparingly, he said, noting that WHO guidelines recommend that the drug only be used for those with high fever (38.5°C or higher).
Beasley stressed that infants should not be switched to aspirin, which can cause the rare but potentially fatal Reye’s syndrome.
Current usage of paracetamol also increased the risk of asthma in a dose-dependent fashion. Children taking the drug on a regular basis were over three times as likely to have symptoms compared to those who were not taking it at all (odds ratio 3.23).
Dr. Chiang Wen Chin, an associate consultant in the department of pediatric allergy, immunology and rheumatology at KK Women’s and Children’s Hospital (KKH), Singapore, said that paracetamol use over the past 50 years has been safe and that the drug would remain first line for the majority of children (10mg/kg 4 to 6 hourly).
She added that ibuprofen can be given as a second line antipyretic, with tepid sponging also an option if the fever does not resolve.
Chiang noted, however, that there is a group of children who display angioedema and uticaria from high doses of paracetamol. [Pediatrics 2005 Nov;116(5):e675-80]
“We have demonstrated this in our own local patients that have presented to our clinic in KKH. Most of these children have allergic rhinitis, although not all of these have asthma,” she said.
“Our understanding of this pathophysiology is that paracetamol is a nonspecific COX-1 and COX-2 inhibitor, especially at high doses, and that this may result in a shunting of arachidonic acid production to predominantly leukotriene production, resulting in the release of various mediators such as mast cells and histamine release,” she said.
Beasley added that further studies – including randomized controlled trials of paracetamol in infancy – are needed to better understand the association with asthma.
David Brill
Exposure to paracetamol during infancy could increase the subsequent risk of developing asthma, new research suggests.
Children aged 6 to 7 had a 46 percent increased risk of having asthma symptoms if they had received paracetamol for fever during their first year of life, data from the International Study of Asthma and Allergies in Childhood showed.
Use of the drug in infancy was also associated with an increased risk of rhinoconjunctivitis and eczema (odds ratios 1.48 and 1.35, respectively).
The authors of the Lancet study reviewed questionnaires completed by the parents or guardians of 205,487 children in 31 countries. [372(9643):1039-48]
“Because it was an epidemiological study we were unable to determine whether the relationship was causal … but when you put it together with all the other evidence we have it does suggest that paracetamol might be an important risk factor for the development of asthma,” said lead researcher Professor Richard Beasley, Medical Research Institute of New Zealand, Wellington.
Paracetamol should remain the preferred drug for relief of fever and pain in infancy but should be used sparingly, he said, noting that WHO guidelines recommend that the drug only be used for those with high fever (38.5°C or higher).
Beasley stressed that infants should not be switched to aspirin, which can cause the rare but potentially fatal Reye’s syndrome.
Current usage of paracetamol also increased the risk of asthma in a dose-dependent fashion. Children taking the drug on a regular basis were over three times as likely to have symptoms compared to those who were not taking it at all (odds ratio 3.23).
Dr. Chiang Wen Chin, an associate consultant in the department of pediatric allergy, immunology and rheumatology at KK Women’s and Children’s Hospital (KKH), Singapore, said that paracetamol use over the past 50 years has been safe and that the drug would remain first line for the majority of children (10mg/kg 4 to 6 hourly).
She added that ibuprofen can be given as a second line antipyretic, with tepid sponging also an option if the fever does not resolve.
Chiang noted, however, that there is a group of children who display angioedema and uticaria from high doses of paracetamol. [Pediatrics 2005 Nov;116(5):e675-80]
“We have demonstrated this in our own local patients that have presented to our clinic in KKH. Most of these children have allergic rhinitis, although not all of these have asthma,” she said.
“Our understanding of this pathophysiology is that paracetamol is a nonspecific COX-1 and COX-2 inhibitor, especially at high doses, and that this may result in a shunting of arachidonic acid production to predominantly leukotriene production, resulting in the release of various mediators such as mast cells and histamine release,” she said.
Beasley added that further studies – including randomized controlled trials of paracetamol in infancy – are needed to better understand the association with asthma.
Compulsory CME to improve care in Indonesia
Medical Tribune November 2008 P12
David Brill
The introduction of mandatory continuing medical education(CME) in Indonesia will be of great benefit to both doctors and patients, according to the head of Ikatan Dokter Indonesia (IDI), the Indonesian medical association.
The new regulation, adopted in May last year, requires doctors to attain 250 continuing professional development (CPD) points every 5 years in order to obtain a certificate of competency, without which they cannot renew their registration and practice license.
“Every doctor in the world has an obligation – in keeping with the Hippocratic Oath and ethical codes of conduct – to continuously maintain, update and upgrade their knowledge and competencies,” said IDI president Dr. Fachmi Idris.
“The goal of CPD (and CME is the one of CPD activities) is ultimately to benefit patients,” he said. Other areas in which physicians can obtain CPD points include caring for patients, journal reading and teaching, among others.
Fachmi added that ensuring geographical and financial access to CME programs are the two major challenges that the IDI has faced so far in implementing the new system.
Doctors in Indonesia can gain CME points by participating in accredited symposia, seminars and workshops. Points will also be available through an online system which is currently under development.
Family physicians may obtain points through events organized for both general practitioners and specialists. However, family physicians will be able to obtain the necessary points faster by attending events that are organized for general practitioners than those organized for specialists, as they will be awarded more points for attending events geared towards general practice.
The association recently appointed CMPMedica, publisher of Medical Tribune, Medical Progress and the Journal of Paediatrics, Obstetrics and Gynaecology, as the first external, accredited CME provider in Indonesia. CMPMedica will help provide additional print, online and live avenues to help Indonesian doctors obtain the appropriate CME.
Globally, there is a trend toward making CME mandatory, although it remains voluntary in most countries in the Asia Pacific region. Singapore was among the first countries in the region to make the practice compulsory, beginning in January 2003.
The IDI was first given the authority to standardize and provide CME under the Medical Practice Law of 2004.
David Brill
The introduction of mandatory continuing medical education(CME) in Indonesia will be of great benefit to both doctors and patients, according to the head of Ikatan Dokter Indonesia (IDI), the Indonesian medical association.
The new regulation, adopted in May last year, requires doctors to attain 250 continuing professional development (CPD) points every 5 years in order to obtain a certificate of competency, without which they cannot renew their registration and practice license.
“Every doctor in the world has an obligation – in keeping with the Hippocratic Oath and ethical codes of conduct – to continuously maintain, update and upgrade their knowledge and competencies,” said IDI president Dr. Fachmi Idris.
“The goal of CPD (and CME is the one of CPD activities) is ultimately to benefit patients,” he said. Other areas in which physicians can obtain CPD points include caring for patients, journal reading and teaching, among others.
Fachmi added that ensuring geographical and financial access to CME programs are the two major challenges that the IDI has faced so far in implementing the new system.
Doctors in Indonesia can gain CME points by participating in accredited symposia, seminars and workshops. Points will also be available through an online system which is currently under development.
Family physicians may obtain points through events organized for both general practitioners and specialists. However, family physicians will be able to obtain the necessary points faster by attending events that are organized for general practitioners than those organized for specialists, as they will be awarded more points for attending events geared towards general practice.
The association recently appointed CMPMedica, publisher of Medical Tribune, Medical Progress and the Journal of Paediatrics, Obstetrics and Gynaecology, as the first external, accredited CME provider in Indonesia. CMPMedica will help provide additional print, online and live avenues to help Indonesian doctors obtain the appropriate CME.
Globally, there is a trend toward making CME mandatory, although it remains voluntary in most countries in the Asia Pacific region. Singapore was among the first countries in the region to make the practice compulsory, beginning in January 2003.
The IDI was first given the authority to standardize and provide CME under the Medical Practice Law of 2004.
Chronic disease management: Depression
Medical Tribune November 2008 P14-15
Depression is a serious global health issue. Some 121 million people are affected worldwide, according to 2001 estimates from the WHO, with 1 million committing suicide each year and a further 10 to 20 million attempting to do so.
The prevalence of depression in the general adult population of Singapore is around 5 percent. This figure is lower than in the US but comparable to most developed European countries. The prevalence in developing Asian countries is unclear but is likely to rise, placing an increasing burden on society and healthcare systems.
The WHO, as part of a new program launched on World Mental Health Day 2008, recently called on governments and donors to urgently upscale mental health services and better integrate mental health into primary care. Depression in particular is increasingly treatable, and making an early and effective diagnosis in this setting will lead to considerable improvements in outcome.
Diagnosis
Routine screening for depression is not recommended but should be carried out among those who are at the highest risk. There are several risk factors which GPs should be aware of in order to effectively target these patients.
The presence of multiple medical problems is strongly associated with depression. Chronic but stable conditions such as heart disease, stroke and cancer all place a strain upon patients’ wellbeing, and the coexistence of more than three conditions has been shown to significantly increase depression risk.
The link between depression and diabetes, for example, is well established. Depressed patients often lose the motivation to take their medications, which contributes to a worsening of their diabetes. This can be a two-way process, with the resulting deterioration of blood sugar control affecting the vessels and tissues in the brain, leading to a further worsening of depressive symptoms and an even greater loss of motivation.
GPs should also consider the social factors affecting their patients, as this type of information is invaluable in identifying those who should be screened for depression. Do they live alone? Are they recently divorced or widowed? Is there support from their family? Are they likely to have financial problems?
Once the GP has identified a high-risk patient they can initiate screening with two quick, simple questions: “Have you persistently felt depressed in the last 2 weeks to a month? Have you experienced a loss of interest in your daily activities over this time period?” If the patient answers yes to either of these questions then the physician should move on to try and identify further symptoms. A formal diagnosis can then be established according to the criteria laid out in the relevant guidelines.
There are, however, two major obstacles to initiating this process. The first is shyness on the part of the patient. Asian patients tend to perceive doctors as being primarily concerned with their physical wellbeing and may not expect to discuss mental health issues with them. They are often shy and might find the subject awkward.
Doctors nonetheless have a responsibility to overcome this barrier and broach the subject. This can be done by gradually and tactfully guiding the conversation in the right direction. Ask the patient gently about their mood, how they have been feeling in light of recent problems, and whether there are any other issues they would like to discuss. If they clam up, try not to charge in and pry them open in a single visit. Primary care physicians have the advantage of seeing patients regularly, and introducing the subject in one visit might make it easier to return to at a later date.
The second barrier, however, lies with the doctor, since the process of diagnosing depression can only begin if they are willing to ask these difficult questions. There is sometimes a reluctance to open up Pandora’s Box which, although understandable, needs to be overcome. This fear typically lies in the unknown, so doctors can avoid this by reading around the subject and being prepared for what might follow. Continuing Medical Education courses and workshops are often available to help physicians gain confidence in dealing with these issues, while there is a wide range of useful information available on the internet for further reading (see below).
Once doctors are comfortable with broaching the subject they can also use their intuition to guide them in making an early diagnosis. Depressed patients may seem withdrawn and quieter than usual, or may display a steady deterioration in chronic conditions which were previously well controlled. These signs should all arouse suspicion that the patient is not simply having a bad day and may be in need of help.
Practice Guidelines
Practice guidelines on major depressive disorder are available from the American Psychiatric Association website. The Ministry of Health in Singapore also publishes its own guidelines on depression, most recently in March 2004. These state that a diagnosis can be made when a depressed mood or loss of interest is accompanied by a minimum of four specific symptoms (from a list of eight) over a period of 2 or more weeks.
Depression can be a culturally sensitive issue, and guidelines will need to be applied within the context of the local social environment. The ability to adhere to the various guidelines will also depend heavily on the availability of local resources.
A range of advice and information is also available from the Malaysian Psychiatric Association and the Hong Kong College of Psychiatrists.
Treatment
Once the criteria for diagnosis are fulfilled GPs should move on to discuss treatment with their patients. If the patient is not severely agitated or suicidal then it can be useful to spread this discussion over more than one clinic visit. Start by making them aware that they have a medical condition which goes beyond just experiencing difficulties in life, and let them know that it is treatable and that safe and effective medications are available. This will give the patient time to digest the information, discuss the options with their family and do their own research before committing to a plan of action.
This approach also gives the GP a little more time to review options and prepare for prescribing an antidepressant. Medication access and guidelines will vary by country, but GPs should typically aim to begin with a selective serotonin reuptake inhibitor (SSRI) or a tricyclic antidepressant (TCA) for 4 to 6 weeks and wait to see whether there is a response. Algorithms such as the Texas Implementation of Medication Algorithm (see below) can then be used to guide further decisions around medication use.
Patients may have common misunderstandings about medications which physicians should try to allay. They may fear that the medications are addictive, or they may expect them to provide instantaneous relief. Managing these expectations in advance is important, and can help prevent patients from becoming disappointed or frustrated and stopping their medications.
Close follow-up is also crucial. Guidelines suggest that medication use should continue for 6 months to a year even if the patient shows signs of recovery. Early discontinuation leads to a higher risk of relapse, so it is important to make sure that patients finish their course. Side effects such as gastrointestinal complaints, drowsiness, dry eyes and dry throat will also need to be managed and patients should be warned about these in advance.
Psychotherapy, where available, is also a useful tool for treating depression. Few GPs are trained in psychotherapy themselves, and they should prepare for this eventuality by thoroughly researching the options in the local community and knowing how and where to refer their patients.
Treatment can be augmented by attempting to tackle some of the underlying triggers for depression. Rather than focusing solely on medical issues, GPs should also explore a patient’s psychosocial problems to understand what is troubling them. Community resources and support groups may be on hand to help, and many patients will benefit from further advice and referrals. With patients facing many problems this approach can be time-consuming for GPs, and they may like to plan ahead and deal with these issues one session at a time.
Patients with multiple psychiatric disorders or very complex or refractory depression should generally be referred on to a specialist center, particularly if they show signs of suicidal thoughts or self-harming behavior.
These centers may also offer further training which can help primary care physicians to improve their knowledge of depression. The Institute of Mental Health, for example, offers a partnership program for GPs which seeks to provide continuity of care for stable patients and increase the accessibility of treatment within the community. Participants complete a series of lectures and guided clinical sessions on depression and other mental health disorders, and can subsequently receive case consults and phone advice for difficult cases. Having specialist advice on hand can take some of the pressure off busy GPs, and can help them feel more comfortable discussing depression with their patients.
Conclusion
Depression is becoming easier to treat as our understanding of the condition continues to improve. Medications are safer and more effective than ever before and there is a wide range of information available to guide our clinical decisions. Primary care is an important setting for making an early diagnosis, and physicians should be proactive in screening patients who are at high risk.
Online Resources:
The American Psychiatric Association practice guidelines:
http://www.psych.org/MainMenu/PsychiatricPractice/PracticeGuidelines_1.aspx
The World Psychiatric Association:
http://www.worldpsychiatricassociation.org/
Texas Implementation of Medication Algorithm (TIMA):
http://www.dshs.state.tx.us/mhprograms/disclaimer.shtm
Institute of Mental Health patient information: http://www.imh.com.sg/patient_education/depression.htm
Depression.com:
http://www.depression.com/
Depression is a serious global health issue. Some 121 million people are affected worldwide, according to 2001 estimates from the WHO, with 1 million committing suicide each year and a further 10 to 20 million attempting to do so.
The prevalence of depression in the general adult population of Singapore is around 5 percent. This figure is lower than in the US but comparable to most developed European countries. The prevalence in developing Asian countries is unclear but is likely to rise, placing an increasing burden on society and healthcare systems.
The WHO, as part of a new program launched on World Mental Health Day 2008, recently called on governments and donors to urgently upscale mental health services and better integrate mental health into primary care. Depression in particular is increasingly treatable, and making an early and effective diagnosis in this setting will lead to considerable improvements in outcome.
Diagnosis
Routine screening for depression is not recommended but should be carried out among those who are at the highest risk. There are several risk factors which GPs should be aware of in order to effectively target these patients.
The presence of multiple medical problems is strongly associated with depression. Chronic but stable conditions such as heart disease, stroke and cancer all place a strain upon patients’ wellbeing, and the coexistence of more than three conditions has been shown to significantly increase depression risk.
The link between depression and diabetes, for example, is well established. Depressed patients often lose the motivation to take their medications, which contributes to a worsening of their diabetes. This can be a two-way process, with the resulting deterioration of blood sugar control affecting the vessels and tissues in the brain, leading to a further worsening of depressive symptoms and an even greater loss of motivation.
GPs should also consider the social factors affecting their patients, as this type of information is invaluable in identifying those who should be screened for depression. Do they live alone? Are they recently divorced or widowed? Is there support from their family? Are they likely to have financial problems?
Once the GP has identified a high-risk patient they can initiate screening with two quick, simple questions: “Have you persistently felt depressed in the last 2 weeks to a month? Have you experienced a loss of interest in your daily activities over this time period?” If the patient answers yes to either of these questions then the physician should move on to try and identify further symptoms. A formal diagnosis can then be established according to the criteria laid out in the relevant guidelines.
There are, however, two major obstacles to initiating this process. The first is shyness on the part of the patient. Asian patients tend to perceive doctors as being primarily concerned with their physical wellbeing and may not expect to discuss mental health issues with them. They are often shy and might find the subject awkward.
Doctors nonetheless have a responsibility to overcome this barrier and broach the subject. This can be done by gradually and tactfully guiding the conversation in the right direction. Ask the patient gently about their mood, how they have been feeling in light of recent problems, and whether there are any other issues they would like to discuss. If they clam up, try not to charge in and pry them open in a single visit. Primary care physicians have the advantage of seeing patients regularly, and introducing the subject in one visit might make it easier to return to at a later date.
The second barrier, however, lies with the doctor, since the process of diagnosing depression can only begin if they are willing to ask these difficult questions. There is sometimes a reluctance to open up Pandora’s Box which, although understandable, needs to be overcome. This fear typically lies in the unknown, so doctors can avoid this by reading around the subject and being prepared for what might follow. Continuing Medical Education courses and workshops are often available to help physicians gain confidence in dealing with these issues, while there is a wide range of useful information available on the internet for further reading (see below).
Once doctors are comfortable with broaching the subject they can also use their intuition to guide them in making an early diagnosis. Depressed patients may seem withdrawn and quieter than usual, or may display a steady deterioration in chronic conditions which were previously well controlled. These signs should all arouse suspicion that the patient is not simply having a bad day and may be in need of help.
Practice Guidelines
Practice guidelines on major depressive disorder are available from the American Psychiatric Association website. The Ministry of Health in Singapore also publishes its own guidelines on depression, most recently in March 2004. These state that a diagnosis can be made when a depressed mood or loss of interest is accompanied by a minimum of four specific symptoms (from a list of eight) over a period of 2 or more weeks.
Depression can be a culturally sensitive issue, and guidelines will need to be applied within the context of the local social environment. The ability to adhere to the various guidelines will also depend heavily on the availability of local resources.
A range of advice and information is also available from the Malaysian Psychiatric Association and the Hong Kong College of Psychiatrists.
Treatment
Once the criteria for diagnosis are fulfilled GPs should move on to discuss treatment with their patients. If the patient is not severely agitated or suicidal then it can be useful to spread this discussion over more than one clinic visit. Start by making them aware that they have a medical condition which goes beyond just experiencing difficulties in life, and let them know that it is treatable and that safe and effective medications are available. This will give the patient time to digest the information, discuss the options with their family and do their own research before committing to a plan of action.
This approach also gives the GP a little more time to review options and prepare for prescribing an antidepressant. Medication access and guidelines will vary by country, but GPs should typically aim to begin with a selective serotonin reuptake inhibitor (SSRI) or a tricyclic antidepressant (TCA) for 4 to 6 weeks and wait to see whether there is a response. Algorithms such as the Texas Implementation of Medication Algorithm (see below) can then be used to guide further decisions around medication use.
Patients may have common misunderstandings about medications which physicians should try to allay. They may fear that the medications are addictive, or they may expect them to provide instantaneous relief. Managing these expectations in advance is important, and can help prevent patients from becoming disappointed or frustrated and stopping their medications.
Close follow-up is also crucial. Guidelines suggest that medication use should continue for 6 months to a year even if the patient shows signs of recovery. Early discontinuation leads to a higher risk of relapse, so it is important to make sure that patients finish their course. Side effects such as gastrointestinal complaints, drowsiness, dry eyes and dry throat will also need to be managed and patients should be warned about these in advance.
Psychotherapy, where available, is also a useful tool for treating depression. Few GPs are trained in psychotherapy themselves, and they should prepare for this eventuality by thoroughly researching the options in the local community and knowing how and where to refer their patients.
Treatment can be augmented by attempting to tackle some of the underlying triggers for depression. Rather than focusing solely on medical issues, GPs should also explore a patient’s psychosocial problems to understand what is troubling them. Community resources and support groups may be on hand to help, and many patients will benefit from further advice and referrals. With patients facing many problems this approach can be time-consuming for GPs, and they may like to plan ahead and deal with these issues one session at a time.
Patients with multiple psychiatric disorders or very complex or refractory depression should generally be referred on to a specialist center, particularly if they show signs of suicidal thoughts or self-harming behavior.
These centers may also offer further training which can help primary care physicians to improve their knowledge of depression. The Institute of Mental Health, for example, offers a partnership program for GPs which seeks to provide continuity of care for stable patients and increase the accessibility of treatment within the community. Participants complete a series of lectures and guided clinical sessions on depression and other mental health disorders, and can subsequently receive case consults and phone advice for difficult cases. Having specialist advice on hand can take some of the pressure off busy GPs, and can help them feel more comfortable discussing depression with their patients.
Conclusion
Depression is becoming easier to treat as our understanding of the condition continues to improve. Medications are safer and more effective than ever before and there is a wide range of information available to guide our clinical decisions. Primary care is an important setting for making an early diagnosis, and physicians should be proactive in screening patients who are at high risk.
Online Resources:
The American Psychiatric Association practice guidelines:
http://www.psych.org/MainMenu/PsychiatricPractice/PracticeGuidelines_1.aspx
The World Psychiatric Association:
http://www.worldpsychiatricassociation.org/
Texas Implementation of Medication Algorithm (TIMA):
http://www.dshs.state.tx.us/mhprograms/disclaimer.shtm
Institute of Mental Health patient information: http://www.imh.com.sg/patient_education/depression.htm
Depression.com:
http://www.depression.com/
UPLIFT trial reassures on tiotropium safety
Medical Tribune November 2008 P16
David Brill
Doctors can be reassured about prescribing inhaled tiotropium as a treatment for chronic obstructive pulmonary disease (COPD), one of Singapore’s leading respiratory experts has advised in light of a recent trial publication.
The Understanding Potential Long-Term Impacts on Function with Tiotropium (UPLIFT) study found that tiotropium was safe and significantly reduced the risk of cardiac adverse events among patients with moderate to very severe COPD.
The safety of inhaled anticholinergics had been called into question following the publication of two separate studies in September which linked the class of drugs to an increased risk of cardiovascular mortality.
One of the papers – a meta-analysis published in the Journal of the American Medical Association (JAMA) – reported a 58 percent increase in the risk of cardiovascular death, myocardial infarction or stroke among COPD patients taking either tiotropium or ipratropium. [2008 Sep 24;300(12):1439-50]
The US Food and Drug Administration (FDA) is conducting a thorough review of the findings from UPLIFT and expects to receive the full data set in November. However, the complete analysis could take several months, according to a statement on the FDA website.
The 4-year UPLIFT study, published in The New England Journal of Medicine, involved 5,993 patients from 37 countries who were randomized to tiotropium (18 μg once daily) or placebo. [2008 Oct 9;359(15):1543-54]
Dr. Ong Kian Chung, president of the Singapore COPD Association, said that he was happy with the safety data from UPLIFT and would continue to prescribe tiotropium as normal.
“I’m personally not too convinced that there is any significant complication from using these medications,” he said.
“The data from the meta-analysis isn’t enough to deny the patient the effectiveness of a long-acting anticholinergic. I think it’s more likely that it is a statistical fluke than a truly increased risk,” said Ong, who is currently a private practitioner at Mount Elizabeth Medical Centre, and was a co-investigator for the UPLIFT trial.
Patients in UPLIFT were allowed to continue their usual respiratory care with the exception of other inhaled anticholinergics, such as ipratropium, a shorter-acting formulation than the study
drug tiotropium. The use of these drugs was permitted, however, in the event of a serious exacerbation of COPD.
Dr. Sonal Singh, lead authorof the JAMA meta-analysis, questioned this aspect of the UPLIFT design and said that the trial does not invalidate the findings of the meta-analysis since the usage of ipratropium for exacerbations has not been reported.
“There might be differences in the risk between the long-acting and the short-acting, but UPLIFT is not going to answer that question because it was not designed that way,” he said.
“In one arm you have the long-acting and in the other arm you have people using the short-acting, so it’s not a valid comparison,” he said, adding that the meta-analysis demonstrated a higher cardiovascular risk with short-acting ipratropium than with long-acting tiotropium (risk ratios 1.70 and 1.43, respectively).
The meta-analysis incorporated 17 trials involving 14,783 patients.
A second paper, a nested case-control study including 32,130 cases and 320,501 controls, found an odds ratio of 1.34 for cardiovascular death associated with ipratropium. [Ann Intern Med 2008 Sep 16;149(6):380-90]
Tiotropium in UPLIFT was delivered with the HandiHaler inhalation device manufactured by Boehringer Ingelheim, which co-sponsored the trial with Pfizer.
Dr. Iylen Benedict, regional medical affairs director for Boehringer Ingelheim, said that the study by Singh et al. is methodologically flawed and pointed out that the majority of the evidence on ipratropium comes from a single study, the Lung Health Study. [Am J Respir Crit Care Med 2002;166(3):333-9]
“In this study, most of the cardiovascular deaths occurred among patients who were not using their medication,” she said.
“Other limitations [of the metaanalysis] include the inability to adjust for treatment duration and accounting for patients who discontinue the trial early, apparent double-counting of trials and combining placebo and active comparator drugs in the control group.”
Benedict also reiterated that the use of other anticholinergics such as ipratropium was not allowed in UPLIFT, and that the decision to allow any intervention in the face of a life-threatening exacerbation, as deemed necessary by a physician, was an ethical position.
She added that there are currently no plans for a trial looking specifically at cardiovascular outcomes with tiotropium, but confirmed that the full UPLIFT data will be provided to the FDA for the safety analysis.
UPLIFT did not reach its primary endpoint of significantly reducing the decline in forced expiratory volume 1, but did demonstrate significant improvements in lung function, exacerbations and quality of life with tiotropium therapy.
The trial included patients from seven Asian countries, including Singapore, Hong Kong, Malaysia and the Philippines. The results were first presented at the annual meeting of the European Respiratory Society, held recently in Berlin, Germany.
David Brill
Doctors can be reassured about prescribing inhaled tiotropium as a treatment for chronic obstructive pulmonary disease (COPD), one of Singapore’s leading respiratory experts has advised in light of a recent trial publication.
The Understanding Potential Long-Term Impacts on Function with Tiotropium (UPLIFT) study found that tiotropium was safe and significantly reduced the risk of cardiac adverse events among patients with moderate to very severe COPD.
The safety of inhaled anticholinergics had been called into question following the publication of two separate studies in September which linked the class of drugs to an increased risk of cardiovascular mortality.
One of the papers – a meta-analysis published in the Journal of the American Medical Association (JAMA) – reported a 58 percent increase in the risk of cardiovascular death, myocardial infarction or stroke among COPD patients taking either tiotropium or ipratropium. [2008 Sep 24;300(12):1439-50]
The US Food and Drug Administration (FDA) is conducting a thorough review of the findings from UPLIFT and expects to receive the full data set in November. However, the complete analysis could take several months, according to a statement on the FDA website.
The 4-year UPLIFT study, published in The New England Journal of Medicine, involved 5,993 patients from 37 countries who were randomized to tiotropium (18 μg once daily) or placebo. [2008 Oct 9;359(15):1543-54]
Dr. Ong Kian Chung, president of the Singapore COPD Association, said that he was happy with the safety data from UPLIFT and would continue to prescribe tiotropium as normal.
“I’m personally not too convinced that there is any significant complication from using these medications,” he said.
“The data from the meta-analysis isn’t enough to deny the patient the effectiveness of a long-acting anticholinergic. I think it’s more likely that it is a statistical fluke than a truly increased risk,” said Ong, who is currently a private practitioner at Mount Elizabeth Medical Centre, and was a co-investigator for the UPLIFT trial.
Patients in UPLIFT were allowed to continue their usual respiratory care with the exception of other inhaled anticholinergics, such as ipratropium, a shorter-acting formulation than the study
drug tiotropium. The use of these drugs was permitted, however, in the event of a serious exacerbation of COPD.
Dr. Sonal Singh, lead authorof the JAMA meta-analysis, questioned this aspect of the UPLIFT design and said that the trial does not invalidate the findings of the meta-analysis since the usage of ipratropium for exacerbations has not been reported.
“There might be differences in the risk between the long-acting and the short-acting, but UPLIFT is not going to answer that question because it was not designed that way,” he said.
“In one arm you have the long-acting and in the other arm you have people using the short-acting, so it’s not a valid comparison,” he said, adding that the meta-analysis demonstrated a higher cardiovascular risk with short-acting ipratropium than with long-acting tiotropium (risk ratios 1.70 and 1.43, respectively).
The meta-analysis incorporated 17 trials involving 14,783 patients.
A second paper, a nested case-control study including 32,130 cases and 320,501 controls, found an odds ratio of 1.34 for cardiovascular death associated with ipratropium. [Ann Intern Med 2008 Sep 16;149(6):380-90]
Tiotropium in UPLIFT was delivered with the HandiHaler inhalation device manufactured by Boehringer Ingelheim, which co-sponsored the trial with Pfizer.
Dr. Iylen Benedict, regional medical affairs director for Boehringer Ingelheim, said that the study by Singh et al. is methodologically flawed and pointed out that the majority of the evidence on ipratropium comes from a single study, the Lung Health Study. [Am J Respir Crit Care Med 2002;166(3):333-9]
“In this study, most of the cardiovascular deaths occurred among patients who were not using their medication,” she said.
“Other limitations [of the metaanalysis] include the inability to adjust for treatment duration and accounting for patients who discontinue the trial early, apparent double-counting of trials and combining placebo and active comparator drugs in the control group.”
Benedict also reiterated that the use of other anticholinergics such as ipratropium was not allowed in UPLIFT, and that the decision to allow any intervention in the face of a life-threatening exacerbation, as deemed necessary by a physician, was an ethical position.
She added that there are currently no plans for a trial looking specifically at cardiovascular outcomes with tiotropium, but confirmed that the full UPLIFT data will be provided to the FDA for the safety analysis.
UPLIFT did not reach its primary endpoint of significantly reducing the decline in forced expiratory volume 1, but did demonstrate significant improvements in lung function, exacerbations and quality of life with tiotropium therapy.
The trial included patients from seven Asian countries, including Singapore, Hong Kong, Malaysia and the Philippines. The results were first presented at the annual meeting of the European Respiratory Society, held recently in Berlin, Germany.
Wednesday, February 11, 2009
Asia takes action on drug-resistant tuberculosis
David Brill
The Lancet Infectious Diseases October 2008
Article link
Africa and eastern Europe have largely dominated recent attention around strengthening tuberculosis control, but Asia could yet prove the decisive battleground in the international war on the disease. At a gathering of countries from WHO's Western Pacific Region (WPR) in Tokyo (July 22—24) Pieter van Maaren, regional advisor for tuberculosis (WHO, Manila, Philippines),
accused Asian nations of complacency, saying: “if we are going to avoid a public-health disaster, we have to accelerate action”. Representatives from all eight of the countries that attended—representing around 95% of the region's multidrug-resistant (MDR) tuberculosis burden—acknowledged the issue and agreed to raise their commitment to it.
Strengthening diagnostic laboratory facilities is a major component of WHO's strategy for the control of MDR tuberculosis in the region. Senior laboratory managers from the WPR will be attending a workshop in Hong Kong in October to discuss how to implement the latest technologies, including molecular line probe assays that can give a diagnosis of MDR tuberculosis in 2 days. These tests are being introduced through a UNITAID-funded project, announced in June. Laboratory capacity is a serious concern in the SEAR, which is home to only two of the 26 centres in WHO's global Supranational Laboratory Network, a network that provides assistance with MDR-tuberculosis testing to national facilities.
“For us in this region the emphasis is on using this window of opportunity to put in cost-effective interventions to prevent MDR tuberculosis. It's less about trying to catch people once they've developed MDR disease, which is what we are seeing in eastern Europe and in Africa, but rather building that barrier to stop people developing MDR tuberculosis in the first place”, said Nani Nair, SEAR's regional tuberculosis advisor (WHO, New Delhi, India).
In Tokyo, delegates also promised to commit to providing better access to treatment, with countries being encouraged to submit proposals to the Global Fund to finance the purchasing of drugs for MDR tuberculosis. Management programmes supported by the Green Light Committee are currently operating in six SEAR countries, while UNITAID funding is available for drug procurement in three.
Nair told TLID: “…if all current plans can be implemented successfully then the long-term outlook for control of MDR in the SEAR is very good”. At present, however, she estimates that only half the required budget has been raised. The region does not contain any major international donors, and to make up this shortfall countries must rely on funding from their own governments, donors from other regions, and international initiatives such as the Global Fund and UNITAID.
China meanwhile is looking into health-care reforms and how they can be integrated into scalable new programmes for MDR-tuberculosis treatment and control. In the wake of the severe acute respiratory syndrome epidemic in 2003 it became a legal requirement for health-care systems to report all new tuberculosis cases within 24 h. Individual patients from across the country are now entered into an online database and can be tracked centrally to ensure that they receive appropriate treatment.
The project has caught the attention of the Bill & Melinda Gates Foundation, who have pledged to spend some US$900 million on tuberculosis worldwide by 2015. Representatives from the Foundation have been in discussions with the Chinese government about how new diagnostic technologies can be integrated into this system to detect multidrug resistance at the first point of contact. “Their surveillance system is phenomenal, and they've scaled it up so that 90% of their referral hospitals are using it. Having these online mechanisms for tracking tuberculosis cases and ensuring that those patients get optimal therapy lays the foundation for a truly innovative programme for controlling MDR tuberculosis that goes beyond the standard interventions”, said Senior Program Officer for Tuberculosis Peter Small (Bill & Melinda Gates Foundation, Seattle, WA, USA), who recently returned from a fact-finding trip to the country. He added that he was “very impressed by the government's commitment” to tackling MDR tuberculosis.
How current efforts to control MDR tuberculosis in Asia will affect the longer-term global spread of the disease remains to be seen. Small is in no doubt, however, as to the importance of the task. “What the world is doing with MDR tuberculosis right now, through inaction, is committing ourselves to a future epidemic of much more complicated tuberculosis. I suspect that future generations will judge us harshly if we fail to intervene”, he said.
Images courtesy of WHO/P Virot.
The Lancet Infectious Diseases October 2008
Article link
This article also appeared on the Stop TB homepage of the WHO's Western Pacific Region Office.
Africa and eastern Europe have largely dominated recent attention around strengthening tuberculosis control, but Asia could yet prove the decisive battleground in the international war on the disease. At a gathering of countries from WHO's Western Pacific Region (WPR) in Tokyo (July 22—24) Pieter van Maaren, regional advisor for tuberculosis (WHO, Manila, Philippines),
accused Asian nations of complacency, saying: “if we are going to avoid a public-health disaster, we have to accelerate action”. Representatives from all eight of the countries that attended—representing around 95% of the region's multidrug-resistant (MDR) tuberculosis burden—acknowledged the issue and agreed to raise their commitment to it. The WPR alone makes up a quarter of the world's tuberculosis cases—a similar proportion to Africa. Together with the South-East Asia Region (SEAR), more than 300 000 cases are estimated to be MDR, with only 1% of patients accessing appropriate treatment. The prevalence of MDR tuberculosis is highest in China (one in every ten new tuberculosis cases), which remains second only to the former Soviet Union in terms of prevalence.
Strengthening diagnostic laboratory facilities is a major component of WHO's strategy for the control of MDR tuberculosis in the region. Senior laboratory managers from the WPR will be attending a workshop in Hong Kong in October to discuss how to implement the latest technologies, including molecular line probe assays that can give a diagnosis of MDR tuberculosis in 2 days. These tests are being introduced through a UNITAID-funded project, announced in June. Laboratory capacity is a serious concern in the SEAR, which is home to only two of the 26 centres in WHO's global Supranational Laboratory Network, a network that provides assistance with MDR-tuberculosis testing to national facilities.
“For us in this region the emphasis is on using this window of opportunity to put in cost-effective interventions to prevent MDR tuberculosis. It's less about trying to catch people once they've developed MDR disease, which is what we are seeing in eastern Europe and in Africa, but rather building that barrier to stop people developing MDR tuberculosis in the first place”, said Nani Nair, SEAR's regional tuberculosis advisor (WHO, New Delhi, India).
In Tokyo, delegates also promised to commit to providing better access to treatment, with countries being encouraged to submit proposals to the Global Fund to finance the purchasing of drugs for MDR tuberculosis. Management programmes supported by the Green Light Committee are currently operating in six SEAR countries, while UNITAID funding is available for drug procurement in three.
Nair told TLID: “…if all current plans can be implemented successfully then the long-term outlook for control of MDR in the SEAR is very good”. At present, however, she estimates that only half the required budget has been raised. The region does not contain any major international donors, and to make up this shortfall countries must rely on funding from their own governments, donors from other regions, and international initiatives such as the Global Fund and UNITAID.
China meanwhile is looking into health-care reforms and how they can be integrated into scalable new programmes for MDR-tuberculosis treatment and control. In the wake of the severe acute respiratory syndrome epidemic in 2003 it became a legal requirement for health-care systems to report all new tuberculosis cases within 24 h. Individual patients from across the country are now entered into an online database and can be tracked centrally to ensure that they receive appropriate treatment.
The project has caught the attention of the Bill & Melinda Gates Foundation, who have pledged to spend some US$900 million on tuberculosis worldwide by 2015. Representatives from the Foundation have been in discussions with the Chinese government about how new diagnostic technologies can be integrated into this system to detect multidrug resistance at the first point of contact. “Their surveillance system is phenomenal, and they've scaled it up so that 90% of their referral hospitals are using it. Having these online mechanisms for tracking tuberculosis cases and ensuring that those patients get optimal therapy lays the foundation for a truly innovative programme for controlling MDR tuberculosis that goes beyond the standard interventions”, said Senior Program Officer for Tuberculosis Peter Small (Bill & Melinda Gates Foundation, Seattle, WA, USA), who recently returned from a fact-finding trip to the country. He added that he was “very impressed by the government's commitment” to tackling MDR tuberculosis.
How current efforts to control MDR tuberculosis in Asia will affect the longer-term global spread of the disease remains to be seen. Small is in no doubt, however, as to the importance of the task. “What the world is doing with MDR tuberculosis right now, through inaction, is committing ourselves to a future epidemic of much more complicated tuberculosis. I suspect that future generations will judge us harshly if we fail to intervene”, he said.
Images courtesy of WHO/P Virot.
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