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New medication for dry eye disease

July 12, 2016

The U.S. Food and Drug Administration approved Xiidra (lifitegrast ophthalmic solution) for the treatment of signs and symptoms of dry eye disease, on Monday, July 11, 2016. Xiidra is the first medication in a new class of drugs, called lymphocyte function-associated antigen 1 (LFA-1) antagonist, approved by the FDA for dry eye disease.

“Normal tear production is needed for clear vision and eye health,” said Edward Cox, M.D., director of the Office of Antimicrobial Products in the FDA’s Center for Drug Evaluation and Research. “This approval will provide a new treatment option for patients with dry eye disease.”

Dry eye disease includes a group of conditions in which the eye does not produce an adequate volume of tears or when the tears are not of the correct consistency. The chance of experiencing dry eye increases with age, affecting approximately five percent of the adult population age 30-40 and 10 to 15 percent of adults over age 65, and is more common among women. When severe and left untreated, this condition can lead to pain, ulcers or scars on the part of the eye called the cornea. Dry eye can make it more difficult to perform some activities, such as using a computer or reading for an extended period of time, and it can decrease tolerance for dry environments, such as the air inside an airplane.

The safety and efficacy of Xiidra was assessed in over a thousand patients, in four separate, randomized, controlled studies. These studies included patients 19–97 years of age, of which the majority were female (76 percent). Patients were randomized equally to receive either Xiidra eyedrops or placebo eyedrops, which were used twice a day for twelve weeks. The studies found that groups treated with Xiidra demonstrated more improvement in both the signs and the symptoms of eye dryness than the groups treated with placebo.

The most common side effects of Xiidra include eye irritation, discomfort or blurred vision and an unusual taste sensation (dysgeusia).

Dry eye disease does not routinely occur in children. Safety and efficacy in pediatric patients below the age of 17 years has not been studied.

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Empagliflozin offers clear CV benefits in patients with T2DM

16 Jul 2016

Empagliflozin has high SGLT2 selectivity

“SGLT2 inhibitors such as empagliflozin offer a novel, insulin-independent approach for achieving glycaemic control,” said Lee.

He noted that glycosuria is absent under normal physiological circumstances because glucose from the glomerular filtrate is reabsorbed by the kidneys. SGLT2 is a transporter that facilitates this process, and it is associated with approximately 90 percent of glucose reabsorption in the kidneys. Thus, glycaemic control can be achieved by halting renal glucose reabsorption through SGLT2 inhibition.

“Of the SGLT2 inhibitors currently available for T2DM treatment, empagliflozin has a higher SGLT2 selectivity than dapagliflozin and canagliflozin,” said Lee. (Table) [Jardiance Product Information; Forxiga Product Information;  Invokana Product Information; Diabetes Obes Metab 2015;17:188-197]

 

Empagliflozin has been shown to produce clinically meaningful HbA1c reduction in patients on different background therapies for glycaemic control, including those with suboptimal response to metformin, metformin plus sulphonylurea, basal insulin, and multiple insulin injections. [Diabetes Care2013;36:3396-3404; Diabetes Care 2014;37:1650-1659; Diabetes Obes Metab 2015;17:936-948;Diabetes Care 2014;37:1815-1823]

“Despite the availability of a variety of effective glucose-lowering agents for T2DM patients, many patients have other comorbidities and cardiovascular [CV] risk factors that cannot be adequately addressed with glucose control alone. We therefore need to look for agents that may also address some of these CV risk factors,” suggested Lee.

Optimal management of dysglycaemia

“Optimal management of patients with dysglycaemia requires more than lifestyle modification and glycaemic control,” said Rydén. “Their blood pressure and lipid levels also need to be adequately controlled and platelets stabilized. Ideally, any glucose-lowering agent for these patients should affect as many of these mechanisms as possible.”

“It is well known that elevation in blood glucose levels causes vascular damages. Therefore, normalization of blood glucose levels should theoretically be CV protective,” he noted. “However, trials of most existing therapies have generally been disappointing in this respect.

“There has been plenty of controversy over whether glucose-lowering therapies have adverse or beneficial effects on CV outcomes among patients with T2DM, but much seems to depend on the class of agent used. Recently, the SGLT2 inhibitor empagliflozin has been shown to have beneficial CV effects when administered as an add-on therapy to standard care,” remarked Rydén.

Empagliflozin reduces adverse CV outcomes

Empagliflozin has been proven to reduce the risk of adverse CV outcomes. In the ground-breaking EMPA-REG OUTCOME (Empagliflozin-Renal Excretion of Glucose Outcome) study, 7,020 adult patients with T2DM and established CVD were randomized to receive placebo (n=2,333), empagliflozin 10 mg/day (n=2,345) or empagliflozin 25 mg/day (n=2,342) in addition to standard care. [N Engl J Med2015;373:2117-2128; Eur Heart J 2016;37:1526-1534]

“As expected, the researchers observed a relatively modest decrease in HbA1c levels, small reductions in systolic blood pressure and weight, and slightly elevated LDL-cholesterol levels. However, the most surprising and impressive finding was the 14 percent reduction in the composite primary endpoint of CV death, non-fatal MI or stroke,” said Rydén.

The study also showed that empagliflozin significantly reduced the risk of hospitalization for heart failure, CV mortality and all-cause mortality even among high-risk patients with heart failure at baseline. (Figure 2) [Eur Heart J 2016;37:1526-1534]

 

Conclusion

“The 34 percent reduction in first hospitalization for heart failure or CV death and the 39 percent reduction in all-cause mortality with empagliflozin are striking, particularly since the benefits were clearly observed in patients with and without heart failure at baseline,” said Rydén.

“A hypothetical mechanism to explain these findings is the reduction in myocardial preload and afterload due to volume and sodium depletion by empagliflozin. What is interesting is that we are now talking about a glucose-lowering drug that has completely different capacities. The drug is available in the market for treating patients of the kind investigated in the EMPA-REG OUTCOME trial. Moreover, the results open a new field of research, which may offer further hope for patients with T2DM,” concluded Rydén.

 

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Empagliflozin delays kidney disease and dialysis in diabetes outcome trial

20 Jun 2016

Empagliflozin significantly delays the progression of kidney disease and reduces renal events in patients with type 2 diabetes mellitus (T2DM) at high cardiovascular (CV) risk, new data from the EMPA-REG OUTCOME (Empagliflozin-Renal Excretion of Glucose Outcome) trial have shown.

A 39 percent reduction in risk of incident or worsening nephropathy was demonstrated with empagliflozin vs placebo (p<0.001) in a trial population with one-third of patients having prevalent kidney disease (estimated glomerular filtration rate [eGFR] 30-60 mL/min/1.73m2 and/or macroalbuminuria) at baseline. [N Engl J Med 2016; doi: 10.1056/NEJMoa1515920]

“Both the 10 mg and 25 mg doses of empagliflozin demonstrated the same effect on nephropathy,” reported lead author Professor Christoph Wanner of the Wurzburg University Clinic, Wurzburg, Germany, at the American Diabetes Association’s 76th Scientific Sessions in New Orleans, LA, US. “The effect was consistent in different subgroups of patients.”

While empagliflozin’s effect on nephropathy was driven by a 38 percent risk reduction in new-onset macroalbuminuria (p<0.0001), the results also showed a 55 percent reduced risk of initiation of dialysis (p=0.049) and a 44 percent reduced risk of doubling of serum creatinine (p=0.0009) with empagliflozin vs placebo.

“When the ‘hard’ renal outcomes of doubling of serum creatinine, initiation of dialysis and death due to renal disease were analyzed together, a 46 percent risk reduction was seen with empagliflozin vs placebo [p<0.001], with the curves beginning to diverge at 1.5 years,” said Wanner.

The researchers also analyzed renal outcomes in patients with prevalent kidney disease at baseline. In these patients, empagliflozin reduced the risk of incident or worsening nephropathy by 42 percent (p<0.001).

“eGFR remained stable in the empagliflozin arms throughout the study, but a natural progression was seen in the placebo arm,” said Wanner.

“The adjusted mean difference in eGFR change from baseline with empagliflozin vs placebo was 4.7 mL/min/1.73m2 when patients were followed up at a median of 34 days after their last on-treatment eGFR measurement,” he continued. “As nephrologists, we all know what 4.7 mL/min/1.73m2 means in pushing dialysis further down the road.”

“The safety and tolerability of empagliflozin in patients with chronic kidney disease at baseline were similar to that in the overall trial population,” added Wanner. “Acute renal failure and acute kidney injury occurred at lower rates in the empagliflozin vs placebo arm.”

The EMPA-REG OUTCOME trial was conducted in 7,020 T2DM patients with established CV disease. Patients were randomized to receive empagliflozin 10 mg or 25 mg daily or placebo, and assessed for the primary outcome of major adverse CV events (CV mortality, nonfatal MI, nonfatal stroke). Assessment of renal outcomes was a pre-specified objective, with incident or worsening nephropathy defined as progression to macroalbuminuria, doubling of serum creatinine accompanied by eGFR ≤45 mL/min/1.73m2, initiation of dialysis, or death due to renal disease.

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Poor hydration linked to higher BMI, obesity

20 Jul 2016

Lack of hydration is associated with a higher obesity risk, according to a recent US study.

Individuals with inadequate hydration were more likely to be obese (odds ratio [OR], 1.59, 95 percent confidence interval [CI], 1.35-1.88; p<0.001) than those who with adequate hydration. Inadequate hydration was also linked to higher body mass index (BMI; 1.32 kg/m2 higher than adequately hydrated individuals, 95 percent CI, 0.85-1.79; p<0.001). [Ann Fam Med 2016;14:320-324]

“[Findings of this study] highlight a novel relationship between hydration and BMI that may have important clinical implications,” said the authors. “[The relationship between hydration, BMI and obesity] suggests that water, an essential nutrient, may deserve greater focus in weight management research and clinical strategies,” they said.

Using data from the National Health and Nutrition Examination Survey (NHANES) 2009 to 2012, researchers from the University of Michigan, Ann Arbor, Michigan, US recruited 9,528 adults (aged 18-64 years) to identify a link between inadequate hydration and BMI or obesity. Urine osmolality was utilized as a marker of hydration; almost 33 percent of the participants did not have adequate hydration (urine osmolality ≥800 mOsm/kg).

According to the authors, adequate hydration is not included in many treatment guidelines for weight management. “Obese individuals have higher water needs than nonobese individuals,” they said, suggesting that clinicians who may not be aware of the difference in water requirements between individuals with higher and lower BMIs may not be advising their obese patients accurately.

The authors cautioned that due to the cross-sectional nature of the study, causality and directionality could not be established, and that one-time measurement of urine osmolality may not necessarily indicate the participants’ usual hydration levels.

 

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Stenting through the wrist reduces risk of death in heart disease patients

13 Jul 2016

Inserting stents by radial access for percutaneous coronary intervention (PCI) reduced bleeding and risk of death in patients with coronary artery disease (CAD) as opposed to femoral access, according to a recent meta-analysis of 24 randomized trials.

“These findings support the use of radial access as the default approach for coronary angiography followed by PCI in the whole spectrum of patients with CAD undergoing invasive management, and strongly support a change in the ‘femoral first’ paradigm to a ‘radial first’ approach,” said lead author Dr. Giuseppe Ferrante of the Department of Cardiovascular Medicine at Humanitas Research Hospital in Milan, Italy.

In the meta-analysis which pooled data from 22,843 patients in 24 randomized studies, patients who underwent radial access had a 29 percent lower risk of death from any cause compared with those who had intervention through femoral access (odds ratio [OR], 0.71, 95 percent confidence interval [CI], 0.59-0.87; p=0.001). [JACC Cardiovasc Interv 2016;doi:10.1016/j.jcin.2016.04.014]

Risk of major adverse cardiovascular events (MACE) also decreased by 16 percent with radial access in comparison to femoral access (OR, 0.84, 95 percent CI, 0.75-0.94; p=0.002).

Additionally, there was a significant reduction of risks for major bleeding by 47 percent (OR, 0.53, 95 percent CI, 0.42-0.65; p<0.001) and major vascular complications by 77 percent (OR, 0.23, 95 percent CI, 0.16-0.35; p<0.001) with radial access in contrast to femoral access.

Risks of stroke and myocardial infarction were similar using both methods.

Importantly, the researchers found that radial access improved clinical outcomes mentioned above across a broad spectrum of stable and unstable CAD, including ST segment elevation myocardial infarction (STEMI), non-ST segment elevation (NSTE) acute coronary syndromes (ACS), and unstable angina.

“As much as possible, all eligible patients with a good radial pulse and positive Allen’s test [could be considered for transradial PCI],” said Dr. Jack Tan Wei Chieh, a senior consultant cardiologist and director of the Coronary Care Unit at the National Heart Centre Singapore in Singapore who was unaffiliated with the study.

At least 70 percent of all his pre-scheduled cases for coronary intervention in Singapore were performed through radial access, he added.

“Several anatomic features give the wrist an advantage over the groin,” said Dr. John Bittl, a cardiologist at Munroe Regional Medical Center in Ocala, Florida, US, in a separate commentary. “With the redundant vascular supply of the hand… loss of a radial pulse has fewer consequences than loss of the common femoral artery pulse.” [JACC Cardiovasc Interv 2016;doi:10.1016/j.jcin.2016.05.026]

However, patients with small radial arteries, upper-extremity haemodialysis access, and abnormal Allen’s test results are not favourable candidates for PCI through radial access, he said.

Tan agreed, adding that, “[Transradial PCI is] not for renal failure patients and post-bypass cases. Patients who require larger French guide catheters, or who have poor radial pulses with failure to demonstrate good collateral filling of the hand from the Ulnar artery [are also not recommended].”

Certain anatomical features of Asians could also limit radial access for the procedure, said Tan.

“The radial accesses for elderly ladies are smaller, more tortuous and tend to have spasms with minimal manipulation.”

The main challenge in performing transradial PCI lies in overcoming the learning curve to attain mastery of technical skills, said Tan. Previous studies have reported that high procedure volumes were often required by cardiologists to achieve proficiency. [Int J Cardiol 1998;64:231–239]

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Young Children With Sleep Apnea May Face Learning Difficulties: Study

– Sleep apnea in young children may affect youngsters’ attention, memory and language development, a new study suggests.

The researchers added that as sleep apnea worsens, the risk of these problems also may increase.

“Although evidence suggesting the presence of cognitive deficits in children with sleep apnea has been around for quite some time, the relatively small groups studied made it difficult to demonstrate a strong relationship between increasing cognitive issues and increasing sleep apnea severity,” said Dr. Leila Gozal, from the University of Chicago.

Sleep apnea causes people to experience repetitive pauses in breathing while they sleep. This causes oxygen levels to drop temporarily, according to the U.S. National Heart, Lung, and Blood Institute.

While the new study with children did not prove cause-and-effect, previous research has shown that sleep apnea in adults is associated with trouble concentrating, memory issues, poor decision-making, depression and stress.

The new study involved almost 1,400 public schoolchildren with sleep apnea. The kids ranged in age from 5 to 7. Some, but not all, of the children snored.

The researchers divided the children into four groups based on the severity of their sleep apnea.

The kids participated in an overnight sleep study and answered detailed questions about their sleep. The children also completed tests to measure certain aspects of brain function, including language and decision-making skills.

After comparing the results in each group, the researchers found that even mild problems such as snoring had a negative effect on children’s thinking abilities, the researchers reported in a news release from the American Thoracic Society.

Gozal said the findings suggest that the development of simple brain function tests that could be used along with current clinical evaluation of children with habitual snoring might help guide the treatment of children with sleep apnea.

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Zika Destroys Fetal Brain Cells, Lab Study Finds

The terrible birth defects caused by Zika virus appear to be the result of an immune system response that triggers prenatal brain cell suicide and obstructs fetal brain development, a new lab study reports.

The virus apparently activates an immune receptor called TLR3, which the body uses to identify and defend against invading viruses, said lead researcher Tariq Rana. He is a professor of pediatrics and genetics at the University of California, San Diego.

The hyper-activated TLR3 then proceeds to turn off genes that fetal stem cells need to specialize into brain cells, and appears to switch on genes that trigger cell suicide, Rana said.

“We all have an innate immune system that evolved specifically to fight off viruses, but here the virus turns that very same defense mechanism against us,” Rana explained. “By activating TLR3, the Zika virus blocks genes that tell stem cells to develop into the various parts of the brain.”

These findings help explain how Zika causes microcephaly, an abnormally small brain and skull development, and other neonatal brain-related birth defects, Rana said. They also show why there’s no similar effect in adults, since their brains are already fully developed.

There’s also good news for the potential prevention of brain birth defects due to Zika. Rana and his team successfully blocked this process in laboratory stem cell samples by using a chemical that inhibits the action of TLR3.

A drug that safely blocks TLR3 could possibly save babies from birth defects if given to Zika-infected women during the early stages of pregnancy, he said.

“If some mom comes into the clinic and the doctor thinks there is a Zika infection established, you could give this med, and once the first trimester is done, you can take them off the med,” Rana suggested.

Zika is the first mosquito-borne virus ever proven to cause birth defects, according to the U.S. Centers for Disease Control and Prevention.

To figure out why this happens, Rana and his team used human embryonic stem cells to create a laboratory model of a first-trimester human brain, also called a “cerebral organoid.” The model’s stem cells were designed to specialize and grow into the various different cells in the brain, much the same as they do during a fetus’ first trimester.

Researchers then infected their model with Zika and found that a developing brain shrinks when exposed to the virus.

Five days after infection, Zika-infected organoids had decreased in size by an average 16 percent, the researchers found. By comparison, healthy brain organoids in a control sample had grown an average of 22.6 percent.

Rana’s team noticed that the TLR3 gene had been activated in the Zika-infected model brains.

TLR3’s job is to sense viruses and activate an immune response. But the researchers found TLR3 activation influenced 41 genes in the fetal brain and caused a disastrous chain-reaction that both prompted cells to die off and interfered with stem cells’ ability to grow into different brain cells.

By adding a chemical TLR3 inhibitor, Rana’s team found they could partially protect developing brain cells against Zika, although the virus still wound up doing some damage to their model brain.

Rana said this research has only been conducted in human and mouse cells, and needs to be replicated in actual organisms before it can be used to create any therapy to counter Zika.

But infectious disease expert Dr. Amesh Adalja called the work an “elegant study that begins to unravel how Zika is capable of causing microcephaly in the developing fetus.”

Adalja, a senior associate with the University of Pittsburgh Medical Center’s Center for Health Security, said, “We had known prior to this study that Zika had the capacity to infect neural progenitor cells and cause damage.”

With this study, he added, “we now have an elucidation of one mechanism that the virus uses, TLR3. This discovery opens up avenues for further understanding of the entire cascade of changes in gene expression that are caused by Zika infection.”

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New Guidelines Issued on Breast, Genital Plastic Surgery for Teen Girls

hd60993A growing interest among teenaged girls in plastic surgery on their breasts or genitals has prompted a leading ob/gyn group to recommend that doctors first talk to these young women about “normal” sexual development.

“Our membership has been telling us this is coming up more and more frequently with their adolescent patients,” said Dr. Julie Strickland. She is chair of the Adolescent Health Care Committee of the American College of Obstetricians and Gynecologists (ACOG).

The new recommendations also suggest that physicians screen these patients for body dysmorphic disorder, which is an obsession with an imagined or slight defect in appearance.

There are already guidelines from the American Society of Plastic Surgeons (ASPS) on breast augmentation and reduction among teenagers. If it’s strictly for cosmetic reasons, the society recommends surgery should generally be delayed until age 18.

But, Strickland said, there’s no guidance for cases where teenagers want labiaplasty — where surgery is used to reduce the inner labia, the folds of skin that surround the vaginal opening.

Normal labia come in all sizes and shapes, Strickland said, and there’s no widely accepted definition of labial “hypertrophy,” or enlargement. Nor are there clear guidelines on when surgery might be appropriate for teenagers.

The new guidelines appear in the May issue of Obstetrics & Gynecology.

When girls are worried about the appearance of their breasts or genitals, Strickland said, the anxiety can often be “diffused” by letting them know there is a wide variation in “normal” development.

Even in this day and age, she noted, many girls do not know what their genitals are “supposed” to look like. “Despite all of the anatomy books that have been published over the years, we’re lacking in descriptions of normative female genital development,” Strickland said.

Nationwide, about 8,000 13- to 19-year-olds underwent breast augmentation in 2014, according to the ASPS. Statistics on breast reduction are harder to come by, but in 2010 about 4,600 were performed on 13- to 19-year-olds.

The ASPS does not track labiaplasty figures, and it’s not clear how many teenagers have the procedure each year, according to ACOG.

No one knows exactly why teenagers are voicing more concerns about their labial development, either, Strickland said.

“One theory is that girls these days are seeing images of ‘idealized’ bodies,” Strickland said. “There have also been cultural changes, with more girls grooming their pubic hair. That may make them more self-conscious about the appearance of their genitals.”

Then there are the yoga pants and other form-fitting clothes that can either make girls scrutinize their appearance, or be physically uncomfortable, she added.

And it is actually physical discomfort that seems to be the main issue for teenage girls who want labiaplasty, said Dr. David Song, president of the ASPS. Song is also chief of plastic and reconstructive surgery at the University of Chicago.

“It’s pretty rare to have a teenager coming in for cosmetic reasons,” Song said.

When the inner labia protrude from the outer labia, he explained, it can be “very uncomfortable” to wear tighter clothing, or to exercise at all. In those cases, surgery to reduce the inner labia may help a girl feel better physically and emotionally, Song said.

He agreed that it’s important to be sure teenagers are mature enough, and fully informed of the risks, before any plastic surgery. With labiaplasty, ACOG says, the potential risks include infection, scarring, and pain during sex.

According to Song, board-certified plastic surgeons are also trained to screen for body dysmorphic disorder and other mental health issues, like depression.

“They understand when they should be referring patients to a mental health professional,” Song said.

That’s why it’s key, he added, for parents and young women to make sure they’re seeing a surgeon who is board-certified.

When it comes to breast surgery, the ASPS does recommend that it generally be delayed to age 18. But, Song said, the issue is “not black-and-white,” and there are cases where earlier may be better.

An example, he said, would be a younger teen whose breast growth is far out of proportion to the rest of her body — to the point that it’s causing her physical discomfort.

According to Strickland, the bottom line for parents is this: Listen to your daughter’s concerns about her development, and be able to reassure her that she’s going through normal changes. If you’re not sure of what’s “normal,” talk to your pediatrician or family doctor, Strickland said.

“It’s typical for teenagers to question whether they’re ‘normal’ or not,” she noted. “So we shouldn’t be ‘horrified’ if they come to us with these questions. We need to respond sensitively and honestly.”

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Endometriosis linked to increased risk of coronary heart disease

Women with endometriosis, a painful uterus condition, may be at a higher risk for coronary heart disease (CHD), a new study suggests.

The link was found to be strongest among young women. Having had a hysterectomy or oophorectomy was also tied to a higher risk of CHD, which explained partially the association between endometriosis and CHD.

Researchers analysed the potential connection between laparoscopically confirmed endometriosis and subsequent CHD among 116,430 women in the Nurses’ Health Study II (1989–2009). Excluded from the study were those with a history of heart disease and stroke.

Women with endometriosis had a higher risk of myocardial infarction, angiographically confirmed angina, coronary artery bypass graft surgery/coronary angioplasty procedure/stent, or any of these CHD endpoint combined when compared with women without the gynecologic disease.

The result was independent of potential demographic, anthropometric, family history, reproductive, and lifestyle confounders.

Relative risk for the combined CHD endpoint was highest among women aged ≤40 years and decreased as age increased (40<age≤50 years, 50<age≤55 years and age >55 years.

Women who had hysterectomy/oophorectomy had a higher risk of combined CHD compared with those who had not undergone the procedure. Greater frequency of hysterectomy/oophorectomy and earlier age at surgery after endometriosis diagnosis explain the 42 percent association between the gynaecologic condition and CHD.

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Managing dengue fever in primary care

Dengue fever is caused by the dengue virus and borne by the Aedes mosquito. The disease is now endemic in over 100 countries, according to the World Health Organization, but is still most common in Southeast Asian and countries in the Western Pacific. The virus causes flu-like symptoms that generally resolve on their own with supportive care but severe cases require further management and possibly hospitalization. Primary care doctors are frequently the first point of contact for people with dengue fever.

 

Dengue fever is a mosquito borne infection caused by the dengue virus, the most common mosquito borne viral infection in the world. We no longer talk about dengue as a disease affecting Asian countries – at least half of the world population is at risk for dengue because of where they live and their exposure to the virus from mosquitoes bites.

Since 2013, the total number of dengue cases recorded in Singapore has remained high at more than 10,000 cases annually. This is likely the result of a combination of factors such as high mosquito population, warmer weather, increasing urban density and low herd immunity in the Singapore local resident population.

Primary care doctors probably play the biggest role in identifying and caring for patients with dengue fever. Most of the time patients will go to their family doctor to seek medical advice  first, as the symptoms of early dengue infection cannot be differentiated from other viral illnesses. If dengue is suspected, nonsteroidal anti-inflammatory drugs (NSAIDS) and intramuscular injections should be avoided due to the risk of bleeding. The family physician should monitor the patient regularly throughout the course of illness. If the doctor is concerned that the patient may be at risk for severe dengue, the doctor should then refer the patient to hospital for further medical evaluation.

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Dengue fever: running the course

Dengue fever is a self-limiting illness. Once a person is bitten by a virus-carrying mosquito he/she will come down with flu-like symptoms after an incubation period of 3-7 days. The patient may experience high fever, body aches and pains, loss of appetite and, in some cases, nausea and vomiting. Most patients will recover from the infection after about a week of illness.

One of the hallmarks of dengue fever occurs around day 4-5 of illness – the fever begins to improve but the blood platelet count starts to fall. This might cause patients to present with petechial rashes, which are small capillary bleeds just under the skin that look like small red dots. They are harmless but can be alarming and usually send patients back to the doctor who, under suspicion of dengue fever, would refer the patient to a hospital or polyclinic for a blood test.

Depending on how low the platelet levels are, and if the patient is otherwise well (if they are young, healthy, and able to drink sufficient fluids), they can be sent home and instructed to rest. Polyclinic doctors can continue to monitor the patient without referring to a hospital.

However, if the platelets are low and the patient is unwell, has poor appetite, is not able to drink sufficient fluids, or  if there is a worry of dengue complications that may result in severe dengue,  doctors may refer the patient to hospital for further management.

Plasma leaks and bleeding

The most important thing about dengue virus is its ability to cause severe disease. It is not well understood how the virus interacts with the cell lining of blood vessels but in severe dengue, plasma leaks into the surrounding tissues and accumulates. Fluid can accumulate in the lungs as well, resulting in hypotension and shock if the person does not receive fluid resuscitation in time.

The other feared complication is bleeding. Bleeding can occur in the gut, gums, urinary tract and brain. Women may also experience heavy menstrual bleeds.

Patients over 65 years, those with other medical conditions such as diabetes, pregnant women, and young children may be at risk for more severe forms of dengue infection. However, who is at risk for bleeding is not well understood.

Some other clues that a patient might be experiencing severe dengue include restlessness, abdominal pain, persistent vomiting, and bleeding of the gums or blood in the vomitus or stool. These are important symptoms for a primary care doctor to look out for to decide if a patient can be sent home to rest or come to hospital attention. If in doubt, medical practitioners should refer the patient to the hospital for further assessment.

No “magic bullet” for dengue

There is no curative treatment for dengue infection. Rather, medications are given to alleviate the signs and symptoms. Aspirin should not be given to patients. It can cause severe bleeding. Paracetamol are usually prescribed to relieve fever, muscle and joint aches, and headache. Bed rest is essential and the patient should consume plenty of water which will help to alleviate the illness.

In general, dengue fever is self-limiting. Death rarely occurs in severe cases and most well developed countries have trained medical personnel and proper care facilities to manage severe disease. The fatality rate is less than 1 percent in such countries.

Theoretically, a person may contract dengue fever four times as there are four different serotypes of virus. It is not uncommon to get dengue fever at least twice in a lifetime for people living in endemic areas. However, patients cannot fall ill with the same serotype twice as they will have developed antibodies against that serotype.

Evaluation of the usefulness of the Sanofi Pasteur dengue vaccine is ongoing. It is currently not approved for use in Singapore. The vaccine was found to be safe and among individuals aged 9 years and older, efficacy was higher than in younger children with an overall efficacy against any of the four serotypes of 60 percent.

Conclusion

Dengue fever is the most common mosquito borne viral infection worldwide. Most of the time, it is a self-limiting illness though its presentation cannot be differentiated from other viral illnesses. Severe dengue can occur in a subgroup of patients at high risk and is characterized by plasma leakage and/or bleeding. It is important to recognize the symptoms of severe disease early so that patients can be referred for proper medical care at the critical stages of illness to prevent complications and death.