Actionable evidence: How to tackle obesity in primary care?

Scenario: A 45 year old male with a BMI of 32 presents to his primary care physician. What intervention should be suggested to him to reduce his BMI? Should only behavioral modification be adequate or should orlistat be added to it?

Evidence: A recent study titled “Effectiveness of Primary Care–Relevant Treatments forObesity in Adults: A Systematic Evidence Review for the U.S. PreventiveServices Task Force" published in the Annals of Internal Medicine looks into the evidence.

The study tried to answer 4 key questions –

1. Is there direct evidence that primary care screening programs for adult obesity or overweight improve health outcomes or result in short-term (12 to 18 mo) or sustained (>18 mo) weight loss or improved physiologic measures? a) How well is weight loss maintained after an intervention is completed?
2. Do primary care–relevant interventions (behaviorally based interventions and/or pharmacotherapy) in obese or overweight adults lead to improved health outcomes? a) What are common elements of efficacious interventions? b) Are there differences in efficacy between patient subgroups (i.e., age 65 y or older, sex, race/ethnicity, degree of obesity, baseline cardiovascular risk)?
3. Do primary care–relevant interventions in obese or overweight adults lead to short-term or sustained weight loss, with or without improved physiologic measures? a) How well is weight loss maintained after an intervention is completed? b) What are common elements of efficacious interventions? c) Are there differences in efficacy between patient subgroups (i.e., age 65 y or older, sex, race/ethnicity, degree of obesity, baseline cardiovascular risk)?
4. Do primary care–relevant interventions in obese or overweight adults lead to short-term or sustained weight loss, with or without improved physiologic measures? a) How well is weight loss maintained after an intervention is completed? b) What are common elements of efficacious interventions? c) Are there differences in efficacy between patient subgroups (i.e., age 65 y or older, sex, race/ethnicity, degree of obesity, baseline cardiovascular risk)?

Outcome: The first key question remains unanswered as the authors were unable to identify any study comparing screening vs non-screening of obese individuals.

The second, third and fourth key questions were answered. The summary –

Behavioral interventions

Parameter	Outcome
Weight Loss	Weighted mean difference in mean weight change between behavioral intervention and control group is -3.01 kg 95% CI (-4.02 to -2.01) at 12 to 18 months. Behavioral interventions lasting longer continued to show weight loss. Weight los was maintained up to a year following active intervention phase.
Mortality	No difference in death rate but limited by small number of trials.
Cardiovascular disease	No difference in CVD events or CVD related deaths in 3 large good quality trials
Hospitalization	No difference, limited by low hospitalization rate.
Health related quality of life/depression	No difference in depression, small favorable change of health related quality of life with weight loss
Incidence of diabetes mellitus	Weight loss of 4 to 7 kg reduced diabetes incidence by 50% or more over 2 to 3 years.
Glucose tolerance	Mean decrease in glucose level = 0.30 mmol/L (5.4 mg/dL)
Lipids	Weighted mean difference in LDL cholesterol level between treatment and control group = -4.94 mg/dL 95%CI (-7.32 to -2.56)
Blood pressure	Weighted mean difference in mean change in blood pressure between treatment and control group = -2.48 mmHg 95%CI (-3.25 to -1.71)
Waist circumference	-2.7 cm 95%CI( -4.1 to 1.4)
Adverse effects	None

Orlistat (Note- Almost all the trials of orlistat had simultaneous behavioral interventions)

Parameter	Outcome
Weight Loss	Weighted mean difference between behavioral intervention and control group is -2.98 kg 95% CI (-3.92 to -2.05).
Mortality	There were 4 studies which reported this outcome. Each study reported 1 death in in the orlistat group, but no clear relationship with treatment.
Cardiovascular disease	Not reported.
Hospitalization	Not reported.
Health related quality of life/depression	No difference in depression, Orlistat had greater satisfaction with treatment, less overweight distress and improvement in the vitality subscale of SF – 36.
Incidence of diabetes mellitus	Decreased incidence by 9-10% but concerns regarding generalizability and reliability.
Glucose tolerance	Mean decrease in glucose level = 0.31 mmol/L (5.5 mg/dL). Glucose reductions are greater in orlistat than placebo possibly because they were conducted in diabetic patients.
Lipids	Weighted mean difference in LDL cholesterol level between treatment and control group = -11.37 mg/dL 95%CI (-15.75 to -7.00)
Blood pressure	Weighted mean difference in mean change in blood pressure between treatment and control group = -2.04 mmHg 95%CI (-2.97 to -1.11)
Waist circumference	-2.3 cm 95%CI( -3.6 to -0.9)
Adverse effects	Gastrointestinal symptoms of mild to moderate intensity which resolves spontaneously, liver injury, vitamin E and K deficiency, increased incidence of hypoglycemia.

The authors also examined metformin which had modest effects on weight loss -2.85 kg 95%CI (-3.52 to -2.18).

Comment

The behavioral interventions included counseling regarding the importance of diet and exercise. There the interventions were not described fuly in the study. There was variability in the methods employed for behavioral modifications in the between the studies. On the other hand, orlistat studies had high attrition rate and were mostly funded by pharmaceutical companies.

Bottom line

In the primary care setting, behavioral intervention is effective and safe and should be considered as a first line therapy for weight loss. Orlistat may be added later. There are significant adverse effects associated with orlistat. Metformin may be tried in diabetics.

Leblanc ES, O'Connor E, Whitlock EP, Patnode CD, & Kapka T (2011). Effectiveness of primary care-relevant treatments for obesity in adults: a systematic evidence review for the u.s. Preventive services task force. Annals of internal medicine, 155 (7), 434-47 PMID: 21969342

Actionable evidence: Injectable contraceptives increase the risk of HIV infection

I was thinking of a new category of posts which I would be calling actionable evidence. Actionable evidence is that evidence which you can immediately put into practice; these are of direct clinical relevance. So to start this off I have selected a very important study that came out in the Lancet Infectious Diseases titled “Use of hormonal contraceptives and risk of HIV-1 transmission: a prospective cohort study”. Here is the main outcome of the study –

Risk of HIV acquisition in women

	Hazard ratio (95% CI) Adjusted Cox proportional hazards regression analysis	Hazard ratio (95% CI) Adjusted marginal structural models analysis
Any Hormonal Contraception	1.98 (1.06-3.68)*	1.84 (0.98-3.47)
Injectable	2.05 (1.04-4.04)*	2.19 (1.01-4.74)*
Oral	1.80 (0.55-5.82)	1.63 (0.47-5.66)
	*significant

Risk of transmission from women to men

	Hazard ratio (95% CI) Adjusted Cox proportional hazards regression analysis	Hazard ratio (95% CI) Adjusted marginal structural models analysis
Any Hormonal Contraception	1.97 (1.12-3.45)*	2.05 (1.12-3.74)*
Injectable	1.95 (1.06-3.58)*	3.01 (1.47-6.16)*
Oral	2.09 (0.75-5.84)	2.35 (0.79-6.95)
	*significant

Recommendation of the authors - Women should be counseled about potentially increased risk of HIV-1 acquisition and transmission with hormonal contraception, especially injectable methods, and about the importance of dual protection with condoms to decrease HIV-1 risk.

Comment –

Injectable contraceptives are used as suitable contraceptive method by many women. It has the advantage of ease of use. For example, DMPA (depot medroxyprogestrone acetate), one of the injectable contraceptives, can be taken at 3 monthly intervals. You don’t have to worry about contraceptives during these 3 months which is a problem with the oral pill, which has to be taken daily and one might forget to take it.

The study was of prospective cohort design with African serodiscordant (one partner with HIV infection and other partner free from infection) couples, though the majority of the data is taken secondarily from a randomized control trial. Basically the authors recruited HIV serodiscordant couples and subsequently they tested the HIV uninfected partner to see if they are getting infected. After doing this, they compared if the rate of infection  was more in seronegative subjects who were using hormonal contraceptives or in case of male subjects whose female partners were using hormonal contraceptives with those who were not using hormonal contraceptives. They followed the subjects for 24 months with mean follow up in seronegative women being 18 months and mean follow up of 18.7 months for seronegative men.

Overall this is a well conducted study, though there are few issues related to the methods. Firstly, the contraceptive use was self reported. Secondly, the use of injectable hormonal contraception was quite low among the participants but the study was adequately powered. Thirdly, the incidence of HIV infection was quite low. Fourthly, it is not clear to me whether the assessors were blinded to the nature of contraception use by the participants.

Before you ask the obvious, the authors controlled for the number of unprotected sexual intercourse. Even after controlling for unprotected sexual intercourse, injectable hormonal contraceptives significantly increased the risk of HIV infection. This suggests that something other than just unsafe sex is at play here.

Bottom line – Injectable hormonal contraceptives might increase the risk of HIV infection, evidence from observational study. All women using injectable hormonal contraceptives should be counseled to use condoms during intercourse to prevent HIV infection. Randomized controlled trial needed to see if the association holds.

Heffron R, Donnell D, Rees H, Celum C, Mugo N, Were E, de Bruyn G, Nakku-Joloba E, Ngure K, Kiarie J, Coombs RW, Baeten JM, & for the Partners in Prevention HSV/HIV Transmission Study Team (2011). Use of hormonal contraceptives and risk of HIV-1 transmission: a prospective cohort study. The Lancet infectious diseases PMID: 21975269

I want a female doctor! Well no body is stopping you.

This post on cloud nine blog irked me considerably.  The premise of the post is an important one but the blog author takes it to an illogical extreme.

“India boasts of thousands of qualified doctors- with Indian degrees and the lesser mortals with Russian degrees. So, how does it feel when you end up in a hospital for delivery and the gynecologist about to examine you is a male? Yes, you read it right- a male gynecologist? Or how it would be to consult a male radiologist for a mammogram? A male radiologist who examines female genitalia? Though female gynecologists are aplenty, women often find themselves in tough corners when it comes to taking medical help in extreme cases. India is not a country that has limited medical aid and so why should the women compromise?”

First things first, you just don’t wake up one fine morning and end up in the delivery room of a hospital. There are 40 weeks before that. There is ample time to choose your gynaecologist who will deliver your baby. Same way you can always choose your radiologist. But that’s not the point, the point is what is the problem if a male gynaecologist examines a female patient or for that matter when a male doctor examines a female patient? Surely any one is bound to feel uncomfortable when one’s private’s are examined but note the word “examine” – it’s for the patient’s benefit, not for the doctor’s enjoyment. If at any moment the patient is feeling uncomfortable, they can walkout, complain against the doctor and do what not. But when you refuse to be examined by someone purely on the basis the presence or absence of one chromosome, it amounts to discrimination.

“We are a very conservative society and so it irks me when it comes to women consulting such male doctors in hospitals providing health care, especially in Government run hospitals and departmental health units. You can all it medical ethics, professionalism or anything under the sun, but a MALE IS A MALE! And there are few perverted men who put Hippocrates to shame...You must look at the way they handle their stethoscopes when they check women!”

Again such blatant prejudice against a person based on their chromosome! Ethics, professionalism doesn’t matter right? Well how would it feel if you heard it from a male chauvinist that a FEMALE IS A FEMALE, not point in letting them get a job or education, a FEMALE IS A FEMALE? And it is amusing to hear non-medics referencing Hippocrates! If you read the Hippocratic Oath, you will find that he was not quite the saint you consider him to be (by our present sensibilities of course).

“There are Government hospitals and primary health centers that have a single male/ female doctor taking care of everything starting from a delivery to mammogram. Probably that might be the reason why most rural women shun these hospitals.”

Not familiar with reality, are we? Happens when we make up arguments from thin air to support our preconceived prejudices.

“Let there be no bullshitting saying- this is an insult to doctors of the world and all that blah, blah...How many of you know the unfair advantage doctors take on such unlucky women? Whether there is a chaperone or no chaperone, their sexual apparatus goes on an overdrive, sensing helpless victims. Sexual Boundary Violations ( SBVs) have burgeoned at an alarming rate in India-  which include unnecessary physical examinations, inappropriate touching, sexual jokes with patient, sexual touch and finally there are cases of sexual intercourse too...Read this study published in Indian Journal of Medical Ethics. Unless the doctors try to get their medical ethics right, this problem will be persistent in Indian society. And will the Government bring a bill to say- " Women doctors for women and male doctors for men"??? That is a million dollar question.”

Let’s talk about the study shall we? It is apparent that the blog author has no experience in reading or evaluating medical literature. Happens. If I commented on an Astrophysics article same thing would have happened to me. One point in the study makes the whole study wobbly and unreliable. The authors of the study designed a questionnaire but it was not validated. Why this is important? Let us suppose you want to measure blood pressure and you made your own blood pressure measuring instrument. Unless you validate your instrument by calibrating it with a standard blood pressure measuring device, your instrument is useless.

The most illogical part of the whole post is that of the government bill!! To put the non-sense in perspective consider this example. Some terrorist who were Muslim hijacked a plane and crashed it into the twin towers. Thus the government must bring a bill to prevent all Muslims from flying! Ridiculous you say? Replace some terrorists who were Muslims with some doctors who were male and hijacking a plane with any misdeed you may think and ban them from examining females. That’s how ridiculous and non-sensical the whole premise is.