Recent trends in the prevalence of overweight and obesity among Canadian children

Background:Previous studies have shown an increase in the prevalence of overweight and obesity among Canadian children from 23.3% to 34.7% during 1978–2004. We examined the most recent trends by applying current definitions of overweight and obesity based on World Health Organization (WHO) body mass index (BMI) thresholds and recently validated norms for waist circumference and waist:height ratio.Methods:We examined directly measured height and weight data from the Canadian Community Health Survey (2004–2005) and the Canadian Health Measures Survey (2009–2013). We calculated z scores for BMI, height and weight based on the 2014 WHO growth charts for Canada, including the new extension of weight-for-age beyond 10 years. To calculate z scores for waist circumference and waist:height ratios, we used new charts from the reference population in the US NHANES III (National Health and Nutrition Examination Survey, 1988–1994).Results:Data were available for 14 014 children aged 3–19 years for the period 2004–2013. We observed a decline in the prevalence of overweight or obesity, from 30.7% (95% confidence interval [CI] 29.7% to 31.6%) to 27.0% (95% CI 25.3% to 28.7%) (p < 0.001) and stabilization in the prevalence of obesity at about 13%. These trends persisted after we adjusted for age, sex and race/ethnicity. Although they declined, the median z scores for BMI, weight and height were positive and higher than those in the WHO reference population. The z scores for waist circumference and waist:height ratio were negative, which indicated that the Canadian children had less central adiposity than American children in historic or contemporary NHANES cohorts.Interpretation:After a period of dramatic growth, BMI z scores and the prevalence of overweight or obesity among Canadian children decreased from 2004 to 2013, which attests to progress against this important public health challenge.Ongoing pan-Canadian surveys such as the Canadian Community Health Survey (CCHS) and Canadian Health Measures Survey (CHMS) are important to evaluate the health of our population using representative national samples.^1,2 Self-reported heights and weights replaced direct measurement during 1978–2004, which underestimated true rates of overweight and obesity.³ A subsequent comparison of directly measured heights and weights during the same period showed an alarming increase in the prevalence of overweight or obesity among Canadian children aged 2–17 years, from 23.3% (95% confidence interval [CI] 20.5% to 26.0%) to 34.7% (95% CI 33.0% to 36.4%) based on the new World Health Organization (WHO) definitions.¹In Canada, the definitions of overweight and obesity changed with the introduction of the 2010 WHO growth charts for Canada.^4,5 Previous definitions were based on body mass index (BMI) percentiles from the 2000 US Centers for Disease Control and Prevention (CDC) growth charts.⁶ In addition to revising these percentile thresholds, the WHO charts were based on a different reference population; as a result, the proportion of Canadian children classified as overweight or obese increased with the introduction of the new WHO charts.^1,7,8 Moreover, the absolute percentile thresholds now vary by age, with toddlers (2 to ≤ 5 yr) having higher thresholds to define overweight and obesity than older children (age > 5 to 19 yr).⁴Results from the United States have shown a decline in obesity rates among toddlers and a plateau in rates among older children;^9,10 stabilization has also been noted in other jurisdictions (e.g., Germany and Australia).^11–16 We undertook this study to determine the most recent trends in the prevalence of overweight and obesity among Canadian children using the current WHO weight charts for Canada applied to a representative sample of children.     

Visibility of the urethral meatus and risk of urinary tract infections in uncircumcised boys

Background:

Uncircumcised boys are at higher risk for urinary tract infections than circumcised boys. Whether this risk varies with the visibility of the urethral meatus is not known. Our aim was to determine whether there is a hierarchy of risk among uncircumcised boys whose urethral meatuses are visible to differing degrees.

Methods:

We conducted a prospective cross-sectional study in one pediatric emergency department. We screened 440 circumcised and uncircumcised boys. Of these, 393 boys who were not toilet trained and for whom the treating physician had requested a catheter urine culture were included in our analysis. At the time of catheter insertion, a nurse characterized the visibility of the urethral meatus (phimosis) using a 3-point scale (completely visible, partially visible or nonvisible). Our primary outcome was urinary tract infection, and our primary exposure variable was the degree of phimosis: completely visible versus partially or nonvisible urethral meatus.

Results:

Cultures grew from urine samples from 30.0% of uncircumcised boys with a completely visible meatus, and from 23.8% of those with a partially or nonvisible meatus (p = 0.4). The unadjusted odds ratio (OR) for culture growth was 0.73 (95% confidence interval [CI] 0.35–1.52), and the adjusted OR was 0.41 (95% CI 0.17–0.95). Of the boys who were circumcised, 4.8% had urinary tract infections, which was significantly lower than the rate among uncircumcised boys with a completely visible urethral meatus (unadjusted OR 0.12 [95% CI 0.04–0.39], adjusted OR 0.07 [95% CI 0.02–0.26]).

Interpretation:

We did not see variation in the risk of urinary tract infection with the visibility of the urethral meatus among uncircumcised boys. Compared with circumcised boys, we saw a higher risk of urinary tract infection in uncircumcised boys, irrespective of urethral visibility.Urinary tract infections are one of the most common serious bacterial infections in young children.^1–6 Prompt diagnosis is important, because children with urinary tract infection are at risk for bacteremia⁶ and renal scarring.^1,7 Uncircumcised boys have a much higher risk of urinary tract infection than circumcised boys,^{1,3,4,6,8–12} likely as a result of heavier colonization under the foreskin with pathogenic bacteria, which leads to ascending infections.^13,14 The American Academy of Pediatrics recently suggested that circumcision status be used to select which boys should be evaluated for urinary tract infection.¹ However, whether all uncircumcised boys are at equal risk for infection, or whether the risk varies with the visibility of the urethral opening, is not known. It has been suggested that a subset of uncircumcised boys with a poorly visible urethral opening are at increased risk of urinary tract infection,^15–17 leading some experts to consider giving children with tight foreskins topical cortisone or circumcision to prevent urinary tract infections.^13,18–21We designed a study to challenge the opinion that all uncircumcised boys are at increased risk for urinary tract infections. We hypothesized a hierarchy of risk among uncircumcised boys depending on the visibility of the urethral meatus, with those with a partially or nonvisible meatus at highest risk, and those with a completely visible meatus having a level of risk similar to that of boys who have been circumcised. Our primary aim was to compare the proportions of urinary tract infections among uncircumcised boys with a completely visible meatus with those with a partially or nonvisible meatus.     

Considerations of physicians about the depth of palliative sedation at the end of life

Background:

Although guidelines advise titration of palliative sedation at the end of life, in practice the depth of sedation can range from mild to deep. We investigated physicians’ considerations about the depth of continuous sedation.

Methods:

We performed a qualitative study in which 54 physicians underwent semistructured interviewing about the last patient for whom they had been responsible for providing continuous palliative sedation. We also asked about their practices and general attitudes toward sedation.

Results:

We found two approaches toward the depth of continuous sedation: starting with mild sedation and only increasing the depth if necessary, and deep sedation right from the start. Physicians described similar determinants for both approaches, including titration of sedatives to the relief of refractory symptoms, patient preferences, wishes of relatives, expert advice and esthetic consequences of the sedation. However, physicians who preferred starting with mild sedation emphasized being guided by the patient’s condition and response, and physicians who preferred starting with deep sedation emphasized ensuring that relief of suffering would be maintained. Physicians who preferred each approach also expressed different perspectives about whether patient communication was important and whether waking up after sedation is started was problematic.

Interpretation:

Physicians who choose either mild or deep sedation appear to be guided by the same objective of delivering sedation in proportion to the relief of refractory symptoms, as well as other needs of patients and their families. This suggests that proportionality should be seen as a multidimensional notion that can result in different approaches toward the depth of sedation.Palliative sedation is considered to be an appropriate option when other treatments fail to relieve suffering in dying patients.^1,2 There are important questions associated with this intervention, such as how deep the sedation must be to relieve suffering and how important it is for patients and their families for the patient to maintain a certain level of consciousness.¹ In the national guidelines for the Netherlands, palliative sedation is defined as “the intentional lowering of consciousness of a patient in the last phase of life.”^3,4 Sedatives can be administered intermittently or continuously, and the depth of palliative sedation can range from mild to deep.^1,5Continuous deep sedation until death is considered the most far reaching and controversial type of palliative sedation. Nevertheless, it is used frequently: comparable nationwide studies in Europe show frequencies of 2.5% to 16% of all deaths.^6–8 An important reason for continuous deep sedation being thought of as controversial is the possible association of this practice with the hastening of death,^9–11 although it is also argued that palliative sedation does not shorten life when its use is restricted to the patient’s last days of life.^12,13 Guidelines for palliative sedation often advise physicians to titrate sedatives,^2,3,14 which means that the dosages of sedatives are adjusted to the level needed for proper relief of symptoms. To date, research has predominantly focused on the indications and type of medications used for sedation. In this study, we investigated how physicians decide the depth of continuous palliative sedation and how these decisions relate to guidelines.     

Risk of cancer among patients with herpes zoster infection: a population-based study

Background:

Whether the risk of cancer is increased among patients with herpes zoster is unclear. We investigated the risk of cancer among patients with herpes zoster using a nationwide health registry in Taiwan.

Methods:

We identified 35 871 patients with newly diagnosed herpes zoster during 2000–2008 from the National Health Insurance Research Database in Taiwan. We analyzed the standardized incidence ratios for various types of cancer.

Results:

Among patients with herpes zoster, 895 cases of cancer were reported. Patients with herpes zoster were not at increased risk of cancer (standardized incidence ratio 0.99, 95% confidence interval 0.93–1.06). Among the subgroups stratified by sex, age and years of follow-up, there was also no increased risk of overall cancer.

Interpretation:

Herpes zoster is not associated with increased risk of cancer in the general population. These findings do not support extensive investigations for occult cancer or enhanced surveillance for cancer in patients with herpes zoster.Herpes zoster, or shingles, is caused by reactivation of the varicella–zoster virus, a member of the Herpesviridae family. Established risk factors for herpes zoster include older age, chronic kidney disease, malignant disease and immunocompromised conditions (e.g., those experienced by patients with AIDS, transplant recipients, and those taking immunosuppressive medication because of autoimmune diseases).^1–5 Herpes zoster occurs more frequently among patients with cancer than among those without cancer;^6,7 however the relation between herpes zoster and risk of subsequent cancer is not well established.In 1955, Wyburn-Mason and colleagues reported several cases of skin cancer that arose from the healed lesions of herpes zoster.⁸ In 1972, a retrospective cohort study and a case series reported a higher prevalence of herpes zoster among patients with cancer, especially hematological cancer;^6,7 however, they did not investigate whether herpes zoster was a risk factor for cancer. In 1982, Ragozzino and colleagues found no increased incidence of cancer (including hematologic malignancy) among patients with herpes zoster.⁹ There have been reports of significantly increased risk of some subtypes of cancer among patients aged more than 65 years with herpes zoster¹⁰ and among those admitted to hospital because of herpes zoster.¹¹ Although these studies have suggested an association between herpes zoster and subsequent cancer, their results might not be generalizable because of differences in the severity of herpes zoster in the enrolled patients.Whether the risk of cancer is increased after herpes zoster remains controversial. The published studies^8–11 were nearly all conducted in western countries, and data focusing on Asian populations are lacking.¹² The results from western countries may not be directly generalizable to other ethnic groups because of differences in cancer types and profiles. Recently, a study reported that herpes zoster ophthalmicus may be a marker of increased risk of cancer in the following year.¹³ In the present study, we investigated the incidence rate ratio of cancer, including specific types of cancer, after diagnosis of herpes zoster.     

Cost-effectiveness of diacetylmorphine versus methadone for chronic opioid dependence refractory to treatment

Background:

Although diacetylmorphine has been proven to be more effective than methadone maintenance treatment for opioid dependence, its direct costs are higher. We compared the cost-effectiveness of diacetylmorphine and methadone maintenance treatment for chronic opioid dependence refractory to treatment.

Methods:

We constructed a semi-Markov cohort model using data from the North American Opiate Medication Initiative trial, supplemented with administrative data for the province of British Columbia and other published data, to capture the chronic, recurrent nature of opioid dependence. We calculated incremental cost-effectiveness ratios to compare diacetylmorphine and methadone over 1-, 5-, 10-year and lifetime horizons.

Results:

Diacetylmorphine was found to be a dominant strategy over methadone maintenance treatment in each of the time horizons. Over a lifetime horizon, our model showed that people receiving methadone gained 7.46 discounted quality-adjusted life-years (QALYs) on average (95% credibility interval [CI] 6.91–8.01) and generated a societal cost of $1.14 million (95% CI $736 800–$1.78 million). Those who received diacetylmorphine gained 7.92 discounted QALYs on average (95% CI 7.32–8.53) and generated a societal cost of $1.10 million (95% CI $724 100–$1.71 million). Cost savings in the diacetylmorphine cohort were realized primarily because of reductions in the costs related to criminal activity. Probabilistic sensitivity analysis showed that the probability of diacetylmorphine being cost-effective at a willingness-to-pay threshold of $0 per QALY gained was 76%; the probability was 95% at a threshold of $100 000 per QALY gained. Results were confirmed over a range of sensitivity analyses.

Interpretation:

Using mathematical modelling to extrapolate results from the North American Opiate Medication Initiative, we found that diacetylmorphine may be more effective and less costly than methadone among people with chronic opioid dependence refractory to treatment.Opioid substitution with methadone is the most common treatment of opioid dependence.^1–3 Participation in a methadone maintenance treatment program has been associated with decreases in illicit drug use,⁴ criminality⁵ and mortality.^6,7 However, longitudinal studies have shown that most people who receive opioid substitution treatment are unable to abstain from illicit drug use for sustained periods, either switching from treatment to regular opioid use or continuing to use opioids while in treatment.^8–13 An estimated 15%–25% of the most marginalized methadone clients do not benefit from treatment in terms of sustained abstention from the use of illicit opioids.¹⁴The North American Opiate Medication Initiative was a randomized controlled trial that compared supervised, medically prescribed injectable diacetylmorphine and optimized methadone maintenance treatment in people with long-standing opioid dependence and multiple failed treatment attempts with methadone or other forms of treatment.¹⁵ The trial was conducted in two Canadian cities (Vancouver, British Columbia; and Montréal, Quebec). Both treatment protocols included a comprehensive range of psychosocial services (e.g., addiction counselling, relapse prevention, case management, and individual and group interventions) and primary care services (e.g., testing for blood-borne diseases, provision of HIV treatment, and treatment of acute and chronic physical and mental health complications of substance use) in keeping with Health Canada best practices.¹⁶ The results of the trial confirmed findings of prior studies showing diacetylmorphine to be more effective than methadone maintenance treatment in retaining opioid-dependent patients in treatment^15,17–20 and improving health and social functioning.^19,21,22 Diacetylmorphine treatment has been proposed to reach a specific population of people with opioid dependence refractory to treatment who are at high risk of adverse health consequences and engagement in criminal activities to acquire the illicit drugs.For guiding policy-makers, the North American Opiate Medication Initiative alone does not address all the important considerations for decision-making. In addition to political challenges associated with the therapy,²³ there remains concern over the direct cost of diacetylmorphine over the long term, because it can be as much as 10 times greater than conventional methadone maintenance treatment.²¹ The North American Opiate Medication Initiative was only one year in duration, but a policy to introduce diacetylmorphine might have both positive and negative longer-term implications.We extrapolated outcomes from the North American Opiate Medication Initiative to estimate the long-term cost-effectiveness of diacetylmorphine versus methadone maintenance treatment for chronic, refractory opioid dependence.     

Plasma bicarbonate and risk of type 2 diabetes mellitus

Background:

Several biomarkers of metabolic acidosis, including lower plasma bicarbonate and higher anion gap, have been associated with greater insulin resistance in cross-sectional studies. We sought to examine whether lower plasma bicarbonate is associated with the development of type 2 diabetes mellitus in a prospective study.

Methods:

We conducted a prospective, nested case–control study within the Nurses’ Health Study. Plasma bicarbonate was measured in 630 women who did not have type 2 diabetes mellitus at the time of blood draw in 1989–1990 but developed type 2 diabetes mellitus during 10 years of follow-up. Controls were matched according to age, ethnic background, fasting status and date of blood draw. We used logistic regression to calculate odds ratios (ORs) for diabetes by category of baseline plasma bicarbonate.

Results:

After adjustment for matching factors, body mass index, plasma creatinine level and history of hypertension, women with plasma bicarbonate above the median level had lower odds of diabetes (OR 0.76, 95% confidence interval [CI] 0.60–0.96) compared with women below the median level. Those in the second (OR 0.92, 95% CI 0.67–1.25), third (OR 0.70, 95% CI 0.51–0.97) and fourth (OR 0.75, 95% CI 0.54–1.05) quartiles of plasma bicarbonate had lower odds of diabetes compared with those in the lowest quartile (p for trend = 0.04). Further adjustment for C-reactive protein did not alter these findings.

Interpretation:

Higher plasma bicarbonate levels were associated with lower odds of incident type 2 diabetes mellitus among women in the Nurses’ Health Study. Further studies are needed to confirm this finding in different populations and to elucidate the mechanism for this relation.Resistance to insulin is central to the pathogenesis of type 2 diabetes mellitus.¹ Several mechanisms may lead to insulin resistance and thereby contribute to the development of type 2 diabetes mellitus, including altered fatty acid metabolism, mitochondrial dysfunction and systemic inflammation.² Metabolic acidosis may also contribute to insulin resistance. Human studies using the euglycemic and hyperglycemic clamp techniques have shown that mild metabolic acidosis induced by the administration of ammonium chloride results in reduced tissue insulin sensitivity.³ Subsequent studies in rat models have suggested that metabolic acidosis decreases the binding of insulin to its receptors.^4,5 Finally, metabolic acidosis may also increase cortisol production,⁶ which in turn is implicated in the development of insulin resistance.⁷Recent epidemiologic studies have shown an association between clinical markers of metabolic acidosis and greater insulin resistance or prevalence of type 2 diabetes mellitus. In the National Health and Nutrition Examination Survey, both lower serum bicarbonate and higher anion gap (even within ranges considered normal) were associated with increased insulin resistance among adults without diabetes.⁸ In addition, higher levels of serum lactate, a small component of the anion gap, were associated with higher odds of prevalent type 2 diabetes mellitus in the Atherosclerosis Risk in Communities study⁹ and with higher odds of incident type 2 diabetes mellitus in a retrospective cohort study of the risk factors for diabetes in Swedish men.¹⁰ Other biomarkers associated with metabolic acidosis, including higher levels of serum ketones,¹¹ lower urinary citrate excretion¹² and low urine pH,¹³ have been associated in cross-sectional studies with either insulin resistance or the prevalence of type 2 diabetes mellitus. However, it is unclear whether these associations are a cause or consequence. We sought to address this question by prospectively examining the association between plasma bicarbonate and subsequent development of type 2 diabetes mellitus in a nested case–control study within the Nurses’ Health Study.     

Inflammatory ocular adverse events with the use of oral bisphosphonates: a retrospective cohort study

Background:

There have been several published reports of inflammatory ocular adverse events, mainly uveitis and scleritis, among patients taking oral bisphosphonates. We examined the risk of these adverse events in a pharmacoepidemiologic cohort study.

Methods:

We conducted a retrospective cohort study involving residents of British Columbia who had visited an ophthalmologist from 2000 to 2007. Within the cohort, we identified all people who were first-time users of oral bisphosphonates and who were followed to the first inflammatory ocular adverse event, death, termination of insurance or the end of the study period. We defined an inflammatory ocular adverse event as scleritis or uveitis. We used a Cox proportional hazard model to determine the adjusted rate ratios. As a sensitivity analysis, we performed a propensity-score–adjusted analysis.

Results:

The cohort comprised 934 147 people, including 10 827 first-time users of bisphosphonates and 923 320 nonusers. The incidence rate among first-time users was 29/10 000 person-years for uveitis and 63/10 000 person-years for scleritis. In contrast, the incidence among people who did not use oral bisphosphonates was 20/10 000 person-years for uveitis and 36/10 000 for scleritis (number needed to harm: 1100 and 370, respectively). First-time users had an elevated risk of uveitis (adjusted relative risk [RR] 1.45, 95% confidence interval [CI] 1.25–1.68) and scleritis (adjusted RR 1.51, 95% CI 1.34–1.68). The rate ratio for the propensity-score–adjusted analysis did not change the results (uveitis: RR 1.50, 95% CI 1.29–1.73; scleritis: RR 1.53, 95% CI 1.39–1.70).

Interpretation:

People using oral bisphosphonates for the first time may be at a higher risk of scleritis and uveitis compared to people with no bisphosphonate use. Patients taking bisphosphonates must be familiar with the signs and symptoms of these conditions, so that they can immediately seek assessment by an ophthalmologist.Oral bisphosphonates are the most frequently prescribed class of medications for the prevention of osteoporosis. Most literature about the safety of bisphosphonates has mainly focused on long-term adverse events, including atypical fractures,¹ atrial fibrillation,² and esophageal and colon cancer.³Uveitis and scleritis are ocular inflammatory diseases that are associated with major morbidity. Anterior uveitis is the most common type of uveitis with an estimated 11.4–100.0 cases/100 000 person-years.^4,5 Both diseases require immediate treatment to prevent further complications, which may include cataracts, glaucoma, macular edema and scleral perforation. Numerous case reports and case series have described an association between the use of oral bisphosphonates and anterior uveitis^6–8 and scleritis.^8,9 In most reported cases, severe eye pain was reported within days of taking an oral bisphosphonates, and the symptom resolved after stopping the agent.^6,9 Only one large epidemiologic study has examined the association between the use of bisphosphonates and ocular inflammatory diseases.¹⁰ This study did not find an association, but it was limited by a small number of events and a lack of power. Thus, the association between uveitis or scleritis and the use of oral bisphosphonates is not fully known. Given that early intervention may prevent complications, we performed a pharmacoepidemiologic study to assess the true risk of these potentially serious conditions.     

Emergency health care use and follow-up among sociodemographic groups of children who visit emergency departments for mental health crises

Background:

Previous studies of differences in mental health care associated with children’s sociodemographic status have focused on access to community care. We examined differences associated with visits to the emergency department.

Methods:

We conducted a 6-year population-based cohort analysis using administrative databases of visits (n = 30 656) by children aged less than 18 years (n = 20 956) in Alberta. We measured differences in the number of visits by socioeconomic and First Nations status using directly standardized rates. We examined time to return to the emergency department using a Cox regression model, and we evaluated time to follow-up with a physician by physician type using a competing risks model.

Results:

First Nations children aged 15–17 years had the highest rate of visits for girls (7047 per 100 000 children) and boys (5787 per 100 000 children); children in the same age group from families not receiving government subsidy had the lowest rates (girls: 2155 per 100 000 children; boys: 1323 per 100 000 children). First Nations children (hazard ratio [HR] 1.64; 95% confidence interval [CI] 1.30–2.05), and children from families receiving government subsidies (HR 1.60, 95% CI 1.30–1.98) had a higher risk of return to an emergency department for mental health care than other children. The longest median time to follow-up with a physician was among First Nations children (79 d; 95% CI 60–91 d); this status predicted longer time to a psychiatrist (HR 0.47, 95% CI 0.32–0.70). Age, sex, diagnosis and clinical acuity also explained post-crisis use of health care.

Interpretation:

More visits to the emergency department for mental health crises were made by First Nations children and children from families receiving a subsidy. Sociodemographics predicted risk of return to the emergency department and follow-up care with a physician.Emergency departments are a critical access point for mental health care for children who have been unable to receive care elsewhere or are in crisis.¹ Care provided in an emergency department can stabilize acute problems and facilitate urgent follow-up for symptom management and family support.^1,2Race, ethnic background and socioeconomic status have been linked to a crisis-oriented care patterns among American children.^3,4 Minority children are less likely than white children to have received mental health treatment before an emergency department visit,^3,4 and uninsured children are less likely to receive an urgent mental health evaluation when needed.⁴ Other studies, however, have shown no relation between sociodemographic status and mental health care,^5,6 and it may be that different health system characteristics (e.g., pay-for-service, insurance coverage, publicly funded care) interact with sociodemographic status to influence how mental health resources are used. Canadian studies are largely absent in this discussion, despite a known relation between lower income and poorer mental health status,⁷ nationwide documentation of disparities faced by Aboriginal children,^8–10 and government-commissioned reviews that highlight deficits in universal access to mental health care.¹¹We undertook the current study to examine whether sociodemographic differences exist in the rates of visits to emergency departments for mental health care and in the use of post-crisis health care services for children in Alberta. Knowledge of whether differences exist for children with mental health needs may help identify children who could benefit from earlier intervention to prevent illness destabilization and children who may be disadvantaged in the period after the emergency department visit. We hypothesized that higher rates of emergency department use, lower rates of follow-up physician visits after the initial emergency department visit, and a longer time to physician follow-up would be observed among First Nations children and children from families receiving government social assistance.     

Change in appropriate referrals to nephrologists after the introduction of automatic reporting of the estimated glomerular filtration rate

Background:

Use of the serum creatinine concentration, the most widely used marker of kidney function, has been associated with under-reporting of chronic kidney disease and late referral to nephrologists, especially among women and elderly people. To improve appropriateness of referrals, automatic reporting of the estimated glomerular filtration rate (eGFR) by laboratories was introduced in the province of Ontario, Canada, in March 2006. We hypothesized that such reporting, along with an ad hoc educational component for primary care physicians, would increase the number of appropriate referrals.

Methods:

We conducted a population-based before–after study with interrupted time-series analysis at a tertiary care centre. All referrals to nephrologists received at the centre during the year before and the year after automatic reporting of the eGFR was introduced were eligible for inclusion. We used regression analysis with autoregressive errors to evaluate whether such reporting by laboratories, along with ad hoc educational activities for primary care physicians, had an impact on the number and appropriateness of referrals to nephrologists.

Results:

A total of 2672 patients were included in the study. In the year after automatic reporting began, the number of referrals from primary care physicians increased by 80.6% (95% confidence interval [CI] 74.8% to 86.9%). The number of appropriate referrals increased by 43.2% (95% CI 38.0% to 48.2%). There was no significant change in the proportion of appropriate referrals between the two periods (−2.8%, 95% CI −26.4% to 43.4%). The proportion of elderly and female patients who were referred increased after reporting was introduced.

Interpretation:

The total number of referrals increased after automatic reporting of the eGFR began, especially among women and elderly people. The number of appropriate referrals also increased, but the proportion of appropriate referrals did not change significantly. Future research should be directed to understanding the reasons for inappropriate referral and to develop novel interventions for improving the referral process.Until recently, the serum creatinine concentration was used universally as an index of the glomerular filtration rate (GFR) to identify and monitor chronic kidney disease.¹ The serum creatinine concentration depends on several factors, the most important being muscle mass.¹ Women as compared with men, and elderly people as compared with young adults, tend to have lower muscle mass for the same degree of kidney function and thus have lower serum creatinine concentrations.^2,3 Consequently, the use of the serum creatinine concentration is associated with underrecognition of chronic kidney disease, delayed workup for chronic kidney disease and late referral to nephrologists, particularly among women and elderly people. Late referral has been associated with increased mortality among patients receiving dialysis.^3–11In 1999, the Modification of Diet in Renal Disease formula was introduced to calculate the estimated GFR (eGFR).^12,13 This formula uses the patient’s serum creatinine concentration, age, sex and race (whether the patient is black or not). All of these variables are easily available to laboratories except race. Laboratories report the eGFR for non-black people, with advice to practitioners to multiply the result by 1.21 if their patient is black. Given that reporting of the eGFR markedly improves detection of chronic kidney disease,^14,15 several national organizations recommended that laboratories automatically calculate and report the eGFR when the serum creatinine concentration is requested.^16–19 These organizations also provided guidelines on appropriate referral to nephrology based on the value.Although several studies have reported increases in referrals to nephrologists after automatic reporting of the eGFR was introduced,^20–26 there is limited evidence on the impact that such reporting has had on the appropriateness of referrals. An increase in the number of inappropriate referrals would affect health care delivery, diverting scarce resources to the evaluation of relatively mild kidney disease. It also would likely increase wait times for all nephrology referrals and have a financial impact on the system because specialist care is more costly than primary care.We conducted a study to evaluate whether the introduction of automatic reporting of the eGFR by laboratories, along with ad hoc educational activities for primary care physicians, had an impact on the number and appropriateness of referrals to nephrologists.     

Mediterranean diets and metabolic syndrome status in the PREDIMED randomized trial

Background:

Little evidence exists on the effect of an energy-unrestricted healthy diet on metabolic syndrome. We evaluated the long-term effect of Mediterranean diets ad libitum on the incidence or reversion of metabolic syndrome.

Methods:

We performed a secondary analysis of the PREDIMED trial — a multicentre, randomized trial done between October 2003 and December 2010 that involved men and women (age 55–80 yr) at high risk for cardiovascular disease. Participants were randomly assigned to 1 of 3 dietary interventions: a Mediterranean diet supplemented with extra-virgin olive oil, a Mediterranean diet supplemented with nuts or advice on following a low-fat diet (the control group). The interventions did not include increased physical activity or weight loss as a goal. We analyzed available data from 5801 participants. We determined the effect of diet on incidence and reversion of metabolic syndrome using Cox regression analysis to calculate hazard ratios (HRs) and 95% confidence intervals (CIs).

Results:

Over 4.8 years of follow-up, metabolic syndrome developed in 960 (50.0%) of the 1919 participants who did not have the condition at baseline. The risk of developing metabolic syndrome did not differ between participants assigned to the control diet and those assigned to either of the Mediterranean diets (control v. olive oil HR 1.10, 95% CI 0.94–1.30, p = 0.231; control v. nuts HR 1.08, 95% CI 0.92–1.27, p = 0.3). Reversion occurred in 958 (28.2%) of the 3392 participants who had metabolic syndrome at baseline. Compared with the control group, participants on either Mediterranean diet were more likely to undergo reversion (control v. olive oil HR 1.35, 95% CI 1.15–1.58, p < 0.001; control v. nuts HR 1.28, 95% CI 1.08–1.51, p < 0.001). Participants in the group receiving olive oil supplementation showed significant decreases in both central obesity and high fasting glucose (p = 0.02); participants in the group supplemented with nuts showed a significant decrease in central obesity.

Interpretation:

A Mediterranean diet supplemented with either extra virgin olive oil or nuts is not associated with the onset of metabolic syndrome, but such diets are more likely to cause reversion of the condition. An energy-unrestricted Mediterranean diet may be useful in reducing the risks of central obesity and hyperglycemia in people at high risk of cardiovascular disease. Trial registration: ClinicalTrials.gov, no. ISRCTN35739639.Metabolic syndrome is a cluster of 3 or more related cardiometabolic risk factors: central obesity (determined by waist circumference), hypertension, hypertriglyceridemia, low plasma high-density lipoprotein (HDL) cholesterol levels and hyperglycemia. Having the syndrome increases a person’s risk for type 2 diabetes and cardiovascular disease.^1,2 In addition, the condition is associated with increased morbidity and all-cause mortality.^1,3–5 The worldwide prevalence of metabolic syndrome in adults approaches 25%^6–8 and increases with age,⁷ especially among women,^8,9 making it an important public health issue.Several studies have shown that lifestyle modifications,¹⁰ such as increased physical activity,¹¹ adherence to a healthy diet^12,13 or weight loss,^14–16 are associated with reversion of the metabolic syndrome and its components. However, little information exists as to whether changes in the overall dietary pattern without weight loss might also be effective in preventing and managing the condition.The Mediterranean diet is recognized as one of the healthiest dietary patterns. It has shown benefits in patients with cardiovascular disease^17,18 and in the prevention and treatment of related conditions, such as diabetes,^19–21 hypertension^22,23 and metabolic syndrome.²⁴Several cross-sectional^25–29 and prospective^30–32 epidemiologic studies have suggested an inverse association between adherence to the Mediterranean diet and the prevalence or incidence of metabolic syndrome. Evidence from clinical trials has shown that an energy-restricted Mediterranean diet³³ or adopting a Mediterranean diet after weight loss³⁴ has a beneficial effect on metabolic syndrome. However, these studies did not determine whether the effect could be attributed to the weight loss or to the diets themselves.Seminal data from the PREDIMED (PREvención con DIeta MEDiterránea) study suggested that adherence to a Mediterranean diet supplemented with nuts reversed metabolic syndrome more so than advice to follow a low-fat diet.³⁵ However, the report was based on data from only 1224 participants followed for 1 year. We have analyzed the data from the final PREDIMED cohort after a median follow-up of 4.8 years to determine the long-term effects of a Mediterranean diet on metabolic syndrome.     

Use of thiazolidinediones and the risk of bladder cancer among people with type 2 diabetes: a meta-analysis

Background:

Patients with type 2 diabetes have a 40% increased risk of bladder cancer. Thiazolidinediones, especially pioglitazone, may increase the risk. We conducted a systematic review and meta-analysis to evaluate the risk of bladder cancer among adults with type 2 diabetes taking thiazolidinediones.

Methods:

We searched key biomedical databases (including MEDLINE, Embase and Scopus) and sources of grey literature from inception through March 2012 for published and unpublished studies, without language restrictions. We included randomized controlled trials (RCTs), cohort studies and case–control studies that reported incident bladder cancer among people with type 2 diabetes who ever (v. never) were exposed to pioglitazone (main outcome), rosiglitazone or any thiazolidinedione.

Results:

Of the 1787 studies identified, we selected 4 RCTs, 5 cohort studies and 1 case–control study. The total number of patients was 2 657 365, of whom 3643 had newly diagnosed bladder cancer, for an overall incidence of 53.1 per 100 000 person-years. The one RCT that reported on pioglitazone use found no significant association with bladder cancer (risk ratio [RR] 2.36, 95% confidence interval [CI] 0.91–6.13). The cohort studies of thiazolidinediones (pooled RR 1.15, 95% CI 1.04–1.26; I² = 0%) and of pioglitazone specifically (pooled RR 1.22, 95% CI 1.07–1.39; I² = 0%) showed significant associations with bladder cancer. No significant association with bladder cancer was observed in the two RCTs that evaluated rosiglitazone use (pooled RR 0.87, 95% CI 0.34–2.23; I² = 0%).

Interpretation:

The limited evidence available supports the hypothesis that thiazolidinediones, particularly pioglitazone, are associated with an increased risk of bladder cancer among adults with type 2 diabetes.People with type 2 diabetes are at increased risk of several types of cancer, including a 40% increased risk of bladder cancer, compared with those without diabetes.^1,2 The strong association with bladder cancer is hypothesized to be a result of hyperinsulinemia, whereby elevated insulin levels in type 2 diabetes stimulate insulin receptors on neoplastic cells, promoting cancer growth and division.^1,3–5 Additional risk factors for bladder cancer include increased age, male sex, smoking, occupational and environmental exposures and urinary tract disease.⁶ Exogenous insulin and other glucose-lowering medications such as sulfonylureas, metformin and thiazolidinediones, may further modify the risk of bladder cancer.¹Data from the placebo-controlled PROactive trial of pioglitazone (PROspective pioglitAzone Clinical Trial in macroVascular Events) suggested a higher incidence of bladder cancer among pioglitazone users than among controls.⁷ Subsequent randomized controlled trials (RCTs) and observational studies have reported conflicting results for pioglitazone, with various studies reporting a significant increase,^8,9 a nonsignificant increase¹⁰ and even a decreased risk¹¹ of bladder cancer.To test the hypothesis that pioglitazone use is associated with an increased risk of bladder cancer, we conducted a systematic review and meta-analysis of RCTs and observational studies reporting bladder cancer among adults with type 2 diabetes taking pioglitazone. To clarify the possibility of a drug-class effect, we also examined data for all thiazolidinediones and for rosiglitazone alone.     

Incidence and causes of end-stage renal disease among Aboriginal children and young adults

Background:

Although Aboriginal adults have a higher risk of end-stage renal disease than non-Aboriginal adults, the incidence and causes of end-stage renal disease among Aboriginal children and young adults are not well described.

Methods:

We calculated age- and sex-specific incidences of end-stage renal disease among Aboriginal people less than 22 years of age using data from a national organ failure registry. Incidence rate ratios were used to compare rates between Aboriginal and white Canadians. To contrast causes of end-stage renal disease by ethnicity and age, we calculated the odds of congenital diseases, glomerulonephritis and diabetes for Aboriginal people and compared them with those for white people in the following age strata: 0 to less than 22 years, 22 to less than 40 years, 40 to less than 60 years and older than 60 years.

Results:

Incidence rate ratios of end-stage renal disease for Aboriginal children and young adults (age < 22 yr, v. white people) were 1.82 (95% confidence interval [CI] 1.40–2.38) for boys and 3.24 (95% CI 2.60–4.05) for girls. Compared with white people, congenital diseases were less common among Aboriginal people aged less than 22 years (odds ratio [OR] 0.56, 95% CI 0.36–0.86), and glomerulonephritis was more common (OR 2.18, 95% CI 1.55–3.07). An excess of glomerulonephritis, but not diabetes, was seen among Aboriginal people aged 22 to less than 40 years. The converse was true (higher risk of diabetes, lower risk of glomerulonephritis) among Aboriginal people aged 40 years and older.

Interpretation:

The incidence of end-stage renal disease is higher among Aboriginal children and young adults than among white children and young adults. This higher incidence may be driven by an increased risk of glomerulonephritis in this population.Compared with white Canadians, Aboriginal Canadians have a higher prevalence of end-stage renal disease,^1,2 which is generally attributed to their increased risk for diabetes. However, there has been limited investigation of the incidence and causes of end-stage renal disease among Aboriginal children and young adults. Because most incident cases of diabetes are identified in middle-aged adults, an excess risk of end-stage renal disease in young people would not be expected if the high risk of diabetes is responsible for higher overall rates of end-stage renal disease among Aboriginal people. About 12.3% of children with end-stage renal disease in Canada are Aboriginal,³ but only 6.1% of Canadian children (age < 19 yr) are Aboriginal.^4,5A few reports suggest that nondiabetic renal disease is common among Aboriginal populations in North America.^2,6–8 Aboriginal adults in Saskatchewan are twice as likely as white adults to have end-stage renal disease caused by glomerulonephritis,^7,8 and an increased rate of mesangial proliferative glomerulonephritis has been reported among Aboriginal people in the United States.^6,9 These studies suggest that diabetes may be a comorbid condition rather than the sole cause of kidney failure among some Aboriginal people in whom diabetic nephropathy is diagnosed using clinical features alone.We estimated incidence rates of end-stage renal disease among Aboriginal children and young adults in Canada and compared them with the rates seen among white children and young adults. In addition, we compared relative odds of congenital renal disease, glomerulonephritis and diabetic nephropathy in Aboriginal people with the relative odds of these conditions in white people.     

Body mass index and all-cause mortality in a large Chinese cohort

Background

Obesity is known to be associated with an increased risk of death, but current definitions of obesity are based on data from white populations. We examined the association between body mass index (BMI) and the risk of death in a large population of adult Chinese people.

Methods

We examined the association between body mass index (BMI) and all-cause mortality prospectively among 58 738 men and 65 718 women aged 20 years and older enrolled in 1998–1999 from four national health screening centres in Taiwan. We used Cox proportional hazards regression analyses to estimate the relative risks of all-cause mortality for different BMI categories during a maximum follow-up of 10 years.

Results

A total of 3947 participants died during the follow-up period. The lowest risk of death was observed among men and women who had a BMI of 24.0–25.9 (mean 24.9). After adjustment for age, smoking status, alcohol intake, betel-nut chewing, level of physical activity, income level and education level, we observed a U-shaped association between BMI and all-cause mortality. Similar U-shaped associations were observed when we analyzed data by age (20–64 or ≥ 65 years), smoking (never, < 10 pack-years or ≥ 10 pack-years) and presence of a pre-existing chronic disease, and after we excluded deaths that occurred in the first three years of follow-up.

Interpretation

BMI and all-cause mortality had a U-shaped association among adult Chinese people in our study. The lowest risk of death was among adults who had a BMI of 24.0–25.9 (mean 24.9). Our findings do not support the use of a lower cutoff value for overweight and obesity in the adult Chinese population.The prevalence of obesity has dramatically increased in past decades in both developed and developing countries. The World Health Organization (WHO) reported that 1.6 billion adults are overweight and at least 400 million are obese.¹ The WHO further predicted that by the year 2015, about 2.3 billion adults will be overweight and more than 700 million will be obese.¹ In Taiwan, according to a national survey performed between 1993–1996 and 2005–2008, the prevalence of overweight and obesity (defined as body mass index [BMI] ≥ 24 kg/m²) had increased dramatically, from 33.4% to 50.8% among men and from 31.7% to 36.9% among women.²Overweight and obesity have been recognized as important and independent risk factors for many chronic diseases such as diabetes mellitus, hypertension, stroke, cardiovascular diseases and malignant diseases.^3–7 Substantial epidemiologic evidence shows that obesity is associated with an increased risk of cardiovascular-related and all-cause mortality.^8,9 Therefore, obesity has become a major public health problem around the world.Current definitions of obesity and overweight in adults are based on data from white populations. The WHO has proposed another definition for Asian people, but most of the data it used were from cross-sectional studies.¹⁰ One study showed that, for a given BMI, Asian people had higher body fat than white people.¹¹ Furthermore, the association between BMI and all-cause mortality has been reported to be J-shaped or U-shaped. Most of the studies involved white people, with only a few involving Asian populations. Gu and colleagues reported a U-shaped association between BMI and all-cause mortality among Chinese people.¹² However, they included only middle-aged adults over 40 years old and not all adults over 20 years.We designed a large prospective cohort study to assess the association between BMI and all-cause mortality in a nationwide representative sample of Chinese adults over 20 years old in Taiwan. We also intended to find the optimal BMI cutoff values for overweight and obesity among Chinese adults.     

Risk of vascular events in patients with polymyalgia rheumatica

Background:

Polymyalgia rheumatica is one of the most common inflammatory rheumatologic conditions in older adults. Other inflammatory rheumatologic disorders are associated with an excess risk of vascular disease. We investigated whether polymyalgia rheumatica is associated with an increased risk of vascular events.

Methods:

We used the General Practice Research Database to identify patients with a diagnosis of incident polymyalgia rheumatica between Jan. 1, 1987, and Dec. 31, 1999. Patients were matched by age, sex and practice with up to 5 patients without polymyalgia rheumatica. Patients were followed until their first vascular event (cardiovascular, cerebrovascular, peripheral vascular) or the end of available records (May 2011). All participants were free of vascular disease before the diagnosis of polymyalgia rheumatica (or matched date). We used Cox regression models to compare time to first vascular event in patients with and without polymyalgia rheumatica.

Results:

A total of 3249 patients with polymyalgia rheumatica and 12 735 patients without were included in the final sample. Over a median follow-up period of 7.8 (interquartile range 3.3–12.4) years, the rate of vascular events was higher among patients with polymyalgia rheumatica than among those without (36.1 v. 12.2 per 1000 person-years; adjusted hazard ratio 2.6, 95% confidence interval 2.4–2.9). The increased risk of a vascular event was similar for each vascular disease end point. The magnitude of risk was higher in early disease and in patients younger than 60 years at diagnosis.

Interpretation:

Patients with polymyalgia rheumatica have an increased risk of vascular events. This risk is greatest in the youngest age groups. As with other forms of inflammatory arthritis, patients with polymyalgia rheumatica should have their vascular risk factors identified and actively managed to reduce this excess risk.Inflammatory rheumatologic disorders such as rheumatoid arthritis,^1,2 systemic lupus erythematosus,^2,3 gout,⁴ psoriatic arthritis^2,5 and ankylosing spondylitis^2,6 are associated with an increased risk of vascular disease, especially cardiovascular disease, leading to substantial morbidity and premature death.^2–6 Recognition of this excess vascular risk has led to management guidelines advocating screening for and management of vascular risk factors.^7–9Polymyalgia rheumatica is one of the most common inflammatory rheumatologic conditions in older adults,¹⁰ with a lifetime risk of 2.4% for women and 1.7% for men.¹¹ To date, evidence regarding the risk of vascular disease in patients with polymyalgia rheumatica is unclear. There are a number of biologically plausible mechanisms between polymyalgia rheumatica and vascular disease. These include the inflammatory burden of the disease,^12,13 the association of the disease with giant cell arteritis (causing an inflammatory vasculopathy, which may lead to subclinical arteritis, stenosis or aneurysms),¹⁴ and the adverse effects of long-term corticosteroid treatment (e.g., diabetes, hypertension and dyslipidemia).^15,16 Paradoxically, however, use of corticosteroids in patients with polymyalgia rheumatica may actually decrease vascular risk by controlling inflammation.¹⁷ A recent systematic review concluded that although some evidence exists to support an association between vascular disease and polymyalgia rheumatica,¹⁸ the existing literature presents conflicting results, with some studies reporting an excess risk of vascular disease^19,20 and vascular death,^21,22 and others reporting no association.^23–26 Most current studies are limited by poor methodologic quality and small samples, and are based on secondary care cohorts, who may have more severe disease, yet most patients with polymyalgia rheumatica receive treatment exclusively in primary care.²⁷The General Practice Research Database (GPRD), based in the United Kingdom, is a large electronic system for primary care records. It has been used as a data source for previous studies,²⁸ including studies on the association of inflammatory conditions with vascular disease²⁹ and on the epidemiology of polymyalgia rheumatica in the UK.³⁰ The aim of the current study was to examine the association between polymyalgia rheumatica and vascular disease in a primary care population.     

Optimal cut-off score for diagnosing depression with the Patient Health Questionnaire (PHQ-9): a meta-analysis

Background:

The brief Patient Health Questionnaire (PHQ-9) is commonly used to screen for depression with 10 often recommended as the cut-off score. We summarized the psychometric properties of the PHQ-9 across a range of studies and cut-off scores to select the optimal cut-off for detecting depression.

Methods:

We searched Embase, MEDLINE and PsycINFO from 1999 to August 2010 for studies that reported the diagnostic accuracy of PHQ-9 to diagnose major depressive disorders. We calculated summary sensitivity, specificity, likelihood ratios and diagnostic odds ratios for detecting major depressive disorder at different cut-off scores and in different settings. We used random-effects bivariate meta-analysis at cutoff points between 7 and 15 to produce summary receiver operating characteristic curves.

Results:

We identified 18 validation studies (n = 7180) conducted in various clinical settings. Eleven studies provided details about the diagnostic properties of the questionnaire at more than one cut-off score (including 10), four studies reported a cut-off score of 10, and three studies reported cut-off scores other than 10. The pooled specificity results ranged from 0.73 (95% confidence interval [CI] 0.63–0.82) for a cut-off score of 7 to 0.96 (95% CI 0.94–0.97) for a cut-off score of 15. There was major variability in sensitivity for cut-off scores between 7 and 15. There were no substantial differences in the pooled sensitivity and specificity for a range of cut-off scores (8–11).

Interpretation:

The PHQ-9 was found to have acceptable diagnostic properties for detecting major depressive disorder for cut-off scores between 8 and 11. Authors of future validation studies should consistently report the outcomes for different cut-off scores.Depressive disorders are still under-recognized in medical settings despite major associated disability and costs. The use of short screening questionnaires may improve the recognition of depression in different medical settings.¹ The depression module of the Patient Health Questionnaire (PHQ-9) has become increasingly popular in research and practice over the past decade.² In its initial validation study, a score of 10 or higher had a sensitivity of 88% and a specificity of 88% for detecting major depressive disorders. Thus, a score of 10 has been recommended as the cut-off score for diagnosing this condition.³In a recent review of the PHQ-9, Kroenke and colleagues argued against inflexible adherence to a single cut-off score.² A recent analysis of the management of depression in general practice in the United Kingdom showed that the accuracy of predicting major depressive disorder could be improved by using 12 as the cut-off score.⁴Given the widespread use of PHQ-9 in screening for depression and that certain cut-off scores are being recommended as part of national strategies to screen for depression (based on initial validation studies, which might not be generalizable),^4,5 we attempted to determine whether the cut-off of 10 is optimum for screening for depression. This question could not be answered by two previous systematic reviews^6,7 because of the small number of primary studies available at the time. We also aimed to provide greater clarity about the proper use of PHQ-9 given the many settings in which it is used.     

Zinc for the treatment of the common cold: a systematic review and meta-analysis of randomized controlled trials

Background:

Results of randomized controlled trials evaluating zinc for the treatment of the common cold are conflicting. We conducted a systematic review and meta-analysis to evaluate the efficacy and safety of zinc for such use.

Methods:

We searched electronic databases and other sources for studies published through to Sept. 30, 2011. We included all randomized controlled trials comparing orally administered zinc with placebo or no treatment. Assessment for study inclusion, data extraction and risk-of-bias analyses were performed in duplicate. We conducted meta-analyses using a random-effects model.

Results:

We included 17 trials involving a total of 2121 participants. Compared with patients given placebo, those receiving zinc had a shorter duration of cold symptoms (mean difference −1.65 days, 95% confidence interval [CI] −2.50 to −0.81); however, heterogeneity was high (I² = 95%). Zinc shortened the duration of cold symptoms in adults (mean difference −2.63, 95% CI −3.69 to −1.58), but no significant effect was seen among children (mean difference −0.26, 95% CI −0.78 to 0.25). Heterogeneity remained high in all subgroup analyses, including by age, dose of ionized zinc and zinc formulation. The occurrence of any adverse event (risk ratio [RR] 1.24, 95% CI 1.05 to 1.46), bad taste (RR 1.65, 95% CI 1.27 to 2.16) and nausea (RR 1.64, 95% CI 1.19 to 2.27) were more common in the zinc group than in the placebo group.

Interpretation:

The results of our meta-analysis showed that oral zinc formulations may shorten the duration of symptoms of the common cold. However, large high-quality trials are needed before definitive recommendations for clinical practice can be made. Adverse effects were common and should be the point of future study, because a good safety and tolerance profile is essential when treating this generally mild illness.The common cold is a frequent respiratory infection experienced 2 to 4 times a year by adults and up to 8 to 10 times a year by children.^1–3 Colds can be caused by several viruses, of which rhinoviruses are the most common.⁴ Despite their benign nature, colds can lead to substantial morbidity, absenteeism and lost productivity.^5–7Zinc, which can inhibit rhinovirus replication and has activity against other respiratory viruses such as respiratory syncytial virus,⁸ is a potential treatment for the common cold. The exact mechanism of zinc’s activity on viruses remains uncertain. Zinc may also reduce the severity of cold symptoms by acting as an astringent on the trigeminal nerve.^9,10A recent meta-analysis of randomized controlled trials concluded that zinc was effective at reducing the duration and severity of common cold symptoms.¹¹ However, there was considerable heterogeneity reported for the primary outcome (I² = 93%), and subgroup analyses to explore between-study variations were not performed. The efficacy of zinc therefore remains uncertain, because it is unknown whether the variability among studies was due to methodologic diversity (i.e., risk of bias and therefore uncertainty in zinc’s efficacy) or differences in study populations or interventions (i.e., zinc dose and formulation).We conducted a systematic review and meta-analysis to evaluate the efficacy and safety of zinc for the treatment of the common cold. We sought to improve upon previous systematic reviews^11–17 by exploring the heterogeneity with subgroups identified a priori, identifying new trials by instituting a broader search and obtaining additional data from authors.     

Diagnostic accuracy of case-finding questions to identify perinatal depression

Background:

Guidelines for perinatal mental health care recommend the use of two case-finding questions about depressed feelings and loss of interest in activities, despite the absence of validation studies in this context. We examined the diagnostic accuracy of these questions and of a third question about the need for help asked of women receiving perinatal care.

Methods:

We evaluated self-reported responses to two case-finding questions against an interviewer-assessed diagnostic standard (DSM-IV criteria for major depressive disorder) among 152 women receiving antenatal care at 26–28 weeks’ gestation and postnatal care at 5–13 weeks after delivery. Among women who answered “yes” to either question, we assessed the usefulness of asking a third question about the need for help. We calculated sensitivity, specificity and likelihood ratios for the two case-finding questions and for the added question about the need for help.

Results:

Antenatally, the two case-finding questions had a sensitivity of 100% (95% confidence interval [CI] 77%–100%), a specificity of 68% (95% CI 58%–76%), a positive likelihood ratio of 3.03 (95% CI 2.28–4.02) and a negative likelihood ratio of 0.041 (95% CI 0.003–0.63) in identifying perinatal depression. Postnatal results were similar. Among the women who screened positive antenatally, the additional question about the need for help had a sensitivity of 58% (95% CI 38%–76%), a specificity of 91% (95% CI 78%–97%), a positive likelihood ratio of 6.86 (95% CI 2.16–21.7) and a negative likelihood ratio of 0.45 (95% CI 0.25–0.80), with lower sensitivity and higher specificity postnatally.

Interpretation:

Negative responses to both of the case-finding questions showed acceptable accuracy for ruling out perinatal depression. For positive responses, the use of a third question about the need for help improved specificity and the ability to rule in depression.The occurrence of depressive symptoms during the perinatal period is well-recognized. The estimated prevalence is 7.4%–20% antenatally^1,2 and up to 19.2% in the first three postnatal months.³ Antenatal depression is associated with malnutrition, substance and alcohol abuse, poor self-reported health, poor use of antenatal care services and adverse neonatal outcomes.⁴ Postnatal depression has a substantial impact on the mother and her partner, the family, mother–baby interaction and on the longer-term emotional and cognitive development of the baby.⁵Screening strategies to identify perinatal depression have been advocated, and specific questionnaires for use in the perinatal period, such as the Edinburgh Postnatal Depression Scale,⁶ were developed. However, in their current recommendations, the UK National Screening Committee⁷ and the US Committee on Obstetric Practice⁸ state that there is insufficient evidence to support the implementation of universal perinatal screening programs. The initial decision in 2001 by the National Screening Committee to not support universal perinatal screening⁹ attracted particular controversy in the United Kingdom; some service providers subsequently withdrew resources for treatment of postnatal depression, and subsequent pressure by perinatal community practitioners led to modification of the screening guidance in order to clarify the role of screening questionnaires in the assessment of perinatal depression.¹⁰In 2007, the National Institute for Health and Clinical Excellence issued clinical guidelines for perinatal mental health care in the UK, which included guidance on the use of questionnaires to identify antenatal and postnatal depression.¹¹ In this guidance, a case-finding approach to identify perinatal depression was strongly recommended; it involved the use of two case-finding questions (sometimes referred to as the Whooley questions), and an additional question about the need for help asked of women who answered “yes” to either of the initial questions (Box 1).

Box 1:

Case-finding questions recommended for the identification of perinatal depression¹⁰

• “During the past month, have you often been bothered by feeling down, depressed or hopeless?”
• “During the past month, have you often been bothered by having little interest or pleasure in doing things?”
• A third question should be considered if the woman answers “yes” to either of the initial screening questions: “Is this something you feel you need or want help with?”

Useful case-finding questions should be both sensitive and specific so they accurately identify those with and without the condition. The two case-finding questions have been validated in primary care samples^12,13 and examined in other clinical populations^14–16 and are endorsed in recommendations by US and Canadian bodies for screening depression in adults.^17,18 However, at the time the guidance from the National Institute for Health and Clinical Excellence was issued, there were no validation studies conducted in perinatal populations. A recent systematic review¹⁹ identified one study conducted in the United States that validated the two questions against established diagnostic criteria in 506 women attending well-child visits postnatally;²⁰ sensitivity and specificity of the questions were 100% and 44% respectively at four weeks. The review failed to identify studies that validated the two questions and the additional question about the need for help against a gold-standard measure.We conducted a validation study to assess the diagnostic accuracy of this brief case-finding approach against gold-standard psychiatric diagnostic criteria for depression in a population of women receiving perinatal care.