Nature and Nurture in Suicide Attempts.

In adoptees, the risk for suicidality was increased with the combination of suicidality in the biological parent and psychiatric hospitalization in the adoptive mother.

Ambiguity and controversy permeate discussions about how genetics and environment might each contribute to suicidal behavior. Using three decades of Swedish registry data, these investigators compared the histories of 2516 adoptees who had at least one biological parent who died by suicide or was hospitalized for suicidal behavior (S+) and 5875 adoptees who had a biological parent with psychiatric hospitalization but never for a suicide attempt (S–).

Lifetime psychiatric hospitalizations for all causes were similar for S+ and S– adoptees (17% and 16%). Analyses also examined the long-term effect of adoptive parents’ psychiatric hospitalizations when the adoptees were children (age, <18 years). Among adoptees with psychiatrically hospitalized adoptive mothers, S+ children (n=38) had significantly greater risk than S– children (n=111) for hospitalization related to suicide attempt or to drug use disorder (hazard ratios, 4.2 and 4.3, respectively). Among subjects whose adoptive mothers had not been hospitalized, these risks did not differ between S+ and S– adoptees. Psychiatric hospitalizations in adoptive fathers did not significantly alter these risks.

Comment: This study has several limitations: Data on biological fathers were missing for 46% of adoptees with suicidal biological parents and 29% of adoptees whose biological parents did not have suicide-related psychiatric hospitalizations; only psychiatric difficulties resulting in hospitalizations were measured; and the number of children adopted by biological relatives was unknown. Even with these limitations, the results indicate that having either a suicidal biological parent or a psychiatrically hospitalized adoptive mother does not increase risks for hospitalizations related to suicidal behavior or drug use disorder, but that the combination of those factors increases adoptees’ hospitalization risks more than fourfold. Early attention to the psychiatric health of adopting mothers may help prevent these difficulties in biologically vulnerable, adopted children.

Source:Journal Watch Psychiatry


Insomnia Drugs Linked to Increased Mortality.

But confounding could partly explain the findings in this observational study.

Hypnotic drugs, which many adults take for insomnia, have been associated with increased risks for cancer and death. Investigators clarified the extent of those risks by analyzing the medical records of 10,531 case patients (mean age, 54) who received prescriptions for hypnotic drugs and records of 23,674 matched controls who did not receive such prescriptions. Mortality data were acquired using the Social Security Death Index.

After a mean follow-up of 2.5 years, 6.1% of patients who received hypnotic drug prescriptions and 1.2% of patients who did not receive such prescriptions had died. Adjusted for multiple variables (e.g., age, tobacco use, body-mass index) and stratified by multiple comorbidities, the hazard ratios (HRs) for all-cause death were 3.6 for patients prescribed 1 to 18 doses yearly, 4.4 for patients prescribed 18 to 132 doses yearly, and 5.3 for patients prescribed >132 doses yearly compared with nonusers — a dose–response relation. The results were similar when the analysis was restricted to zolpidem (Ambien) or temazepam (Restoril), the most commonly prescribed hypnotic drugs. Patients who were prescribed >132 doses yearly of any hypnotic drug were also at significantly increased risk for cancer (HR, 1.4 compared with nonusers).

Comment: In this study, receiving a prescription for a hypnotic drug — even for 18 doses yearly — was associated with increased all-cause mortality risk, and receiving a prescription for many doses (>132 doses yearly) was associated with increased cancer risk. Given its design, this study does not prove that hypnotic drugs cause death or cancer. In addition, the authors were unable to control for psychiatric diagnoses such as depression or anxiety; therefore, residual confounding is possible. Nevertheless, the authors appropriately question the safety of these commonly prescribed drugs.

Source:Journal Watch General Medicine

Treatment of Alzheimer Disease: Stop, Add, or Switch?

This randomized study finds little evidence of benefit from combining medications in patients with moderate-to-severe AD.

Pharmacotherapy for moderate-to-severe Alzheimer disease (AD) often starts with an acetylcholinesterase inhibitor and subsequently adds or substitutes memantine, the N-methyl-D-aspartate–receptor antagonist. Little controlled evidence exists on the effects of continuing, stopping, or switching medications. This double-blind, placebo-controlled study (planned sample size of 430 patients) enrolled 295 community-dwelling patients with moderate-to-severe AD (Mini-Mental State Examination [MMSE] scores, 5–13) who were already receiving donepezil 10 mg for at least 6 weeks. Donepezil was continued or discontinued (discontinuers received placebo) and augmented with memantine or placebo. Authors established “clinically relevant” changes at 52 weeks on the MMSE (change, 1.4 points) and the Bristol Activities of Daily Living Scale.

Although cognitive and functional status declined in all patients, deterioration differed among groups. Donepezil continuers had better cognitive function (MMSE change, 1.9 points) and less functional impairment than donepezil discontinuers; these changes equaled 32% and 23%, respectively, of the deterioration in double-placebo recipients. Donepezil had a greater effect in moderate than in severe AD. Memantine recipients had better cognition and function than placebo recipients, but these differences were not clinically meaningful. Combining medications did not improve the benefit from donepezil.

Comment: The clinical question is whether slower deterioration in Alzheimer disease translates into a prolonged improved quality of life. These data suggest that the answer is yes for continuing donepezil for patients with moderate-to-severe AD. Combination therapy, frequently implemented in the U.S., showed no benefit. Memantine had a statistically, but not clinically, significant effect.

Other notable points: A larger study sample might have yielded additional differences. The findings may not pertain to patients with mild AD. Whether findings generalize to other acetylcholinesterase inhibitors is unclear. Memantine alone remains effective in persons who cannot take acetylcholinesterase inhibitors. Also, in an earlier study (JAMA 2004; 291:317), adjunctive memantine showed positive effects, which conflicts with the current results.

Source:Journal Watch Psychiatry

Preventing Venous Thromboembolism in Neurosurgery.

A calf-compression device significantly reduced VTE in patients undergoing neurosurgical procedures.

Venous thromboembolism (VTE) is both common and difficult to prevent in neurosurgical patients. Anticoagulant thromboprophylaxis is effective, but it increases the risks for intracranial and other major bleeding. Conversely, graduated compression stockings and intermittent pneumatic compression devices are safe but are of limited efficacy.

To examine the utility of a new, portable, battery-powered calf-compression device (Venowave), investigators conducted an industry-supported study involving 150 neurosurgical patients who were randomized to wear graduated compression stockings with or without the Venowave device. Venowave users and nonusers were well-matched in terms of cranial pathology (more than half had tumors), surgical site, and duration of surgery. Patients underwent screening venography approximately 1 week after admission.

Venowave users experienced a significantly lower rate of VTE than controls (4.0% vs. 18.7%; relative risk, 0.21; P=0.008) as well as a nonsignificantly lower rate of proximal deep vein thrombosis (2.7% and 8.0%, respectively). No pulmonary embolism occurred. Benefit was observed in all major subgroups examined, including age, sex, body-mass index, cranial pathology, and duration of surgery. Although the device was meant to be worn continuously, it was discontinued at night by 49% of users because it interfered with sleep.

Comment: In this small study, the Venowave, when used in conjunction with graduated compression stockings, significantly decreased the frequency of asymptomatic VTE. A larger study will be required to determine if it reduces the incidence of symptomatic VTE, especially fatal pulmonary embolism.

Source: Journal Watch Oncology and Hematology

Left Main PCI: Mapping the Territory

As the number of ULMCA procedures gradually increases, factors associated with better and worse outcomes are emerging.

Percutaneous coronary intervention (PCI) in unprotected left main coronary arteries (ULMCAs) is a new frontier in interventional cardiology. Recently upgraded guideline recommendations reflect evidence that the procedure can be safe and effective in selected patients. In this study from the National Cardiovascular Data Registry, investigators examined trends in ULMCA PCI from 2004 through 2008 at 693 centers.

Of 131,004 patients with 50% ULMCA stenosis, 5627 (4.3%) underwent PCI. PCI recipients were older (72 vs. 68) and had more comorbidities than non-PCI recipients. Over the 5-year study period, the proportion of patients receiving PCI for ULMCA increased from 3.8% to 4.9%. Most low-urgency patients (82%) received drug-eluting stents (DESs). Survival to hospital discharge was 95% in the overall cohort and 87% in PCI recipients. In-hospital mortality was higher in high-urgency patients and in those with high EuroSCOREs (a measure of surgical risk).

Medicare inpatient claims (allowing follow-up data collection) were available for 2765 PCI recipients. Major adverse events occurred in 58% by 30 months of follow-up and included death (43%), myocardial infarction (8%), and repeat revascularization (18%). Event rates were higher in high-urgency patients, those with high EuroSCOREs, and those with bifurcation lesions. Mortality risk was lower with DESs than with bare-metal stents (hazard ratio, 0.60).

Comment: In 2008, percutaneous coronary intervention for unprotected left main disease was still relatively infrequent, and major adverse events were common in patients aged 65, particularly those with high clinical urgency, comorbidities, or bare-metal stents. Since 2008, changes have occurred in technique (e.g., more single drug-eluting stent placements, use of intravascular ultrasound) and patient selection (e.g., fewer distal bifurcations, lower-risk patients). Continual reassessment of procedural results, both in registry studies and in randomized comparisons with surgery, is essential.

Source: Journal Watch Cardiology

CT Angiography Potentially Useful for Diagnosing Invasive Mold Disease.

Computed tomographic pulmonary angiography performed in 36 immunocompromised patients identified 10 of 12 individuals with proven or probable invasive mold disease.

Invasive mold disease (IMD) is an important cause of morbidity and mortality in immunocompromised patients. The finding of a “halo sign” (an area of ground-glass attenuation surrounding a nodule) on high-resolution computed tomography (HRCT) has been considered suggestive of this infection but not diagnostic. However, angioinvasion — a characteristic of IMD — can be detected by computed tomographic pulmonary angiography (CTPA) as blood-vessel interruption at the border of a focal lesion.

In a recent single-center study, researchers in Italy explored the diagnostic usefulness of CTPA in 36 immunocompromised patients with clinically suspected IMD and positive HRCT findings. Among these patients, 5 (14%) had proven, 7 (19%) had probable, and 24 (67%) had possible IMD at final diagnosis, based on European Organization for Research and Treatment of Cancer/Mycosis Study Group criteria.

CTPA showed an interruption of the arterial vessels, consistent with angioinvasive fungal disease, in all 5 patients with proven IMD (100%), as well as in 5 of 7 with probable IMD (71%) and 9 of 24 with possible IMD (37.5%). Among the 16 patients with positive CTPA findings, 12 had a halo sign on HRCT and 4 did not (P=0.001).

Comment: These data suggest that CTPA, available in most medical centers, may be a useful tool for diagnosing IMD in high-risk patients with suspicious but nonspecific findings on HRCT. Editorialists and the authors note potential complications of the procedure, including acute kidney injury and other adverse events related to use of contrast media, as well as increased exposure to radiation.

Source:Journal Watch Infectious Diseases

White Rice Postulated to Increase Diabetes Risk .

A meta-analysis finds increased risk for type 2 diabetes with high consumption of white rice. A comment in BMJ cautions against major dietary changes, however.

Researchers examined the association between white rice consumption and diabetes risk in four observational studies comprising some 350,000 subjects; two thirds were from Western countries. Participants were free of self-reported diabetes at baseline and were followed for 4 to 22 years.

In comparisons between subjects in the highest and lowest consumption categories, the relative risk for diabetes was roughly 1.3 overall. Asian populations showed a significantly higher risk (1.55), whereas Western populations — with consumption levels roughly one fifth that of Asians — showed a 1.12 relative risk. The authors speculate that white rice’s reduced nutrient content may play a role in the increased risk, in addition to its glycemic load.

An editorialist comments that the findings “cannot support large scale action.”


Adenoma Miss Rates of Trainees.

Trainees need to conduct an estimated 450 colonoscopies to achieve a miss rate of <25% in 60-year-old patients.

An important issue in colonoscopy training is how to measure the detection abilities of trainees. In a recent study conducted at a single hospital in California, trainees had their adenoma miss rates measured by tandem colonoscopy. A total of 218 patients underwent a colonoscopy performed by a trainee and then a second colonoscopy performed by an attending endoscopist.

The unassisted cecal intubation rate for the trainees was 70% overall, ranging from 43% for those who had conducted fewer than 100 colonoscopies to 90% after 250 examinations. The overall adenoma detection rate was 54%. For the 147 patients who had complete withdrawals performed by both the trainee and the attending physician, the trainees had an overall adenoma miss rate of 27% and an overall advanced adenoma miss rate of 9%. Increased experience of the trainee and older age of the patient were independent predictors of a lower adenoma miss rate. To achieve an adenoma miss rate of <25% in 60-year-old patients, approximately 450 exams would be needed.

Comment: This study provides some useful benchmarks about what can be expected of fellows with regard to adenoma miss rates and number of cases needed to achieve acceptable detection rates.

Source:Journal Watch Gastroenterology.


Rocuronium and Succinylcholine Are Equally Effective at Doses 1 mg/kg.

No significant differences in intubation time, conditions, or success rates were noted.

This author conducted a structured literature review of studies that compared succinylcholine and rocuronium at doses 1 mg/kg to determine whether the two agents are similarly effective in providing optimal conditions for emergency intubation. Of seven papers that were considered relevant, three were conducted in the emergency department (ED) setting, and one was a Cochrane review.

A prospective cohort analysis of 578 ED patients showed that succinylcholine provided paralysis 5 seconds earlier than rocuronium (the difference was not considered clinically relevant), and the two agents produced similar intubating conditions. A retrospective study of 327 ED patients showed no significant difference in first-attempt intubation success between the two ganets.The Cochrane review found no difference between the two agents in producing excellent or acceptable intubating conditions. The remaining four studies, which were conducted in the surgery setting, had similar findings.

Comment: Succinylcholine and rocuronium at ED-appropriate doses (>1 mg/kg) produce virtually identical intubating conditions. At these doses, however, rocuronium paralysis lasts up to 45 minutes, versus 6 to 10 minutes for succinylcholine. Assessing a patient for a possible difficult airway and preparing a backup airway are essential in all intubations.

Source:Journal Watch Emergency Medicine