Am J Clin Nutr. 2011 Dec; 94(6): 1383-91
Millward DJ, Stephen JM

Ann Clin Psychiatry. 2012 Feb; 24(1): 91-109
Ramasubbu R, Taylor VH, Saaman Z, Sockalingham S, Li M, Patten S, Rodin G, Schaffer A, Beaulieu S, McIntyre RS

Medical comorbidity in patients with mood disorders has become an increasingly important clinical and global public health issue. Several specific medical conditions are associated with an increased risk of mood disorders, and conversely, mood disorders are associated with increased morbidity and mortality in patients with specific medical disorders.To help understand the bidirectional relationship and to provide an evidence-based framework to guide the treatment of mood disorders that are comorbid with medical illness, we have reviewed relevant articles and reviews published in English-language databases (to April 2011) on the links between mood disorders and several common medical conditions, evaluating the efficacy and safety of pharmacologic and psychosocial treatments. The medical disorders most commonly encountered in adult populations (ie, cardiovascular disease, cerebrovascular disease, cancer, human immunodeficiency virus, hepatitis C virus, migraine, multiple sclerosis, epilepsy, and osteoporosis) were chosen as the focus of this review.Emerging evidence suggests that depression comorbid with several medical disorders is treatable and failure to treat depression in medically ill patients may have a negative effect on medical outcomes.This review summarizes the available evidence and provides treatment recommendations for the management of comorbid depression in medically ill patients.

Ann Clin Psychiatry. 2012 Feb; 24(1): 69-81
McIntyre RS, Alsuwaidan M, Goldstein BI, Taylor VH, Schaffer A, Beaulieu S, Kemp DE

One goal of the Canadian Network for Mood and Anxiety Treatments (CANMAT) is to develop evidence-based and best practice educational programs and recommendations. Our group conducted a comprehensive literature review to provide evidence-based recommendations for treating metabolic comorbidity in individuals with major depressive disorder (MDD) and bipolar disorder (BD).We searched PubMed for all English-language articles published January 1966 to November 2010 using BD and MDD cross-referenced with metabolic syndrome, obesity, diabetes mellitus, hypertension, and dyslipidemia. That search was augmented by a review of articles reporting outcomes of an intervention targeting components of metabolic syndrome in individuals with MDD or BD.Consensus exists for the recommendation that individuals with MDD and BD should be routinely screened for risk factors that increase risk for metabolic syndrome. For excess weight, the best-studied pharmacologic approaches are metformin and topiramate, with emerging evidence for liraglutide and modafinil. For binge eating disorder, the best evidence in mood disorders was for cognitive-behavioral therapy as well as topiramate, zonisamide, and in select cases selective serotonin reuptake inhibitors. For dysglycemia, dyslipidemia, and hypertension, evidence supports cognitive-behavioral interventions and anti-diabetic, antilipidemic, and antihypertensive treatments.Comprehensive care of individuals with mood disorders should include routine evaluation of the risk and presence of metabolic syndrome and its components. Systematic evaluation of preventative and targeted treatments of metabolic syndrome in mood disorder populations is insufficient.

Ann Clin Psychiatry. 2012 Feb; 24(1): 56-68
Rosenbluth M, Macqueen G, McIntyre RS, Beaulieu S, Schaffer A

The association between mood disorders and personality disorders (PDs) is complicated clinically, conceptually, and neurobiologically. There is a need for recommendations to assist clinicians in treating these frequently encountered patients.The literature was reviewed with the purpose of identifying clinically relevant themes. MedLine searches were supplemented with manual review of the references in relevant papers. From the extant evidence, consensus-based recommendations for clinical practice were developed.Key issues were identified with regards to the overlap of PDs and mood disorders, including whether certain personality features predispose to mood disorders, whether PDs can reliably be recognized if there is an Axis I disorder present, whether personality disturbances arise as a consequence or are a forme fruste of mood disorders, and whether personality traits or disorders modify treatment responsiveness and outcome of mood disorders.This paper describes consensus-based clinical recommendations that arise from a consideration of how signals from the literature can impact clinical practice in the treatment of patients with comorbid mood and personality pathology. Additional treatment studies of patients with the comorbid conditions are required to further inform clinical practice.

Ann Clin Psychiatry. 2012 Feb; 24(1): 38-55
Beaulieu S, Saury S, Sareen J, Tremblay J, Schütz CG, McIntyre RS, Schaffer A

Mood disorders, especially bipolar disorder (BD), frequently are associated with substance use disorders (SUDs). There are well-designed trials for the treatment of SUDs in the absence of a comorbid condition. However, one cannot generalize these study results to individuals with comorbid mood disorders, because therapeutic efficacy and/or safety and tolerability profiles may differ with the presence of the comorbid disorder. Therefore, a review of the available evidence is needed to provide guidance to clinicians facing the challenges of treating patients with comorbid mood disorders and SUDs.We reviewed the literature published between January 1966 and November 2010 by using the following search strategies on PubMed. Search terms were bipolar disorder or depressive disorder, major (to exclude depression, postpartum; dysthymic disorder; cyclothymic disorder; and seasonal affective disorder) cross-referenced with alcohol or drug or substance and abuse or dependence or disorder. When possible, a level of evidence was determined for each treatment using the framework of previous Canadian Network for Mood and Anxiety Treatments recommendations. The lack of evidence-based literature limited the authors' ability to generate treatment recommendations that were strictly evidence based, and as such, recommendations were often based on the authors' opinion.Even though a large number of treatments were investigated for alcohol use disorder (AUD), none have been sufficiently studied to justify the attribution of level 1 evidence in comorbid AUD with major depressive disorder (MDD) or BD. The available data allows us to generate first-choice recommendations for AUD comorbid with MDD and only third-choice recommendations for cocaine, heroin, and opiate SUD comorbid with MDD. No recommendations were possible for cannabis, amphetamines, methamphetamines, or polysubstance SUD comorbid with MDD. First-choice recommendations were possible for alcohol, cannabis, and cocaine SUD comorbid with BD and only second-choice recommendations for heroin, amphetamine, methamphetamine, and polysubstance SUD comorbid with BD. No recommendations were possible for opiate SUD comorbid with BD. Finally, psychotherapies certainly are considered an essential component of the overall treatment of SUDs comorbid with mood disorders. However, further well-designed studies are needed in order to properly assess their potential role in specific SUDs comorbid with a mood disorder.Although certain treatments show promise in the management of mood disorders comorbid with SUDs, additional well-designed studies are needed to properly assess their potential role in specific SUDs comorbid with a mood disorder.

Ann Clin Psychiatry. 2012 Feb; 24(1): 6-22
Schaffer A, McIntosh D, Goldstein BI, Rector NA, McIntyre RS, Beaulieu S, Swinson R, Yatham LN

Comorbid mood and anxiety disorders are commonly seen in clinical practice. The goal of this article is to review the available literature on the epidemiologic, etiologic, clinical, and management aspects of this comorbidity and formulate a set of evidence- and consensus-based recommendations. This article is part of a set of Canadian Network for Mood and Anxiety Treatments (CANMAT) Comorbidity Task Force papers.We conducted a PubMed search of all English-language articles published between January 1966 and November 2010. The search terms were bipolar disorder and major depressive disorder, cross-referenced with anxiety disorders/symptoms, panic disorder, agoraphobia, generalized anxiety disorder, social phobia, obsessive-compulsive disorder, and posttraumatic stress disorder. Levels of evidence for specific interventions were assigned based on a priori determined criteria, and recommendations were developed by integrating the level of evidence and clinical opinion of the authors.Comorbid anxiety symptoms and disorders have a significant impact on the clinical presentation and treatment approach for patients with mood disorders. A set of recommendations are provided for the management of bipolar disorder (BD) with comorbid anxiety and major depressive disorder (MDD) with comorbid anxiety with a focus on comorbid posttraumatic stress disorder, use of cognitive-behavioral therapy across mood and anxiety disorders, and youth with mood and anxiety disorders.Careful attention should be given to correctly identifying anxiety comorbidities in patients with BD or MDD. Consideration of evidence- or consensus-based treatment recommendations for the management of both mood and anxiety symptoms is warranted.

Ann Clin Psychiatry. 2012 Feb; 24(1): 2-3
McIntyre RS, Schaffer A, Beaulieu S

PLoS Negl Trop Dis. 2012 Jan; 6(1): e1490
Holt KE, Dutta S, Manna B, Bhattacharya SK, Bhaduri B, Pickard DJ, Ochiai RL, Ali M, Clemens JD, Dougan G

Typhoid fever, caused by Salmonella enterica serovar Typhi (S. Typhi), is a major health problem especially in developing countries. Vaccines against typhoid are commonly used by travelers but less so by residents of endemic areas.We used single nucleotide polymorphism (SNP) typing to investigate the population structure of 372 S. Typhi isolated during a typhoid disease burden study and Vi vaccine trial in Kolkata, India. Approximately sixty thousand people were enrolled for fever surveillance for 19 months prior to, and 24 months following, Vi vaccination of one third of the study population (May 2003-December 2006, vaccinations given December 2004).A diverse S. Typhi population was detected, including 21 haplotypes. The most common were of the H58 haplogroup (69%), which included all multidrug resistant isolates (defined as resistance to chloramphenicol, ampicillin and co-trimoxazole). Quinolone resistance was particularly high among H58-G isolates (97% Nalidixic acid resistant, 30% with reduced susceptibility to ciprofloxacin). Multiple typhoid fever episodes were detected in 22 households, however household clustering was not associated with specific S. Typhi haplotypes.Typhoid fever in Kolkata is caused by a diverse population of S. Typhi, however H58 haplotypes dominate and are associated with multidrug and quinolone resistance. Vi vaccination did not obviously impact on the haplotype population structure of the S. Typhi circulating during the study period.

PLoS Negl Trop Dis. 2012 Jan; 6(1): e1488
Peacock SJ, Limmathurotsakul D, Lubell Y, Koh GC, White LJ, Day NP, Titball RW

Burkholderia pseudomallei is a Category B select agent and the cause of melioidosis. Research funding for vaccine development has largely considered protection within the biothreat context, but the resulting vaccines could be applicable to populations who are at risk of naturally acquired melioidosis. Here, we discuss target populations for vaccination, consider the cost-benefit of different vaccination strategies and review potential vaccine candidates.Melioidosis is highly endemic in Thailand and northern Australia, where a biodefense vaccine might be adopted for public health purposes. A cost-effectiveness analysis model was developed, which showed that a vaccine could be a cost-effective intervention in Thailand, particularly if used in high-risk populations such as diabetics. Cost-effectiveness was observed in a model in which only partial immunity was assumed. The review systematically summarized all melioidosis vaccine candidates and studies in animal models that had evaluated their protectiveness. Possible candidates included live attenuated, whole cell killed, sub-unit, plasmid DNA and dendritic cell vaccines. Live attenuated vaccines were not considered favorably because of possible reversion to virulence and hypothetical risk of latent infection, while the other candidates need further development and evaluation. Melioidosis is acquired by skin inoculation, inhalation and ingestion, but routes of animal inoculation in most published studies to date do not reflect all of this. We found a lack of studies using diabetic models, which will be central to any evaluation of a melioidosis vaccine for natural infection since diabetes is the most important risk factor.Vaccines could represent one strand of a public health initiative to reduce the global incidence of melioidosis.

PLoS One. 2012; 7(1): e30936
Joling KJ, van Marwijk HW, Smit F, van der Horst HE, Scheltens P, van de Ven PM, Mittelman MS, van Hout HP

Family caregivers of dementia patients are at increased risk of developing depression or anxiety. A multi-component program designed to mobilize support of family networks demonstrated effectiveness in decreasing depressive symptoms in caregivers. However, the impact of an intervention consisting solely of family meetings on depression and anxiety has not yet been evaluated. This study examines the preventive effects of family meetings for primary caregivers of community-dwelling dementia patients.A randomized multicenter trial was conducted among 192 primary caregivers of community dwelling dementia patients. Caregivers did not meet the diagnostic criteria for depressive or anxiety disorder at baseline. Participants were randomized to the family meetings intervention (n = 96) or usual care (n = 96) condition. The intervention consisted of two individual sessions and four family meetings which occurred once every 2 to 3 months for a year. Outcome measures after 12 months were the incidence of a clinical depressive or anxiety disorder and change in depressive and anxiety symptoms (primary outcomes), caregiver burden and quality of life (secondary outcomes). Intention-to-treat as well as per protocol analyses were performed.A substantial number of caregivers (72/192) developed a depressive or anxiety disorder within 12 months. The intervention was not superior to usual care either in reducing the risk of disorder onset (adjusted IRR 0.98; 95% CI 0.69 to 1.38) or in reducing depressive (randomization-by-time interaction coefficient = -1.40; 95% CI -3.91 to 1.10) or anxiety symptoms (randomization-by-time interaction coefficient = -0.55; 95% CI -1.59 to 0.49). The intervention did not reduce caregiver burden or their health related quality of life.This study did not demonstrate preventive effects of family meetings on the mental health of family caregivers. Further research should determine whether this intervention might be more beneficial if provided in a more concentrated dose, when applied for therapeutic purposes or targeted towards subgroups of caregivers.Controlled-Trials.com ISRCTN90163486.

PLoS One. 2012; 7(1): e30841
Zhang Y, Zhang G, Hendrix LR, Tesh VL, Samuel JE

The ability of Coxiella burnetii to modulate host cell death may be a critical factor in disease development. In this study, human monocytic THP-1 cells were used to examine the ability of C. burnetii Nine Mile phase II (NMII) to modulate apoptotic signaling. Typical apoptotic cell morphological changes and DNA fragmentation were detected in NMII infected cells at an early stage of infection. FACS analysis using Annexin-V-PI double staining showed the induction of a significant number of apoptotic cells at an early stage of NMII infection. Double staining of apoptotic cell DNA and intracellular C. burnetii indicates that NMII infected cells undergoing apoptosis. Interestingly, caspase-3 was not cleaved in NMII infected cells and the caspase-inhibitor Z-VAD-fmk did not prevent NMII induced apoptosis. Surprisingly, the caspase-3 downstream substrate PARP was cleaved in NMII infected cells. These results suggest that NMII induces apoptosis during an early stage of infection through a caspase-independent pathway in THP-1 cells. In addition, NMII-infected monocytes were unable to prevent exogenous staurosporine-induced apoptotic death. Western blot analysis indicated that NMII infection induced the translocation of AIF from mitochondria into the nucleus. Cytochrome c release and cytosol-to-mitochondrial translocation of the pore-forming protein Bax in NMII infected cells occurred at 24 h post infection. These data suggest that NMII infection induced caspase-independent apoptosis through a mechanism involving cytochrome c release, cytosol-to-mitochondrial translocation of Bax and nuclear translocation of AIF in THP-1 monocytes. Furthermore, NMII infection increased TNF-α production and neutralization of TNF-α in NMII infected cells partially blocked PARP cleavage, suggesting TNF-α may play a role in the upstream signaling involved in NMII induced apoptosis. Antibiotic inhibition of C. burnetii RNA synthesis blocked NMII infection-induced PARP activation. These results suggest that both intracellular C. burnetii replication and secreted TNF-α contribute to NMII infection-triggered apoptosis during an early stage of infection.

PLoS One. 2012; 7(1): e30728
von Knorring N, Gafos M, Ramokonupi M, Jentsch U,

BACKGROUND: Quality control (QC) and evaluation of HIV rapid test procedures are an important aspect of HIV prevention trials. We describe QC and performance of two rapid tests, Determine™ and Uni-Gold™ used in a microbicide clinical trial in rural KwaZulu-Natal, South Africa. METHODS/RESULTS: Internal QC of both HIV rapid tests was conducted at the trial site using a Uni-Gold control kit (Uni-Gold™Recombigen® HIV). Both assays produced the expected results for a total of 4637 QC tests. Study participants were tested for HIV at screening and, if enrolled, at regular time points throughout the study. Positive or discordant results were confirmed by a double HIV immunoassay testing strategy at a local laboratory. Overall, 15292 HIV rapid test were performed. Sensitivity and specificity of Determine was 98.95% (95% CI: 97.72-99.61) and 99.83% (95% CI: 99.70-99.91) respectively [positive predictive value (PPV) 97.91% (95% CI: 96.38-98.92)], for Uni-Gold it was 99.30% (95% CI: 98.21-99.81) and 99.96% (95% CI: 99.88-99.99) respectively [PPV 99.47% (95% CI: 98.46-99.89)]. CONCLUSIONS: The results suggest that a Uni-Gold control kit can be used for internal QC of both Uni-Gold and the HIV-1 component of the Determine rapid tests. Both rapid tests performed proficiently in the trial population.