Efficacy and safety of antidepressant augmentation of continued antipsychotic treatment in patients with schizophrenia.

OBJECTIVE: To evaluate the efficacy and safety of antidepressant augmentation of antipsychotics in schizophrenia. METHODS: Systematic literature search (PubMed/MEDLINE/PsycINFO/Cochrane Library) from database inception until 10/10/2017 for randomized, double-blind, efficacy-focused trials comparing adjunctive antidepressants vs. placebo in schizophrenia. RESULTS: In a random-effects meta-analysis (studies = 42, n = 1934, duration = 10.1 ± 8.1 weeks), antidepressant augmentation outperformed placebo regarding total symptom reduction [standardized mean difference (SMD) = -0.37, 95% confidence interval (CI) = -0.57 to -0.17, P < 0.001], driven by negative (SMD = -0.25, 95% CI = -0.44-0.06, P = 0.010), but not positive (P = 0.190) or general (P = 0.089) symptom reduction. Superiority regarding negative symptoms was confirmed in studies augmenting first-generation antipsychotics (FGAs) (SMD = -0.42, 95% CI = -0.77, -0.07, P = 0.019), but not second-generation antipsychotics (P = 0.144). Uniquely, superiority in total symptom reduction by NaSSAs (SMD = -0.71, 95% CI = -1.21, -0.20, P = 0.006) was not driven by negative (P = 0.438), but by positive symptom reduction (SMD = -0.43, 95% CI = -0.77, -0.09, P = 0.012). Antidepressants did not improve depressive symptoms more than placebo (P = 0.185). Except for more dry mouth [risk ratio (RR) = 1.57, 95% CI = 1.04-2.36, P = 0.03], antidepressant augmentation was not associated with more adverse events or all-cause/specific-cause discontinuation. CONCLUSIONS: For schizophrenia patients on stable antipsychotic treatment, adjunctive antidepressants are effective for total and particularly negative symptom reduction. However, effects are small-to-medium, differ across antidepressants, and negative symptom improvement seems restricted to the augmentation of FGAs.

Episodic evolution of pyrin in primates: human mutations recapitulate ancestral amino acid states.

Familial Mediterranean fever (FMF; MIM 249100) is an autosomal recessive disease characterized by recurrent attacks of fever with synovial, pleural or peritoneal inflammation. The disease is caused by mutations in the gene encoding the pyrin protein. Human population studies have revealed extremely high allele frequencies for several different pyrin mutations, leading to the conclusion that the mutant alleles confer a selective advantage. Here we examine the ret finger protein (rfp) domain (which contains most of the disease-causing mutations) of pyrin during primate evolution. Amino acids that cause human disease are often present as wild type in other species. This is true at positions 653 (a novel mutation), 680, 681, 726, 744 and 761. For several of these human mutations, the mutant represents the reappearance of an ancestral amino acid state. Examination of lineage-specific dN/dS ratios revealed a pattern consistent with the signature of episodic positive selection. Our data, together with previous human population studies, indicate that selective pressures may have caused functional evolution of pyrin in humans and other primates.

To study the prevalence and profile of metabolic syndrome, levels of hs-CRP, Lp(a) and serum ferritin in young Indian patients (< or = 45 years) with acute myocardial infarction.

OBJECTIVE: To study the prevalence and profile of metabolic syndrome, levels of hs-CRP, Lp(a) and serum ferritin in young Indian patients (< or = 45 years) with acute MI. METHODS: A total of 80 subjects in two groups (40 cases and 40 controls) of age < or = 45 years were studied. Diagnosis of MI was made using the American College of Cardiology and European Society of Cardiology guidelines for acute MI. Patients were assessed for presence of MetS, diagnosed as per modified ATP III criteria. The anthropometric measurements (including height, weight, waist circumference) and sample collection for lipid profile, fasting blood sugar, hs-CRP, Lp(a) and serum ferritin were done after seventy two hours of admission. RESULTS: The mean age for cases was 39.23 +/- 4.80 years and for controls it was 38.9 +/- 4.23 years. 19 (47.5%) patients out of 40 in group 1 fulfilled > or = 3/5 criteria for MetS while only 8 (20%) subjects in control group had MetS. Among five components of metabolic syndrome, increased waist circumference was most predominant factor followed by decreased HDL, increased TG, increased blood pressure and impaired fasting glucose. The mean value of serum ferritin was 279.33 +/- 46.69 mg in case group as compared to 245.15 +/- 56.94 in control group. hs-CRP (16.048 +/- 10.27 mg/l vs 1.8 +/- 1.6 mg/l) and Lp(a) (38.74 +/- 26.15 mg/dl vs 20.54 +/- 16.27 mg/dl) levels were significantly raised in cases as compared to control subjects. CONCLUSION: The present study revealed high prevalence of metabolic syndrome (47.5%) in young patients with acute MI. Serum hsCRP, a diagnostic and prognostic novel marker of inflammation was also significantly elevated in cases. Its relationship with metabolic syndrome is also well established. Lp(a) and serum ferritin were also raised in cases.

Motor unit firing variability and synchronization during short-term light-load training in older adults.

We compared motor unit synchronization and firing rate variability within and across synergistic hand muscles during a pinching task following short-term light-load training to improve force steadiness in older adults. A total of 183 motor unit pairs before training and 158 motor unit pairs after training were recorded with intramuscular fine-wire electrodes within and across the first dorsal interosseous (FDI) and adductor pollicis (AdP) muscles during a pinch task performed by ten older adults before and after a 4-week short-term light-load training program. Nine younger adults performed the same experimental sessions 4 weeks apart with no training intervention. Two-minute sustained contractions of 2, 4, 8, and 12% maximal voluntary contraction (MVC) were performed with the non-dominant hand. The coefficient of variation (CV) of force was greater in older than in younger adults and was lower at the 2 and 4% MVC levels in both the finger (0.12 +/- 0.01 vs. 0.08 +/- 0.01, and 0.08 +/- 0.01 vs. 0.05 +/- 0.01, respectively) and thumb (0.11 +/- 0.01 vs. 0.08 +/- 0.01, and 0.09 +/- 0.01 vs. 0.05 +/- 0.01, respectively) compared to higher force levels following training in the older adults. There were no changes in CIS or k'-1 values following training. Motor unit firing rate variability significantly decreased at low force levels in the FDI muscle and also tended to decrease with training in the AdP muscle (p = 0.06). No changes occurred in the younger control group. These findings are the first to show that motor unit synchronization does not change during light-load training. Thus, it is likely that force steadiness in older adults improves by reducing motor unit firing variability rather than by changing motor unit synchronization.

High risk of post-infectious irritable bowel syndrome in patients with Clostridium difficile infection.

BACKGROUND: Infectious enteritis is a commonly identified risk factor for irritable bowel syndrome (IBS). The incidence of Clostridium difficile infection (CDI) is on the rise. However, there is limited information on post-infectious IBS (PI-IBS) development following CDI and the host- and infection-related risk factors are not known. AIM: To determine the incidence and risk factors for PI-IBS following CDI. METHODS: A total of 684 cases of CDI identified from September 2012 to November 2013 were surveyed. Participants completed the Rome III IBS questionnaire and details on the CDI episode. Predictive modelling was done using logistic regression to evaluate risk factors for PI-IBS development. RESULTS: A total of 315 CDI cases responded (46% response rate) and 205 were at-risk (no pre-CDI IBS) for PI-IBS development. A total of 52/205 (25%) met the Rome III criteria for IBS ≥6 months following CDI. IBS-mixed was most common followed by IBS-diarrhoea. In comparison to those without subsequent PI-IBS, greater percentage of PI-IBS patients had CDI symptoms >7 days, nausea, vomiting, abdominal pain during CDI, anxiety and a higher BMI. Using logistic regression, CDI symptoms >7 days [Odds ratio (OR): 2.96, P = 0.01], current anxiety (OR: 1.33, P < 0.0001) and a higher BMI (OR: 1.08, P = 0.004) were independently associated with PI-IBS development; blood in the stool during CDI was protective (OR: 0.44, P = 0.06). CONCLUSIONS: In this cohort study, new-onset IBS is common after CDI. Longer CDI duration, current anxiety and higher BMI are associated with the diagnosis of C. difficile PI-IBS. This chronic sequela should be considered during active management and follow-up of patients with CDI.

(13) C mannitol as a novel biomarker for measurement of intestinal permeability.

BACKGROUND: Gastrointestinal (GI) and non-GI disorders are associated with altered intestinal permeability, which can be measured in vivo by urinary excretion after oral lactulose and mannitol ingestion. Inadvertent dietary consumption of (12) Carbon ((12) C, regular) mannitol in food or from other sources may interfere with the test's interpretation. (13) Carbon ((13) C) constitutes 1% of carbon in nature and (13) C mannitol is a stable isotope. Our aim was to determine the performance of (13) C mannitol for measurement of intestinal permeability. METHODS: Ten healthy volunteers underwent intestinal permeability assay using coadministered (12) C mannitol, (13) C mannitol and lactulose, followed by timed urine collections. Urinary sugar concentrations were measured using tandem high performance liquid chromatography-mass spectrometry. KEY RESULTS: We found that (13) C mannitol can be distinguishable from (12) C mannitol on tandem mass spectrometry. In addition, (13) C mannitol had ~20-fold lower baseline contamination compared to (12) C mannitol. We describe here the (13) C mannitol assay method for the measurement of intestinal permeability. CONCLUSIONS & INFERENCES: In conclusion, (13) C mannitol is superior to (12) C mannitol for measurement of intestinal permeability. It avoids issues with baseline contamination and erratic excretions during the testing period.

Candidemia--an under-recognized nosocomial infection in Indian hospitals.

OBJECTIVE: To study the occurrence of candidemia as a nosocomial infection in a large Indian teaching hospital and to evaluate the predisposing factors for development of such infections. METHODS: One hundred and one hospitalized patients that developed signs and symptoms of nosocomial bloodstream infections were screened for candidemia and were analyzed for the various predisposing factors like the age of the patient, the duration of hospitalization before the development of fever, neutropenia, use of chemotherapeutic agents, central venous catheters, broad spectrum antibiotics, infection with HIV, diabetes mellitus, use of corticosteroids, administration of total parenteral nutrition, haemodialysis, use of mechanical ventilation, hematological or other malignancies, underlying disease, and any surgical procedure performed on the patient. Candidemic patients were followed up for outcome and the effect of nosocomial candidemia on mortality was assessed and analyzed statistically. RESULTS: Out of the 101 patients, seven patients had candidemia, an incidence in study population of 6.9%. Three (42.8%) were infected with albicans and the rest with non-albicans candidemia. All the patients with candidemia were admitted in the Intensive Care Units. Amongst the risk factors, the length of hospitalization (p = 0.018), broad-spectrum antibiotics (p = 0.045), central venous catheters (p = 0.005), mechanical ventilation (p = 0.0139) and total parenteral nutrition (p = 0.001) were found to be significantly related to acquisition of nosocomial candidemia. Mortality in the candidemic patients was influenced only by the age of the patients (p = 0.001). Although the mortality amongst the candidemic patients was twice as much as that of the patients not having this infection, still the difference did not reach significance (p = 0.117). CONCLUSION: Candidemia is an important problem in Indian hospitals. Diagnostic delays could be shortened by more active screening for candidemia especially in the intensive care settings. The rising incidence of non-albicans candidemia in the United States probably is true here as well. There should be a concerted effort to control known risk factors especially in intensive care units.

Successful pregnancy in untreated limited Wegener's granulomatosis.

A thirty four year old female presented with upper and lower respiratory symptoms in the third trimester of pregnancy. After the delivery of a healthy baby, the symptoms progressed to involve multiple organ systems and eventually a diagnosis of limited Wegener's Granulomatosis (Carrington-Liebow syndrome) was made. The extremely rare combination of WG and pregnancy, especially the onset of disease in late pregnancy is discussed. The successful outcome of pregnancy even without treatment of WG is the highlight of the case.

Nutritional status of the elderly.

Elderly become vulnerable to malnutrition owing to inappropriate dietary intake, poor economic status and social deprivation. Elderly are known to be easily subjected to inanition and avitaminosis resulting in multiple nutritional deficiencies. Urban slum dwellers, rural poor and those living alone appear to be at a higher risk of poor dietary intake. Though food consumption patterns of rural and urban elderly show a distinct difference, these are greatly influenced by regional dietary patterns. The diets of institutionalised and free living elderly reveal adequate nutrient intakes except iron and vitamin A. The nutrients least adequately supplied in the diets of Indian elderly are calcium, Iron, vitamin A, riboflavin and niacin along with energy deficits. Changes in body composition which mark the onset of the ageing process, include decline in lean body mass and increase in adipose tissue. A high prevalence of iron deficiency anaemia has also been reported among Indian elderly.

Clinical, histopathologic & immunologic features of cutaneous lesions in acute meningococcaemia.

Fifty children with culture proven acute meningococcaemia were studied during the winter outbreak of the disease in 1986-87. Purpuric lesions were seen in 60 per cent, erythematous papules in 32 per cent, faint pink macules in 28 per cent, conjunctival petechiae in 10 per cent and herpes labialis in 20 per cent. Histopathology of skin lesions showed that the primary damage was to the dermal vessels, the extent of damage depending on the type of skin involvement. Diplococci in Gram's stained sections were seen frequently in purpuric as compared to the other skin lesions. They were located in degenerating neutrophils, endothelial cells, fibrin clots or freely in the vascular lumen. Electron microscopic study showed vascular changes accompanied by a perivascular phagocytic response. Both light and electronmicroscopy indicated the involvement of the coagulative mechanism in the pathogenesis of meningococcaemia. However, clinical parameters of clotting were often within normal limits. In the case of a child (who died eventually), a low platelet count and prolonged coagulation indices were observed. Sera from some of the children were tested for the presence of antibodies against meningococci by indirect immunofluorescence. Antibodies were detected in the sera and they may have a role in regulating the severity and course of the illness. The significance of immunoglobulin deposits in the skin lesions is not clear.

Serum and urinary cation changes on acute induction to high altitude (3200 and 3771 metres).

Twenty subjects each were rapidly inducted by road to 3200 ad 3771 m. Serum and urinary sodium, potassium, calcium, and magnesium were measured during 10 d at high altitude. At 3200 m, only serum potassium increased significantly on the 10th day. At 3771 m, serum potassium did not increase. Serum sodium generally remained low, serum magnesium increased, while calcium decreased significantly. Urinary volume over 24 h decreased more and for longer duration at 3771 m than at 3200 m. Urinary cations did not change significantly at 3200 m. At 3771 m, sodium and potassium excretion decreased on days 1 and 3 later returned towards preinduction levels. Magnesium and calcium decreased throughout the high-altitude stay. Significant changes were noticed in serum and urinary cations on exposure to high altitude when adequate caloric intakes were not ensured.

Congenital syphilitic hepatitis.

Hepatitis is a known manifestation of congenital syphilis, however hepatitis developing during penicillin therapy is unknown. Ten patients of congenital syphilis were studied and serial liver enzymes were done before and after starting penicillin therapy. Eight of the ten patients developed hepatitis after initiating penicillin therapy. Whether hepatitis in these cases was secondary to toxic reaction to the products of treponemal lysis or an autoimmune reaction needs to be investigated.

Leiomyosarcoma of the larynx: diagnosis aided by advances in immunohistochemical staining.

We present only the 12th reported case of a laryngeal leiomyosarcoma. This tumor was diagnosed with the aid of the newer immunohistochemical stains on archival paraffin-embedded tissue. The diagnosis and management of these tumors is based largely on the patterns seen in the small number of earlier reported cases of head and neck leiomyosarcomas and laryngeal sarcomas.

An unusual phaeoid fungi: Ulocladium, as a cause of chronic allergic fungal sinusitis.

Allergic fungal sinusitis (AFS) has been recognized as an important cause of chronic sinusitis commonly caused by Aspergillus spp. and various dematiaceous fungi like Bipolaris, Alternaria, Curvalaria, and etc. Ulocladium botrytis is a non pathogenic environmental dematiaceous fungi, which has been recently described as a human pathogen. Ulocladium has never been associated with allergic fungal sinusitis but it was identified as an etiological agent of AFS in a 35 year old immunocompetent female patient presenting with chronic nasal obstruction of several months duration to our hospital. The patient underwent FESS and the excised polyps revealed Ulocladium as the causative fungal agent.