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OBJECTIVES/GOALS: Total hip replacement (THR) improves function for those with arthritis, but not all patients have equal access to this elective procedure. To better geographically target healthcare resources, we explored whether geographic socioeconomic disadvantage is associated with incidence of elective THR. METHODS/STUDY POPULATION: We performed a cross-sectional analysis of data in the state of Maryland from 2013-2019. We categorized 5-digit zipcodes into national quartiles of socioeconomic disadvantage using the Area Deprivation Index (ADI). For each zipcode, we calculated the THR incidence rate using Maryland Health Services Cost Review Commission (HSCRC) inpatient and outpatient data in those age 65 years and older. We included only elective THRs. We analyzed the association between a zipcode’s disadvantage quartile and THR incidence rate using multivariate linear regression, correcting for differences across zipcodes in gender, race, and ethnicity distributions, and distance to the nearest hospital performing THRs. RESULTS/ANTICIPATED RESULTS: We analyzed 414 zipcodes with overall average THR rate of 370.8 per 100,000 persons >65yo per year. Relative to zipcodes in the least socioeconomically disadvantaged quartile, those in the second-least disadvantaged had 82.2 fewer THRs per 100,000 persons >65yo per year, those in the second-most disadvantaged had 144.2 fewer, and those in the most disadvantaged had 207.4 fewer (all p65yo per year, those in the second-most disadvantaged had 136.2 fewer, and those in the most disadvantaged had 182.9 fewer (all p <.05). DISCUSSION/SIGNIFICANCE OF IMPACT: More socioeconomically disadvantaged areas have significantly lower rates of elective THR, independent of differences in demographics and hospital proximity. These findings show how disparities can affect access and outcomes, and should inform targeting of community-level education and intervention.
In this study, we explored the attitudes towards Medically Unexplained Symptoms (MUS) of 500 GP's in Karachi, Pakistan. Using a questionnaire previously developed by Reid et al (2001), we aimed to investigate whether GP's attitudes towards medically unexplained symptoms are similar to those of GP's in the developed world.
500 GP's on the database of primary care centres at the Pakistan Institute of Learning and Living in Karachi, were all sent a covering letter explaining the purpose of the survey with a case vignette, a questionnaire, and a stamped addressed envelope. One month later, non-respondents received a telephone call from an investigator to remind them of the study.
Of the 429 respondents, 68.5% (294) were male and 31.5% (135) female. Although 80.2% of respondents felt that the main role of GP's was to provide support and reassurance, 76.9% of respondents also agreed that GP's had a role in referring patients with MUS for further investigations to identify a cause. 204 (47.55%) respondents agreed that somatization was useful concept, only 146 (34.03%) felt that there was effective treatment for it.
For the most part Pakistani GPs’ attitudes towards MUS are similar to those of their counterparts in the West. Both agree that the GP had an important role in providing reassurance and counselling. However, our survey also shows that Pakistani GP's are less likely to place emphasis on an underlying psychiatric diagnosis and tend to focus on looking for an underlying physical cause.
Depression is a global public health problem with highest rates in women in low income countries including Pakistan. There are no treatment trials from such countries comparing the efficacy of antidepressant treatment with a group psychological intervention.
We conducted a preliminary RCT in an urban primary care clinic in Karachi, Pakistan. Consecutive eligible women scoring > 12 on the CIS-R and > 18 on HDRS (n=66) were randomly assigned to antidepressant or group psychosocial treatment. The primary outcome measure was HDRS score; secondary outcome measures were disability and quality of life.
96% patients were assessed at 3 & 6 months after baseline. At 6 months response (50% reduction of HDRS score) occurred in 20 (60.6%) and 22(66.7%) of the psychosocial and antidepressant groups respectively. There was also significant reduction in disability and improvement in health related quality of life in both groups.
Low costs antidepressants and group psychosocial treatment on the principles of CBT merit further assessment as primary treatments for depression in low income countries.
Depression is a global public health problem with highest rates in women in low income countries including Pakistan. Paediatricians may be a resource to help with maternal depression. Little is known in low income countries about the prevalence of depression and its social correlates in mothers of children attending paediatric clinics.
Using cross-sectional design consecutive women attending the paediatric clinic were screened using the Edinburgh Postnatal Depression Scale (n=185). Women scoring 12 or more (n=70) and a random sample of low scorers (n=16) were interviewed using the Clinical Interview Schedule Revised (CIS-R) to confirm the diagnosis of depression, the Oslo scale was used to measure social stress and EQ-5D for health related quality of life.
The prevalence of maternal depression was 51%. The mean age of the sample was 26 years. Depressed mothers were more likely to be living in a joint family household, they were less educated and they and their husbands were less likely to be employed. The depressed mothers had more financial difficulties and they were more likely to sleep hungry during the last month due to financial problems. The depressed mothers had less social support and poorer quality of life compared to non depressed mothers.
Maternal depression in this health care setting is high and it is associated with social stress and poor social support. Paediatric appointments may be an opportunity for care and care delivery for maternal depression.
In high income countries depression is common among general trauma patients and is associated with a poor outcome. In the absence of previous reports from a developing country we evaluated the relationship of psychological distress to physical injury, musculoskeletal complaints, and social factors in Pakistan.
One thousand and fourteen patients were recruited from a busy orthopaedic outpatient clinic at a general hospital in Karachi (90.5% response rate). Research assistants administered the Self Rating Questionnaire (SRQ) to measure psychological distress, the Oslo social support questionnaire, and the Brief Disability Questionnaire (BDQ). The surgeons documented the diagnosis and, if appropriate, rated symptoms as medically unexplained.
An SRQ score of 9 or more, which indicates probable depressive disorder, occurred in 45.6% of men & 76.1% of women. A high SRQ score was associated with female sex, divorced, separated or widowed status, little or no education, low income and little social support. Even after these were controlled for there was a significantly higher SRQ score in patients with arthritis, backache/prolapsed intervertebral disc, major fracture and other bone pathology. Overall there was no difference in SRQ score between patients with medically explained (by trauma or organic disease) or unexplained symptoms.
Depressive disorder appears to be very common in orthopaedic out patients in this low income country and both social circumstances and nature of bone pathology are associated with such depression. Treatment should address this extreme psychological distress.
There is some evidence that anti-inflammatory treatment may have beneficial effects in schizophrenia and major depression. Statins are cholesterol-lowering agents but have been found to be anti-inflammatory and also decrease C-reactive protein (CRP). Ondansetron is a serotonin (5-HT3) receptor antagonist widely used to prevent nausea and vomiting in patients receiving chemotherapy for cancer. Small studies have suggested that adjunctive Ondansetron is efficacious against schizophrenia symptoms. We carried out a feasibility study in schizophrenia patients (within 5 years of first diagnosis) to explore the adjunctive use of simvastatin and ondansetron on positive, negative and general psychopathology.
This was a 12 week rater blind placebo controlled study. All to gather 36 patients with DSM-IV diagnosis of schizophrenia were recruited, 12 in each arm. Patients were assessed at baseline and at 12 weeks using PANSS, CGI, GAF and AIMS.
Both simvastatin and ondansetron provide some evidence of a reduction in symptoms compared to treatment as usual (TAU) on PANSS total score, although, this was not statistically significant. In the secondary analyses, no significant differences were seen on CGI, GAF and AIMS.
Anti-inflammatory treatments have shown to have some beneficial effects in schizophrenia. Both simvastatin and ondansetron provide some evidence of a reduction in symptoms compared to treatment as usual. This study has led to a larger SMRI-funded, double blind, randomized control trial.
Immune mechanisms have been implicated in the pathogenesis of schizophrenia. This has lead to clinical trials of re-purposing drugs with off-target anti-inflammatory actions. They include the antibiotic minocycline and simvastatin (HMP-Co reductase inhibitor), which decrease microglial activation, and ondansetron a 5-HT3-receptor antagonist that has limited effects on cytokine production. This presentation will address their efficacy and mechanism of action.
1) Update on trials with minocycline including our own positive finding on negative symptoms (PMID: 16959472)
2) Present new results with ondansetron and simvastatin summarised below.
Ondansetron (8mg) and simvastatin (40mg) vs placebos in 2x2 design (PMID: 23782463). Patients aged 18-65, stable treatment, DSM IV schizophrenia-related diagnosis. PANSS and cognition at 0,3,6 months.
The four cells of the 2x2 design contained 302 patients. The interaction between ondansetron and simvastatin was significant at p=.006 reflecting the lower scores in the 3 active treatment groups than in the P+P group. Ondansetron improved verbal (p=.007) and visual list learning (p=.02) with no other treatment effects on cognition.
Minocycline appears to benefit negative symptoms in early psychosis with a minor effect on cognition. Simvastatin had limited effects in our patients with established schizophrenia but its anti-inflammatory effects could be worth investigating in early psychosis. Ondansetron has a significant effect on new learning, which might be expected from its 5-HT3 antagonist properties. This may underlie a benefit on negative symptoms reported by others and us.
There is strong association between depression and mortality rates among patients with CHF. Despite the massive burden of cardiac disease as well as that of depression in Pakistan, there is limited data regarding the prevalence of depression in patients suffering from CHF. The aim of this study was to assess prevalence of depression in patients with CHF and to compare the health related quality of life of depressed and non-depressed patients with CHF.
A total of 1009 patients diagnosed with CHF were recruited from different public hospitals in Karachi, Pakistan. Depression was assessed at baseline using the Beck Depression Inventory (BDI) and health related quality of life was assessed using Euro Qol (EQ-5D).
Of the 1009 participants recruited to the study, 66.4% (n = 670) met the threshold for depression using the BDI measure. Of the depressed patients, 66.7% (n = 447) were male. Preliminary results indicate that participants who were depressed at baseline had poorer health related quality of life on EQ-5D measures as compared to those who were non-depressed (mean EQ-5D descriptive score 10.45 in depressed patients vs 7.37 in non-depressed patients and mean EQ-5D visual scale score 35.09 in depressed patients vs 52.19 in non-depressed patients).
Considering the high prevalence of depression and its serious negative impact on quality of life of patients suffering from chronic physical illness, it is important to design and test culturally adapted psychosocial interventions to reduce depression and improve quality of life for these patients.
Disclosure of interest
The authors have not supplied their declaration of competing interest.
Low-intensity psychosocial interventions have been effective in targeting perinatal depression, but relevant mechanisms of change remain unknown.
To examine three theoretically informed mediators of the Thinking Healthy Programme Peer-delivered (THPP), an evidence-based psychosocial intervention for perinatal depression, on symptom severity in two parallel, randomised controlled trials in Goa, India and Rawalpindi, Pakistan.
Participants included pregnant women aged ≥18 years with moderate to severe depression, as defined by a Patient Health Questionnaire 9 (PHQ-9) score ≥10, and were randomised to either THPP or enhanced usual care. We examine whether three prespecified variables (patient activation, social support and mother–child attachment) at 3 months post-childbirth mediated the effects of THPP interventions of perinatal depressive symptom severity (PHQ-9) at the primary end-point of 6 months post-childbirth. We first examined individual mediation within each trial (n = 280 in India and n = 570 in Pakistan), followed by a pooled analysis across both trials (N = 850).
In both site-specific and pooled analyses, patient activation and support at 3 months independently mediated the intervention effects on depressive symptom severity at 6 months, accounting for 23.6 and 18.2% of the total effect of THPP, respectively. The intervention had no effect on mother–child attachment scores, thus there was no evidence that this factor mediated the intervention effect.
The effects of the psychosocial intervention on depression outcomes in mothers were mediated by the same two factors in both contexts, suggesting that such interventions seeking to alleviate perinatal depression should target both social support and patient activation levels.
We use experimental methods to investigate subsidy incidence, the transfer of subsidy payments from intended recipients to other economic agents, in privately negotiated spot markets. Our results show that market outcomes in treatments with a subsidy given to either buyers or sellers are significantly different from both a no-subsidy treatment and the competitive prediction of a 50% subsidy incidence. The disparity in incidence across treatments relative to predicted levels suggests that incidence equivalence does not hold in this market setting. Moreover, we find no statistical difference in market outcomes when benefits are framed as a “subsidy” versus a schedule shift.
A third of patients diagnosed with major depressive disorder (MDD) experience treatment-resistant depression (TRD). Relatively few pharmacological agents have established efficacy for TRD. Therefore, the evaluation of novel treatments for TRD is a pressing priority. Statins are pleiotropic agents and preclinical studies as well as preliminary clinical trials have suggested that these drugs may have antidepressant properties.
To report on a protocol for a 12-week, randomised, double-blind, placebo-controlled trial of add-on treatment with simvastatin for patients meeting DSM-5 criteria for MDD who have failed to respond to at least two adequate trials with approved antidepressants. The trial has been registered with Clinicaltrials.gov in (ClinicalTrials.gov identifier: NCT03435744).
After screening and randomisation to the two parallel arms of the trial, 75 patients will receive simvastatin and 75 patients will receive placebo as adjuncts to treatment as usual. The primary outcome is change in Montgomery–Åsberg Depression Rating Scale scores from baseline to week 12 and secondary outcomes include changes in scores on the 24-item Hamilton Rating Scale for Depression, the Clinical Global Impression scale, the 7-item Generalized Anxiety Disorder scale and change in body mass index from baseline to week 12. Assessments will take place at screening, baseline, and weeks 2, 4, 8 and 12. Checklists for adverse effects will be undertaken at each visit. Simvastatin (20 mg) will be given once daily. Other secondary outcomes include C-reactive protein and plasma lipids measured at baseline and week 12.
This trial will assess simvastatin's efficacy and tolerability as an add-on treatment option for patients with TRD and provide insights into its putative mechanisms of action.
As the first trial investigating the use of simvastatin as an augmentation strategy in patients with TRD, if the results indicate that adjuvant simvastatin is efficacious in reducing depressive symptoms, it will deliver immediate clinical benefit.
Declaration of interest
I.B.C. and N.H. have given lectures and advice to Eli Lilly, Bristol Myers Squibb, Lundbeck, Astra Zeneca and Janssen pharmaceuticals for which they or their employing institution have been reimbursed. R.R. and M.M.H. have received educational grants and support for academic meetings from Pfizer, Roche, Novartis and Nabiqasim. A.H.Y. has been commissioned to provide lectures and advice to all major pharmaceutical companies with drugs used in affective and related disorders. A.H.Y. has undertaken investigator-initiated studies from Astra Zeneca, Eli Lilly, Lundbeck and Wyeth. None of the companies have a financial interest in this research.
Oligodeoxynucleotides (ODNs) containing cytosine-phosphate-guanosine sequence (CpG) is considered as an immune stimulator when it is fed to animals. These synthetic molecules mount different immune responses in the animals including mice, chickens, ducks, dogs and horses. CpG ODNs induce specific antigenic immunity against co-administered vaccines and are well tolerated in healthy individuals and are capable of stimulating toll-like receptors (TLRs) such as TLR-9 to activate innate immunity. The CpG ODNs can be used as an adjuvant in different vaccines synthesised specifically for poultry diseases caused by viruses and bacteria. In chickens, CpG ODNs stimulate TLRs involved in humoral immunity. CpG ODNs have been used as mucosal vaccine adjuvants against several pathogens, including avian influenza and Newcastle disease. The CpG ODNs function to protect the chickens from Newcastle disease by producing plasma dendric cells (pDCs) which ultimately produce interferons (INFs). The inoculation of CpG ODNs along with the cationic microparticles and DNA vaccine for infectious bursal disease virus result in the influx of T cells and a reduction of antigen load. When CpG ODNs are used against avian leucosis, they result in significantly higher antibody titres. In many other vaccines e.g., infectious laryngotracheitis, infectious bronchitis, herpes, viral enteritis, Marek's disease virus, E. coli and Salmonella spp. including CpG ODNs exhibit immunostimulatory effects. In conclusion, CpG ODNs may be used as effective adjuvants in viral, bacterial and parasitic vaccines in poultry.
Little is known about Clostridium difficile infection (CDI) in Asia. The aims of our study were to explore (i) the prevalence, risk factors and molecular epidemiology of CDI and colonization in a tertiary academic hospital in North-Eastern Peninsular Malaysia; (ii) the rate of carriage of C. difficile among the elderly in the region; (iii) the awareness level of this infection among the hospital staffs and students. For stool samples collected from hospital inpatients with diarrhea (n = 76) and healthy community members (n = 138), C. difficile antigen and toxins were tested by enzyme immunoassay. Stool samples were subsequently analyzed by culture and molecular detection of toxin genes, and PCR ribotyping of isolates. To examine awareness among hospital staff and students, participants were asked to complete a self-administered questionnaire. For the hospital and community studies, the prevalence of non-toxigenic C. difficile colonization was 16% and 2%, respectively. The prevalence of CDI among hospital inpatients with diarrhea was 13%. Out of 22 C. difficile strains from hospital inpatients, the toxigenic ribotypes 043 and 017 were most common (both 14%). In univariate analysis, C. difficile colonization in hospital inpatients was significantly associated with greater duration of hospitalization and use of penicillin (both P < 0·05). Absence of these factors was a possible reason for low colonization in the community. Only 3% of 154 respondents answered all questions correctly in the awareness survey. C. difficile colonization is prevalent in a Malaysian hospital setting but not in the elderly community with little or no contact with hospitals. Awareness of CDI is alarmingly poor.
The aim of this feasibility trial was to evaluate the feasibility and acceptability of the locally adapted Group Problem Management Plus (PM+) intervention for women in the conflict affected settings in Swat, Pakistan.
This mixed-methods study incorporated a quantitative component consisting of a two arm cluster randomised controlled feasibility trial, and qualitative evaluation of the acceptability of the Group PM+ to a range of stakeholder groups. For the quantitative component, on average from each of the 20 Lady Health Workers (LHWs) catchment area (20 clusters), six women were screened and recruited for the trial with score of >2 on the General Health Questionnaire and score of >16 on the WHO Disability Assessment Schedule. These LHW clusters were randomised on a 1 : 1 allocation ratio using a computer-based software through a simple randomisation method to the Group PM+ intervention or Enhanced Usual Care. The Group PM+ intervention consisted of five weekly sessions of 2 h duration delivered by local non-specialist females under supervision. The primary outcome was individual psychological distress, measured by levels of anxiety and depression on the Hospital Anxiety and Depression Scale at 7th week after baseline. Secondary outcomes include symptoms of depression, post-traumatic stress disorder (PTSD), general psychological profile, levels of functioning and generalised psychological distress. Intervention acceptability was explored through in-depth interviews.
The results show that lay-helpers with no prior mental health experience can be trained to achieve the desired competency to successfully deliver the intervention in community settings under supervision. There was a good intervention uptake, with Group PM+ considered useful by participants, their families and lay-helpers. The outcome evaluation, which was not based on a large enough study to identify statistically significant results, indicated statistically significant improvements in depression, anxiety, general psychological profile and functioning. The PTSD symptoms and depressive disorder scores showed a trend in favour of the intervention.
This trial showed robust acceptance in the local settings with delivery by non-specialists under supervision by local trained females. The trial paves the way for further adaptation and exploration of the outcomes through larger-scale implementation and definitive randomised controlled trials in the local settings.
The Permian is regarded as one of the most crucial intervals during echinoid evolution because crown group echinoids are first widely known from the Permian. New faunas provide important information regarding the diversity of echinoids during this significant interval as well as the morphological characterization of the earliest crown group and latest stem group echinoids. A new fauna from the Capitanian Lamar Member of the Bell Canyon Formation in the Guadalupe Mountains of West Texas comprises at least three new taxa, including Eotiaris guadalupensis Thompson n. sp. an indeterminate archaeocidarid, and Pronechinus? sp. All specimens represented are silicified and known from disarticulated or semiarticulated interambulacral and ambulacral plates and spines. This assemblage is one of the most diverse echinoid assemblages known from the Permian and, as such, informs the paleoecological setting in which the earliest crown group echinoids lived. This new fauna indicates that crown group echinoids occupied the same environments as stem group echinoids of the Archaeocidaridae and Proterocidaridae. Furthermore, the echinoids described herein begin to elucidate the order of character transitions that likely took place between stem group and crown group echinoids. At least one of the morphological innovations once thought to be characteristic of early crown group echinoids, crenulate tubercles, was in fact widespread in a number of stem group taxa from the Permian as well. Crenulate tubercles are reported from two taxa, and putative cidaroid style U-shaped teeth are present in the fauna. The presence of crenulate tubercles in the archaeocidarid indicates that crenulate tubercles were present in stem group echinoids, and thus the evolution of this character likely preceded the evolution of many of the synapomorphies that define the echinoid crown group.
The loss of information resulting from taphonomic degradation could represent a significant bias in the study of morphological diversity. This potential bias is even more concerning given the uneven effect of taphonomy across taxonomic groups, depositional facies, and stratigraphic successions and in response to secular changes through the Phanerozoic. The effect of taphonomic degradation is examined using character-based morphological data sets describing disparity in Paleozoic crinoids and blastozoans. Characters were sequentially excluded from the analyses following progressive taphonomic loss to determine how morphologic metrics, such as the relative distribution of taxa in morphospace and partial disparity, changed with increasing taphonomic alteration. Blastozoans showed very little change in these metrics with decreasing preservational quality, which is a result of characters that create distance in morphospace being recognizable in isolated plates. The opposite result is present in crinoids as the characters that are important in structuring the morphospace require intact modules (i.e., the calyx) to accurately assess. Temporal and stratigraphic trends produced encouraging results in that patterns could be largely recovered even with exaggerated taphonomic biases. However, certain parts of a stratigraphic sequence should be avoided and morphological outliers could potentially play a larger role through time, though both of these biases can be easily identified and avoided. The methods presented in this study provide a way to assess potential taphonomic biases in character-based studies of morphological diversity.