A randomised double-blind placebo-controlled trial of minocycline and/or omega-3 fatty acids added to treatment as usual for at risk Mental States: The NAYAB study.

BACKGROUND: Inflammatory mechanisms are thought to contribute to the onset of psychosis in persons with an at-risk mental state (ARMS). We investigated whether the anti-inflammatory properties of minocycline and omega-3 polyunsaturated fatty acids (omega-3), alone or synergistically, would prevent transition to psychosis in ARMS in a randomised, double-blind, placebo-controlled trial in Pakistan. METHODS: 10,173 help-seeking individuals aged 16-35 years were screened using the Prodromal Questionaire-16. Individuals scoring 6 and over were interviewed using the Comprehensive Assessment of At-Risk Mental States (CAARMS) to confirm ARMS. Participants (n = 326) were randomised to minocycline, omega-3, combined minocycline and omega-3 or to double placebo for 6 months. The primary outcome was transition to psychosis at 12 months. FINDINGS: Forty-five (13.8 %) participants transitioned to psychosis. The risk of transition was greater in those randomised to omega-3 alone or in combination with minocycline (17.3.%), compared to 10.4 % in those not exposed to omega-3; a risk-ratio (RR) of 1.67, 95 % CI [0.95, 2.92] p = 0.07. The RR for transitions on minocycline vs. no minocycline was 0.86, 95 % CI [0.50, 1.49] p > 0.10. In participants who did not become psychotic, CAARMS and depression symptom scores were reduced at six and twelve months (mean CAARMS difference = 1.43; 95 % CI [0.33, 1.76] p < 0.01 in those exposed to omega-3. Minocycline did not affect CAARMS or depression scores. INTERPRETATION: In keeping with other studies, omega-3 appears to have beneficial effects on ARMS and mood symptom severity but it increased transition to psychosis, which may reflect metabolic or developmental consequences of chronic poor nutrition in the population. Transition to psychosis was too rare to reveal a preventative effect of minocycline but minocycline did not improve symptom severity. ARMS symptom severity and transition to psychosis appear to have distinct pathogeneses which are differentially modulated by omega-3 supplementation. FUNDING: The study was funded by the Stanley Research Medical Institute.

Mental health in the aftermath of COVID-19: A new normal.

The COVID-19 pandemic with its subsequent mental health consequences has challenged the word view of most people. A genome typically of 26,000-32,000 bases long RNA has shut down the wheel of man made progress. The social isolation after the lock-down has not only led to economic difficulties but also adverse psychological reactions. The most common reaction is stress, anxiety and depression when faced with life-threatening circumstances. People have to deal with the imminent issue of death which is anxiety provoking in itself. This calls for dealing with the immediate mental health consequences with the aide of technological advancements as discussed in this write-up. A new inter-personal ethics need to emerge which is scientifically correct and in-line with age old values.

Sleep-disordered breathing and psychiatric disorders.

Sleep-disordered breathing, the commonest form of which is obstructive sleep apnoea (OSA) is increasingly recognised as a treatable cause of morbidity. It shares many risk factors with psychiatric disorders including behaviours such as smoking and physical comorbidity. Many symptoms of the two overlap, leaving OSA often undetected and undertreated. In the few studies that assess the two, OSA is commonly comorbid with depression (17-45%) and schizophrenia (up to 55%) and possibly bipolar. There is some limited evidence that treating OSA can ameliorate psychiatric symptoms. Some psychotropics, such as narcotics, cause sleep-disordered breathing (SDB), whilst weight-inducing neuroleptics may exacerbate it. An extreme form of SDB, sudden infant death syndrome (SIDS), is a risk in mothers with substance abuse. Being aware of these common comorbidities may help improve psychiatric patient's treatment and quality of life.

Systemic Amyloid A Protein Amyloidosis With Gastrointestinal Involvement.

Systemic amyloidosis is a multiorgan deposition of misfolded amyloid protein fibrils. The systemic amyloid A protein (AA) amyloidosis type predominantly involves the kidney and is mostly an under-recognized complication among persons who inject drugs. Gastrointestinal involvement in systemic AA amyloidosis that is associated with illicit drug use is uncommon. In this report, we present a case of a 40-year-old man with history of injection drug use, recurrent skin and soft-tissue infection, and renal AA amyloidosis that presented with painless bloody bowel movement, which initially resolved with conservative management. Upon further evaluation, the patient was found to have empyema that required antibiotic therapy and bilateral pleural drain. His hospital course was further complicated by multiple episodes of hematochezia requiring gastrointestinal consultation. Subsequent gastrointestinal biopsy revealed amyloid deposit.

Evaluation of online chat-based artificial intelligence responses about inflammatory bowel disease and diet.

INTRODUCTION: The USA has the highest age-standardized prevalence of inflammatory bowel disease (IBD). Both genetic and environmental factors have been implicated in IBD flares and multiple strategies are centered around avoiding dietary triggers to maintain remission. Chat-based artificial intelligence (CB-AI) has shown great potential in enhancing patient education in medicine. We evaluate the role of CB-AI in patient education on dietary management of IBD. METHODS: Six questions evaluating important concepts about the dietary management of IBD which then were posed to three CB-AI models - ChatGPT, BingChat, and YouChat three different times. All responses were graded for appropriateness and reliability by two physicians using dietary information from the Crohn's and Colitis Foundation. The responses were graded as reliably appropriate, reliably inappropriate, and unreliable. The expert assessment of the reviewing physicians was validated by the joint probability of agreement for two raters. RESULTS: ChatGPT provided reliably appropriate responses to questions on dietary management of IBD more often than BingChat and YouChat. There were two questions that more than one CB-AI provided unreliable responses to. Each CB-AI provided examples within their responses, but the examples were not always appropriate. Whether the response was appropriate or not, CB-AIs mentioned consulting with an expert in the field. The inter-rater reliability was 88.9%. DISCUSSION: CB-AIs have the potential to improve patient education and outcomes but studies evaluating their appropriateness for various health conditions are sparse. Our study showed that CB-AIs have the ability to provide appropriate answers to most questions regarding the dietary management of IBD.

Acute Pancreatitis Following Percutaneous Mechanical Thrombectomy of Left Common Iliac Vein.

While parental or oral anticoagulation remains a mainstay of therapy for thrombosis, in sporadic clinical situations, percutaneous mechanical thrombectomy is favored. Percutaneous mechanical thrombectomy is a well-tolerated subtype of catheter-directed intervention resulting in thrombus breakdown and removal. This procedure combines endovascular mechanical thrombectomy in combination with pharmacologic thrombolysis allowing for a significant reduction in procedure time. Similar to other catheter-based procedures, common complications include hemorrhage, dissection, pseudoaneurysm, and perforations. Acute pancreatitis, in contrast, is a rare complication of percutaneous mechanical thrombectomy with only limited cases reported and is hypothesized to occur secondary to release of heme byproducts. Here, we present a case of acute pancreatitis following outpatient percutaneous mechanical thrombectomy of the left common iliac vein that ultimately required hospitalization, intensive care unit (ICU) admission, and standard medical management for pancreatitis.

Cerebrospinal fluid liver pseudocyst: A bizarre long-term complication of ventriculoperitoneal shunt: A case report.

BACKGROUND: Ventriculoperitoneal (VP) shunt placement has become a standard of care procedure in managing hydrocephalus for drainage and absorption of cerebrospinal fluid (CSF) into the peritoneum. Abdominal pseudocysts containing CSF are the common long-term complication of this frequently performed procedure, mainly because VP shunts have significantly prolonged survival. Of these, liver CSF pseudocysts are rare entities that may cause shunt dysfunction, affect normal organ function, and therefore pose therapeutic challenges. CASE SUMMARY: A 49-year-old man with history of congenital hydrocephalus status post bilateral VP shunt placement presented with progressively worsening dyspnea on exertion, abdominal discomfort/distention. Abdominal computed tomography (CT) scan revealed a large CSF pseudocyst in the right hepatic lobe with the tip of VP shunt catheter into the hepatic cyst cavity. Patient underwent robotic laparoscopic cyst fenestration with a partial hepatectomy, and repositioning of VP shunt catheter to the right lower quadrant of the abdomen. Follow-up CT demonstrated a significant reduction in hepatic CSF pseudocyst. CONCLUSION: A high index of clinical suspicion is required for early detection of liver CSF pseudocysts since their presentation is often asymptomatic and cunning early in the course. Late-stage liver CSF pseudocysts could have adverse outcomes on the treatment course of hydrocephalus as well as on hepatobiliary dysfunction. There is paucity of data to define the management of liver CSF pseudocyst in current guidelines due to rare nature of this entity. The reported occurrences have been managed by laparotomy with debridement, paracentesis, radiological imaging guided fluid aspiration and laparoscopic-associated cyst fenestration. Robotic surgery is an additional minimally invasive option in the management of hepatic CSF pseudocyst; however, its use is limited by lack of widespread availability and cost of surgery.

Effect of Adjunctive Simvastatin on Depressive Symptoms Among Adults With Treatment-Resistant Depression: A Randomized Clinical Trial.

Importance: Immune-metabolic disturbances have been implicated in the pathophysiology of major depressive disorder and may be more prominent in individuals with treatment-resistant depression (TRD). Preliminary trials suggest that lipid-lowering agents, including statins, may be useful adjunctive treatments for major depressive disorder. However, no adequately powered clinical trials have assessed the antidepressant efficacy of these agents in TRD. Objective: To assess the efficacy and tolerability of adjunctive simvastatin compared with placebo for reduction of depressive symptoms in TRD. Design, Setting, and Participants: This 12-week, double-blind, placebo-controlled randomized clinical trial was conducted in 5 centers in Pakistan. The study involved adults (aged 18-75 years) with a Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition) major depressive episode that had failed to respond to at least 2 adequate trials of antidepressants. Participants were enrolled between March 1, 2019, and February 28, 2021; statistical analysis was performed from February 1 to June 15, 2022, using mixed models. Intervention: Participants were randomized to receive standard care plus 20 mg/d of simvastatin or placebo. Main Outcomes and Measures: The primary outcome was the difference between the 2 groups in change in Montgomery-Åsberg Depression Rating Scale total scores at week 12. Secondary outcomes included changes in scores on the 24-item Hamilton Rating Scale for Depression, the Clinical Global Impression scale, and the 7-item Generalized Anxiety Disorder scale and change in body mass index from baseline to week 12. C-reactive protein and plasma lipids were measured at baseline and week 12. Results: A total of 150 participants were randomized to simvastatin (n = 77; median [IQR] age, 40 [30-45] years; 43 [56%] female) or placebo (n = 73; median [IQR] age, 35 [31-41] years; 40 [55%] female). A significant baseline to end point reduction in Montgomery-Åsberg Depression Rating Scale total score was observed in both groups and did not differ significantly between groups (estimated mean difference for simvastatin vs placebo, -0.61; 95% CI, -3.69 to 2.46; P = .70). Similarly, there were no significant group differences in any of the secondary outcomes or evidence for differences in adverse effects between groups. A planned secondary analysis indicated that changes in plasma C-reactive protein and lipids from baseline to end point did not mediate response to simvastatin. Conclusions and Relevance: In this randomized clinical trial, simvastatin provided no additional therapeutic benefit for depressive symptoms in TRD compared with standard care. Trial Registration: ClinicalTrials.gov Identifier: NCT03435744.

Vaccination in Chronic Liver Disease: An Update.

Patients with chronic liver disease (CLD) with or without cirrhosis remain at risk of developing hepatic decompensation when infected with viral or bacterial pathogens. The Advisory Committee on Immunization Practices (ACIP) currently recommends vaccination in CLD against hepatitis A virus (HAV), hepatitis B virus (HBV), influenza, pneumococcus, herpes zoster, tetanus, diphtheria, pertussis, and SARS-CoV-2. Inactivated vaccines are preferred over live attenuated ones, especially in transplant recipients where live vaccines are contraindicated. As the severity of the liver disease progresses, vaccine efficacy declines, and therefore, vaccines should be ideally administered early in the disease course for optimal immune response. Despite the strong recommendations, overall vaccination coverage in CLD remains poor; however, it is encouraging to note that in recent years coverage against influenza and pneumococcus has shown some improvement. Inadequate access to healthcare, lack of information on vaccine safety, poor financial reimbursement for healthcare providers, and vaccine misinformation are often responsible for low immunization rates. This review summarizes the impact of vaccine-preventable illness in those with CLD, updated vaccine guidelines, seroconversion rates in the vaccinated, and barriers faced by healthcare professionals in immunizing those with liver disease.

Culturally adapted psychoeducation for bipolar disorder in a low-resource setting: protocol for a multicentre randomised controlled trial.

BACKGROUND: Bipolar disorder is a source of marked disability, morbidity and premature death. There is a paucity of research on personalised psychosocial interventions for bipolar disorder, especially in low-resource settings. A pilot randomised controlled trial (RCT) of a culturally adapted psychoeducation intervention for bipolar disorder (CaPE) in Pakistan reported higher patient satisfaction, enhanced medication adherence, knowledge and attitudes regarding bipolar disorder, and improvement in mood symptom scores and health-related quality of life measures compared with treatment as usual (TAU). AIMS: The current protocol describes a larger multicentre RCT to confirm the clinical and cost-effectiveness of CaPE in Pakistan. Trial registration: NCT05223959. METHOD: A multicentre individual, parallel-arm RCT of CaPE in 300 Pakistani adults with bipolar disorder. Participants over the age of 18, with a diagnosis of bipolar I or II disorder who are currently euthymic, will be recruited from seven sites: Karachi, Lahore, Multan, Rawalpindi, Peshawar, Hyderabad and Quetta. Time to recurrence will be the primary outcome assessed using the Longitudinal Interval Follow-up Evaluation (LIFE). Secondary measures will include mood symptoms, quality of life and functioning, adherence to psychotropic medications, and knowledge and attitudes regarding bipolar disorder. RESULTS: This trial will assess the effectiveness of the CaPE intervention compared with TAU in reducing the time to recurrence for people with bipolar disorder currently in remission in Pakistan and determine the effect on clinical outcomes, quality of life and functioning. CONCLUSIONS: A successful trial might lead to rapid implementation of CaPE in clinical practice, not only in Pakistan, but also in other low-resource settings, including those in high-income countries, to improve clinical outcomes, social and occupational functioning, and quality of life in South Asian and other minority group patients with bipolar disorder.

Students' research: tradition ahead of its time.

This view point describes the experience of introducing research at an undergraduate level during clinical rotation in psychiatry. Objective of this initiative was to encourage critical thinking, self directed learning and sensitization to mental health issues. This contributed to student learning besides galvanizing their interest in the subject. The opinion piece aims to expose various issues to students' research in the context of medical education in Pakistan.

Magnetic resonance imaging findings in patients with schizophrenia.

OBJECTIVE: To determine structural abnormalities in the brain of patients with schizophrenia by Magnetic Resonance Imaging (MRI). STUDY DESIGN: Comparative study. PLACE AND DURATION OF STUDY: The Departments of Radiology and Psychiatry, the Aga Khan University Hospital, Karachi, from January 2007 to June 2008. METHODOLOGY: Thirty-three cases of schizophrenia (n=33) and thirty-three age-matched controls, (n=33) were enrolled for this study. Screening Magnetic Resonance Imaging (MRI) of brain was done in order to see structural changes in brain matter. Findings were compared among groups using chi-square and Fisher's exact test with significance at p < 0.05. RESULTS: Among the total of 66 (n=66) MRI films studied for brain abnormalities, brain atrophy, presence of septum pellucidum and enlarged Virchow-Robins spaces were significantly associated with schizophrenia (p < 0.001). There was no significant difference between cases and controls for ventricular dilatation (p=0.5). Sinusitis was mostly associated with controls and well correlated with their symptoms (p < 0.001). CONCLUSION: Brain atrophy was the most commonly seen brain change in the studied sample of patients with schizophrenia. MRI brain can be used to identify structural abnormalities in patients with schizophrenia.

Ischemic Colitis in Buerger's Disease: Case Presentation and Review.

Buerger's disease is a type of vasculitis that predominantly affects small to medium arteries and the veins of the upper and lower extremities. Intestinal vessels are rarely involved. This is a case report of a 38-year-old male, smoker, with known Buerger's disease who was found to have ischemic colitis of the sigmoid colon on biopsy and inferior mesenteric artery occlusion on computed tomography (CT) angiography. Intestinal ischemia is a rare complication in Buerger's disease. Patients may present with vague abdominal symptoms. Given the very low incidence of intestinal involvement, social history and clinical correlation are of chief importance for early detection. Smoking cessation is paramount, as it is the mainstay treatment of the underlying disease.

Gastric Mucormycosis: An Infection of Fungal Invasion into the Gastric Mucosa in Immunocompromised Patients.

Primary gastric mucormycosis is a rare but potentially lethal fungal infection due to the invasion of Mucorales into the gastric mucosa. It may result in high mortality due to increased risk of complications in immunocompromised patients. Common predisposing risk factors to develop gastric mucormycosis are prolonged uncontrolled diabetes mellitus with or without diabetic ketoacidosis (DKA), solid organ or stem cell transplantation, underlying hematologic malignancy, and major trauma. Abdominal pain, hematemesis, and melena are common presenting symptoms. The diagnosis of gastric mucormycosis can be overlooked due to the rarity of the disease. A high index of suspicion is required for early diagnosis and management of the disease, particularly in immunocompromised patients. Radiological imaging findings are nonspecific to establish the diagnosis, and gastric biopsy is essential for histological confirmation of mucormycosis. Prompt treatment with antifungal therapy is the mainstay of treatment with surgical resection reserved in cases of extensive disease burden or clinical deterioration. We presented a case of acute gastric mucormycosis involving the body of stomach in a patient with poorly controlled diabetes and chronic renal disease, admitted with acute onset of abdominal pain. Complete resolution of lesion was noted with 16 weeks of medical treatment with intravenous amphotericin B and posaconazole.

The Pathophysiology of Gastrointestinal and Hepatic Manifestations of COVID-19.

Coronavirus disease 2019 (COVID-19), also known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is the sixth international public health emergency. While COVID-19 classically manifests as a respiratory illness, SARS-CoV-2 may infect multiple organ systems and cause a wide array of presentations. The gastrointestinal tract has become increasingly recognized as a site of SARS-CoV-2 infection with reports of diarrhea, nausea, and liver failure, with or without concomitant respiratory involvement. In this case series and literature review, we report three cases of SARS-CoV-2 infected patients that presented with predominantly gastrointestinal symptoms or laboratory abnormalities such as diarrhea, anorexia, and transaminitis. The receptor for SARS-CoV-2, angiotensin-converting enzyme 2 (ACE2), as well as the necessary protease to facilitate viral entry, transmembrane protease serine-2 (TMPRSS2), and to a lesser extent, cathepsins, have been demonstrated to be present throughout the gastrointestinal tract, thus facilitating viral entry and pathogenesis. Furthermore, multiple reports have demonstrated evidence of viral shedding outside the nasopharynx, including the stool, for prolonged time periods even in the absence of detection of viral RNA in the nasopharynx. As such, testing for SARS-CoV-2 in stool samples with reverse transcription polymerase chain reaction (RT-PCR) assays for detection of viral RNA could aid in identifying patients that lack classic respiratory symptoms, present with atypical symptoms, or in those with a high index of suspicion (e.g. elevated inflammatory markers), but test negative on the classic nasopharyngeal swab. Furthermore, this underscores the potential for atypical transmission, with a focus on fecal-oral transmission and the need for strict hand hygiene.

Black esophagus: a syndrome of acute esophageal necrosis associated with active alcohol drinking.

Black esophagus, also known as acute esophageal necrosis (AEN) syndrome, is a rare entity characterized by patchy or diffuse circumferential black pigmentation of the esophageal mucosa from ischemic necrosis. It may present with life-threatening upper gastrointestinal hemorrhage resulting in high mortality in immunocompromised patients. Advanced age with multiple comorbidities compounded with compromised hemodynamic states are poor prognostic factors. Findings on laboratory work-up and radiological imaging are non-specific. After initial resuscitation, endoscopic evaluation and histological examination of esophageal biopsy are diagnostic. Early recognition and aggressive resuscitation are the fundamental principles for the management of AEN and better outcome of the disease. We report a case of a 56-year-old woman with diabetes mellitus, gastro-esophageal reflux disease, and active alcohol binging who presented with hematemesis and acute epigastric pain due to AEN. This case illustrates a rare etiology of AEN due to active alcohol drinking, which may be overlooked. Physician awareness about this etiology is important as early recognition and timely management may improve survival.

Minocycline and celecoxib as adjunctive treatments for bipolar depression: a multicentre, factorial design randomised controlled trial.

BACKGROUND: Several small studies suggest that the adjunctive use of anti-inflammatory agents might improve depressive symptoms in bipolar disorder. However, there are few well designed, appropriately powered clinical trials assessing the efficacy of these novel treatment strategies. We aimed to assess the efficacy of adjunctive minocycline or celecoxib in this setting. METHODS: This double-blind, 12-week, randomised, placebo-controlled trial was done in four outpatient psychiatric clinics in Pakistan. Eligible participants were adults (aged 18-65 years) with DSM-5 bipolar disorder (type I or II) and a major depressive episode. In a 2 × 2 factorial design, participants were randomly assigned (1:1:1:1) to receive either active minocycline plus active celecoxib, active minocycline plus placebo celecoxib, placebo minocycline plus active celecoxib, or placebo minocycline plus placebo celecoxib. The primary outcome was the mean change from baseline to week 12 in score on the 17-item Hamilton Depression Rating Scale (HAMD-17), assessed in all randomised participants (missing data were imputed and assumed to be missing at random). The trial was registered with ClinicalTrials.gov, NCT02703363. FINDINGS: 266 (17%) of 1542 patients assessed between May 1, 2016, and March 31, 2019, were randomly assigned to receive minocycline plus celecoxib (n=68), minocycline plus placebo (n=66), celecoxib plus placebo (n=66), or placebo plus placebo (n=66). From baseline to week 12, depressive symptoms as per HAMD-17 reduced in all four groups (from 24·5-25·2 to 11·3-12·8), but these reductions did not differ significantly between the groups. In terms of main effects, reductions in HAMD-17 did not differ for patients treated with minocycline (mean adjusted difference vs non-minocycline 1·48 [95% CI -0·41 to 3·36]; p=0·123) or for celecoxib (mean adjusted difference vs non-celecoxib -0·74 [-2·61 to 1·14]; p=0·443). Rates of serious adverse effects did not differ between groups (31 participants had a manic switch, two self-harmed, and one died in a motor vehicle accident). INTERPRETATION: We found no evidence that minocycline or celecoxib was superior to placebo for the treatment of bipolar depression. This large trial casts doubt on the potential therapeutic benefits of adjunctive anti-inflammatory drugs for the acute management of bipolar depression. FUNDING: Stanley Medical Research Institute.

Body Dysmorphic Disorder: gender differences and prevalence in a Pakistani medical student population.

BACKGROUND: Body dysmorphic disorder (BDD) is a psychiatric disorder characterized by a preoccupation with an imagined or slight defect which causes significant distress or impairment in functioning. Few studies have assessed gender differences in BDD in a non clinical population. Also no study assessed BDD in medical students. This study was designed to determine the point prevalence of BDD in Pakistani medical students and the gender differences in prevalence of BDD, body foci of concern and symptoms of BDD. METHODS: The medical students enrolled in a medical university in Karachi, Pakistan filled out a self-report questionnaire which assessed clinical features of BDD. BDD was diagnosed according to the DSM-IV criteria. RESULTS: Out of the 156 students, 57.1% were female. A total of 78.8% of the students reported dissatisfaction with some aspect of their appearance and 5.8% met the DSM-IV criteria for BDD. The male to female ratio for BDD was 1.7. Regarding gender differences in body foci of concern, the top three reported foci of concern in male students were head hair (34.3%), being fat (32.8%), skin (14.9%) and nose(14.9%), whereas in females they were being fat (40.4%), skin (24.7%) and teeth (18%). Females were significantly more concerned about being fat (p = 0.005). Male students were significantly more concerned about being thin (p = 0.01) and about head hair (p = 0.012). CONCLUSION: BDD is fairly common in our medical student population, with a higher prevalence in males. Important gender differences in BDD symptomatology and reported body foci of concern were identified which reflected the influence of media on body image perception. The impact of cultural factors on the prevalence as well as gender differences in BDD symptomatology was also established.

Schizophrenia: a concept.

Much of the current research-work into biological basis of mental disorders is predicted on implicit concept of disease that is less critical and sophisticated as it should be. It is remarkable, how the fundamental conceptual frame work of schizophrenia, as proposed by Professor Emil Kraepelin has stayed the same, since its inception almost 100-years ago. This review explores these issues besides highlighting alternative disease classification that suits behavioural neuroscience research.