Gabapentinoids and Risk for Severe Exacerbation in Chronic Obstructive Pulmonary Disease : A Population-Based Cohort Study.

BACKGROUND: North American and European health agencies recently warned of severe breathing problems associated with gabapentinoids, including in patients with chronic obstructive pulmonary disease (COPD), although supporting evidence is limited. OBJECTIVE: To assess whether gabapentinoid use is associated with severe exacerbation in patients with COPD. DESIGN: Time-conditional propensity score-matched, new-user cohort study. SETTING: Health insurance databases from the Régie de l'assurance maladie du Québec in Canada. PATIENTS: Within a base cohort of patients with COPD between 1994 and 2015, patients initiating gabapentinoid therapy with an indication (epilepsy, neuropathic pain, or other chronic pain) were matched 1:1 with nonusers on COPD duration, indication for gabapentinoids, age, sex, calendar year, and time-conditional propensity score. MEASUREMENTS: The primary outcome was severe COPD exacerbation requiring hospitalization. Hazard ratios (HRs) associated with gabapentinoid use were estimated in subcohorts according to gabapentinoid indication and in the overall cohort. RESULTS: The cohort included 356 gabapentinoid users with epilepsy, 9411 with neuropathic pain, and 3737 with other chronic pain, matched 1:1 to nonusers. Compared with nonuse, gabapentinoid use was associated with increased risk for severe COPD exacerbation across the indications of epilepsy (HR, 1.58 [95% CI, 1.08 to 2.30]), neuropathic pain (HR, 1.35 [CI, 1.24 to 1.48]), and other chronic pain (HR, 1.49 [CI, 1.27 to 1.73]) and overall (HR, 1.39 [CI, 1.29 to 1.50]). LIMITATION: Residual confounding, including from lack of smoking information. CONCLUSION: In patients with COPD, gabapentinoid use was associated with increased risk for severe exacerbation. This study supports the warnings from regulatory agencies and highlights the importance of considering this potential risk when prescribing gabapentin and pregabalin to patients with COPD. PRIMARY FUNDING SOURCE: Canadian Institutes of Health Research and Canadian Lung Association.

Concomitant Use of Selective Serotonin Reuptake Inhibitors With Oral Anticoagulants and Risk of Major Bleeding.

Importance: Selective serotonin reuptake inhibitors (SSRIs) are commonly prescribed antidepressants associated with a small increased risk of major bleeding. However, the risk of bleeding associated with the concomitant use of SSRIs and oral anticoagulants (OACs) has not been well characterized. Objectives: To assess whether concomitant use of SSRIs with OACs is associated with an increased risk of major bleeding compared with OAC use alone, describe how the risk varies with duration of use, and identify key clinical characteristics modifying this risk. Design, Setting, and Participants: A population-based, nested case-control study was conducted among patients with atrial fibrillation initiating OACs between January 2, 1998, and March 29, 2021. Patients were from approximately 2000 general practices in the UK contributing to the Clinical Practice Research Datalink. With the use of risk-set sampling, for each case of major bleeding during follow-up, up to 30 controls were selected from risk sets defined by the case and matched on age, sex, cohort entry date, and follow-up duration. Exposures: Concomitant use of SSRIs and OACs (direct OACs and vitamin K antagonists [VKAs]) compared with OAC use alone. Main Outcomes and Measures: The main outcome was incidence rate ratios (IRRs) of hospitalization for bleeding or death due to bleeding. Results: There were 42 190 patients with major bleeding (mean [SD] age, 74.2 [9.3] years; 59.8% men) matched to 1 156 641 controls (mean [SD] age, 74.2 [9.3] years; 59.8% men). Concomitant use of SSRIs and OACs was associated with an increased risk of major bleeding compared with OACs alone (IRR, 1.33; 95% CI, 1.24-1.42). The risk peaked during the initial months of treatment (first 30 days of use: IRR, 1.74; 95% CI, 1.37-2.22) and persisted for up to 6 months. The risk did not vary with age, sex, history of bleeding, chronic kidney disease, and potency of SSRIs. An association was present both with concomitant use of SSRIs and direct OACs compared with direct OAC use alone (IRR, 1.25; 95% CI, 1.12-1.40) and concomitant use of SSRIs and VKAs compared with VKA use alone (IRR, 1.36; 95% CI, 1.25-1.47). Conclusions and Relevance: This study suggests that among patients with atrial fibrillation, concomitant use of SSRIs and OACs was associated with an increased risk of major bleeding compared with OAC use alone, requiring close monitoring and management of risk factors for bleeding, particularly in the first few months of use.

Effect of Music Tempo on Pattern Reversal Visual Evoked Potential in Young Adults-Multisensory Stochastic Resonance: A Pilot Study.

Stochastic resonance (SR) is a phenomenon in which an intermediate level of noise enhances the response of a weak input signal. This phenomenon is experimentally used for rehabilitation and treatment of visuomotor disorders associated with low amplitude and higher latency P100 VEPs. We presupposed that shortly it will be possible to develop and design new devices that enable multisensory SR in the audio-visual modality for human sensorimotor enhancement and rehabilitation purposes. This study was newer in which the auditory noise was used in the form of song of different tempos and their amplitude and latency of P100 PRVEP (pattern reversal visual evoked potential) was compared. Whether the different tempos song may affects the PRVEP. This study was conducted on 57 healthy volunteers in AIIMS Bhopal. The subjects were placed in front of a computer displaying a checkerboard 8x8 size. Electrodes were pasted on their scalp. The average latencies and amplitudes of the PRVEP were recorded at resting, then with the stimulus of acoustic noise in the form of low and high tempo song. The PRVEP were recorded for each event. We found that low- and high-tempo songs do not affect the latency component of PRVEP, while it significantly affects amplitude. Music therapy can help with vision rehabilitation, especially in patients with low amplitude PRVEP. A more significant number of samples for further study in this field in multisensory SR with visual evoked potentials (VEP) are necessary. We can also conclude that a sound-free environment is essential during VEP recording.

Concomitant Use of Selective Serotonin Reuptake Inhibitors and Oral Anticoagulants and Risk of Major Bleeding: A Systematic Review and Meta-analysis.

BACKGROUND: Selective serotonin reuptake inhibitors (SSRIs), the most prescribed antidepressants, are associated with a modestly increased risk of major bleeding. However, in patients treated with both SSRIs and oral anticoagulants (OACs), the risk of major bleeding may be substantial. OBJECTIVE: To assess the risk of major bleeding associated with concomitant use of SSRIs and OACs, compared with OAC use alone. METHODS: We searched MEDLINE, Embase, PsycINFO, and the Cochrane Central Register of Controlled Trials (from inception to December 1, 2021) for clinical trials and observational studies assessing the association between concomitant use of SSRIs and OACs and the risk of major bleeding. Given sufficient homogeneity of studies, we conducted a random-effects meta-analysis to estimate a pooled hazard ratio (HR) of major bleeding associated with concomitant use of SSRIs and OACs, compared with OAC use alone. RESULTS: The review comprised 14 studies, including 7 cohort and 7 nested case-control studies. Following assessment of clinical and methodological heterogeneity, eight studies with a total of 98,070 patients were eligible for the meta-analysis. The pooled HR of major bleeding associated with concomitant use of SSRIs and OACs was 1.35 (95% confidence interval [CI]: 1.14-1.58). In secondary analyses, the pooled HR for concomitant use of SSRIs and direct OACs was 1.47 (95% CI: 1.03-2.10). CONCLUSION: Concomitant use of SSRIs and OACs was associated with an increased risk of major bleeding. Overall, our findings suggest that physicians may need to tailor treatment according to individual patient risk factors for bleeding when prescribing SSRIs to patients using OACs.

Oral Anticoagulants and the Risk of Dementia in Patients With Nonvalvular Atrial Fibrillation: A Population-Based Cohort Study.

BACKGROUND AND OBJECTIVES: Nonvalvular atrial fibrillation (NVAF) is associated with an increased risk of dementia. Oral anticoagulants (OACs) are essential for stroke prevention in NVAF, and studies have shown a possible protective effect on dementia. However, findings have been inconsistent and hampered by methodological limitations. Thus, we assessed whether the use of OACs is associated with a decreased incidence of dementia in patients with NVAF. In addition, we explored the impact of the cumulative duration of OAC use on the incidence of dementia. METHODS: Using the UK Clinical Practice Research Datalink, we formed a cohort of all patients aged 50 years or older with an incident diagnosis of NVAF between 1988 and 2017 and no prior OAC use, with a follow-up until 2019. Patients were considered unexposed until 6 months after their first OAC prescription for latency considerations and exposed thereafter until the end of follow-up. We used time-dependent Cox regression models to estimate hazard ratios (HRs), adjusted for 54 covariates, with 95% CIs for dementia associated with OAC use, compared with nonuse. We also assessed whether the risk varied with the cumulative duration of OAC use, compared with nonuse, by comparing prespecified exposure categories defined in a time-varying manner and by modeling the HR using a restricted cubic spline. RESULTS: The cohort included 142,227 patients with NVAF, with 8,023 cases of dementia over 662,667 person-years of follow-up (incidence rate 12.1, 95% CI 11.9-12.4 per 1,000 person-years). OAC use was associated with a decreased risk of dementia (HR 0.88, 95% CI 0.84-0.92) compared with nonuse. A restricted cubic spline also indicated a decreased risk of dementia, reaching a low at approximately 1.5 years of cumulative OAC use and stabilizing thereafter. Moreover, OAC use decreased the risk in patients aged 75 years and older (HR 0.84, 95% CI 0.80-0.89), but not in younger patients (HR 0.99, 95% CI 0.90-1.10). DISCUSSION: In patients with incident NVAF, OACs were associated with a decreased risk of dementia, particularly in elderly individuals. This warrants consideration when weighing the risks and benefits of anticoagulation in this population. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that in patients with NVAF, OAC use (vs nonuse) is associated with a decreased risk of dementia.

Risk factors of gallbladder cancer in Karachi-a case-control study.

BACKGROUND: Gallbladder carcinoma (GC) is a relatively rare malignancy worldwide but is the second commonest gastrointestinal cancer in Pakistani women. Gallstones have a positive association with GC but other factors also influence in causation. METHODS: This is a retrospective case control study over a period of 19 years. The cases (Group A) were patients with histopathological proven carcinoma gallbladder (N = 60) and controls were patients with cholelithiasis but no carcinoma gallbladder on histopathology (N = 120). Multivariate regression analysis was done to calculate the odds ratio, 95% confidence interval and P-Value. A positive relationship was found between size of stone > 1 cm, solitary stone, age > 55 years and multi-parity in women. RESULTS: There were 60 patients in Group A and 120 patients in Group B. mean age of diagnosis in Group A patients was 57 ± 2.4 years while mean age of diagnosis in Group B patients was 48 ± 1.35 years. Sixty seven percent of cancer group patients were female as compared to 78% females in non-cancer group. In Group A, 69% of female patients were multiparous (parity of more than 5) while 43% of group B patients were multiparous. For body mass index (BMI), both groups were not very different in our study population i.e. around 78% patients in each group has BMI of more than 23 Kg/m2. In Group A, 37% (n = 22) have solitary stones as compared to 15% (n = 18) in group B. similarly Group A patients has larger stone size as compared to Group B i.e.59% (n = 36) patients in Group A have stones of more than 1 cm when compared to 35% (n = 41) patients in Group B. After using multivariate regression analysis, age more than 55 years (OR - 7.27, p value- < 0.001), solitary stone (OR - 3.33, p value - 0.002) and stone of more than 1 cm (OR - 2.73, p value - 0.004) were found to be independent risk factors for development of gallbladder cancer. CONCLUSION: Most of the patients (78%) with GC were female, and the statistically significant risk factors were older age, solitary stones and stones size more than one centimeter. A case can be made for prophylactic cholecystectomy in such a high risk group. However a population based study is required to calculate the true incidence of GC in Karachi and a prospective multi center study is needed to produce strong evidence for screening and prophylactic cholecystectomy. TRIAL REGISTRATION: As this was a retrospective review of medical records, as per institution policy, its gives waiver from any registration (ethical/trial).

Hepatic vein and inferior vena caval thrombus extending into the right atrium: a rare complication of amoebic liver abscess.

Amoebic liver abscess is an endemic in developing countries but few cases of associated vascular complications have been reported. The authors report a very rare vascular complication of hepatic veins and inferior vena caval (IVC) thrombosis extending into the right atrium in a young male with large amoebic liver abscess. Optimal result was achieved with early diagnosis on CT scan, percutaneous drainage of abscess, intravenous metronidazole, peri-operative anticoagulation, sternotomy and thrombectomy.

Intussusceptions in adults: clinical features and operative procedures.

OBJECTIVE: To determine the clinical presentation and treatment outcomes of adult patients with intussusceptions. STUDY DESIGN: Case series. PLACE AND DURATION OF STUDY: The Aga Khan University Hospital, Karachi, from January 1988 to December 2008. METHODOLOGY: Medical records of patients with diagnosis of intussusceptions in adults (above 15 years of age) from January 1988 to December 2008 were retrieved through ICD 9 coding system. Patients with complete records were included in the study and those with incomplete medical record or under 30 days follow-up were excluded. Data was analyzed on SPSS version 16. The treatment outcomes were hospital stay, 30 days-morbidity, mortality and recurrence of intussusceptions during follow-up period. RESULTS: The mean age of the 19 patients was 37 years with male predominance. Most patients presented with acute bowel obstruction. In 14 patients, small bowel were involved. CT scan diagnosed intussusception in 10 out of 12 patients. Benign lead point were found in 80% cases. Eighteen patients were treated surgically. Fourteen (70%) patients underwent resection with primary anastomosis while in 4 patients only reduction was done. In resection group, 11 patients had resection after reduction and in 3 patients only resection was done. There was no recurrence in resection group. One recurrence was noticed in the reduction group and one patient died of advanced gastrointestinal malignancy in the nonoperative group. CONCLUSION: Intussusception is a rare cause of acute intestinal obstruction in adult population. CT scan is a promising diagnostic tool to establish pre-operative diagnosis. Early surgical resection could achieve optimal outcome. Small bowel intussusception could be reduced before resection if there is no doubt about bowel viability. In most of the patients the lead point could be benign disease.

Ileosigmoid knotting- a rare variant of bowel volvulus.

Two patients with acute intestinal obstruction underwent exploratory laparotomy after adequate fluid resuscitation and radiological imaging. A preoperative diagnosis of sigmoid volvulus and an operative diagnosis of ileosigmoid knotting or compound volvulus were established.

A unique variant of intestinal tuberculosis.

Duodenum is a rare site of involvement in intestinal tuberculosis. We report a 19 years old boy who presented with nonbilious vomiting and weight loss. His workup showed stricture in ascending colon, multiple liver abscesses with pneumobilia on CT scan. Upper GI endoscopy revealed stricture in 2nd part of duodenum distally. He was operated and duodenojejunostomy with limited right hemicolectomy (for stricture in this part of gut) were done. Biopsy report was suggestive of tuberculosis. Antituberculous treatment was started. He responded well and gained 20 kg weight at 3 months follow-up.

Femtosecond Laser-Assisted Intraocular Lens Fragmentation: Low Energy Transection.

PURPOSE: To describe a case of femtosecond laser-assisted hydrophobic intraocular lens transection. METHODS: Case report. RESULTS: Femtosecond laser-assisted transection of a one-piece acrylic hydrophobic intraocular lens for explantation via a small surgical incision was successfully performed with low energy parameters. CONCLUSIONS: This case illustrates a novel and effective clinical application of the femtosecond laser. [J Refract Surg. 2017;33(9):646-648.].

An unusual case of breast ulceration.

We present an unusual case of breast ulceration secondary to heroin injection in a pregnant woman.

Prevalence study to elucidate the transmission pathways of Helicobacter pylori at oral and gastroduodenal sites of a South Indian population.

INTRODUCTION: Since the discovery of Helicobacter pylori (H. pylori), much progress has been made worldwide in the field of its epidemiology. In spite of these advancements, many aspects of epidemiology still remain unclear, particularly among populations with low socio-economic status. The present study was designed to elucidate the different routes of transmission of H. pylori in the Hyderabad (South India) population and to investigate the impact of certain factors, such as age, gender, and lifestyle. METHODS: Samples used for the study included saliva and biopsy samples of 400 symptomatic subjects from Hyderabad, India. The patients were retrospectively grouped, based on histopathology of the biopsy and 16S rRNA amplification of both saliva and biopsy as H. pylori positive and negative. RESULTS: This study showed that the prevalence of H. pylori in both saliva and biopsy samples increased with age. In addition, the H. pylori infection was found more commonly in the saliva and biopsy samples among males (64 percent and 60 percent, respectively) than females (53.3 percent and 64 percent, respectively). Similarly, 71.6 percent and 73.5 percent of those who consumed municipal water acquired H. pylori (which were respectively found in their saliva and biopsy samples) compared to a lesser proportion (12.6 percent and 12.6 percent, respectively) of those who consumed boiled or filtered water. The study also found that subjects who preferred home-cooked food (57.1 percent and 57.7 percent) showed a lower prevalence of H. pylori in saliva and biopsy samples, respectively, compared to those (80 percent and 88 percent) who frequently ate out. CONCLUSION: The results of the present study suggest that besides the oral-oral route, the transmission of H. pylori also takes place through the consumption of food prepared under unhygienic conditions. Consumption of municipal tap water also has a high impact in the transmission of H. pylori.

Rapid diagnosis of Helicobacter pylori infection in dyspeptic patients using salivary secretion: a non-invasive approach.

INTRODUCTION: Current guidelines that recommend Helicobacter pylori eradication treatment without endoscopy in selected patients underscore the importance of non-invasive testing. The accuracy of saliva as a non-invasive specimen was compared with that of invasive tests in pretreatment diagnosis of H. pylori infection. METHODS: One hundred patients undergoing gastroscopy were grouped into 80 symptomatic and 20 asymptomatic subjects and were investigated for the presence of H. pylori in saliva and stomach. Samples tested comprised saliva and gastric biopsies collected from each patient. Exclusion criteria were history of peptic ulcer, bleeding ulcer, cancer or recent use of antibiotics, proton pump inhibitors and non-steroidal anti-inflammatory drugs. Two sets of primers homologous to 534 bp fragment of H. pylori DNA, which have been shown previously to be highly specific and sensitive, were used for the polymerase chain reaction (PCR) amplification. RESULTS: 72 (90 percent) of the symptomatic group and 10 asymptomatic subjects were infected with H. pylori in the stomach as determined by histology and direct PCR amplification of biopsy DNA obtained from each subject. H. pylori DNA was identified in the saliva of 70 (87.5 percent) symptomatic subjects and 12 (60 percent) asymptomatic control subjects. CONCLUSION: High rates of detection using saliva as a specimen indicate that saliva of the infected person could serve as a reliable non-invasive alternative to detect the presence of H. pylori infection in comparison to the currently available standard diagnostic tests.

Evidence on the presence of two distinct alkaline phosphatases in Serratia marcescens.

Certain strains of Serratia marcescens synthesized two different types of alkaline phosphatase (APase), constitutive (CAPase) and inducible (IAPase) APases, in low phosphate medium. Synthesis of the IAPase was repressed in the presence of high phosphate. Purification and separation of these electrophoretically distinct APases was achieved by using fractional (NH(4))(2)SO(4) precipitation, adsorption on a DEAE-cellulose column and elution of enzymes by a linear sodium chloride gradient. Starch gel electrophoresis of certain fractions revealed the separation of not only IAPase from CAPase but its separation into four distinct isozymes. CAPase gave maximum enzyme activity around pH 9.5, whereas for IAPase a broad range of enzyme activity was found between pH 8.5 and 10.5. Reversible inactivation at low pH occurred for IAPase but very little with CAPase. CAPase was more thermolabile than IAPase at 95 degrees C. The two APases were found to be distinct in their kinetic as well as immunological properties, suggesting two distinct enzyme species.

Prevalence of pulmonary tuberculosis on the roof of the world.

SETTING: The Shimshal Valley, a remote village in Northern Pakistan, is one of the seven Pamirs of Central Asia, widely known as the roof of the world. OBJECTIVE: To investigate the prevalence of pulmonary tuberculosis (TB) in the Shimshal Valley. DESIGN: The Rapid Village Survey Method (RVS) was used to investigate the prevalence of pulmonary tuberculosis. The selection criteria were chronic cough, hemoptysis, past history of TB and close contact with a tuberculous patient. After clinical examination, a chest radiograph was done and a single spot sputum sample was obtained for smear examination. RESULTS: The total population of the village was 1077, of whom 231 cases were studied. Overcrowding affected 75% of the study population. The prevalence of smear positive pulmonary TB in the village studied was 554 per 100000 population, and the prevalence of active smear-negative TB was estimated at 1949/100 000. The prevalence of active pulmonary TB increased with age and the only risk factor for active TB was age over 45 years. Of the 21 cases with a past history of pulmonary TB, only 38% had completed a full course of chemotherapy. CONCLUSION: Pulmonary TB is a very serious health issue in the rural community (Shimshal Valley) of Pakistan. This study highlights the lack of efficacy of national tuberculosis control programs in the country.