Pharmacologic Treatment of Insomnia Disorder: An Evidence Report for a Clinical Practice Guideline by the American College of Physicians.

BACKGROUND: Pharmacologic interventions are often prescribed for insomnia disorder. PURPOSE: To assess the benefits, harms, and comparative effectiveness of pharmacologic treatments for adults with insomnia disorder. DATA SOURCES: Several electronic databases (2004-September 2015), reference lists, and U.S. Food and Drug Administration (FDA) documents. STUDY SELECTION: 35 randomized, controlled trials of at least 4 weeks' duration that evaluated pharmacotherapies available in the United States and that reported global or sleep outcomes; 11 long-term observational studies that reported harm information; FDA review data for nonbenzodiazepine hypnotics and orexin receptor antagonists; and product labels for all agents. DATA EXTRACTION: Data extraction by single investigator confirmed by a second reviewer; dual-investigator assessment of risk of bias; consensus determination of strength of evidence. DATA SYNTHESIS: Eszopiclone, zolpidem, and suvorexant improved short-term global and sleep outcomes compared with placebo, although absolute effect sizes were small (low- to moderate-strength evidence). Evidence for benzodiazepine hypnotics, melatonin agonists, and antidepressants, and for most pharmacologic interventions in older adults, was insufficient or low strength. Evidence was also insufficient to compare efficacy within or across pharmacotherapy classes or versus behavioral therapy. Harms evidence reported in trials was judged insufficient or low strength; observational studies suggested that use of hypnotics for insomnia was associated with increased risk for dementia, fractures, and major injury. The FDA documents reported that most pharmacotherapies had risks for cognitive and behavioral changes, including driving impairment, and other adverse effects, and they advised dose reduction in women and in older adults. LIMITATIONS: Most trials were small and short term and enrolled individuals meeting stringent criteria. Minimum important differences in outcomes were often not established or reported. Data were scant for many treatments. CONCLUSION: Eszopiclone, zolpidem, and suvorexant may improve short-term global and sleep outcomes for adults with insomnia disorder, but the comparative effectiveness and long-term efficacy of pharmacotherapies for insomnia are not known. Pharmacotherapies for insomnia may cause cognitive and behavioral changes and may be associated with infrequent but serious harms. PRIMARY FUNDING SOURCE: Agency for Healthcare Research and Quality. ( PROSPERO: CRD42014009908).

Psychological and Behavioral Interventions for Managing Insomnia Disorder: An Evidence Report for a Clinical Practice Guideline by the American College of Physicians.

BACKGROUND: Psychological and behavioral interventions are frequently used for insomnia disorder. PURPOSE: To assess benefits and harms of psychological and behavioral interventions for insomnia disorder in adults. DATA SOURCES: Ovid MEDLINE, Embase, the Cochrane Central Register of Controlled Trials, and PsycINFO through September 2015, supplemented with hand-searching. STUDY SELECTION: Randomized, controlled trials of psychological or behavioral interventions that were published in English and enrolled adults with insomnia disorder lasting 4 or more weeks. DATA EXTRACTION: Data extraction by single investigator confirmed by a second reviewer; dual investigator assessment of risk of bias; consensus determination of strength of evidence. DATA SYNTHESIS: Sixty trials with low to moderate risk of bias compared psychological and behavioral interventions with inactive controls or other psychological and behavioral interventions. Cognitive behavioral therapy for insomnia (CBT-I) improved posttreatment global and most sleep outcomes, often compared with information or waitlist controls (moderate-strength evidence). Use of CBT-I improved several sleep outcomes in older adults (low- to moderate-strength evidence). Multicomponent behavioral therapy improved several sleep outcomes in older adults (low- to moderate-strength evidence). Stimulus control improved 1 or 2 sleep outcomes (low-strength evidence). Evidence for other comparisons and for harms was insufficient to permit conclusions. LIMITATIONS: A wide variety of comparisons limited the ability to pool data. Trials did not always report global outcomes and infrequently conducted remitter or responder analysis. Comparisons were often information or waitlist groups, and publication bias was possible. CONCLUSION: Use of CBT-I improves most outcomes compared with inactive controls. Multicomponent behavioral therapy and stimulus control may improve some sleep outcomes. Evidence on other outcomes, comparisons, and long-term efficacy were limited. PRIMARY FUNDING SOURCE: Agency for Healthcare Research and Quality. ( PROSPERO: CRD42014009908).

Sleep Disturbances in Posttraumatic Stress Disorder: Updated Review and Implications for Treatment.

Sleep disturbances are common in adults with PTSD and range from insomnia and nightmares to periodic leg movements and disruptive nocturnal behaviors. Together these findings suggest profound disturbances in rapid eye movement (REM) and non-REM (NREM) sleep, although there is a lack of consensus regarding a distinct profile of objective sleep disturbances associated with PTSD. Prospective, longitudinal studies have established that sleep disturbances represent a risk factor for the development and course of PTSD, suggesting that sleep is an important neurobiological mechanism in the etiology and maintenance of this disorder. This research highlights the importance of early identification and treatment of sleep disturbances in at-risk and trauma exposed populations. A number of psychological and pharmacological treatments are effective at treating sleep disturbances in PTSD. Additional research is needed to further develop clinical guidelines informing when and how to integrate sleep-specific treatment with PTSD focused clinical care.

Urdu translation of the Hamilton Rating Scale for Depression: Results of a validation study.

OBJECTIVE: To develop a standardized validated version of the Hamilton Rating Scale for Depression (HAM-D) in Urdu. METHODS: After translation of the HAM-D into the Urdu language following standard guidelines, the final Urdu version (HAM-D-U) was administered to 160 depressed outpatients. Inter-item correlation was assessed by calculating Cronbach alpha. Correlation between HAM-D-U scores at baseline and after a 2-week interval was evaluated for test-retest reliability. Moreover, scores of two clinicians on HAM-D-U were compared for inter-rater reliability. For establishing concurrent validity, scores of HAM-D-U and BDI-U were compared by using Spearman correlation coefficient. The study was conducted at Mayo Hospital, Lahore, from May to December 2014. RESULTS: The Cronbach alpha for HAM-D-U was 0.71. Composite scores for HAM-D-U at baseline and after a 2-week interval were also highly correlated with each other (Spearman correlation coefficient 0.83, p-value < 0.01) indicating good test-retest reliability. Composite scores for HAM-D-U and BDI-U were positively correlated with each other (Spearman correlation coefficient 0.85, p < 0.01) indicating good concurrent validity. Scores of two clinicians for HAM-D-U were also positively correlated (Spearman correlation coefficient 0.82, p-value < 0.01) indicated good inter-rater reliability. CONCLUSION: The HAM-D-U is a valid and reliable instrument for the assessment of Depression. It shows good inter-rater and test-retest reliability. The HAM-D-U can be a tool either for clinical management or research.

Insomnia during pregnancy: Diagnosis and Rational Interventions.

UNLABELLED: Sleep disturbances are common in pregnancy. Insomnia is a frequent sleep disturbance experienced by pregnant women which can be primary or due to co-morbid conditions. The differential diagnosis of insomnia in pregnancy includes anxiety disorders, mood disorders, breathing related sleep disorders and restless legs syndrome. Early interventions to treat the sleep disturbance are recommended to avoid adverse pregnancy outcomes. Management strategies include improving sleep hygiene, behavioral therapies, and pharmacotherapy. The risks of pharmacotherapy must be weighed against their benefits due to the possible risk of teratogenicity associated with some medications. METHODS: We searched PubMed and Google Scholar employing a combination of key words: pregnancy, sleep disturbances, Obstructive Sleep Apnea, Sleep disorders and insomnia. We included original studies, review articles, meta-analysis and systematic reviews in our search prioritizing articles from the last 10-15 years. Articles older than 15 years were only included if their findings had not been superseded by more recent data. Further selection of articles was done from bibliographies and references of selected articles. CONCLUSION: Sleep disturbances in pregnancy are common and cause considerable morbidity. Management includes a combination of non-pharmacological and pharmacological treatments carefully weighing the risks and benefits of each for the expectant mother and fetus.

Actigraphy in post traumatic stress disorder.

UNLABELLED: Patients with posttraumatic stress disorder (PTSD) frequently complain of sleep disturbances such as insomnia and nightmares. Evaluation of sleep disturbances is often difficult due to the subjective nature of the complaints. Polysomnography (PSG) and other sleep studies are generally not indicated in the evaluation of insomnia or nightmares associated with PTSD. Actigraphy, (electronic activity monitoring) has been used in research to evaluate sleep disturbances in patients with PTSD. We reviewed the literature on the use of actigraphy in evaluation of sleep problems in patients with PTSD. METHODS: A literature search for articles on the topic was conducted on PubMed using the search algorithm (actigraphy[Title/Abstract] OR actigraphic[Title/Abstract]) AND PTSD[Title/Abstract]. Out of 11 search results, 9 studies in which application of actigraphy had relevance to the primary objective and outcome in PTSD patients with sleep problems were selected for review. We also handpicked one additional article from personal communication with our colleagues who have done some of these studies. CONCLUSION: Actigraphy has been used to evaluate circadian rhythm sleep disorders. Use of actigraphy in psychiatry clinics is uncommon. There is no data to support that there are specific actigraphic sleep related findings in PTSD patients. However, it can be a useful tool to complement the use of sleep diaries when assessing sleep and wake patterns in patients with PTSD.

Bleeding Outcomes of Direct Oral Anticoagulants and Vitamin K Antagonists for Acute Venous Thromboembolism: A Cross-Sectional Study.

BACKGROUND: Venous thromboembolism (VTE) is a widespread and significant cause of morbidity and mortality on a global scale. The primary objective of this cross-sectional study is to examine the impact of anticoagulant therapy on major organ hemorrhage events in patients diagnosed with acute venous thromboembolism (VTE). Specifically, this research compares the effects of vitamin K antagonists (VKAs) and direct oral anticoagulants (DOACs). MATERIALS AND METHODS: This retrospective observational study examined the medical records of 46 patients who had been diagnosed with VTE and were receiving treatment with DOACs or VKAs. The documentation of patient characteristics encompassed demographic information, comorbidities, and treatment particulars. Within 30 days of hospital admission, the incidence of significant organ bleeding events, with an emphasis on gastrointestinal and intracranial hemorrhage, was the primary outcome evaluated. RESULTS: Overall, 46 patients with VTE who were treated with oral anticoagulation therapy participated in the study. Twenty-four and 22 patients were administered VKAs and DOACs, respectively. The similarity in baseline characteristics between the DOAC and VKA groups ensured that the analyses were well-matched. The examination of bleeding sites unveiled subtle variations, as the DOAC group exhibited a progressive increase in the incidence of intracranial bleeding (12, 55.5%), while the VKA group demonstrated a surge in upper gastrointestinal bleeding (12, 50%) as well. While lacking statistical significance, these observed patterns are consistent with prior research that indicates that DOACs may have a lower risk of catastrophic hemorrhage in comparison to VKAs. The overall in-hospital mortality rate for patients treated with VKA was 33.3% (n=8), while that treated with DOAC was 18.2% (n=4). These differences did not reach statistical significance (P>0.05). In a similar vein, the evaluation of mortality associated with hemorrhage revealed six (25%) in the group receiving VKA and three (13.6%) in the group receiving DOAC; the P value was not statistically significant (P>0.05). CONCLUSIONS: This study contributes valuable insights into bleeding outcomes associated with anticoagulant therapy for acute VTE. The nuanced differences in bleeding patterns highlight the complexity of anticoagulant selection, emphasizing the importance of considering bleeding site considerations. The comparable mortality rates support existing evidence regarding the favorable safety profile of DOACs.

Nocturnal Awakening & Sleep Duration in Veterans with PTSD: An Actigraphic Study.

OBJECTIVE: To assess whether awakenings from sleep and sleep duration in Post Traumatic Stress Disorder (PTSD) were related to demography, posttraumatic or depressive symptoms, subjective sleep quality, and daytime sleepiness. METHODS: Sample consisted of 23 veterans with lifetime PTSD and current sleep disturbance not due to apnea or other diagnosable conditions. Data collection included demography, two weeks of actigraphy, Beck Depression Inventory, Posttraumatic Checklist, Clinical Assessment of Posttraumatic Symptoms, Pittsburgh Sleep Quality Index, and Epworth Sleepiness Scale. RESULTS: The study revealed that awakenings increased with younger age. Variability in awakenings also increased with younger age (p = 0.002). More awakenings were associated with shorter sleep duration. CONCLUSIONS: These paradoxical observations regarding younger age and more awakening may be related to increased sleep symptoms early in the course and then gradual waning of posttraumatic symptoms over time, since awakenings tend to increase with age in normals (rather than decrease, as we observed).

Effect of Thymectomy on Outcomes of Myasthenia Gravis Patients: A Case-Control Study at a Tertiary Care Hospital.

Background and objective Myasthenia gravis (MG) is an acquired autoimmune disease mediated by antibodies affecting the neuro-muscular junction on the postsynaptic membrane, resulting in neuromuscular transmission obstruction and, consequently, muscle weakening. It is believed that the thymus gland plays a critical role in the production of these antibodies. Screening patients for thymoma and surgical excision of the thymus gland is a crucial part of the treatment. To compare the odds of good outcomes in Myasthenia Gravis patients with or without thymectomy. Material and methods A retrospective case-control study was conducted at the Department of Medicine and Neurology, Ayub Teaching Hospital, Abbottabad, Pakistan, from October 2020 to September 2021. A purposive sampling technique was employed. Thirty-two MG patients with thymectomy and 64 MG patients without thymectomy were selected for investigation. Controls and cases were matched on the basis of sex and age (1:2). A positive EMG study, acetylcholine receptor antibodies, and a pyridostigmine test were used to make the diagnosis of MG. Patients were called to the outpatient department for assessment of treatment outcomes. Primary outcome evaluation was done using the Myasthenia Gravis Foundation of America Post-Intervention Status (MGFA-PIS) tool at the last follow-up after one year. Results A sample of 96 patients was evaluated, of which 63 (65%) were females and 33 (34%) were males. The mean age for Group 1 (cases) was 35 years ±8.9 and for Group 2 (controls) was 37± 11.1. Age and Osserman stages were shown to be the two most crucial prognostic factors in our study. However, there are several other factors in our study that are linked to a poor response, such as a greater BMI, dysphagia, thymoma, older age, and a longer duration of disease. Conclusions Our findings indicate that none of the analysed groups had significantly worse outcomes as a result of the current clinical practice of thymectomy patient selection.

An Unrecognized Cause of Elevated Procalcitonin Level.

Diabetic Ketoacidosis (DKA) is a preventable yet serious complication of diabetes that is commonly associated with type 1 diabetes but can also occur in other forms of diabetes, including type 2. Infection is a primary cause of DKA and can lead to elevated levels of procalcitonin (PCT), which is a biomarker used to differentiate bacterial infections from non-infectious inflammation. However, some cases of DKA have shown increased PCT levels even in the absence of bacterial infection, and the underlying mechanism of this observation is not fully understood. To gain a better understanding of how non-infectious inflammation affects PCT levels, further research is needed. While PCT is a helpful biomarker, it should be interpreted in the context of the patient's overall clinical picture, including signs and symptoms of infection or inflammation and underlying medical conditions that may be contributing to their presentation. A systematic approach to evaluating and managing patients with DKA can minimize the risk of unnecessary antibiotic use and ensure optimal treatment. We present a 31-year-old male who was admitted to the ICU with DKA, and further investigations revealed elevated PCT levels. Despite conducting several studies and cultures, including blood and urine, no infections were detected. The patient was treated for DKA with hydration and insulin administration without the use of antibiotics, and his PCT levels subsequently decreased.

Effectiveness of Proton Pump Inhibitor Therapy in the Prevention of Bleeding After Prophylactic Endoscopic Variceal Band Ligation.

Background Endoscopic variceal ligation (EVL) is a surgical intervention that can work well to curb variceal bleeding in people with liver cirrhosis. However, it could make ulcer bleeding worse and be fatal in some cases. The widespread use of proton pump inhibitors (PPI) in cirrhotic individuals with variceal bleeding is empirical rather than based on scientific data. According to many studies, PPIs reduce the size of post-EVL ulcers. This study aimed to see if PPI use could reduce rebleeding after endoscopy therapy in cirrhotic patients with variceal bleeding. Methodology A retrospective cross-sectional study was conducted at a tertiary care hospital from August 2019 to September 2021. Cirrhotic patients with bleeding gastroesophageal varices (GEVs) who had undergone EVL at the same hospital were enrolled in the study. Medical records were organized, and the sample was divided into two groups based on whether or not PPI was given. Both PPI and non-PPI patients had their endoscopic findings, initial hemostasis outcomes, rebleeding rates, bleeding-related mortality rates, and treatment-related comorbidities compared. Results A total of 46 patients were selected for the study and divided into two groups (PPI group n=28 and non-PPI group n=18). The majority of the patients were males. The PPI group had a mean age of 58.6 ±7.8 years, whereas the non-PPI group had a mean age of 53.6 ±4.4 years. Hepatitis B virus (HBV) infection was the most prevalent cause of cirrhosis in both groups. After endoscopic treatment, three patients (16%) in the non-PPI group suffered a variceal hemorrhage. Bleeding-related fatalities and the time it took for the bleeding to stop varied significantly between the two groups. History of variceal bleeding (relative risk (RR)=1.45; 95% confidence interval (CI), 1.60-7.67; p=0.02), presence of gastric varices (RR=2.23; 95% CI, 2.56-9.832; p=0.035), and not administering PPIs (RR =7.542; 95% CI, 3.98-29.13; p=0.008) were linked with rebleeding. The presence of red concurrent esophageal varices (RR=6.37; 95% CI, 0.562-15.342; p=0.002) and failure to provide PPIs (RR=2.3; 95% CI, 1.621-25.64; p=0.04) were linked with post-EVL bleeding in a multivariate analysis. Conclusions Proton pump inhibitors reduce the occurrence of early bleeding and adverse events after EVL in cirrhotic patients. Not prescribing PPIs and the presence of GEVs were substantially related to a higher risk of bleeding during preventative EVL. Not initiating PPI medication immediately was the sole predictor of bleeding complications in patients who had undergone EVL without gastric varix treatment. To lower the risk of post-EVL ulcer bleeding, we recommend PPI use in patients undergoing EVL.

Fall Prevalence and Associated Risk Factors in the Hospitalised Adult Population: A Crucial Step Towards Improved Hospital Care.

Background Falls among the adult population are a major global health concern with severe repercussions for individuals and healthcare systems. The purpose of this study was to investigate the prevalence and associated risk factors of falls in hospitalized patients in order to improve hospital care for elderly adults. Materials and methods The research was conducted at two institutions of tertiary care in Abbottabad, Pakistan. After extensive screening and obtaining informed consent, a total of 210 participants aged 50 and older were enrolled in the study. Mental status, history of falls, ambulation/elimination status, vision, gait/balance, systolic blood pressure, medication use, and predisposing diseases were evaluated using the Long Term Care Fall Risk Assessment Form. Additionally, the Dynamic Gait Index was utilized to evaluate various aspects of gait. Results 58.6% of participants reported a history of falls in the previous year, according to the findings. BMI, imbalance, vertigo, and fear of falling were significantly associated with an increased risk of falls in older individuals. The Long-Term Care Fall Risk Assessment, the Montreal Cognitive Assessment (MoCA), the Dynamic Gait Index (DGI), and the Mini-BESTest scores revealed that patients with a history of falls had inferior functional and cognitive outcomes. Falls were more common among individuals with a robust BMI, especially men. Conclusions The study results highlight the multifactorial nature of falls in the adult population and the need for targeted interventions to address modifiable risk factors. To enhance hospital care for high-risk patients, proactive fall prevention strategies, including regular risk assessments and individualized interventions, should be implemented. This study provides important insights into the prevalence and causes of accidents among hospitalized patients, particularly in developing nations such as Pakistan. ​​​​​​.

The Impact of Diabetes on Morbidity and Mortality Following Thyroidectomy.

OBJECTIVES: To explore the association between diabetes and outcomes in thyroidectomy patients. METHODS: This retrospective cohort analysis used the 2015-2017 American College of Surgeons National Surgery Quality Improvement Program database. Current Procedural Terminology (CPT) codes were used to identify thyroidectomy cases (60210, 60212, 60220, 60225, 60240, 60252, 60254, 60260, 60270, and 60271). Demographics, comorbidities, and complication incidences were compared between diabetic and nondiabetic patients using Pearson's chi-square test/Fisher's exact test as appropriate. The independent effect of diabetes on outcomes was analyzed using binary logistic regression. RESULTS: A total of 47,776 (95.4%) nondiabetic and 2307 (4.6%) diabetic patients undergoing thyroidectomy were identified from 2015 to 2017. Chi-square analysis demonstrated that diabetic patients had higher incidences of obesity (55.2% vs. 33.2%; p < 0.001), dyspnea (12.7% vs. 4.8%; p < 0.001), poor functional status (1.9% vs. 0.4%; p < 0.001), ventilator dependence (0.6% vs. 0.1%; p < 0.001), chronic obstructive pulmonary disease (COPD; 6.8% vs. 2.2%; p < 0.001), congestive heart failure (1.1% vs. 0.3%; p < 0.001), acute renal failure (0.3% vs. 0.0%; p < 0.001), hypertension (79.2% vs. 32.4%; p < 0.001), dialysis (2.0% vs. 0.4%; p < 0.001), open wound (1.1% vs. 0.1%; p < 0.001), steroid use (5.3% vs. 2.3%; p < 0.001), bleeding disorders (3.6% vs. 0.9%; p < 0.001), preoperative blood transfusions (0.2% vs. 0.0%; p = 0.001), and systemic sepsis (1.0% vs. 0.3%; p < 0.001). Demographic characteristics were significantly different between the cohorts including gender (p < 0.001), age (p < 0.001), race (p < 0.001), and Hispanic ethnicity (p = 0.033). After adjusting for these factors, logistic regression analyses showed that diabetes was associated with acute renal failure (OR: 5.836; 95% CI: 1.060-32.134; p = 0.043), wound disruption (OR: 6.194; 95% CI: 1.752-21.900; p = 0.005), prolonged length of stay (OR: 1.430; 95% CI: 1.261-1.622; p < 0.001), unplanned readmission (OR: 1.380; 95% CI: 1.096-1.737; p = 0.006), superficial incisional surgical site infections (OR: 0.240; 95% CI: 0.058-0.995; p = 0.049), urinary tract infection occurrences (OR: 2.173; 95% CI: 1.186-3.980; p = 0.012), organ space surgical site infection occurrences (OR: 3.322; 95% CI: 1.016-10.864; p = 0.047), pneumonia occurrences (OR: 2.091; 95% CI: 1.125-3.884; p = 0.020), any medical complication (OR: 1.697; 95% CI: 1.246-2.313; p = 0.001), and any complication (OR: 1.495; 95% CI: 1.136-1.968; p = 0.004). CONCLUSION: Diabetes mellitus is a significant factor associated with increased odds of complications following thyroidectomy. LEVEL OF EVIDENCE: 3 Laryngoscope, 133:3628-3632, 2023.

Effect of Hypoalbuminemia in Patients Undergoing Parathyroidectomy for Primary Hyperparathyroidism.

OBJECTIVES: Treatment for primary hyperparathyroidism is parathyroidectomy. This study identifies the association between hypoalbuminemia (HA) and outcomes in patients undergoing parathyroidectomy for primary hyperparathyroidism. METHODS: This retrospective cohort analysis utilized the 2006-2015 National Surgical Quality Improvement Program database. Current Procedure Terminology codes were used to identify patients undergoing parathyroidectomy for primary hyperparathyroidism. Prolonged length of stay (LOS) was defined as a duration of 2 days or greater. Demographics and comorbidities were compared between HA (serum albumin <3.5 g/dL) and non-HA cohorts using chi-square analysis. The independent effect of HA on adverse outcomes was analyzed using binary logistic regression. RESULTS: A total of 7183 cases with primary hyperparathyroidism were classified into HA (n = 381) and non-HA (n = 6802) cohorts. HA patients had increased complications, including renal insufficiency (0.8% vs. 0.0%, p = 0.001), sepsis (1.0% vs. 0.1%, p = 0.003), pneumonia (0.8% vs. 0.1%, p = 0.018), acute renal failure (1.0% vs. 0.0%, p < 0.001), and unplanned intubation (1.3% vs. 0.2%, p = 0.004). HA patients had increased risk of death (1.6% vs. 0.1%, p < 0.001), prolonged LOS (40.9% vs. 6.3%, p < 0.001), and any complication (5.5% vs. 1.2%, p < 0.001). Adjusted binary logistic regression indicated HA patients experienced increased odds of progressive renal insufficiency (OR 18.396, 95% CI 1.844-183.571, p = 0.013), prolonged LOS (OR 4.892; 95% CI 3.571-6.703; p < 0.001), unplanned reoperation (OR 2.472; 95% CI 1.012-6.035; p = 0.047), and unplanned readmission (OR 3.541; 95% CI 1.858-6.748; p < 0.001). CONCLUSIONS: HA may be associated with adverse complications in patients undergoing parathyroidectomy for primary hyperparathyroidism. LEVEL OF EVIDENCE: 3 Laryngoscope, 133:2035-2039, 2023.

In vitro analysis of PI3K pathway activation genes for exploring novel biomarkers and therapeutic targets in clear cell renal carcinoma.

OBJECTIVES: The regulation of various cellular functions such as growth, proliferation, metabolism, and angiogenesis, is dependent on the PI3K pathway. Recent evidence has indicated that kidney renal clear cell carcinoma (KIRC) can be triggered by the deregulation of this pathway. The objective of this research was to investigate 25 genes associated with activation of the PI3K pathway in KIRC and control samples to identify four hub genes that might serve as novel molecular biomarkers and therapeutic targets for treating KIRC. METHODS: Multi-omics in silico and in vitro analysis was employed to find hub genes related to the PI3K pathway that may be biomarkers and therapeutic targets for KIRC. RESULTS: Using STRING software, a protein-protein interaction (PPI) network of 25 PI3K pathway-related genes was developed. Based on the degree scoring method, the top four hub genes were identified using Cytoscape's Cytohubba plug-in. TCGA datasets, KIRC (786-O and A-498), and normal (HK2) cells were used to validate the expression of hub genes. Additionally, further bioinformatic analyses were performed to investigate the mechanisms by which hub genes are involved in the development of KIRC. Out of a total of 25 PI3K pathway-related genes, we developed and validated a diagnostic and prognostic model based on the up-regulation of TP53 (tumor protein 53) and CCND1 (Cyclin D1) and the down-regulation of PTEN (Phosphatase and TENsin homolog deleted on chromosome 10), and GSK3B (Glycogen synthase kinase-3 beta) hub genes. The hub genes included in our model may be a novel therapeutic target for KIRC treatment. Additionally, associations between hub genes and infiltration of immune cells can enhance comprehension of immunotherapy for KIRC. CONCLUSION: We have created a new diagnostic and prognostic model for KIRC patients that uses PI3K pathway-related hub genes (TP53, PTEN, CCND1, and GSK3B). Nevertheless, further experimental studies are required to ascertain the efficacy of our model.

Ampreloxetine Versus Droxidopa in Neurogenic Orthostatic Hypotension: A Comparative Review.

Neurogenic orthostatic hypotension (nOH) is a disabling problem of autonomic dysfunction in patients with Parkinson's disease, which is associated with poor quality of life and higher mortality rates. The purpose of this literature review was to explore and compare the efficacy and safety of droxidopa (an existing treatment) and ampreloxetine (a newer medication) in the treatment of nOH. We used a mixed-method literature review that addresses the epidemiology, pathophysiology, and pharmacological and non-pharmacological management of nOH in Parkinson's disease in a general way, with a more exploratory approach to droxidopa- and ampreloxetine-controlled trial studies. We included a total of 10 studies of randomized controlled trials with eight studies focused on droxidopa and two studies focused on ampreloxetine. These two drugs were analyzed and compared based on the collected individual study results. Treatment of nOH in Parkinson's disease patients with droxidopa or ampreloxetine showed clinically meaningful and statistically significant improvements relative to placebo on the components of the OHSA (Orthostatic Hypotension Symptom Assessment) composite score and OHDAS (Orthostatic Hypotension Daily Activity Scale composite scores) composite score. Droxidopa had an improved effect on daily activities, with an associated increase in standing systolic blood pressure (BP), but the long-term efficacy of droxidopa has not been documented. Standing systolic BP was maintained by ampreloxetine and worsened after the withdrawal phase. This highlights the importance of conducting further research which will help us to improve the therapeutic approach for patients with nOH and Parkinson's disease.

Virtual and Augmented Reality in Post-stroke Rehabilitation: A Narrative Review.

Virtual reality (VR) and augmented reality (AR) are noble adjunctive technologies currently being studied for the neuro-rehabilitation of post-stroke patients, potentially enhancing conventional therapy. We explored the literature to find if VR/AR improves neuroplasticity in stroke rehabilitation for a better quality of life. This modality can lay the foundation for telerehabilitation services in remote areas. We analyzed four databases, namely Cochrane Library, PubMed, Google Scholar, and Science Direct, by searching the following keywords: ("Stroke Rehabilitation" [Majr]) AND ("Augmented Reality" [Majr]), Virtual Augmented Reality in Stroke Rehabilitation. All the available open articles were reviewed and outlined. The studies conclude that VR/AR can help in early rehabilitation and yield better results in post-stroke patients in adjunct to conventional therapy. However, due to the limited research on this subject, we cannot conclude that this information is absolute. Moreover, VR/AR was seldom customized according to the needs of stroke survivors, which would have given us the full extent of its application. Around the world, stroke survivors are being studied to verify the accessibility and practicality of these innovative technologies. Observations conclude that further exploration of the extent of the implementations and efficacy of VR and AR, combined with conventional rehabilitation, is fundamental.

Structural Changes in Brain Magnetic Resonance Imaging Associated With Psychogenic Non-epileptic Seizures: An Analytical Cross-Sectional Study.

Background Psychogenic non-epileptic seizures (PNES) are often seen as indicators of poor motor and sensory function caused by psychological responses to stressful experiences. A seizure might trigger these reactions. The aim of our study was to assess the structural changes in brain MRI associated with psychogenic non-epileptic seizures. Methodology A retrospective analytical cross-sectional study at the Department of Medicine and Neurology, Ayub Teaching Hospital, Abbottabad, was conducted from October 2020 to September 2021. The medical records of patients with confirmed PNES were collected and retrospectively evaluated. Results Medical records and MRI scans were accessible for 52 patients with PNES; 10 patients were excluded from the study. The average age of the patients (standard deviation) was 34 (±9) years, and the average age at onset was 31.6 (±5.8) years. Based on the video-EEG recordings, 57.1% of patients (n=24) were classified as having broadly generalized motor seizures, 40% of patients (n=17) were classified as having predominantly akinetic seizures defined primarily by blank spells, and only one patient was classified as having focal motor seizures. Only three patients (7%) had a positive epilepsy family history. Twenty-four (47.6%) patients with brain MRI scans reported abnormal findings, while 22 (52.4%) had normal MRI findings. The majority of patients with abnormal MRIs had nonspecific white matter changes (50%), mesial temporal sclerosis (15%), and cysts (15%). In a statistical analysis, age at the beginning of PNES (p = 0.04), duration of PNES (p=0.01), concomitant epilepsy (p = 0.05), generalized motor seizures (p= 0.03), and focal motor seizures (p= 0.02) were strongly associated with abnormal brain MRI findings. Conclusion Research reveals that persons with PNES have a higher-than-average prevalence of anatomical brain abnormalities. The main takeaway is that these findings lend credence to the growing body of data suggesting that PNES may not be a medical mystery but rather a disorder with physical foundations in the brain. Important implications for diagnosing and treating PNES patients are discussed, as are the outcomes of earlier neuroimaging investigations of PNES. Studying the involvement of structural brain anomalies in the etiology of psychogenic non-epileptic seizures requires further well-designed multicenter studies with larger sample sizes and a consistent imaging approach (PNES). It is crucial to consider any confounding variables, such as co-occurring mental diseases, while designing this study.

Organizing Pneumonia Following Recombinant Zoster Vaccination: A Rare Adverse Reaction.

We describe a case of a severe but rare adverse reaction to recombinant varicella-zoster virus (VZV) vaccination: a 67-year-old female admitted with gradual onset of shortness of breath, hypoxia, and fever following VZV vaccination. The clinical picture and radiologic presentation mimicked COVID-19 pneumonia. However, repeated testing for COVID-19 by PCR was negative. A diagnosis of organizing pneumonia was made on transbronchial biopsies. The patient responded well to steroids and improved both clinically and radiographically. This case illustrates not only a rare and unreported complication from vaccination but also raises the awareness during the COVID-19 pandemic that other etiologies can mimic COVID-19 pneumonia. Physicians should be aware of other diagnoses that can mimic COVID-19 infection.

Prevalence of Non-adherence to Antiepileptic Drugs in Patients With Epilepsy Presenting to Emergency With Fits.

Background Epilepsy is considered when a patient has at least two unprovoked seizures that occurred more than a day apart. Seizure control depends upon several factors, including adequate treatment and its dosage, patients' daily activities, and adherence to antiepileptic medications. The study aimed to assess the rate of adherence to antiepileptic drugs (AED) in patients with epilepsy. Methodology A cross-sectional study was conducted at the Department of Neurology, Ayub Teaching Hospital, Abbottabad, Pakistan, between November 2019 and October 2020. All participants who presented to the emergency room with complaints of seizures, had a known diagnosis of epilepsy, aged above 18 years, with no cognitive dysfunction or severe psychiatric disorders were included in the study. Patients with other neurological disabilities (brain tumors, cerebral palsy, neuromuscular disorder) or severe psychotic episodes and those with undiagnosed cases of epilepsy were excluded from the study. A predefined proforma was used to assess the level of adherence and non-adherence among patients and they were then divided into their respective groups. Results A total of 150 participants were included in the study. Of patients, 110 were adherent to AED treatment while 40 were non-compliant. It was found that the most frequent cause of non-adherence was that patients forgot their pills (72.5%). Of patients, 7.5% stopped taking the medication when symptoms were relieved. About 12.5% reported affordability to be the reason for non-adherence. The rate of poor seizure control was significantly higher in non-adherent patients as compared to adherent patients (77.5% vs. 49.1%, p = 0.001). It was also found that a greater number of non-adherent patients experienced convulsive seizures in the past year as compared to those who were adherent to their medications (p = 0.006). Conclusion To enhance treatment adherence, the practice of prescribing more simpler treatment regimens among physicians can result in better seizure control, as the complexity of the regimen is found to be a major challenge for adjustment of AED regimens in this regard.