Drug Contraindications in Comorbid Diseases: a Protein Interactome Perspective

Adverse drug reactions (ADRs) are leading causes of death and drug withdrawals and frequently co-occur with comorbidities. However, systematic studies on the effects of drugs in comorbidities are lacking. Drug interactions with the cellular protein-protein interaction (PPI) network give rise to ADRs. We selected 6 comorbid disease pairs, identified the drugs used in the treatment of the individual diseases A and B — 44 drugs in anxiety and depression, 128 in asthma and hypertension, 48 in chronic obstructive pulmonary disease and heart failure, 58 in type 2 diabetes and obesity, 58 in Parkinson′s disease and schizophrenia, and 84 in rheumatoid arthritis and osteoporosis — and categorized them based on whether they aggravate the comorbid condition. We constructed drug target networks (DTNs) and examined their enrichment among genes in disease A/B PPI networks, expressed across 53 tissues and involved in ≈1000 pathways. To pinpoint the biological features characterizing the DTNs, we performed principal component analysis and computed the Euclidean distance between DTN component scores and feature loading values. DTNs of disease A drugs not contraindicated in B were affiliated with proteins common to A/B networks or uniquely found in the B network, similarly regulated common pathways, and disease-B specific pathways and tissues. DTNs of disease A drugs contraindicated in B were affiliated with common proteins or those uniquely found in the A network, differentially regulated common pathways, and disease A-specific pathways and tissues. Hence, DTN enrichment in pathways, tissues, and PPI networks of comorbid diseases will help identify drugs contraindications in comorbidities.

SARS-CoV-2 Gastrointestinal Shedding in Hospitalized Children

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a respiratory virus that can cause gastrointestinal (GI) symptoms, with studies demonstrating detection of stool viral RNA weeks after respiratory tract clearance. It is unknown if children who test negative for SARS-CoV-2 on a nasopharyngeal (NP) swab may be shedding the virus in their stool. OBJECTIVE: To measure the prevalence of SARS-CoV-2 stool shedding in children with positive and negative SARS-CoV-2 NP polymerase chain reactions (PCR) tests, and to determine clinical factors associated with GI shedding. METHODS: In this cross-sectional study, we enrolled hospitalized patients 0 to 21 years old with a positive or a negative SARS-CoV-2 NP PCR test who had respiratory and/or GI symptoms. Participants were surveyed, and stool samples were sent for viral PCR testing. Fisher’s exact test was used to evaluate bivariate associations of stool PCR test positivity with categorical variables. RESULTS: Sixty-seven patients were consented; 34 patients did not provide stool samples so 33 patients were included: 17 NP-positive and 16 NP-negative for SARS-CoV-2. Eight of the 17 NP-positive patients had a positive stool PCR test for SARS-CoV-2, while none of the 16 SARS-CoV-2 NP-negative patients had a positive result (P < .01). For the 17 SARS-CoV-2 NP-positive patients, GI symptoms were associated with a positive stool PCR test (P = .05) for SARS-CoV-2, but this association was not found for all 33 patients (P = .11). No associations were found with patients in an immunocompromised state or those with a comorbid condition, fever and/or chills, respiratory symptoms, headache and/or myalgias, or anosmia and/or ageusia. CONCLUSIONS: SARS-CoV-2 GI shedding is common and associated with GI symptoms in NP-positive children, with 47% having positive stool PCRs for SARS-CoV-2. GI shedding was not demonstrated in SARS-CoV-2 NP-negative children.

Dissociative disorder in Mayer Rokitansky Küster Hauser syndrome with pulmonary agenesis: a case report

Background The Mayer Rokitansky Küster Hauser (MRKH) syndrome is a rare congenital disorder characterized by the absence of uterus and vagina in a patient who is phenotypically a female, with 46 XX karyotypes. It affects 1 in 4000 to 5000 female new-borns. Pulmonary agenesis is a rare association in this MRKH syndrome. Females with MRKH face various mental health issues and psychological disturbances, including dissociative disorder which is a stress-related psychiatric disorder. Dissociative disorder in MRKH syndrome is under-recognized and under-treated. Case presentation A 23-year-old unmarried woman presented to the emergency forabnormal behaviour attack. Recurrent episodes of dissociative convulsions were present most of the time with MRKH syndrome as the pertinent stressor. Both antidepressants and psychotherapy helped to decrease the frequency of dissociative convulsions and come interms with the syndrome. Conclusion This case describes dissociative disorder as the presentation and comorbid condition of MRKH syndrome and the impact of MRKH syndrome on the patient. We attempt to explain the occurrence of dissociative disorder in MRKH syndrome and the results of under-recognition and under-treatment of the same. We aim to highlight the presence of commonly treatable conditions associated with a rare syndrome and its effect when untreated and unrecognized.

Evaluation of the effectiveness of drug treatment in patients with arterial hypertension and insomnia

Objective: chronic sleep disturbance is a comorbid condition with arterial hypertension, often combined with affective disorders, anxiety, depression. Forced sleep deprivation in patients with hypertension indicates a high activity of the renin‑angiotensin‑aldosterone system (RAAS) and desynchronosis of biological rhythms caused by a probable deficit in melatonin secretion during the night. Timely elimination of any pathological process associated with insomnia and arterial hypertension (AH) in the early stages of its development is a prerequisite for the effectiveness of therapy. Therefore, initial therapy should help neutralize the adverse effects of RAAS and improve the 24‑hour blood pressure (BP) profile. The aim of this study was to determine the therapeutic effect of monotherapy with an angiotensin converting enzyme (ACE) inhibitor, As well as in combination with a synthetic analogue of melatonin, on the course of hypertension and parameters of systemic hemodynamics in patients with first degree hypertension with insomnia at the onset of the disease. Combined therapy with an ACE inhibitor and a synthetic analogue of MT in patients with hypertension and insomnia was accompanied by an improvement in the clinical state, achievement of the target blood pressure level in most patients, positive dynamics of central blood pressure parameters and indicators reflecting the rigidity of peripheral arteries.

Association of Underlying Comorbidities and progression of COVID-19 Infection Among 2586 Patients Hospitalized in the National Capital Region of India: A Retrospective Cohort Study

Objectives This study is conducted to observe the association of diabetes (DM), hypertension (HTN), and chronic kidney disease on the prognosis and mortality of COVID-19 infection in hospital admitted patients.Methods This is a single centre, observational, retrospective study carried out at Sir Ganga Ram Hospital, Delhi, India. the burden of comorbidities on the prognosis and clinical outcome of COVID-19 patients admitted patients from April 8, 2020, to October 4, 2020. Chi-square and relative risk test were used to observe the association of comorbidities and disease prognosis.Results A total of 2586 patients were included in the study consisting of 69.6% of male patients. All the comorbidities were significantly associated with ICU admission and mortality. The relative risk showed that CKD is most prone to severity as well as mortality of the COVID-19 infection followed by HTN and DM. Further with the increase in comorbidity, the risk of ICU admission and mortality increases.Conclusion Diabetes, hypertension and CKD, all are associated with progression of COVID-19 disease to severity and higher mortality risk. The number of underlying comorbid condition is directly proportional to the progression of disease severity and mortality.

Study of the effect of high blood pressure on the kidney in Children with COVID-19 (Preprint)

UNSTRUCTURED Hypertension is considered as a comorbid condition for the novel coronavirus 2019 (COVID-19). However, there are no reports of “Hypertension crisis” as a presentation or comorbidity of the COVID-19 infection in pediatric patients. In this retrospective observational study, we collected data from total six pediatric patients, diagnosed with confirmed COVID-19 positive who had presented with acute severe hypertension. The mean age of patients was 4.2 years. Four cases were with newly diagnosed nephrotic syndrome and two with chronic kidney disease who were on regular dialysis with no edema or sign of fluid overload, were enrolled. The lowest and highest systolic blood pressures at the time of admission were 160 mmHg and 200 mmHg, respectively. The diastolic blood pressures were between 100-155 mmHg. All patients treated with Labetalol infusion titrated to maximum dosage and continued for at least one week. Our reported children had resistant hypertension and their blood pressure had been controlled with four or five antihypertensive medications. It is crucial to consider the diagnosis of COVID-19 in a patient presenting with a hypertension crisis, even in the absence of classic signs of the virus. Thus from our study we strongly recommend the medical practitioners to consider the probability of COVID-19 infection in cases presenting to the hospital with acute severe hypertension.

Persistent Symptoms Among Frontline Health Workers Post-acute COVID-19 Infection

BackgroundGrowing evidence shows that a significant number of patients with COVID-19 experience prolonged/persistent symptoms, also known as Long COVID. Reports of Long COVID are rising but little is known about prevalence in non-hospitalized patients.ObjectiveWe sought to identify the persistent symptoms of COVID-19 in frontline workers at Right to Care (RTC) South Africa who have past the acute phase of illness with a view to establishing rehabilitation programs for its employees and the community at large.MethodsThis was a cross-sectional survey. We analysed data from 207 eligible COVID-19 positive RTC frontline workers who participated in a post-COVID online self-administered survey. The survey was active for two months. Frequencies and median were calculated for categorical and continuous variables, respectively.ResultsThe survey response rate was 30% (62 out of 207); of the 62 respondents with a median age of 33.5 years (IQR= 30–44 years), 47 (76%) were females. The majority (n=55; 88.7%) self-isolated and 7 (11.3%) were admitted to hospital at time of diagnosis. The most common comorbid condition reported was hypertension particularly among workers aged 45–55 years. Headache, body ache, fatigue, loss of smell, dry cough, fever, and loss of appetite were the most common reported symptoms at time of diagnosis. Persistent symptoms were characterized by fatigue, anxiety, difficulty sleeping, chest pain, muscle pain and brain fog, being the six most reported.ConclusionThe impact of persistent/Long COVID-19 on the health of frontline workers could have direct impact in health service delivery. Given the rise in cases of COVID-19 in South Africa and the world at large, the prevalence of Long COVID is likely to be substantial and therefore need for rehabilitation programs targeted at each of the persistent (Long) COVID symptoms is critical.

Global Unbiased Determination Of Comorbidity (GUDC) In U.S. Older Adults

With age, many adults develop multiple comorbid conditions; and resulting clinical complexity increases markedly so that identifying how specific conditions effect others remains important. Here, our primary objective was rapid unbiased appraisal of pair-wise condition-specific comorbidity; our second objective was identification of common conditions with highest and lowest rates of such comorbidity. In 2016, utilization of ICD-10 codes became mandatory for providers rendering care to Medicare beneficiaries. Universal adoption of ICD-10 coding ensued and concomitantly, all patients had ICD-9 codes replaced with new codes, so that 2017 data represent an opportunity to examine massive amounts of ‘freshly’ coded patient claims data. Evaluating ICD-10 coding data at individual and population levels, we appraised how often two codes were utilized together, i.e. estimated pair-specific comorbidity. Expanding this computationally, we determined the extent to which any given condition was co-coded with all other utilized diagnostic codes, i.e., estimated global, unbiased pair-wise comorbidity. We term this metric the global unbiased dyadic comorbidity (GUDC) value. Based on 40 million claims for a representative sample of 1.5 million older adults across the U.S., GUDC values varied with age and gender but were highly stable across varying comorbid condition prevalence, e.g., common (>1%) vs. less common (1/1000-1/100) prevalence. GUDC values for HIV in older adults were modest, compared to high values for ARDS, we infer substantive progress in HIV management among older adults. We discuss the interpretation and potential applications of GUDC and conclude that access to comorbidity appraisals may advance geriatric care, more study is needed.

Mortality among people hospitalised with covid-19 in Switzerland: a nationwide population-based analysis

Objectives: To investigate mortality among people hospitalised with covid-19 in Switzerland according to epidemic wave, age, sex, comorbid conditions and intensive care unit (ICU) occupancy. Design: Population-based, national study.Setting: Mandatory surveillance reports from all hospitals in Switzerland. Participants: All 22,648 people who tested positive for SARS-CoV-2 infection and were hospitalised between February 24, 2020 and March 01, 2021 in Switzerland with complete information about age, sex, and comorbidities. Main outcome measures: Survival after positive SARS-CoV-2 test among people hospitalised with covid-19 by epidemic wave, age, sex, comorbid conditions and ICU occupancy, expressed as adjusted hazard ratios (aHR) of death and probability of survival over time and at 40 days, all with 95% credible intervals (CrI). Results: Of 22,648 people hospitalised with covid-19, 4,785 (21.1%) died. Bayesian survival models adjusted for age, sex, and the presence of comorbidity showed that survival was lower during the first epidemic wave than the second (standardised predicted survival probability at 40 days 76.1% versus 80.5%; aHR of death 1.38, 95% CrI 1.28 to 1.48). During the second epidemic wave, occupancy among all available ICU beds (certified beds and add-on beds) in Switzerland varied between 51.7% and 78.8%. Modelling the association between survival and ICU occupancy with restricted cubic splines indicated stable survival when ICU occupancy was below 70%, but worse survival when ICU occupancy exceeded 70%. This threshold of 70% occupancy among total available ICU beds corresponded to around 85% occupancy among certified beds. Survival was decreased for men, older people, and patients with comorbid conditions. Comorbid conditions reduced survival more in younger people than in older people. As single comorbid condition, hypertension was not associated with poorer survival, but appeared to increase the risk of death in combination with a cardiovascular disease. Conclusion: Survival after hospitalisation with covid-19 has improved over time, consistent with improved management of severe covid-19. The decreased survival starting at approximately 70% ICU occupancy in Switzerland supports the need to introduce measures for prevention and control of SARS-CoV-2 transmission in the population far before ICUs are full.

The implications of hyperoxia, type 1 diabetes and sex on cardiovascular physiology in mice

Oxygen supplementation, although a cornerstone of emergency and cardiovascular medicine, often results in hyperoxia, a condition characterized by excessive tissue oxygen which results in adverse cardiac remodeling and subsequent injurious effects to physiological function. Cardiac remodeling is further influenced by various risk factors, including pre-existing conditions and sex. Thus, the purpose of this experiment was to investigate cardiac remodeling in Type I Diabetic (Akita) mice subjected to hyperoxic treatment. Overall, we demonstrated that Akita mice experience distinct challenges from wild type (WT) mice. Specifically, Akita males at both normoxia and hyperoxia showed significant decreases in body and heart weights, prolonged PR, QRS, and QTc intervals, and reduced %EF and %FS at normoxia compared to WT controls. Moreover, Akita males largely resemble female mice (both WT and Akita) with regards to the parameters studied. Finally, statistical analysis revealed hyperoxia to have the greatest influence on cardiac pathophysiology, followed by sex, and finally genotype. Taken together, our data suggest that Type I diabetic patients may have distinct cardiac pathophysiology under hyperoxia compared to uncomplicated patients, with males being at high risk. These findings can be used to enhance provision of care in ICU patients with Type I diabetes as a comorbid condition.