Initial Stages Of Illness Research Articles

Core warming of coronavirus disease 2019 (COVID-19) patients undergoing mechanical ventilation-A protocol for a randomized controlled pilot study.

Coronavirus disease 2019 (COVID-19), caused by the virus SARS-CoV-2, is spreading rapidly across the globe, with little proven effective therapy. Fever is seen in most cases of COVID-19, at least at the initial stages of illness. Although fever is typically treated (with antipyretics or directly with ice or other mechanical means), increasing data suggest that fever is a protective adaptive response that facilitates recovery from infectious illness. To describe a randomized controlled pilot study of core warming patients with COVID-19 undergoing mechanical ventilation. This prospective single-site randomized controlled pilot study will enroll 20 patients undergoing mechanical ventilation for respiratory failure due to COVID-19. Patients will be randomized 1:1 to standard-of-care or to receive core warming via an esophageal heat exchanger commonly utilized in critical care and surgical patients. The primary outcome is patient viral load measured by lower respiratory tract sample. Secondary outcomes include severity of acute respiratory distress syndrome (as measured by PaO2/FiO2 ratio) 24, 48, and 72 hours after initiation of treatment, hospital and intensive care unit length of stay, duration of mechanical ventilation, and 30-day mortality. Resulting data will provide effect size estimates to guide a definitive multi-center randomized clinical trial. ClinicalTrials.gov registration number: NCT04426344. With growing data to support clinical benefits of elevated temperature in infectious illness, this study will provide data to guide further understanding of the role of active temperature management in COVID-19 treatment and provide effect size estimates to power larger studies.

COVID-19: unravelling the clinical progression of nature's virtually perfect biological weapon.

Coronavirus disease 2019 (COVID-19) pandemic has shocked the world and caused morbidity and mortality on an unprecedented level in the era of modern medicine. Evidence generated to-date on the virulence and pathogenicity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) suggests that COVID-19 may be considered a perfect storm, caused by a nature’s virtually perfect biological weapon. This conclusion is supported by an updated analysis of pathogenesis and clinical progression of this infectious disease. It is now readily apparent that COVID-19 is not a clear-cut disorder, but is instead a gradually evolving pathology, characterized by a series of stages sustained by different molecular and biological mechanisms. The disease can hence be divided in at least five different phases (incubation, respiratory, pro-inflammatory, pro-thrombotic, and death or remission). Whilst the virus triggers direct cytopathic injury during the initial stage of illness, in the following evolving phases, it is the host itself that undergoes an almost suicidal reaction, sustained, amplified and maintained by the immune, complement and hemostatic systems. Another peculiar property making SARS-CoV-2 a devious and vicious pathogen is the biophysical structure of its receptor biding domain, which needs to be primed by human proteases, thus being less efficiently targetable by the host immune system. The unique pathophysiology of COVID-19 requires the customization of therapy by individual patient characteristics and according to the phase-specific, evolving derangement of the multiple biological pathways.

Dynamics of Activity in the Anterior Cingulate Cortex on Development of Obsessive-Compulsive Disorder: a Combined PET and FMRI Study

Impairment of the cerebral error detection mechanism is believed to be one of the causes of obsessive-compulsive disorder (OCD) and the anterior cingulate cortex (ACC) is the key element supporting this mechanism. However, neuroimaging data on the functional activity of the ACC in patients with OCD in the state of operational rest* and during activity are extremely diverse. An earlier explanation of this fact was the hypothesis that changes in ACC activity depend on the nature of the OCD present. With the aim of testing this hypothesis experimentally, the present studies performed combined PET-fMRI studies of the functional activity of the ACC in patients with OCD in the state of operational rest and on performance of activity presumptively involving the error detection mechanism. This activity was modeled using a Go/NoGo test with two tasks with different levels of difficulty. The ACC in patients in the state of operational rest showed glucose hypermetabolism, which decreased with increases in disease duration. The functional activity of the ACC during performance of actions was decreased in patients with OCD as compared with a group of healthy subjects. In addition, ACC activity on performance of the simpler task was found to increase with the course of illness; conversely, performance of the more difficult task decreased activity. Thus, the data obtained here support the hypothesis. Glucose hypermetabolism in the state of operational rest at the initial stages of illness was replaced by hypometabolism, probably because the ACC stopped carrying out its normal functions, which were compensated for by redistribution of the function among other relatively intact structures. This may lead to distortion of the functional specialization of the ACC, where the functional activity of the ACC in conditions of enhanced cognitive load decreased with increases in the duration of illness, while activity increased in conditions of relatively simple cognitive loading.

Implications of hepatic dysfunction in Kawasaki disease: Time-related changes in aspartate aminotransferase, alanine aminotransferase, total bilirubin, and C-reactive protein levels.

ImportanceThe cause of the hepatic dysfunction that commonly accompanies Kawasaki disease (KD) remains unclear.ObjectiveWe tried to clarify the cause of the hepatic dysfunction.MethodsA total of 381 consecutive patients with acute KD, who had undergone inpatient treatment with intravenous immunoglobulin until the 7th day of illness, were divided into a group of 199 patients with an alanine aminotransferase (ALT) level ≥ 40 IU/L on admission (group I), a group of 52 patients with an ALT level ≥ 40 IU/L at some point after admission (group II), and a group of 130 patients with ALT levels consistently < 40 IU/L throughout hospitalization (group III). Aspartate aminotransferase (AST), ALT, total bilirubin (T‐Bil), and C‐reactive protein (CRP) levels were analyzed over time, and time‐courses were compared.ResultsIn the initial stage of illness, in group I, AST, ALT, T‐Bil peaked on days 1–3, and AST tended to improve significantly on the 4th day (P < 0.001). T‐Bil improved on day 5 (P < 0.01), and ALT improved significantly on day 6 (P < 0.001). CRP increased every day up to day 6 (P < 0.001). In group II, AST and ALT increased after admission, and thereafter CRP increased, then decreased. The frequency of use of aspirin and aspirin doses did not differ significantly in the three groups.InterpretationRecovery from liver dysfunction occurred in the initial stage of illness in group I—within the period of CRP exacerbation, which is an indicator of systemic inflammation.

Structural brain changes in schizophrenia at different stages of the illness: A selective review of longitudinal magnetic resonance imaging studies.

Schizophrenia is a devastating mental disorder accompanied by aberrant structural brain connectivity. The question whether schizophrenia is a progressive brain disorder is yet to be resolved. Thus, it is not clear when these structural alterations occur and how they develop over time. In our selective review, we summarized recent findings from longitudinal magnetic resonance imaging studies investigating structural brain alterations and its impact on clinical outcome at different stages of the illness: (1) subjects at ultra-high risk of developing psychosis, (2) patients with a first episode psychosis, and (3) chronically ill patients. Moreover, we reviewed studies examining the longitudinal effects of medication on brain structure in patients with schizophrenia. (1) Studies from pre-clinical stages to conversion showed a more pronounced cortical gray matter loss (i.e. superior temporal and inferior frontal regions) in those individuals who later made transition to psychosis. (2) Studies investigating patients with a first episode psychosis revealed a decline in multiple gray matter regions (i.e. frontal regions and thalamus) over time as well as progressive cortical thinning in the superior and inferior frontal cortex. (3) Studies focusing on patients with chronic schizophrenia showed that gray matter decreased to a greater extent (i.e. frontal and temporal areas, thalamus, and cingulate cortices)-especially in poor-outcome patients. Very few studies reported effects on white matter microstructure in the longitudinal course of the illness. There is adequate evidence to suggest that schizophrenia is associated with progressive gray matter abnormalities particularly during the initial stages of illness. However, causal relationships between structural changes and illness course-especially in chronically ill patients-should be interpreted with caution. Findings might be confounded by longer periods of treatment and higher doses of antipsychotics or epiphenomena related to the illness.

'They prefer hidden treatment': anti-tuberculosis drug-taking practices and drug regulation in Karakalpakstan.

The joint Médecins Sans Frontières/Ministry of Health Multidrug-Resistant Tuberculosis (MDR-TB) Programme, Karakalpakstan, Uzbekistan. Uzbekistan has high rates of MDR-TB. We aimed to understand patients' and prescribers' attitudes to anti-tuberculosis drug prescription, regulation and drug-taking behaviour. Participants (12 patients, 12 practitioners) were recruited purposively. Data were gathered qualitatively using field notes and in-depth interviews and analysed thematically. Our analysis highlighted two main themes. First, shame and stigma were reported to increase the likelihood of self-treatment and incorrect use of anti-tuberculosis drugs, most commonly at the initial stages of illness. A health system failure to promote health information was perceived, leading to wrong diagnoses and inappropriate therapies. Motivated by shame, patients hid their condition by resorting to drug treatment options outside the programme, compounding the risk of chaotic management and dissemination of erroneous information through lay networks. Second, positive influences on treatment were reported through patients, practitioners and peers working effectively together to deliver the correct information and support, which acted to normalise TB, reduce stigma and prevent misuse of anti-tuberculosis drugs. Effective case finding, patient support and community education strategies are essential. Patients, practitioners and peers working together can help reduce stigma and prevent misuse of anti-tuberculosis drugs.

Effect of dengue fever on serum aminotransferases in children

Background: Dengue infection is associated with liver dysfunction, which tends to become severe with severe dengue. In the acute phase of the disease, an increase occurs in aminotransferases, the levels of which subsequently decrease as the liver function recovers. Significant rise of liver enzymes helps in recognition of severe forms of dengue infection.Methods: The study was conducted in the Department of Pediatrics of Vydehi Institute of Medical Sciences and Research Center, Bangalore from January 2015 to June 2015. 50 patients of 1-14 years age group, who presented with fever of recent duration and serologically positive for dengue, were included in the study.Results: 38% (19) were females and 62% (31) were males. NS1 was positive in 48% (24) and IgM was positive in 52% (26) of patients. IgG was negative in all the patients. AST was raised in 36% (18) of patients, ALT was raised in 34% (17) patients and ALP raised in 42% (21) patients. AST (Mean ± SD 53.84±43.32) was raised more than ALT (Mean ± SD 48.76±41.11)Conclusions: Liver enzymes were mildly elevated in patients with dengue fever in the initial stage of illness. AST was elevated more than ALT.

Peripancreatic cystic lymphangioma with secondary hemorrhage: A rare case report

Lymphangiomas are thought to be true neoplasms, hamartomas or lymphangiectasias. Intra-abdominal lymphangiomas are rare and occur most frequently in children. This is a case report of a 27-year-old female with recurrent episodes of the left-sided upper abdominal pain of 2 years duration. She gives a history of intermittent nausea and vomiting. Liver function test and complete blood count with differential were normal. During the initial stages of illness, the serum lipase was elevated; the serum amylase level was normal all through the entire period. The upper gastrointestinal endoscopy suggested hiatal hernia and mild duodenitis. Two computed tomography scans done at 5 months interval showed a hypodense lesion in the distal tail of pancreas with irregular margins. The size of lesions had decreased from 15 mm × 14 mm to 13.5 mm × 10 mm during this period. Endoscopic ultrasound showed ill-defined area in the distal tail of pancreas and pseudocyst was suspected. Magnetic resonance cholangiopancreatography after 2 months showed a cystic lesion in the tail of pancreas of size 11 mm × 10 mm. Due to increasing severity of pain and fainting spells, the patient was taken up for a distal pancreatectomy. The histopathologic examination confirmed a diagnosis of peripancreatic cystic lymphangioma with secondary hemorrhage. During the postoperative period, the drain amylase was high suggestive of grade A pancreatic fistula. Gradually, the levels decreased, the patient became stable and discharged after pneumococcal vaccination.

Co-circulation of dengue virus serotypes with chikungunya virus in Madhya Pradesh, central India.

Dengue and chikungunya present with very similar signs and symptoms in the initial stage of illness and so it is difficult to distinguish them clinically. Both are transmitted by Aedes aegypti and Aedes albopictus mosquitoes. This study was conducted with the aim to explore the co-circulation of dengue and chikungunya viruses in central India. Samples from suspected dengue cases were subjected to dengue immunoglobulin M (lgM) enzyme-linked immunosorbent assay (ELISA) and dengue-negative samples were tested with chikungunya-specific IgM ELISA. The samples collected in acute phase of illness were tested by nested reverse transcription polymerase chain reaction (nRT-PCR). Chikungunya virus (CHIKV) sequences were analysed to determine their genotype. Of 138 samples screened for dengue, 21 (15.2%) were positive, and of 119samples screened for chikungunya, 13 (10.9%) were positive. Dengue viruses 1 and 4 were found co-circulating with chikungunya virus in Jabalpur, central India. The chikungunya virus detected belonged to the East Central South African genotype. Accurate and timely diagnosis would help in patient management and use of resources. It is advocated to simultaneously test samples for these two diseases in endemic areas. This will also aid in understanding the epidemiology of chikungunya.

Significant impairment of health-related quality of life in mainland Chinese patients with chronic hepatitis B: a cross-sectional survey with pair-matched healthy controls.

ObjectiveFew studies have evaluated health-related quality of life (HRQoL) of patients with chronic hepatitis B (CHB) in mainland China. We aimed at characterizing the impact of CHB on HRQoL in mainland Chinese and finding out factors associated with HRQoL.Methods460 CHB patients (323 with CHB only, 54 with compensated cirrhosis and 83 with decompensated cirrhosis) and 460 pair-matched healthy controls were recruited in Xi’an city. They answered a structured questionnaire including the Short Form 36 version 2 (SF-36v2), the Chronic Liver Disease Questionnaire (CLDQ) (only for patients), and questions on socio-demographic and clinical characteristics. A blood sample was collected from each of patients for liver function tests. SF-36v2 scores were compared between patients and controls overall and by groups by paired-samples t-test, and CLDQ scores and paired differences of SF-36v2 scores were compared among three patient groups by one-way ANOVA or Kruskal-Wallis test. Multi-variable linear regression analyses were performed to identify determinants of HRQoL in patients.ResultsPatients, overall and by groups had significantly lower SF-36v2 scores than controls on all summaries and domains, with differences higher than the suggested minimally important difference values. Both the SF-36v2 and the CLDQ showed that HRQoL of patients with cirrhosis further deteriorated, but compensated and decompensated cirrhosis patients had similar total HRQoL impairments. The gradually increasing impairment with disease progression was confirmed only on physical components. Impaired liver function and currently taken anti-viral treatment were associated with lower HRQoL. Education attainment and annual per capita household income had a positive effect on HRQoL.ConclusionsMainland Chinese CHB patients suffered significant HRQoL impairment on all health dimensions, and the impairment reached a high level on mental health at initial stage of illness and increased gradually on physical health with disease progression. Attention should be paid to the reduction of patients’ treatment cost burden and the provision of early health education accompanied with proper treatments.

Crimean-Congo hemorrhagic fever in a dengue-endemic region: lessons for the future

Crimean-Congo hemorrhagic fever and dengue hemorrhagic fever are endemic in Pakistan. However, the overlap of geographic distribution and early clinical features between the two conditions make a reliable diagnosis difficult in the initial stage of illness. A 16-year-old boy presented with a history of hematemesis and high-grade fever. A preliminary diagnosis of dengue hemorrhagic fever was made and supportive treatment was instituted; however, the patient continued to deteriorate clinically. Dengue IgM antibody testing was negative on the third day of admission. Qualitative polymerase chain reaction test for Crimean-Congo hemorrhagic fever viral RNA was sent but the patient expired shortly after the results became available on the sixth day of admission. Considerable resources had to be expended on contact tracing and administration of ribavirin prophylaxis to all the health-care workers who had come in contact with the patient. It is crucial that Crimean-Congo hemorrhagic fever be recognized and treated at an early stage because of longer term financial and health implications for contacts such as health-care workers in the setting of a developing country. Increased surveillance of dengue and Crimean-Congo hemorrhagic fever cases is warranted for the derivation of reasonably reliable, cost-effective and prompt predictors of disease diagnosis. These predictors can help guide future decisions in the management of similar cases. Ultimately, such a strategy may translate into better cost containment in resource-poor settings. Institution of ribavirin prophylaxis in selected patients also merits consideration.

Vasectomy in Men With Primary Progressive Aphasia

To study the frequency of vasectomy in men with primary progressive aphasia (PPA). PPA is a dementia syndrome in which aphasia emerges in relative isolation during the initial stages of illness. On the basis of a clinical observation in a patient who dated the onset of symptoms to the period after a vasectomy, and because of the curious sharing of the tau protein exclusively by brain and sperm, vasectomy rates were examined in men with PPA. This study used a case control design. Forty-seven men with PPA and 57 men with no cognitive impairment (NC) between 55 and 80 years of age were surveyed about a history of vasectomy. The age-adjusted rate of vasectomy in PPA patients (40%) was higher than in NC (16%, P=0.02). There was a younger age at onset for the patients with vasectomy (58.8 vs. 62.9 y, P=0.03). Vasectomy may constitute one risk factor for PPA in men. Potential mechanisms mediating risk include vasectomy-induced immune responses to sperm, which shares antigenic epitopes with brain. Antisperm antibodies can also develop in women and become risk factors for PPA.

Strategy to mitigate As exposure from drinking water

One of the worst health hazards in Bangladesh is arsenic contamination of drinking water, which demands immediate and urgent remedial measures. The common strategy to control environmental health problems is to erect interventions at three levels: control at source, avoid ingestion and provide heath care The source of arsenic contamination is absolutely geological and almost any method can be applied to control it at source. There is little proven treatment for acute arsenic toxicity, but drinking water free of arsenic can aid the affected people at their initial stage of illness to get rid of the symptoms of arsenic toxicity. Hence, provision of safe drinking water is the foremost element of the arsenic mitigation plan. Identification of affected people and the population at risk of toxicity from arsenic, establishment of a standard value for the presence of arsenic in drinking water, provision of medical and health care and establishment of appropriate research work and study programmes are important elements of the plan. Finally, international, interdisciplinary and inter-organizational co-operation and collaboration have been highly emphasized in the mitigation plan.

Oxidative injury and antioxidant vitamins E and C in Schizophrenia

Susceptibility of Schizophrenic patients to lipid peroxidation relative to healthy control subjects was investigated by measuring the malondialdehyde (MDA) levels in plasma. The main finding was that Schizophrenic patients were more susceptible than control subjects to oxidative damage as evident from increased MDA levels in plasma. Antioxidant levels are also depleted in Schizophrenic patients when compared to normal subjects as evident from decreased levels of vitamins E and C in the plasma. Impaired antioxidant defense and increased lipid peroxidation suggests that treatment with antioxidants (Vitamin E, Vitamin C, beta carotene) at the initial stages of illness may prevent further oxidative injury and deterioration of associated neurological deficits in Schizophrenia.

Oxidative injury and potential use of antioxidants in schizophrenia

There is increasing evidence that oxidative injury contributes to pathophysiology of schizophrenia, indicated by the increased lipid peroxidation products in plasma and CSF, and altered levels of both enzymatic and non-enzymatic antioxidants in chronic and drug-naive first-episode schizophrenic patients. The increased plasma lipid peroxidation is also supported by concomitant lower levels of esterified polyunsaturated essential fatty acids of red blood cell plasma membrane phospholipids. Because membrane phospholipids play a critical role in neuronal signal transduction, oxidative damage of these lipids may contribute to the proposed altered neurotransmitter receptor-mediated signal transduction and thereby alter information processing in schizophrenia. Adjunctive treatment with antioxidants (e.g. vitamins E and C, β-carotene and quinones) at the initial stages of illness may prevent further oxidative injury and thereby ameliorate and prevent further possible deterioration of associated neurological and behavioral deficits in schizophrenia.

The carcinomatous neuromyopathy of oat cell lung cancer.

A prospective controlled clinical-neurophysiological-pathological study of 71 patients with oat cell carcinoma of the lung revealed no increased incidence of peripheral neuropathy at the initial stages of illness. All patients developed neuropathy by the time they had lost 15% of their body weight, but the neuropathy was less severe than in 20 age-matched alcoholic patients with an equal degree of weight loss. The weight loss and peripheral neuropathy progressed with atrophy of type II (adenosine triphosphatase-positive) muscle fibers out of proportion to the patient's loss of body weight. By 40% body weight loss, all the patients had moderate symmetrical peripheral neuropathy, 6 had proximal brachial or lumbosacral plexus metastases, and 9 had distal pressure palsies. Mononeuritis multiplex developed in only 1 patient, who had diabetes mellitus. Two patients developed Eaton-Lambert syndrome, which resolved in 1 when chemotherapy controlled the systemic tumor, with no protein in the tumor postmortem which could produce the characteristic electromyographic findings of the syndrome.

A criteria for clinical evaluation of antibiotics on symptoms of bacillary dysentery. II. Severity of course (author's transl)

In the concept “Severity” of Bacillary Dysentery, evaluation of the length of the course is included.It is useful to express the length of the course by a numerical score not only to evaluate the severity of disease but also to take an objective view of antibiotic effect.Now, a score of 13.4 is assigned to the occurrence of fever in the overall clinical course (Table 1), which is influenced by the degree of fever in the initial stage of illness (Table 3). Similarly, to the days required for normalization of frequency of diarrhea a score of 22.9 is assigned, while 56.7 score is assigned to the days for disappearance of pathological products. In other words, if the total marks for the course of dysentery are 100, the significance of the course of each symptom is shared as the marks shown above. The marks of pathological products are divided into 24.7 for mucus, 18.2 for blood, and 13.8 for pus, respectively, and on calculating the total, the score corresponding to the days required for each disappearance must be added.In such a way, relative importance of each component of illness is summarized in Table 5 as the score with regard to the initial severity.Applying these marks to each case and getting the total score for the clinical course, the severity of the clinical course of Flexner dysentery in the 1930's and in the 1970's was compared. The result was that the cases with severe illness markedly decreased in these days, especially in male children. Classified by symptoms, the latter has become less severe in decreasing order of Fever, Diarrhea and Pathological products respectively.Next, the course between Flexner and Sonne Dysentery in the 1970's was compared. The result was that Sonne was plainly mild and the differentiation was marked, on being classified by symptoms, in order of Pathological products, Diarrhea and Fever.

National Hygienic and Economic Conditions

tions of a nation are closely and doubly related. On the one hand, health constitutes the greatest wealth. Only that nation can progress economically whose individual members can take an active part in universal competition free from disease and illness. On the other hand, experience teaches us that ere long economic calamity infalliby tends to undermine physical powers of resistance and to impair health. Want and sickness are twin sisters. Now sickness opens the door of the house and allows want to enter. Again, it is want which advances, with sickness in its retinue. Thus it is in the life of individuals and none the less, as history shows us, in the life of nations. The present condition in Germany gives new evidence of this close inter-relation of national hygienic and economic conditions. Conversely, to be sure, the development during the last few decades before the war likewise proves this assertion. The struggle against diseases, which unnaturally end the life of man prematurely, has been conducted in Germany with greatest tenacity and with good results. In the years from 1871 to 1880 for every one thousand population the death rate was 27.1; at the close of the century, it was only about 20; in the year 1913, only 15; therefore continued decrease in mortality figures and continued increase in the average longevity are clearly shown. To bring about this result, the constant sanitary development of the whole country is necessary. To this we owe our increased knowledge of the causes of diseases and of the means of combating them. Of great importance in this connection is the 'development of our social statutes, especially those pertaining to the insurance against disease. Particularly in the years 1886 to 1900 the improvement of the conditions of living in Germany may be traced to a decrease in mortality among those in the age of greatest productiveness. The law on sickness insurance prevents hardship resulting from sickness. Every patient is assuredc of a physician, treatment in a ospital and the most necessary means for his subsistence as well as for the subsistence of his family. Consequently, the possibility of convalescence and the return of earning capacity increase. Since the entire nation has to provide the means which accrue to the benefit of the individual in the case of illness, so the entire nation is also most vitally interested in seeing that as few human beings as possible are sick, and that the patients shall be restored to health as soon as possible and their earning capacity renewed. The greater the number of healthy people who are able to work, the more canbe accomplished economically. Every day a workman is ill increases the cost of the product and harms competitive ability. If, therefore, it is to the greatest interest of the entire nation to prevent sickness in general or to do everything possible in the initial stages of illness to decrease its duration or to bring about a final cure without danger of