Current understanding of an Emerging Coronavirus using in silico approach: Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2)

Abstract Novel coronavirus (nCoV) namely SARS-CoV-2 is being found responsible for current PANDEMIC commenced from Wuhan (China) since December 2019 and has been described with epidemiological linkage to China in about 221 countries and territories until now. In this study we have characterized the genetic lineage of SARS-CoV-2 and report the recombination within the genus and subgenus of coronaviruses. Phylogenetic relationship of thirty nine coronaviruses belonging to its four genera and five subgenera was analyzed by using the Neighbor-joining method using MEGA 6.0. Phylogenetic trees of full length genome, various proteins (spike, envelope, membrane and nucleocapsid) nucleotide sequences were constructed separately. Putative recombination was probed via RDP4. Our analysis describes that the SARS-CoV-2 although shows great similarity to Bat-SARS-CoVs sequences through whole genome (giving sequence similarity 89%), exhibits conflicting grouping with the Bat-SARS-like coronavirus sequences (MG772933 and MG772934). Furthermore, seven recombination events were observed in SARS-CoV-2 (NC_045512) by RDP4. But not a single recombination event fulfills the high level of certainty. Recombination mostly housed in spike protein genes than rest of the genome indicating breakpoint cluster arises beyond the 95% and 99% breakpoint density intervals. Genetic similarity levels observed among SARS-CoV-2 and Bat-SARS-CoVs advocated that the latter did not exhibit the specific variant that cause outbreak in humans, proposing a suggestion that SARS-CoV-2 has originated possibly from bats. These genomic features and their probable association with virus characteristics along with virulence in humans require further consideration.

Resumo O novo coronavírus (nCoV), nomeadamente SARS-CoV-2, foi considerado responsável pela pandemia atual iniciada em Wuhan (China) desde dezembro de 2019 e foi descrito com ligação epidemiológica à China em cerca de 221 países e territórios até agora. Neste estudo, caracterizamos a linhagem genética do SARS-CoV-2 e relatamos a recombinação dentro do gênero e subgênero dos coronavírus. A relação filogenética de 39 coronavírus pertencentes a seus quatro gêneros e cinco subgêneros foi analisada usando o método de Neighbour-joining usando MEGA 6.0. Árvores filogenéticas do genoma de comprimento total, várias proteínas (espícula, envelope, membrana e nucleocapsídeo), sequências de nucleotídeos foram construídas separadamente. A recombinação putativa foi testada via RDP4. Nossa análise descreve que o SARS-CoV-2, embora mostre grande semelhança com as sequências de Bat-SARS-CoVs em todo o genoma (dando semelhança de sequência de 89%), exibe agrupamento conflitante com as sequências de coronavírus do tipo Bat-SARS (MG772933 e MG772934) Além disso, sete eventos de recombinação foram observados em SARS-CoV-2 (NC045512) por RDP4. Mas nem um único evento de recombinação preenche o alto nível de certeza. A recombinação está alojada mais em genes de proteína de pico, principalmente, do que no resto do genoma, indicando que o cluster de ponto de interrupção surge além dos intervalos de densidade de ponto de interrupção de 95% e 99%. Os níveis de similaridade genética observados entre SARS-CoV-2 e Bat-SARS-CoVs defendem que o último não exibe a variante específica que causa surto em humanos, sugerindo que SARS-CoV-2 tenha se originado possivelmente de morcegos. Essas características genômicas e sua provável associação com as características do vírus, juntamente com a virulência em humanos, requerem uma consideração mais aprofundada.

Current understanding of an Emerging Coronavirus using in silico approach: Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2) / Compreensão atual de um coronavírus emergente usando abordagem in silico: síndrome respiratória aguda grave - coronavírus-2 (SARS-CoV-2)

Abstract Novel coronavirus (nCoV) namely "SARS-CoV-2" is being found responsible for current PANDEMIC commenced from Wuhan (China) since December 2019 and has been described with epidemiological linkage to China in about 221 countries and territories until now. In this study we have characterized the genetic lineage of SARS-CoV-2 and report the recombination within the genus and subgenus of coronaviruses. Phylogenetic relationship of thirty nine coronaviruses belonging to its four genera and five subgenera was analyzed by using the Neighbor-joining method using MEGA 6.0. Phylogenetic trees of full length genome, various proteins (spike, envelope, membrane and nucleocapsid) nucleotide sequences were constructed separately. Putative recombination was probed via RDP4. Our analysis describes that the "SARS-CoV-2" although shows great similarity to Bat-SARS-CoVs sequences through whole genome (giving sequence similarity 89%), exhibits conflicting grouping with the Bat-SARS-like coronavirus sequences (MG772933 and MG772934). Furthermore, seven recombination events were observed in SARS-CoV-2 (NC_045512) by RDP4. But not a single recombination event fulfills the high level of certainty. Recombination mostly housed in spike protein genes than rest of the genome indicating breakpoint cluster arises beyond the 95% and 99% breakpoint density intervals. Genetic similarity levels observed among "SARS-CoV-2" and Bat-SARS-CoVs advocated that the latter did not exhibit the specific variant that cause outbreak in humans, proposing a suggestion that "SARS-CoV-2" has originated possibly from bats. These genomic features and their probable association with virus characteristics along with virulence in humans require further consideration.

Resumo O novo coronavírus (nCoV), nomeadamente "SARS-CoV-2", foi considerado responsável pela pandemia atual iniciada em Wuhan (China) desde dezembro de 2019 e foi descrito com ligação epidemiológica à China em cerca de 221 países e territórios até agora. Neste estudo, caracterizamos a linhagem genética do SARS-CoV-2 e relatamos a recombinação dentro do gênero e subgênero dos coronavírus. A relação filogenética de 39 coronavírus pertencentes a seus quatro gêneros e cinco subgêneros foi analisada usando o método de Neighbour-joining usando MEGA 6.0. Árvores filogenéticas do genoma de comprimento total, várias proteínas (espícula, envelope, membrana e nucleocapsídeo), sequências de nucleotídeos foram construídas separadamente. A recombinação putativa foi testada via RDP4. Nossa análise descreve que o "SARS-CoV-2", embora mostre grande semelhança com as sequências de Bat-SARS-CoVs em todo o genoma (dando semelhança de sequência de 89%), exibe agrupamento conflitante com as sequências de coronavírus do tipo Bat-SARS (MG772933 e MG772934) Além disso, sete eventos de recombinação foram observados em SARS-CoV-2 (NC045512) por RDP4. Mas nem um único evento de recombinação preenche o alto nível de certeza. A recombinação está alojada mais em genes de proteína de pico, principalmente, do que no resto do genoma, indicando que o cluster de ponto de interrupção surge além dos intervalos de densidade de ponto de interrupção de 95% e 99%. Os níveis de similaridade genética observados entre "SARS-CoV-2" e Bat-SARS-CoVs defendem que o último não exibe a variante específica que causa surto em humanos, sugerindo que "SARS-CoV-2" tenha se originado possivelmente de morcegos. Essas características genômicas e sua provável associação com as características do vírus, juntamente com a virulência em humanos, requerem uma consideração mais aprofundada.

Current understanding of an Emerging Coronavirus using in silico approach: Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2).

Novel coronavirus (nCoV) namely "SARS-CoV-2" is being found responsible for current PANDEMIC commenced from Wuhan (China) since December 2019 and has been described with epidemiological linkage to China in about 221 countries and territories until now. In this study we have characterized the genetic lineage of SARS-CoV-2 and report the recombination within the genus and subgenus of coronaviruses. Phylogenetic relationship of thirty nine coronaviruses belonging to its four genera and five subgenera was analyzed by using the Neighbor-joining method using MEGA 6.0. Phylogenetic trees of full length genome, various proteins (spike, envelope, membrane and nucleocapsid) nucleotide sequences were constructed separately. Putative recombination was probed via RDP4. Our analysis describes that the "SARS-CoV-2" although shows great similarity to Bat-SARS-CoVs sequences through whole genome (giving sequence similarity 89%), exhibits conflicting grouping with the Bat-SARS-like coronavirus sequences (MG772933 and MG772934). Furthermore, seven recombination events were observed in SARS-CoV-2 (NC_045512) by RDP4. But not a single recombination event fulfills the high level of certainty. Recombination mostly housed in spike protein genes than rest of the genome indicating breakpoint cluster arises beyond the 95% and 99% breakpoint density intervals. Genetic similarity levels observed among "SARS-CoV-2" and Bat-SARS-CoVs advocated that the latter did not exhibit the specific variant that cause outbreak in humans, proposing a suggestion that "SARS-CoV-2" has originated possibly from bats. These genomic features and their probable association with virus characteristics along with virulence in humans require further consideration.

Efficacy of Itraconazole in the Prevention of Recurrence of Tinea Versicolor: A Three Year Follow Up.

Pityriasis versicolor (PV) also known as tinea versicolor, which is chronic and superficial fungal skin disease caused by Malassezia yeasts. A permanent cure may difficult to achieve and this may explain the long-term nature of the disease. Consequently, a preventive treatment regimen may help to prevent the recurrence of pityriasis versicolor. Whether, the recurrence of tinea versicolor could be prevented by monthly itraconazole treatment regimen after a short course of itraconazole therapy. Open treatment followed by a randomized, single blind placebo control trial. Multi-center trial was characterized by an open, active treatment phase with itraconazole followed by a randomized placebo controlled treatment for prevention of recurrence. A total 200 patients (150 male and 50 female) were included in this study and was given 200mg itraconazole daily for 7 days (treatment phase). Patients in whom tinea versicolor was mycologically cured divided into Group A and Group B. Active open treatment was followed by preventive itraconazole treatment 200mg twice daily in Group A and placebo in Group B monthly for 6 consecutive months. The patients were diagnosed clinically and confirmed by Wood's lamp examination and KOH microscopy. Clinical improvement in 90%, negative Wood's lamp examination in 86.5% and Mycological cure in 85.5% were found at the end of open treatment. The mycological cure, 171 subjects were taken into this study for preventive treatment phase and divided into two groups- Group A & Group B. Preventive treatment was given in Group A and placebo in Group B. After the preventive treatment, the end point (After 6 months), clinical improvement, negative Wood's lamp examination and mycological cure were found in 81(90%), 76(84.4%) and 75(83.3%) in Group A and 44(55%), 41(51.3%) and 42(52.5%) in Group B respectively. In preventive treatment phase, 1 patient in Group A did not complete the study. No patient experienced any serious adverse effects. Prevention of recurrence of Pityriasis versicolor with itraconazole is as effective as treatment.

Comorbidities in Patients with Psoriasis.

Psoriasis, a chronic inflammatory disease is associated with a long list of comorbidities. In our practice we like to draw attention in comorbidities of psoriatic arthritis and we are adapted with cardiovascular comorbidities. A great deal remains unknown about psoriasis associated comorbidities. An understanding of these comorbidity patterns can help us to ensure better care of patients with psoriasis. Objective of the study was to find out the comorbid conditions in the patients of psoriasis. This observational case control study was conducted 150 diagnosed cases of psoriasis and 150 age matched healthy control. Purposively 150 patients of psoriasis were selected from the Dermatology OPD of Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, Bangladesh from January 2017 to December 2018 as case. After a complete physical examination, a pre-designed structured questionnaire was fulfilled with patients and controls. To detect unknown comorbidities the following tests was done in both groups and compared: Blood sugar, urine routine and microscopic examination, serum creatinine, serum AST, ALT, GGT, and ALP levels measured by an enzymatic method, X-ray chest view, USG of whole abdomen/KUB. The diagnosed comorbidity was listed and referred for treatment accordingly. Charlson-age comorbidity index chart was used to estimate risk of mortality in two groups. The mean age of incident psoriasis was 38.64 years. Diabetes mellitus (4.67%), hypertension (4%), ischemic heart disease (IHD) (3.33%) were the top three comorbidities in patients with psoriasis. among them 11(7.33%) patients of psoriasis was with single comorbidity and 5(3.33%) of them was with multiple comorbidity. In control group 3(2%) participants was detected with comorbidity and that difference was significant statistically. In current study Charlson-Age Comorbidity index (CACI) was used as a tool to estimate the risk of mortality in two groups. The mean CACI score was 2.5 and 1 in two groups respectively and the difference was significant (p<0.05). The estimated risk of death (ERRD) score was calculated form CACI chart and the score was 2.78 and 1.47 in two groups respectively. There was no significant difference in two groups (p>0.05). The rate of occurrence of comorbidity was more in psoriasis group than in control. The listed comorbidity was in mild severity range but the risk of mortality was same in psoriasis group and control.

A Rare Case of Metachromatic Leukodystrophy Confirmed by Arylsulfatase A.

Metachromatic leukodystrophy (MLD) is the rare neurometabolic disease caused by the deficiency of a lysosomal enzyme arylsulfatase A (ARSA) activity. The absence or deficiency of arylsulfatase a leads to accumulation of cerebroside sulfate within the myelinseath of the central nervous system (CNS) and the peripheral nervous system (PNS). This in turn causes the CNS and PNS to progressively deteriorate leading to both features of upper and lower motor neuron dysfunctions. Metachromatic leukodystrophy gets its name from the way cells with an accumulation of salfatides appear when viewed under a microscope. The salfatides form granules that are described as metachromatic which means they pick up colour differently than surrounding cellular material when stained for examination. The clinical features of brain dysfunction like gait disturbance, speech, hearing and visual problems appear gradually, become progressive and fatal over time. Our patient a 5 years and 6 months old developmentally normal boy presenting walking difficulty since his 2 years and 6 months which was gradually increasing. During this period he also developed speech difficulty, seizure followed by unconsciousness and severe respiratory distress for ten days. His investigations were suggestive of metachromatic leukodystrophy. There is no specific treatment to cure the disease. So proper counseling was done regarding the bad prognosis of the disease with symptomatic treatment.

Effect of Spermine-NONOate on acrosome reaction and associated protein tyrosine phosphorylation in Murrah buffalo (Bubalus bubalis) spermatozoa.

The present study was conducted to know the role of Nitric Oxide (NO) on the acrosome reaction (AR) in Murrah buffalo (Bubalus bubalis) spermatozoa. Ejaculated buffalo spermatozoa were washed, suspended in sp-TALP media containing 6 mg BSA/mL and cell concentration was adjusted to 50×10(6) cells/mL. The cells were incubated for 6h in the absence or presence of heparin (10 µg/mL) to induce capacitation. Fully capacitated spermatozoa were incubated in presence of 100 µg/mL Lysophosphatidyl choline (LPC, T1) or 100 µM Spermine-NONOate (T2) or 100 mM L-NAME (T3) or 100 µM Spermine-NONOate+100 mM L-NAME (T4) or 1 mM db-cAMP + 0.1 mM IBMX (T5) or 100µM H-89 (T6) or 100 µM Spermine-NONOate+100 µM H-89 (T7) in combination to induce acrosome reaction. The extent of AR was assessed by dual-staining of spermatozoa with trypan blue/Giemsa stain. AR-associated tyrosine-phosphorylated proteins were detected by SDS-PAGE followed by immunoblotting using monoclonal anti-phosphotyrosine antibody. Significant (P<0.05) number of spermatozoa were acrosome reacted in Spermine-NONOate (T2) treated cells but it was significantly (P<0.05) lower than LPC (T1) induced AR. Addition of Spermine-NONOate + L-NAME (T4) resulted in non significant (P>0.05) decrease in acrosome reaction. On addition of H-89 + Spermine-NONOate (T7) to sperm culture medium, resulted in significant (P<0.05) decrease in the percent acrosome reaction. Conversely, addition of db-cAMP+IBMX (T5, cAMP analogue) resulted in the significantly (P<0.05) higher number of acrosome reacted spermatozoa. Pattern of sperm protein tyrosine phosphorylation was also different in NO induced acrosome reaction compared to that of LPC. The present study concluded that nitric oxide is involved in acrosome reaction of buffalo spermatozoa by causing the tyrosine phosphorylation of proteins mainly p17 and p20 and through activation of cAMP/PKA pathway.

Ondansetron versus granisetron in the prevention of chemotherapy induced nausea and vomiting in children with acute lymphoblastic leukemia.

Effect of ondansetron and granisetron were evaluated in sixty (60) children (age 4-11 years) irrespective of sex, diagnosed case of acute lymphoblastic leukemia (ALL) who received high dose methotrexate and did not receive any antiemetic 24 hours prior to HDMTX. This was a prospective, randomized, double-blind, single center study. Of 60 children, 30 received oral ondansetron (4mg) and rest 30 granisetron (1mg) half an hour before therapy. Drugs were randomly allocated with appropriate code. The patients were followed up from day 1 to day 5 of therapy. Episodes of nausea and vomiting were recorded and scorings was done every 24 hours following chemotherapy. No significant difference was found between two groups according to acute emesis (Day-1) (p=0.053). In day two and day three it was significant (p<0.05). In day four it was significant (p=0.002). Early chemotherapy induced nausea and vomiting (CINV) were controlled 90% in children who received granisetron and 70% in children who received ondansetron. Delayed (Day 2-4) CINV were controlled in 80% of children who received granisetron and 43.4% who received ondansetron (p<0.05). Granisetron group required additional doses only 3.3% cases and ondanseton group 30% cases on the second day (p<0.05). Result was significant between two groups. About 36.7% patients had episodes of nausea on day four of chemotherapy in ondansetron group and it was only 3.3% in granisetron group due to adverse effects of antiemetic drug itself (p=0.001). Maximum episodes of vomiting were found on the second day in ondansetron group 33.3% and in granisetron group 3.3% (p=0.003). Though adverse effects like headache, constipation, abdominal pain and loose motion were common in both group of children but their number was much less in children who received granisetron. On second day of therapy score of nausea and vomiting was maximum in ondansetron and minimum in granisetron treated on day 4 and the result was significant. So, to prevent acute and delayed CINV in children with ALL, oral graniseteron can be considered as more effective and well tolerated with minimum adverse effects compared with ondansetrons.

Back pain and vertebral compression: an unusual presentation of childhood acute lymphoblastic leukemia.

Junayet, a nine years and six months old boy was admitted to the hospital because of back pain and vertebral compression fractures. The boy had been well until two months earlier, when he began to have back pain after falling on his back along with occasional fever. The pain was intermittent initially but gradually it became constant. One month before admission, he fell again and the back pain became deteriorated. He was mildly pale, liver was palpable, skin survey revealed normal, BCG scar mark was present. He had bone pain, cervical lymphadenopathy and a tender swelling on the lumbusacral region. Two weeks before admission, the hematological findings were suggestive of leukemia of lymphoblastic type. Biochemical values were normal except high level of serum lactate dehydrogenase (LDH). Cerebrospinal fluid (CSF) examination was free of malignant cell. Skeletal survey showed diffuse osteopenia of the thoracic and lumber spine with multiple compression fracture of the vertebral bodies of D7, D8, D12 and L1, L3 and L5 with increased disc space. Radiograph of the chest also showed diffuse osteopenia of ribs. Magnetic resonance (MRI) showed uniform signal intensity in the marrow throughout the spine with compressed fracture of the same vertebrae. Bone marrow morphology study and the cytochemistry of the aspirated marrow were consistent with acute lymphoblastic leukemia (ALL-L2). Then, he was started protocol based chemotherapy for induction of remission, consolidation, high dose methotrexate and maintenance therapy. Now, he is on regular follow up with repeated hematological and radiological examinations. Following six month of chemotherapy the boy was found with significant improvement of his physical, hematological and radiological abnormalities.

PCR based rapid detection of Salmonella from poultry samples.

Salmonella is very important from the zoonotic point of view, as it causes many diseases in animals and humans. This study was conducted during September 2005 to February 2006 to develop rapid detection system for Salmonella from poultry samples. In the present study 300 poultry samples were screened for Salmonella. Earlier, isolation and identification of Salmonella from clinical samples by traditional cultural techniques required laborious procedures which can last upto 7 days, whereas amplification of DNA sequences unique to an organism using the PCR improves both the speed of detection and the level of sensitivity at which organisms can be detected and has been increasingly used to identify several bacterial species from food and clinical samples. In this study Salmonella were rapidly detected by targeting invA gene, giving PCR product of 284 bp size. Therefore this technique can be used for the screening of Salmonella in the routine testing.

Cost-effectiveness of proton-pump inhibitors for maintenance therapy of erosive reflux esophagitis.

The relative cost-effectiveness of proton-pump inhibitors (PPIs) in the maintenance therapy of erosive reflux esophagitis was studied. Decision analysis was used to model the cost-effectiveness of PPIs on the basis of clinical trial results. Management decisions in the model were based on published U.S. guidelines and recommendations. Probability estimates were derived from a systematic review of the literature. The model's base-case scenario compared rabeprazole, lansoprazole, and omeprazole for the prevention of symptom recurrence over one year. Meta-analyzed estimates of efficacy were derived from trials by using a generalized logistic regression model with random effects. Medical costs for hospitalization, procedures, and office visits reflected 2000 Medicare payment; drug costs were based on 2000 average wholesale prices. Average costs per patient were comparable among the PPIs (rabeprazole, $1414; lansoprazole, $1671; and omeprazole, $1599). Rabeprazole prevented symptom recurrence in 86% of rabeprazole recipients, versus 68% for lansoprazole and 81% for omeprazole, and yielded the lowest average cost-effectiveness ratio (rabeprazole, $1637 per recurrence prevented; lansoprazole, $2439; and omeprazole, $1968). The model was robust to changes in key variables. When evaluated by decision analysis over a wide range of assumptions, rabeprazole was comparable to other PPIs in terms of cost and offered improved effectiveness for maintenance therapy of erosive reflux esophagitis.

A randomized, double-blind, placebo-controlled trial of single-dose intravenous secretin as treatment for children with autism.

OBJECTIVE: To determine whether a single injection of intravenous secretin results in measurable improvements in socialization and/or communication skills in children with autism. STUDY DESIGN: Sixty subjects with autism were randomly selected and assigned to either treatment or placebo group. Subjects in the treatment group received 2.0 clinical units of secretin per kilogram of body weight as a single intravenous dose. Subjects in the placebo group received normal saline solution. Neurodevelopmental and behavioral assessments were performed for all subjects before injection and at 3 and 6 weeks after injection. RESULTS: Assessment of language skills and parents' behavioral assessments revealed no significant differences between the treatment and placebo groups. Raters' assessments of severity of autistic symptoms did not differ for the 2 groups at 6 weeks after injection. A marginally statistically significant improvement in autistic behaviors was seen in the treatment group at 3 weeks after injection (P =.051). CONCLUSIONS: A single dose of intravenous secretin does not appear to have significant effects on either parents' perception of autistic behaviors or language skills at 6 weeks after injection. Transient, marginally significant improvements in autistic behaviors may occur in some children.

A national inpatient cost estimate of percutaneous endoscopic gastrostomy (PEG)-associated aspiration pneumonia.

OBJECTIVE: To present national estimates of the prevalence and costs of inpatient admissions for aspiration pneumonia (AP) associated with percutaneous endoscopic gastrostomies (PEGs) inserted before or during an admission. STUDY DESIGN: Retrospective analysis using medical claims. PATIENTS AND METHODS: National estimates of the prevalence of inpatient admissions associated with AP and mortality rates were developed, using data from the Nationwide Inpatient Sample of the Hospital Cost and Utilization Project (HCUP-3) Database. The MEDSTAT Group's MarketScan Private Pay Fee-for-Service (FFS) and Medicare FFS databases were used to calculate the percentage of admissions for AP that were preceded by a PEG or that entailed a PEG placement. Associated statistics, such as average length of stay and mean payments for these admissions, also were estimated. RESULTS: Approximately 300,000 inpatient admissions for AP took place in the United States in 1995, of which roughly 70,000 (23.9%) resulted in death. Approximately 10% of all AP admissions occurred after or entailed a PEG placement. After adjusting for differences in patients' age, gender, and health status, the total mean payments were estimated to be $26,618 per patient. This per-patient estimate translates into a national estimate of the cost of PEG-associated AP of approximately $808.2 million. CONCLUSION: The cost of PEG-associated AP is relatively high, as estimated in this study. The high inpatient mortality rates of AP imply that future efforts should be directed toward preventing AP.

Upper gastrointestinal symptoms in a U.S. national sample of adults with diabetes.

BACKGROUND: Individuals with diabetes may be particularly susceptible to motility-related upper gastrointestinal (UGI) symptoms such as abdominal pain or discomfort, bloating, early satiety, nausea, and vomiting. We estimated the prevalence of UGI symptoms in a population-based sample of individuals with diabetes and determined whether cases and population controls differed in prevalence of UGI symptoms and in symptom features. METHODS: Individuals with diabetes (n = 483) and matched controls (n = 422) were recruited from a prior U.S. national health survey for a telephone interview on UGI symptoms. To confirm self-reported diabetes status, cases provided information on clinical management measures. Subjects were asked about UGI symptoms in the month before interview. Affirmative responses to initial questions triggered detailed questions about symptom frequency, timing, duration, and severity. Differences between cases and controls were evaluated. RESULTS: Cases not only had a significantly (P < 0.05) higher overall prevalence of one or more UGI symptoms in the past month (50%) than controls (38%), but they also reported a significantly greater number of UGI symptoms than controls. Almost 10% of cases reported three or more UGI symptoms in the past month compared with 2% of controls. Our study also identified UGI symptom features that were more relevant to cases and showed that one UGI symptom, heartburn, co-occurred significantly more often with UGI symptoms in cases than in controls. CONCLUSIONS: Upper GI symptoms are common in individuals with diabetes and more prevalent than in controls. The symptoms are non-specific and may reflect disruptions in motility or perception.

Cost effectiveness of rabeprazole versus generic ranitidine for symptom resolution in patients with erosive esophagitis.

OBJECTIVE: To compare the cost effectiveness of rabeprazole (RAB) and ranitidine (RAN) in acute and maintenance therapy for erosive esophagitis using symptom response, rather than endoscopic healing, as the clinical outcome. STUDY DESIGN: Decision analysis was used to model the cost effectiveness of competing therapies based on the results of clinical trials of RAB versus RAN and estimates from the medical literature. METHODS: The model's base case scenario compared brand-name RAB (estimated average wholesale price) with generic RAN (25% of the average wholesale price of brand-name RAN). Medical costs for hospitalizations, procedures, and office visits reflected 1998 Medicare payments. The 1-year maintenance model accounted for drug-class switching and symptomatic, rather than endoscopic, recurrences. Effectiveness was reported as the percentage of patients in whom a symptomatic recurrence was prevented. The cost per symptomatic recurrence prevented was reported as an average and an incremental cost-effectiveness ratio. RESULTS: The per-patient cost of RAB therapy was higher than that of RAN therapy ($2020 vs $1917); RAB therapy, however, was more effective than RAN therapy in preventing symptomatic recurrences (74% vs 41%). The average cost-effectiveness ratio was lower for RAB therapy than for RAN therapy ($2748 per symptomatic recurrence prevented vs $4719 per symptomatic recurrence prevented). The cost of preventing one additional symptomatic recurrence with RAB rather than RAN was $313 (incremental cost-effectiveness ratio). Sensitivity analysis conducted on key clinical and cost variables supported the robustness of the decision model. CONCLUSION: This analysis demonstrates that management of esophagitis with RAB is more effective, and may be more cost effective, than management with generic RAN, despite RAB's higher per-unit cost.

Race and sex differences in long-term survival rates for elderly patients with pulmonary embolism.

OBJECTIVES: The goal of this study was to provide estimates of race- and sex-specific survival rates over a 10-year period for a cohort of 49,752 Medicare patients admitted to the hospital in 1984 with a diagnosis of pulmonary embolism. METHODS: Data were derived from Medicare Provider Analysis and Review Record inpatient claims files and the National Death Index file. RESULTS: For a primary diagnosis of pulmonary embolism, median survival times among Black men and women were 2.5 years and 5.2 years, respectively; for White men and women, the median survival times were 4.3 years and 5.9 years, respectively. Median survival times for Black men and women and White men and women with a secondary diagnosis of pulmonary embolism were 0.4 years, 0.7 years, 0.8 years, and 1.4 years, respectively. Survival rates declined with advancing age. CONCLUSIONS: Overall, survival rates among Blacks were lower than those among Whites, and men had lower survival rates than women. These survival estimates provide new insights into outcomes following pulmonary embolism in hospitalized elderly people.