Non-Traumatic Aortic Emergencies - Experience from a Tertiary Care Centre in

Objective: To review the incidence, clinical presentation and outcome of Non traumatic Aortic emergencies in a tertiary care hospital and its evaluation in the Emergency department (ED).Methods: We conducted a retrospective review of cases presented to the ED at Aga Khan University Hospital during 15 year period (1988 - 2002) who had final diagnosis of Aortic Dissection or Ruptured Aortic Aneurysm. Patients without confirmatory investigations were excluded. We aimed at looking for the incidence, clinical presentation, evaluation in the ED and final outcome.Results: Of the 12 cases, 7 had aortic dissection while the remaining 5 had ruptured aortic aneurysm. For Aortic dissection, mean age of presentation was 53 years with male predominance. Most of these patients had chest pain. Most common comorbid condition was hypertension. Pulse deficit was found in 2 cases, murmur in 4 cases, and focal neurologic deficit in 2 cases. Electrocardiogram revealed ischemic changes in 3 cases. Widened mediastinum on chest x-ray was present in all cases. The only initial misdiagnosis was cardiac ischemia. One patient survived to discharge. For patients presenting with ruptured aortic aneurysm, mean age of presentation was 52 yrs with a male predominance. The associated comorbid condition was hypertension. Almost all patients presented classically with abdominal pain, hypotension and palpable mass. No patient survived to discharge.Conclusion: Aortic emergencies although rare, are associated with significant mortality. High index of suspicion and prompt recognition by the emergency physician is of key importanc

Transient Nature of Long-Term Nonprogression and Broad Virus-Specific Proliferative T-Cell Responses with Sustained Thymic Output in HIV-1 Controllers

HIV-1(+) individuals who, without therapy, conserve cellular anti-HIV-1 responses, present with high, stable CD4(+) T-cell numbers, and control viral replication, facilitate analysis of atypical viro-immunopathology. In the absence of universal definition, immune function in such HIV controllers remains an indication of non-progression.CD4 T-cell responses to a number of HIV-1 proteins and peptide pools were assessed by IFN-gamma ELISpot and lymphoproliferative assays in HIV controllers and chronic progressors. Thymic output was assessed by sjTRECs levels. Follow-up of 41 HIV-1(+) individuals originally identified as "Long-term non-progressors" in 1996 according to clinical criteria, and longitudinal analysis of two HIV controllers over 22 years, was also performed. HIV controllers exhibited substantial IFN-gamma producing and proliferative HIV-1-specific CD4 T-cell responses to both recombinant proteins and peptide pools of Tat, Rev, Nef, Gag and Env, demonstrating functional processing and presentation. Conversely, HIV-specific T-cell responses were limited to IFN-gamma production in chronic progressors. Additionally, thymic output was approximately 19 fold higher in HIV controllers than in age-matched chronic progressors. Follow-up of 41 HIV-1(+) patients identified as LTNP in 1996 revealed the transitory characteristics of this status. IFN-gamma production and proliferative T-cell function also declines in 2 HIV controllers over 22 years.Although increased thymic output and anti-HIV-1 T-cell responses are observed in HIV controllers compared to chronic progressors, the nature of nonprogressor/controller status appears to be transitory

Impact of opioid-free analgesia on pain severity and patient satisfaction after discharge from surgery: multispecialty, prospective cohort study in 25 countries

Background: Balancing opioid stewardship and the need for adequate analgesia following discharge after surgery is challenging. This study aimed to compare the outcomes for patients discharged with opioid versus opioid-free analgesia after common surgical procedures.Methods: This international, multicentre, prospective cohort study collected data from patients undergoing common acute and elective general surgical, urological, gynaecological, and orthopaedic procedures. The primary outcomes were patient-reported time in severe pain measured on a numerical analogue scale from 0 to 100% and patient-reported satisfaction with pain relief during the first week following discharge. Data were collected by in-hospital chart review and patient telephone interview 1 week after discharge.Results: The study recruited 4273 patients from 144 centres in 25 countries; 1311 patients (30.7%) were prescribed opioid analgesia at discharge. Patients reported being in severe pain for 10 (i.q.r. 1-30)% of the first week after discharge and rated satisfaction with analgesia as 90 (i.q.r. 80-100) of 100. After adjustment for confounders, opioid analgesia on discharge was independently associated with increased pain severity (risk ratio 1.52, 95% c.i. 1.31 to 1.76; P < 0.001) and re-presentation to healthcare providers owing to side-effects of medication (OR 2.38, 95% c.i. 1.36 to 4.17; P = 0.004), but not with satisfaction with analgesia (beta coefficient 0.92, 95% c.i. -1.52 to 3.36; P = 0.468) compared with opioid-free analgesia. Although opioid prescribing varied greatly between high-income and low- and middle-income countries, patient-reported outcomes did not.Conclusion: Opioid analgesia prescription on surgical discharge is associated with a higher risk of re-presentation owing to side-effects of medication and increased patient-reported pain, but not with changes in patient-reported satisfaction. Opioid-free discharge analgesia should be adopted routinely

Global burden of 288 causes of death and life expectancy decomposition in 204 countries and territories and 811 subnational locations, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

BACKGROUND Regular, detailed reporting on population health by underlying cause of death is fundamental for public health decision making. Cause-specific estimates of mortality and the subsequent effects on life expectancy worldwide are valuable metrics to gauge progress in reducing mortality rates. These estimates are particularly important following large-scale mortality spikes, such as the COVID-19 pandemic. When systematically analysed, mortality rates and life expectancy allow comparisons of the consequences of causes of death globally and over time, providing a nuanced understanding of the effect of these causes on global populations. METHODS The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 cause-of-death analysis estimated mortality and years of life lost (YLLs) from 288 causes of death by age-sex-location-year in 204 countries and territories and 811 subnational locations for each year from 1990 until 2021. The analysis used 56 604 data sources, including data from vital registration and verbal autopsy as well as surveys, censuses, surveillance systems, and cancer registries, among others. As with previous GBD rounds, cause-specific death rates for most causes were estimated using the Cause of Death Ensemble model-a modelling tool developed for GBD to assess the out-of-sample predictive validity of different statistical models and covariate permutations and combine those results to produce cause-specific mortality estimates-with alternative strategies adapted to model causes with insufficient data, substantial changes in reporting over the study period, or unusual epidemiology. YLLs were computed as the product of the number of deaths for each cause-age-sex-location-year and the standard life expectancy at each age. As part of the modelling process, uncertainty intervals (UIs) were generated using the 2·5th and 97·5th percentiles from a 1000-draw distribution for each metric. We decomposed life expectancy by cause of death, location, and year to show cause-specific effects on life expectancy from 1990 to 2021. We also used the coefficient of variation and the fraction of population affected by 90% of deaths to highlight concentrations of mortality. Findings are reported in counts and age-standardised rates. Methodological improvements for cause-of-death estimates in GBD 2021 include the expansion of under-5-years age group to include four new age groups, enhanced methods to account for stochastic variation of sparse data, and the inclusion of COVID-19 and other pandemic-related mortality-which includes excess mortality associated with the pandemic, excluding COVID-19, lower respiratory infections, measles, malaria, and pertussis. For this analysis, 199 new country-years of vital registration cause-of-death data, 5 country-years of surveillance data, 21 country-years of verbal autopsy data, and 94 country-years of other data types were added to those used in previous GBD rounds. FINDINGS The leading causes of age-standardised deaths globally were the same in 2019 as they were in 1990; in descending order, these were, ischaemic heart disease, stroke, chronic obstructive pulmonary disease, and lower respiratory infections. In 2021, however, COVID-19 replaced stroke as the second-leading age-standardised cause of death, with 94·0 deaths (95% UI 89·2-100·0) per 100 000 population. The COVID-19 pandemic shifted the rankings of the leading five causes, lowering stroke to the third-leading and chronic obstructive pulmonary disease to the fourth-leading position. In 2021, the highest age-standardised death rates from COVID-19 occurred in sub-Saharan Africa (271·0 deaths [250·1-290·7] per 100 000 population) and Latin America and the Caribbean (195·4 deaths [182·1-211·4] per 100 000 population). The lowest age-standardised death rates from COVID-19 were in the high-income super-region (48·1 deaths [47·4-48·8] per 100 000 population) and southeast Asia, east Asia, and Oceania (23·2 deaths [16·3-37·2] per 100 000 population). Globally, life expectancy steadily improved between 1990 and 2019 for 18 of the 22 investigated causes. Decomposition of global and regional life expectancy showed the positive effect that reductions in deaths from enteric infections, lower respiratory infections, stroke, and neonatal deaths, among others have contributed to improved survival over the study period. However, a net reduction of 1·6 years occurred in global life expectancy between 2019 and 2021, primarily due to increased death rates from COVID-19 and other pandemic-related mortality. Life expectancy was highly variable between super-regions over the study period, with southeast Asia, east Asia, and Oceania gaining 8·3 years (6·7-9·9) overall, while having the smallest reduction in life expectancy due to COVID-19 (0·4 years). The largest reduction in life expectancy due to COVID-19 occurred in Latin America and the Caribbean (3·6 years). Additionally, 53 of the 288 causes of death were highly concentrated in locations with less than 50% of the global population as of 2021, and these causes of death became progressively more concentrated since 1990, when only 44 causes showed this pattern. The concentration phenomenon is discussed heuristically with respect to enteric and lower respiratory infections, malaria, HIV/AIDS, neonatal disorders, tuberculosis, and measles. INTERPRETATION Long-standing gains in life expectancy and reductions in many of the leading causes of death have been disrupted by the COVID-19 pandemic, the adverse effects of which were spread unevenly among populations. Despite the pandemic, there has been continued progress in combatting several notable causes of death, leading to improved global life expectancy over the study period. Each of the seven GBD super-regions showed an overall improvement from 1990 and 2021, obscuring the negative effect in the years of the pandemic. Additionally, our findings regarding regional variation in causes of death driving increases in life expectancy hold clear policy utility. Analyses of shifting mortality trends reveal that several causes, once widespread globally, are now increasingly concentrated geographically. These changes in mortality concentration, alongside further investigation of changing risks, interventions, and relevant policy, present an important opportunity to deepen our understanding of mortality-reduction strategies. Examining patterns in mortality concentration might reveal areas where successful public health interventions have been implemented. Translating these successes to locations where certain causes of death remain entrenched can inform policies that work to improve life expectancy for people everywhere. FUNDING Bill & Melinda Gates Foundation

Significantly higher lymphoproliferative responses to HIV-1 recombinant antigens mounted by HIV controllers (HIC) compared to HIV-1⁺ viraemic chronic progressors (vCP) and aviraemic chronic progressors (aCP) despite comparable IFN-γ release to HIV-1 peptide pools.

<p>Broad IFN-γ and proliferative responses to HIV-1 Gag p24 in HICs. Box plots show the median with IQR indicated. Whiskers represent the 10^th–90^th percentiles. The Mann-Whitney test was used to compare responses between patient groups, and the Wilcoxon signed rank test to compare paired responses from the same patient. *p<0.05, **p<0.01, ***p<0.001. (a) Lymphoproliferative response to rTat, rRev, rNef, rp24 (Gag) and rgp120 (Env), from HICs (n = 6), vCPs (n = 6) and aCPs (n = 8). The threshold for positivity (SI ≥3) is marked. (b) IFN-γ release (spot forming cells per million PBMC), from HICs (n = 6), vCPs (n = 6) and aCPs (n = 8), in response to stimulation with Tat, Rev, Nef and Gag p24 overlapping peptides. Data represent mean values of triplicate wells with <10% variation among triplicates. The threshold of 20 SFC/10⁶ PBMC is marked. (c) Summation of IFN-γ release in response to stimulation with individual overlapping Gag p24 peptides (1–22) compared to the response to the peptide pool and rp24 protein. Data from two representative HICs is shown. (d) Summation of lymphoproliferative responses, of two representative HICs, to stimulation with individual overlapping Gag p24 peptides (1–22) compared to the response to rp24 protein.</p

Detailed description of characteristics of the study cohorts.

<p>- , data not available; P values between *HIC and vCP, ^#HIC and aCP, †vCP and aCP; bold face indicates statistically significant difference measured to a 95% confidence interval by the Mann-Whitney test; ^‡2^nd or ^§3^rd visit respectively.</p

Higher levels of thymic output in HIV controllers (HIC) compared to age-matched chronic progressors (CP).

<p>(a) Electrophoresis gel showing an example of TREC levels in PBMC of HIC4 compared to the positive control, cord blood. (b) TREC levels in PBMC of 6 HICs compared to previously published data of PBMC from chronic progressors <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0005474#pone.0005474-Imami3" target="_blank">[26]</a>. The two cohorts are age-matched (p = 0.3823; median age HIC 41.2 years, range 26.9–60.2; median age CP 36.5 years, range 20.2–57.7). The CD4 count was significantly higher in HICs than HAART naïve CPs (p<0.0001; HIC median 913.5 cells/µl blood, range 588–1331; CP median 254.5 cells/µl blood, range 13–551).</p

Follow up of 41 “LTNPs” over 132 months since original identification using clinical criteria in 1996.

<p>(a) All available pre-HAART data of CD4 T-cell counts for the cohort of 41 LTNPs since identification (normal range 450–1650 cells/µl blood, marked with horizontal line). (b) All available pre-HAART data of plasma viral load for the cohort of 41 LTNPs since identification. DL = detection limit of assay. Data from each individual are plotted with different symbols and regression lines indicate slopes. Once the patient initiates anti-retroviral therapy their characteristics are no longer shown on the graphs.</p

Longitudinal analysis of T-cell mediated responses, to HIV-1 antigens and peptides, by two HIV controllers over a 79 and 85 month period.

<p>Data is shown from two HICs; HIC 5 and HIC 2, from two and three time points respectively. Data represent mean values of triplicate wells with <10% variation among triplicates. (a) IFN-γ release (spot forming cells/10⁶ PBMC) in response to stimulation with Tat, Rev, Nef and Gag p24 overlapping peptides. The threshold of 20 SFC/10⁶ PBMC is marked. (b) Lymphoproliferative response to rTat, rRev, rNef, rp24 (Gag) and rgp120 (Env). The threshold for positivity (SI ≥3) is marked.</p