Impact of poor medication adherence on clinical outcomes and health resource utilization in patients with hypertension and/or dyslipidemia: systematic review.

INTRODUCTION: We aimed to summarize evidence on the effect of poor medication adherence on clinical outcomes and health resource utilization (HRU) among patients with hypertension and/or dyslipidemia. AREAS COVERED: A systematic review of studies reporting clinical outcomes and HRU for patients by status of adherence to antihypertensives and/or lipid-lowering medications was searched using Embase, MEDLINE, and MEDLINE In-Process and supplemented by manual searches of conference abstracts. In total, 45 studies were included, with most being retrospective observational studies (n = 36). Patients with poor adherence to antihypertensives and lipid-lowering medications compared with those with good adherence showed less reduction of blood pressure (BP) and low-density lipoprotein cholesterol (LDL-c) after 6-12 months follow-up (∆ systolic BP: 1.2 vs. -4.5 mmHg; ∆LDL-c: -14.0 to -18.9 vs. -34.1 to -42.0 mg/dL). Poor adherence was also significantly associated with a higher risk of cardiovascular events (HR: 1.1-1.9) and mortality (HR: 1.4-1.8) in patients with hypertension and dyslipidemia and increased HRU (i.e. outpatient visits, risk of cardiovascular-related and all-cause hospitalization, annual inpatient days, total health-care costs). EXPERT OPINION: Poor adherence is associated with poor clinical outcomes and increased HRU, highlighting the need to enhance medication adherence in patients with hypertension and/or dyslipidemia.

High blood pressure is a leading cause of death and disease burden followed by high lipid levels in blood. Due to the silent nature of the diseases, patients can fall short of optimal medicinal treatment adherence and persistence, leading to poor outcomes and disease complications. The effectiveness of medicinal interventions depends on the appropriate medication-taking behavior of patients as lower adherence can lead to poor treatment benefits. Research was conducted to look for published studies that assessed the effect of lower medication adherence on clinical outcomes and health resource use among patients with high blood pressure, high lipid levels in blood, or both. Researchers were able to find 45 already published studies, from which 32 evaluated the use of blood pressure lowering medications and 7 evaluated the use of lipid-lowering medications, while 6 included patients treated with both types of medications. Refill of pharmacy prescription records was the most common method of assessing treatment adherence. Researchers found that patients with lower adherence to these medications compared with those with good adherence showed less decrease in blood pressure levels and less improvement in blood lipid levels after 6­12 months of follow-up. Patients who had lower adherence also had higher rates of cardiovascular events and deaths and increased usage of health services including visits to outpatient clinics, getting admitted to hospitals, and a longer stay of hospitalizations, leading to a higher overall healthcare cost. These findings suggest lower adherence is associated with poor clinical outcomes and increased health-care resource usage, highlighting the need to improve medication adherence in patients with high blood pressure and high lipid levels in blood.

Severe Acute Respiratory Infection Surveillance during the Initial Phase of the COVID-19 Outbreak in North India: A Comparison of COVID-19 to Other SARI Causes.

INTRODUCTION: World Health Organization proposes severe acute respiratory infection (SARI) case definition for coronavirus disease 2019 (COVID-19) surveillance; however, early differentiation between SARI etiologies remains challenging. We aimed to investigate the spectrum and outcome of SARI and compare COVID-19 to non-COVID-19 causes. PATIENTS AND METHODS: A prospective cohort study was conducted between March 15, 2020, to August 15, 2020, at an adult medical emergency in North India. SARI was diagnosed using a "modified" case definition-febrile respiratory symptoms or radiographic evidence of pneumonia or acute respiratory distress syndrome of ≤14 days duration, along with a need for hospitalization and in the absence of an alternative etiology that fully explains the illness. COVID-19 was diagnosed with reverse transcription-polymerase chain reaction testing. RESULTS: In total, 95/212 (44.8%) cases had COVID-19. Community-acquired pneumonia (n = 57), exacerbation of chronic lung disease (n = 11), heart failure (n = 11), tropical febrile illnesses (n = 10), and influenza A (n = 5) were common non-COVID-19 causes. No between-group differences were apparent in age ≥60 years, comorbidities, oxygenation, leukocytosis, lymphopenia, acute physiology and chronic health evaluation (APACHE)-II score, CURB-65 score, and ventilator requirement at 24-hour. Bilateral lung distribution and middle-lower zones involvement in radiography predicted COVID-19. The median hospital stay was longer with COVID-19 (12 versus 5 days, p = 0.000); however, mortality was similar (31.6% versus 28.2%, p = 0.593). Independent mortality predictors were higher mean APACHE II in COVID-19 and early ventilator requirement in non-COVID-19 cases. CONCLUSIONS: COVID-19 has similar severity and mortality as non-COVID-19 SARI but requires an extended hospital stay. Including radiography in the SARI definition might improve COVID-19 surveillance. HOW TO CITE THIS ARTICLE: Pannu AK, Kumar M, Singh P, Shaji A, Ghosh A, Behera A, et al. Severe Acute Respiratory Infection Surveillance during the Initial Phase of the COVID-19 Outbreak in North India: A Comparison of COVID-19 to Other SARI Causes. Indian J Crit Care Med 2021;25(7):761-767.

Folding studies of purified LamB protein, the maltoporin from the Escherichia coli outer membrane: trimer dissociation can be separated from unfolding.

The folding mechanisms for ß-barrel membrane proteins present unique challenges because acquisition of both secondary and tertiary structure is coupled with insertion into the bilayer. For the porins in Escherichia coli outer membrane, the assembly pathway also includes association into homotrimers. We study the folding pathway for purified LamB protein in detergent and observe extreme hysteresis in unfolding and refolding, as indicated by the shift in intrinsic fluorescence. The strong hysteresis is not seen in unfolding and refolding a mutant LamB protein lacking the disulfide bond, as it unfolds at much lower denaturant concentrations than wild type LamB protein. The disulfide bond is proposed to stabilize the structure of LamB protein by clasping together the two sides of Loop 1 as it lines the inner cavity of the barrel. In addition we find that low pH promotes dissociation of the LamB trimer to folded monomers, which run at about one third the size of the native trimer during SDS PAGE and are much more resistant to trypsin than the unfolded protein. We postulate the loss at low pH of two salt bridges between Loop 2 of the neighboring subunit and the inner wall of the monomer barrel destabilizes the quaternary structure.