Safety and Tolerability of Antimicrobial Agents in the Older Patient.

Older patients are at high risk of infections, which often present atypically and are associated with high morbidity and mortality. Antimicrobial treatment in older individuals with infectious diseases represents a clinical challenge, causing an increasing burden on worldwide healthcare systems; immunosenescence and the coexistence of multiple comorbidities determine complex polypharmacy regimens with an increase in drug-drug interactions and spread of multidrug-resistance infections. Aging-induced pharmacokinetic and pharmacodynamic changes can additionally increase the risk of inappropriate drug dosing, with underexposure that is associated with antimicrobial resistance and overexposure that may lead to adverse effects and poor adherence because of low tolerability. These issues need to be considered when starting antimicrobial prescriptions. National and international efforts have been made towards the implementation of antimicrobial stewardship (AMS) interventions to help clinicians improve the appropriateness and safety of antimicrobial prescriptions in both acute and long-term care settings. AMS programs were shown to decrease consumption of antimicrobials and to improve safety in hospitalized patients and older nursing home residents. With the abundance of antimicrobial prescriptions and the recent emergence of multidrug resistant pathogens, an in-depth review of antimicrobial prescriptions in geriatric clinical practice is needed. This review will discuss the special considerations for older individuals needing antimicrobials, including risk factors that shape risk profiles in geriatric populations as well as an evidence-based description of antimicrobial-induced adverse events in this patient population. It will highlight agents of concern for this age group and discuss interventions to mitigate the effects of inappropriate antimicrobial prescribing.

Is there a Link between Non Melanoma Skin Cancer and Hydrochlorothiazide?

AIMS: Here in we evaluated the association between the use of Hydrochlorothiazide (HCTZ) and the risk of NMSC both, basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). BACKGROUND: Even though the use of HCTZ is not linked with the development of serious adverse drug reactions, non-melanoma skin cancer (NMSC) has been reported in patients treated with the drug in recent years, most likely due to its photosensitizing ability. OBJECTIVE: To evaluate the statistically significant difference (P<0.05) in the development of NMSC between HCTZ users and non-users and the correlation (P<0.05) between HCTZ use and NMSC. METHODS: We performed a retrospective study on patients referred to general practitioners who developed skin cancer or NMSC whether or not they were treated with antihypertensive drugs. Controls were matched with the test by age and sex. We calculated odds ratios (ORs) for skin cancer and NMSC associated with hydrochlorothiazide using conditional logistic regression. RESULTS: We enrolled 19,320 patients in the present study, out of a total of 10,110 (52.3%) who were treated with antihypertensive drugs. Of 10,110 patients, 3,870 were treated with HCTZ (38.3%). During the study, we failed to report an increased risk of NMSC in HCTZ-treated vs. untreated patients. Gender stratification revealed an OR for NMSC of 1.36 for men and 0.56 for women. We did not find a dose-response relationship between HCTZ use and NMSC. CONCLUSION: In the present study, we failed to report an association between the use of HCTZ and the development of NMSC.

Neuron-specific enolase serum levels in COVID-19 are related to the severity of lung injury.

The multifunctional role of neuron-specific enolase (NSE) in lung diseases is well established. As the lungs are greatly affected in COVID-19, we evaluated serum NSE levels in COVID-19 patients with and without dyspnea. In this study, we evaluated both SARS-CoV-2-infected and uninfected patients aged >18 years who were referred to hospitals in Catanzaro, Italy from March 30 to July 30, 2020. Epidemiological, clinical, and radiological characteristics, treatment, and outcome data were recorded and reviewed by a trained team of physicians. In total, 323 patients (178 men, 55.1% and 145 women, 44.9%) were enrolled; of these, 128 were COVID-19 patients (39.6%) and 195 were control patients (60.4%). Westergren's method was used to determine erythroid sedimentation rate. A chemiluminescence assay was used for measurement of interleukin-6, procalcitonin, C-reactive protein, and NSE. We detected significantly higher NSE values (P<0.05) in COVID-19 patients than in controls. Interestingly, within the COVID-19 group, we also observed a further significant increase in dyspnea (Dyspnea Scale and Exercise score: 8.2 ± 0.8; scores ranging from 0 to 10, with higher numbers indicating very severe shortness of breath). These data provide the background for further investigations into the potential role of NSE as a clinical marker of COVID-19 progression.

Adverse Events of Proton Pump Inhibitors: Potential Mechanisms.

OBJECTIVE: We aimed at summarizing current evidence about mechanisms for potentially harmful effects of Proton Pump Inhibitors (PPIs). METHODS: A Pubmed search was performed, and 207 studies concerning the relationship between use of PPIs and cardiovascular diseases, kidney impairment, nutritional disorders, fractures, infections, functional decline, and mortality were selected and reviewed. RESULTS: PPIs may cause potentially harmful effects by several mechanisms, including endothelial dysfunction, hypomagnesemia, drug interactions, reduced absorption of selected nutrients, increased gastric microbiota and small intestine bacterial overgrowth, reduced immune response, tubular-interstitial inflammation, increased bone turnover, accumulation of amyloid in the brain. Clinical and epidemiologic evidence is not consistent in regard to some negative outcomes during PPI treatment. Data from randomized clinical trials seem to deny most of them, but they are usually designed to investigate efficacy of drugs in ideal conditions and are not powered enough to detect adverse events. Besides being at special risk of experiencing negative outcomes during long-term treatment with PPIs, older and complex patients treated with polypharmacy regimens are persistently excluded from randomized clinical trials. Thus, large observational studies involving real-world patients should be considered as an important informative source about potential risks related to PPIs. CONCLUSIONS: Current evidence suggests that use of PPIs may be associated with negative outcomes by eliciting several different pathophysiologic mechanisms. While short-term PPIs could be considered effective and safe in adult patients with acid-related disorders, their long-term and often inappropriate use in patients carrying vulnerability to adverse events and/or high risk of drug-interactions should be avoided.

Medication-Induced Nephrotoxicity in Older Patients.

OBJECTIVE: To summarize current evidence about mechanisms, clinical features, diagnostic issues, and strategies for prevention of medication-induced nephrotoxicity among older people. METHODS: A Pubmed search was performed, and studies concerning age-related changes in kidney structure and function predisposing to nephrotoxicity, pathophysiological mechanisms, kidney drug metabolism enzymes, clinical epidemiology of medication-induced kidney damage, biomarkers for early identification of nephrotoxicity and strategies for prevention of medication-induced nephrotoxicity among older people were selected. Finally, 245 papers were included in the review. RESULTS: Medications may induce nephrotoxicity through several pathophysiological mechanisms. People aged 75 or more are especially exposed to potential nephrotoxic medications or combinations of medications in the context of complex polypharmacy regimens. Estimated glomerular filtration rate (eGFR) may be useful to identify medication-induced alterations in kidney function, but creatinine-based methods have important limitation in older patients. Several innovative biomarkers have been proposed to identify AKI but these methodologies are not standardized and older people have not been evaluated systematically. Factors related to patient, medication, and interactions should be taken into account for effective prevention. CONCLUSIONS: Medication-induced nephrotoxicity is a relevant problem in older populations. Nevertheless, several areas of uncertainty remain to be explored, including the impact of nephrotoxicity on functional outcomes relevant to older patients, the reliability of currently recommended methods for diagnosing and staging AKI, the use of innovative biomarkers in such a heterogeneous population, the effectiveness of preventing strategies and treatments and their impact on functional outcomes.

Pneumonia, lung cancer or Medlar's core?

Here, we report a case of 57-year-old previously healthy man with six-months medical history of significant chronic cough and recurring episodes of fever. Cytology, bacteria, fungi and acid fast bacilli in the sputum were negative. CT scan, initially interpreted as suspected lung cancer, detected by chest x-ray, revealed pneumonia. Bronchoscopy is frequently necessary for the diagnosis as well as the treatment as a routine practice and in this case was applied. Our patient underwent to fiberoptic rigid bronchoscopy in the right upper lobe in general anaesthesia. Unexpectedly, a vegetal FB, Medlar's core instead a tumor, was removed. After two-months follow-up the patient was found healthy without any old or other symptoms.