Long COVID-19 and primary care: Challenges, management and recommendations / COVID-19 prolongado y atención primaria: desafíos, manejo y recomendaciones

Long COVID-19, also known as post-acute sequelae of SARS-CoV-2 infection (PASC), is characterized by persistent symptoms after COVID-19 onset. This article explores the challenges, management strategies, and recommendations for addressing long COVID-19 in primary care settings. The epidemiology of long COVID-19 reveals significant variability, with a substantial portion of COVID-19 survivors experiencing post-acute symptoms. Pathophysiological mechanisms include viral persistence, endothelial dysfunction, autoimmunity, neurological dysregulation, and gastrointestinal dysbiosis. Multiple risk factors, including age, sex, pre-existing comorbidities, smoking, BMI, and acute COVID-19 severity, influence the development of long COVID-19. Effective management requires proactive measures such as vaccination, identification of high-risk populations, public awareness, and post-infection vaccination. Collaboration of primary care physicians with specialists is essential for holistic and individualized patient care. This article underscores the role of primary care physicians in diagnosing, managing, and mitigating the long-term effects of COVID-19. (AU)

La COVID-19 prolongada, también conocida como secuela postaguda de la infección por SARS-CoV-2, se caracteriza por síntomas persistentes después de la aparición de la COVID-19. Este artículo explora los desafíos, las estrategias de manejo y las recomendaciones para abordar la COVID-19 prolongada en entornos de atención primaria. La epidemiología de la COVID-19 prolongada revela una variabilidad significativa, y una parte sustancial de los supervivientes de la COVID-19 experimentan síntomas postagudos. Los mecanismos fisiopatológicos incluyen persistencia viral, disfunción endotelial, autoinmunidad, desregulación neurológica y disbiosis gastrointestinal. Múltiples factores de riesgo, como la edad, el sexo, las comorbilidades preexistentes, el tabaquismo, el IMC y la gravedad aguda de la COVID-19, influyen en el desarrollo de la COVID-19 prolongada. Una gestión eficaz requiere medidas proactivas, como la vacunación, la identificación de poblaciones de alto riesgo, la concienciación pública y la vacunación posterior a la infección. La colaboración de los médicos de atención primaria con los especialistas es esencial para una atención holística e individualizada al paciente. Este artículo subraya el papel de los médicos de atención primaria en el diagnóstico, el tratamiento y la mitigación de los efectos a largo plazo de la COVID-19. (AU)

Long COVID-19 and primary care: Challenges, management and recommendations.

Long COVID-19, also known as post-acute sequelae of SARS-CoV-2 infection (PASC), is characterized by persistent symptoms after COVID-19 onset. This article explores the challenges, management strategies, and recommendations for addressing long COVID-19 in primary care settings. The epidemiology of long COVID-19 reveals significant variability, with a substantial portion of COVID-19 survivors experiencing post-acute symptoms. Pathophysiological mechanisms include viral persistence, endothelial dysfunction, autoimmunity, neurological dysregulation, and gastrointestinal dysbiosis. Multiple risk factors, including age, sex, pre-existing comorbidities, smoking, BMI, and acute COVID-19 severity, influence the development of long COVID-19. Effective management requires proactive measures such as vaccination, identification of high-risk populations, public awareness, and post-infection vaccination. Collaboration of primary care physicians with specialists is essential for holistic and individualized patient care. This article underscores the role of primary care physicians in diagnosing, managing, and mitigating the long-term effects of COVID-19.

Award incentives to improve quality care in internal medicine.

INTRODUCTION: Award incentives encourage higher standards of personal performance, which closely reflects the quality of patient care. We report the development, implementation, and success of our internal medicine department awards program. MATERIALS AND METHODS: An anonymous pre award survey collected responses to understand the need for an awards program in our department. Five awards were celebrated. An anonymous post award survey collected responses to evaluate the effectiveness of the program. RESULTS: A total of 69% (175/253) of pre award survey responses were collected. Among those, 100% (175/175) agreed that employee recognition was important. 68% (119/175) felt that performance should be the deciding criteria for employee recognition. There was a winner in each award category. Post award survey showed 78% (102/130) agreed that the award ceremony incentivized them to increase quality of personal performance. CONCLUSION: In summary, we feel that this transparent, objective, and peer-nominated awards program could serve as an incentivized model for healthcare providers to elevate the standards of personal performance, which in turn will benefit the advancement of patient care.

Novel mutation in GLRB in a large family with hereditary hyperekplexia.

Hereditary hyperekplexia (HH) is a disorder of the inhibitory glycinergic neurotransmitter system. Mutations in five genes have been reported to cause the disease. However, only single mutation in GLRB, the gene encoding beta-subunit of the glycine receptor, in a singleton patient with HH has been found to date. In this study, 13 patients with HH were identified through neurology and genetic clinics. Formal clinical examinations, linkage analysis, homozygosity mapping, in-mutation screening of GLRB and in silico functional analyses were carried out. A novel mutation in GLRB among nine patients was identified. This c.596 T>G perturbation results in the change of the highly conserved methionine at position 177 to arginine. Besides the classical HH phenotype, seven patients had esotropia and few of them had behavioral problems. This study presents a large family with HH as a result of homozygous mutation in GLRB and expands the clinical spectrum of HH to include eye misalignment disorder. Moreover, the report of these familial cases supports the previous evidence in a single patient of an autosomal recessive inheritance of HH because of defects in GLRB.

Biofilm accumulation on endotracheal tubes following prolonged intubation.

OBJECTIVE: To demonstrate that patients who have been intubated for prolonged periods of time will have an increased likelihood of developing bacterial biofilm on their endotracheal tubes. METHODS: We collected endotracheal tubes from patients at the time of extubation, and analysed representative sections with scanning electron microscopy for morphologic evidence of biofilms. RESULTS: From September 2007 to September 2008, 32 endotracheal tubes were analysed with electron microscopy. Patients who had been intubated for 6 days or longer had a significantly higher percentage of endotracheal tubes that exhibited bacterial biofilms, compared with patients intubated for less than 6 days (88.9 versus 57.1 per cent, p = 0.0439). CONCLUSIONS: Longer duration of intubation is associated with a higher incidence of bacterial biofilm. Further research is needed to link the presence of bacterial biofilms to acquired laryngotracheal damage.

Antibacterial activity of Lawsonia inermis Linn (Henna) against Pseudomonas aeruginosa.

OBJECTIVE: To investigate the antibacterial activity of henna (Lawsonia inermis Linn) obtained from different regions of Oman against a wide array of micro-organisms. METHODS: Fresh henna samples were obtained from different regions of Oman as leaves and seeds. 100 g fresh and dry leaves and 50 g of fresh and dry seeds were separately soaked in 500 mL of ethanol for three days, respectively, with frequent agitation. The mixture was filtered, and the crude extract was collected. The crude extract was then heated, at 48 °C in a water bath to evaporate its liquid content. The dry crude henna extract was then tested for its antibacterial activity using well-diffusion antibiotic susceptibility technique. Henna extracts were investigated for their antibacterial activity at different concentrations against a wide array of different micro-organisms including a laboratory standard bacterial strain of Pseudomonas aeruginosa (NCTC 10662) (P. aeruginosa) and eleven fresh clinical isolates of P. aeruginosa obtained from patients attending the Sultan Qaboos University Hospital (SQUH). 2-Hydroxy-p-Nathoqinone-Tech (2-HPNT, MW=174.16, C10H6O3) was included as control (at 50% concentration) along with the henna samples tested. RESULTS: Henna samples demonstrated antibacterial activity against all isolates but the highest susceptibility was against P. aeruginosa with henna samples obtained from Al-sharqyia region. CONCLUSIONS: Omani henna from Al-sharqyia region demonstrates high in vitro anti-P. aeruginosa activity compared with many henna samples from different regions of Oman.

Novel intragenic deletion in OPHN1 in a family causing XLMR with cerebellar hypoplasia and distinctive facial appearance.

X-linked mental retardation (XLMR) is notably a heterogeneous condition and often poses a diagnostic challenge. The oligophrenin 1 gene (OPHN1) is a protein with a Rho-GTPase-activating domain required in the regulation of the G-protein cycle. Mutations in the OPHN1 cause XLMR with cerebellar hypoplasia and distinctive facial appearance. We report a large Saudi family of four boys and one girl affected with XLMR. The boys had moderate MR, seizure disorder, facial dysmorphism, and cerebellar vermis hypoplasia. The girl had mild MR, seizures, and mild cerebellar hypoplasia. A novel deletion of at least exons 7-15 was identified by polymerase chain reaction analysis and multiple ligation probe amplification of the OPHN1 gene. The array comparative genomic hybridization further delineated approximately 68 kb deletion of the 7-15 exons and nearly half of intron 15. In addition, the X-inactivation confirmed random pattern in the girl. Although the affected boys have remarkably similar phenotype, there was some variability in the severity of the seizure disorder and the cerebellar hypoplasia. The report confirms the previous findings that carrier females may be symptomatic.

Infant neurodevelopment following fetal growth restriction: relationship with antepartum surveillance parameters.

OBJECTIVES: To evaluate the relationship between fetal Doppler parameters, biophysical profile score (BPP) and neurodevelopmental delay at 2 years of corrected age in infants who had been growth-restricted in utero. METHODS: This was a prospective observational study including 113 pregnancies complicated by intrauterine growth restriction (IUGR) (abdominal circumference<5th percentile and elevated umbilical artery (UA) pulsatility index). The relationships of UA, middle cerebral artery and ductus venosus (DV) Doppler features, BPP, birth acidemia (artery pH<7.0+/or base deficit>12), gestational age at delivery, birth weight and neonatal morbidity (i.e. bronchopulmonary dysplasia, >Grade 2 intraventricular hemorrhage, or necrotizing enterocolitis) with a 2-year neurodevelopmental delay were evaluated. Best Beginnings Developmental Screen, Bayley Scale of Infant Development II (BSID) and Clinical Adaptive/Clinical Linguistic Auditory Milestone Stage were used. BSID<70, cerebral palsy, abnormal tone, hearing loss and/or blindness defined neurodevelopmental delay. RESULTS: Seventy-two of the 113 pregnancies completed assessment; there were 10 stillbirths, 19 neonatal deaths, three infant deaths and nine pregnancies with no follow-up. Twenty fetuses (27.8%) had UA reversed end-diastolic velocity (REDV), 34 (47.2%) abnormal DV Doppler features and 31 (43.1%) an abnormal BPP. Median gestational age at delivery and birth weight were 30.4 weeks and 933 g, respectively. Twelve infants had acidemia and 28 neonatal morbidity. There were 38 (52.8%) infants with neurodevelopmental delay, including 37 (51.4%) with abnormal tone, 20 (27.8%) with speech delay, 23 (31.9%) with an abnormal neurological examination, eight (11.1%) with a hearing deficit and six (8.3%) with cerebral palsy. Gestational age at delivery was associated with cerebral palsy (r2=0.52, P<0.0001; 92% sensitivity and 83% specificity for delivery at <27 weeks). UA-REDV was associated with global delay (r2=0.31, P=0.006) and birth weight with neurodevelopmental delay (r2=0.54, P<0.0001; 82% sensitivity and 64% specificity for BW<922 g). CONCLUSIONS: Although UA-REDV is an independent contributor to poor neurodevelopment in IUGR no such effect could be demonstrated for abnormal venous Doppler findings or BPP. Gestational age and birth weight remain the predominant factors for poor neurodevelopment in growth-restricted infants.

Incidence of invasive ureaplasma in VLBW infants: relationship to severe intraventricular hemorrhage.

OBJECTIVE: As Ureaplasmas may be pathogens in preterm infants, this study was conducted to determine the incidence of invasive disease with Ureaplasma parvum and Ureaplasma urealyticum and the relationship with adverse outcomes in a prospective cohort of very low birth weight (VLBW) infants. STUDY DESIGN: DNA was extracted from the cord or venous blood and cerebrospinal fluid (CSF) samples obtained from 313 VLBW infants. PCR was performed using primers for the mba gene to detect all 14 serovars and then repeated for all positive samples using species-specific primers. RESULT: Ureaplasma species were detected in serum and/or CSF samples from 74 of 313 (23.6%) infants. U. parvum was the predominant species (70%). Presence of Ureaplasma was significantly associated with elevated interleukin-1beta in cord blood (odds ratio (OR) 2.6, 1.05 to 6.45, P=0.039). Ureaplasma serum-positive infants had a 2.3-fold increased risk of intraventicular hemorrhage > or =grade 3 (OR 2.50; 1.06 to 5.89, P=0.036). CONCLUSION: Invasive Ureaplasma occurs commonly in VLBW infants and may increase the risk for severe intraventricular hemorrhage.

Formulation of inhaled medicines: effect of delivery vehicle on immortalized epithelial cells.

The small volume of airway lining fluid renders it susceptible to alteration by the deposition of inhaled formulations. The increasing popularity of the pulmonary route for drug delivery has led to an increasing number of pharmaceutical excipients being incorporated into inhaled dosage forms. The effects of drug delivery vehicle on airway epithelial cells can be studied with the aid of cell culture models of the respiratory epithelium. The effects of pH, osmolarity, and lactose on epithelial cell layers were studied using 16HBE14o- cells. Mannitol flux was used to assess epithelial permeability, enzymatic conversion of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) was used as a measure of epithelial cell metabolism, and release of the cytosolic enzyme lactate dehydrogenase was used as a measure of cell integrity. The effect of buffer composition on epithelial cell mucus secretion was studied using HT29-clone H cells, with mucus secretion measured using an enzyme-linked lectin assay. The permeability of 16HBE14o- cell layers was increased by apical fluid of pH 5, 6, and 9 as well as osmolarities of 96 and 545 mOsm. MTT conversion was reduced by apical fluid of pH 5 and 6 and osmolarity of 96 mOsm. Lactate dehydrogenase release was only increased by apical fluid of pH 9. No effect of lactose solution (100 mM) on the epithelial cells was observed. Mucus secretion by HT29-clone H cells was lowest in Dulbecco's modified Eagle medium (2.92 +/- 0.23 ng per cell layer) and was increased in phosphate-buffered saline with magnesium and calcium (4.28 +/- 0.38 ng per cell layer) and phosphate-buffered saline without magnesium and calcium (6.56 +/- 0.72 ng per cell layer). These results suggest that the physicochemical properties of inhaled formulations should be carefully controlled. The effect of buffer composition on mucus secretion suggests that even the application of "physiological" solutions may affect the epithelium. These cell models represent an opportunity to investigate the interaction of drug delivery vehicles with the epithelium.

Prophylaxis in RSV infection (Palivizumab)--is it worthwhile?

Respiratory syncytial virus (RSV) is a recognised cause of lower respiratory tract infection in infants and young children. It causes severe respiratory disease in preterm infants with or without chronic lung disease. This study, conducted at Waterford Regional Hospital, evaluates the incidence of RSV infection in hospitalised children, its seasonal variation, and effectiveness of its prevention. Thirty eight percent of admitted children with bronchiolitis were RSV positive in the year 1999 November to March is the peak season for this infection. A highly selected group of 7 preterm children with or without chronic lung disease received Palivizumab prophylaxis. Not one of them acquired RSV infection. The high cost of Palivizumab was the main factor for its restricted use. Palivizumab was found to be effective in preventing RSV infection in our study. Since we had a small number of patients, further studies are needed for its economic and judicious use. Respiratory syncytial virus (RSV) is virulent easily transmissible and the most common cause of lower respiratory tract disease in children of less than 2 years of age. Up to 98% of children attending day care will be infected in single RSV season. Between 0.5% and 3.2% of children with RSV infection require Hospitalisation. Approximately 90,000 hospital admissions and 4500 deaths per year were reported in United States. In Ireland 2807 patients were admitted with Bronchiolitis in 1998. Major risk factors for hospitalisation due to RSV are Prematurity, chronic lung disease, congenital heart disease, compromised immunity and age younger then 6 weeks in otherwise healthy children. No effective treatment of RSV positive bronchiolitis beside supportive care in the form of adequate nutrition and oxygen therapy is available. Antiviral therapies such as Ribavirin has not been proved to be effective in RSV infection. Bronchodilators show variable results. Corticosteroids were not found effective. There is no effective vaccine available as yet. There is no proven method for active immunity. Various immunoglobulins are available for acquiring passive immunity against RSV infection. PREVENT study group in Jan. 1997 showed intravenous immunoglobulin (RSV- IGIV) use in reducing 41% to 63% hospitalisation in RSV patients. But RSV-IGIV was not licensed outside the United States because of risk of transmission of blood borne products, difficulty in administration ie. intravenous access, large fluid volume (15 ml/kg), high protein load (750 mg/kg), shortage of supply and need to postpone live vaccine (eg. MMR, varicella). monoclonal antibody Palivizumab was developed for prophylaxis against RSV infection. Clinical safety and efficacy of Palivizumab were demonstrated in IMpact trial published in Sept. 1998. Reduction in hospitalisation up to 55% was noted in this study. It was a pivotal randomised, double blind, placebo controlled phase 3 study conducted in 139 centres throughout Canada, United States and United Kingdom. We looked at our experience in patients admitted with bronchiolitis in Waterford Regional Hospital. We described the outcome of carefully selected Seven children of high risk group for Palivizumab prophylaxis. Its clinical Implications and cost effectiveness was evaluated in this study.

Comparison of aspiration, touch and scrape preparations simultaneously obtained from surgically excised specimens. Effect of different methods of smear preparation on interpretive cytologic features.

OBJECTIVE: To determine whether three commonly used methods of obtaining and preparing cells for cytologic evaluation--touch preparation (TP), fine needle aspiration (FNA) and scrape preparation--yield essentially comparable material for evaluation or whether important differences exist between them that may influence interpretation. STUDY DESIGN: FNA, TP and scrape preparations were made simultaneously on surgically excised specimens. Thirty breast, 6 lung and 12 colon lesions were studied. Each slide was assessed for qualitative and quantitative features. Cellularity was semiquantitatively scored. RESULTS: Scrape preparations were the most cellular (P < .0001). Scrape and TPs often had larger tissue fragments than FNA. However, fragmentation of epithelial groups into smaller clusters and single cells was often noted on scrape preparations. FNAs tended to have cleaner backgrounds than the other two methods. CONCLUSION: Most often, there are few differences between smears prepared by the three techniques studied. However, scrape preparations may yield smears with smaller clusters and single cells as compared to the other two methods; that is a potential source of diagnostic confusion, particularly with respect to benign breast lesions. Scrape preparations uniformly yield more cellular smears. To the extent that cellularity is an interpretive factor in assessing cytologic specimens, it is important to be aware of the increased cellularity of scrape preparations as compared to the other two techniques.

The lead-chelating effects of substituted dithiocarbamates.

The effectiveness of certain substituted dithiocarbamates in mobilizing lead from preexposed rats was investigated. The animals received 10 mg Pb/kg/day, intragastrically, for 8 weeks and were treated thereafter with 400 mumol/kg, intraperitoneally, of morpholine dithiocarbamate, tetraammonium ethylenediamine diacetic acid dithiocarbamate (EDDTC), ammonium diethanolamine dithiocarbamate (ADDTC), sodium diethyldithiocarbamate, N-benzyl-D-glucamine dithiocarbamate (NBGDTC), or dimercaptosuccinic acid, daily for 5 days. All the chelating agents were effective in lowering the hepatic and renal burden of Pb. ADDTC, EDDTC, and NBGDTC were also able to lower the long bone Pb content. The lowering of Pb burden had no relationship to restoration of Pb-induced hematopoietic alterations. The relatively lower lipophilicity of substituted dithiocarbamates, owing to the presence of hydrophilic groups, seems to be advantageous in preventing passage of metal chelate into the brain. None of the substituted dithiocarbamates caused excessive excretion of urinary Cu and Zn. ADDTC and EDDTC appear to be promising in the management of Pb poisoning.

Interrelationship between iron deficiency and lead intoxication (Part 1).

The influence of lead exposure, iron deficiency, or their combination on certain biochemical parameters in blood, plasma, and urine of rats was investigated in an attempt to identify the specific diagnostic tests of the two conditions and to draw a possible interrelationship between the two factors. The decrease in blood-glutathione peroxidase activity, -packed cell volume, plasma-ceruloplasmin, and-Fe levels and increase in urinary excretion of delta-aminolevulinic acid, plasma-cholesterol, and-total Fe binding capacity occur under Fe deficiency as well as Pb intoxication. However, increase in the activity of blood delta-aminolevulinic acid dehydratase (ALAD) without any change in blood zinc protoporphyrin (ZPP) level appears to be a specific effect of Fe deficiency that could be distinguished from Pb intoxication, a condition characterized by the inhibition in blood ALAD activity accompanied by an increase in blood ZPP level. The linear regression analysis of the data showed that the blood Pb and plasma free cholesterol levels increase with the decrease in plasma Fe level.

Interrelationship between iron deficiency and lead intoxication (Part 2).

The influence of dietary iron deficiency, lead exposure or their combination on certain enzymes, and the accumulation of Pb and essential metal levels in vital organs of rats was investigated. Iron deficiency caused alterations in the activity of muscle, hepatic and renal succinate dehydrogenase, and hepatic mitochondrial succinate cytochrome c reductase, whereas Pb exposure had no influence on these enzymes. There was no synergistic effect of the two factors on the activity of the enzymes. However, feeding of a Fe-deficient diet during Pb exposure enhanced the accumulation of Pb in soft tissues and flat bones. The hepatic copper and zinc levels were lowered upon either feeding a Fe-deficient diet or Pb exposure. However, the synergistic effect of the two factors was evident in hepatic Cu, but not in hepatic Zn. The feeding of a Fe-deficient diet decreased liver, kidney, and spleen levels of Fe, whereas Pb exposure decreased kidney and spleen Fe. The synergistic influence of the two factors could be observed only in liver and kidney.

Natural and induced genetic variability in wheat.

An account is given of the genetic variability in primitive wheats collected from the northwest Pakistan. Apart from genetic sources for disease resistance, drought tolerance, and other plant characters, new sources of possible height reduction in wheat were identified and described. The taller-growing primitive wheats have better emergence, perhaps largely because of their longer coleoptiles. A detailed account is given of comparative genetic studies of height-reducing genes, through both conventional genetic analysis techniques and induced mutation breeding procedures. Both approaches demonstrated the effect of height genes on grain size. At the present time there is a linear relationship between plant height and 1000-kernel weight. Possibilities of achieving a break-through in wheat yields through increased kernel size in short wheats are discussed.