A Systematic review of the Primary Therapeutic interventions used in COVID-19 patients who were reinfected

On March 11th, 2020, COVID-19 was declared a global pandemic. Since then, data has been recorded, correlated and reviewed in an effort to better understand how to combat the spread and lower the morbidity of the disease. In this pursuit, many studies have linked the presence of comorbidities, diabetes among those, with a higher mortality rate. To further this line of thought, this review was meant to investigate the factors affecting this poorer prognosis and the risk of reinfection among this population.

Combination of flow cytometry and functional imaging for monitoring of residual disease in myeloma.

The iliac crest is the sampling site for minimal residual disease (MRD) monitoring in multiple myeloma (MM). However, the disease distribution is often heterogeneous, and imaging can be used to complement MRD detection at a single site. We have investigated patients in complete remission (CR) during first-line or salvage therapy for whom MRD flow cytometry and the two imaging modalities positron emission tomography (PET) and diffusion-weighted magnetic resonance imaging (DW-MRI) were performed at the onset of CR. Residual focal lesions (FLs), detectable in 24% of first-line patients, were associated with short progression-free survival (PFS), with DW-MRI detecting disease in more patients. In some patients, FLs were only PET positive, indicating that the two approaches are complementary. Combining MRD and imaging improved prediction of outcome, with double-negative and double-positive features defining groups with excellent and dismal PFS, respectively. FLs were a rare event (12%) in first-line MRD-negative CR patients. In contrast, patients achieving an MRD-negative CR during salvage therapy frequently had FLs (50%). Multi-region sequencing and imaging in an MRD-negative patient showed persistence of spatially separated clones. In conclusion, we show that DW-MRI is a promising tool for monitoring residual disease that complements PET and should be combined with MRD.

Breastfeeding promotion for infants in neonatal units: a systematic review.

BACKGROUND: Breastfeeding/breastmilk feeding of infants in neonatal units is vital to the preservation of short- and long-term health, but rates are very low in many neonatal units internationally. The aim of this review was to evaluate the effectiveness of clinical, public health and health promotion interventions that may promote or inhibit breastfeeding/breastmilk feeding for infants admitted to neonatal units. METHODS: Systematic review with narrative synthesis. Studies were identified from structured searches of 19 electronic databases from inception to February 2008; hand searching of bibliographies; Advisory Group members helped identify additional sources. INCLUSION CRITERIA: controlled studies of interventions intended to increase breastfeeding/feeding with breastmilk that reported breastmilk feeding outcomes and included infants admitted to neonatal units, their mothers, families and caregivers. Data were extracted and appraised for quality using standard processes. Study selection, data extraction and quality assessment were independently checked. Study heterogeneity prevented meta-analysis. RESULTS: Forty-eight studies were identified, mainly measuring short-term outcomes of single interventions in stable infants. We report here a sub-set of 21 studies addressing interventions tested in at least one good-quality or more than one moderate-quality study. Effective interventions identified included kangaroo skin-to-skin contact, simultaneous milk expression, peer support in hospital and community, multidisciplinary staff training, and Unicef Baby Friendly accreditation of the associated maternity hospital. CONCLUSIONS: Breastfeeding/breastmilk feeding is promoted by close, continuing skin-to-skin contact between mother and infant, effective breastmilk expression, peer support in hospital and community, and staff training. Evidence gaps include health outcomes and costs of intervening with less clinically stable infants, and maternal health and well-being. Effects of public health and policy interventions and the organization of neonatal services remain unclear. Infant feeding in neonatal units should be included in public health surveillance and policy development; relevant definitions are proposed.

Breastfeeding promotion for infants in neonatal units: a systematic review and economic analysis.

OBJECTIVES: To evaluate the effectiveness and cost-effectiveness of interventions that promote or inhibit breastfeeding or feeding with breastmilk for infants admitted to neonatal units, and to identify an agenda for future research. DATA SOURCES: Electronic databases were searched (including MEDLINE and MEDLINE In-Process Citations, EMBASE, CINAHL, Maternity and Infant Care, PsycINFO, British Nursing Index and Archive, Health Management Information Consortium, Cochrane Central Register of Controlled Trials, Science Citation Index, Pascal, Latin American and Caribbean Health Sciences, MetaRegister of Controlled Trials, Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effectiveness, Health Technology Assessment Database, National Research Register) from inception to February 2008. Advisors identified further published or unpublished material. REVIEW METHODS: All papers fulfilled eligibility criteria covering participants, interventions, study design and outcomes. Results from primary studies were assessed and summarised in a qualitative synthesis for each type of intervention and across types of intervention. To estimate long-term cost utility, a decision tree was developed to synthesise data on enhanced staff contact, breastmilk effectiveness, incidence of necrotising enterocolitis (NEC) and sepsis, resource use, survival and utilities. RESULTS: Forty-eight studies met the selection criteria for the effectiveness review, of which 65% (31/48) were RCTs, and 17% (8/48) were conducted in the UK. Seven were rated as good quality and 28 as moderate quality. No studies met the selection criteria for the health economics review. There is strong evidence that short periods of kangaroo skin-to-skin contact increased the duration of any breastfeeding for 1 month after discharge [risk ratio (RR) 4.76, 95% confidence interval (CI) 1.19 to 19.10] and for more than 6 weeks (RR 1.95, 95% CI 1.03 to 3.70) among clinically stable infants in industrialised settings. There is strong evidence for the effectiveness of peer support at home (in Manila) for mothers of term, low birthweight infants on any breastfeeding up to 24 weeks (RR 2.18, 95% CI 1.45 to 3.29) and exclusive breastfeeding from birth to 6 months (RR 65.94, 95% CI 4.12 to 1055.70), and for the effectiveness of peer support in hospital and at home for mothers of infants in Special Care Baby Units on providing any breastmilk at 12 weeks [odds ratio (OR) 2.81, 95% CI 1.11 to 7.14; p = 0.01]. There is more limited evidence for the effectiveness of skilled professional support in a US Neonatal Intensive Care Unit on infants receiving any breastmilk at discharge (OR 2.0, 95% CI 1.2 to 3.2, p = 0.004). Multidisciplinary staff training may increase knowledge and can increase initiation rates and duration of breastfeeding, although evidence is limited. Lack of staff training is an important barrier to implementation of effective interventions. Baby Friendly accreditation of the associated maternity hospital results in improvements in several breastfeeding-related outcomes for infants in neonatal units. Limited evidence suggests that cup feeding (versus bottle feeding) may increase breastfeeding at discharge and reduce the frequency of oxygen desaturation. Breastmilk expression using simultaneous pumping with an electric pump has advantages in the first 2 weeks. Pharmaceutical galactagogues have little benefit among mothers who have recently given birth. Our economic analysis found that additional skilled professional support in hospital was more effective and less costly (due to reduced neonatal illness) than normal staff contact. Additional support ranged from 0.009 quality-adjusted life-years (QALYs) to 0.251 QALYs more beneficial per infant and ranged from 66 pounds to 586 pounds cheaper per infant across the birthweight subpopulations. Donor milk would become cost-effective given improved mechanisms for its provision. CONCLUSIONS: Despite the limitations of the evidence base, kangaroo skin-to-skin contact, peer support, simultaneous breastmilk pumping, multidisciplinary staff training and the Baby Friendly accreditation of the associated maternity hospital have been shown to be effective, and skilled support from trained staff in hospital has been shown to be potentially cost-effective. All these point to future research priorities. Many of these interventions inter-relate: it is unlikely that specific clinical interventions will be effective if used alone. There is a need for national surveillance of feeding, health and cost outcomes for infants and mothers in neonatal units; to assist this goal, we propose consensus definitions of the initiation and duration of breastfeeding/breastmilk feeding with specific reference to infants admitted to neonatal units and their mothers.

Early N-terminal pro-brain natriuretic peptide measurements predict clinically significant ductus arteriosus in preterm infants.

UNLABELLED: We report a blinded, prospective study of the diagnostic utility of N-terminal pro-brain natriuretic peptide (NTproBNP) measurements for predicting clinically significant patent ductus arteriosus (PDA) and assessing closure. METHODS: Plasma NTproBNP was measured during the first week in 100 preterm babies (mean gestation 28.8 +/- 2.9 weeks; mean birth weight 1224 +/- 512 g). Echocardiography was performed between days 5 and 7 by operators, blinded to NTproBNP concentration. RESULTS: NTproBNP peaked on days 2 and 3, declined by day 7. Twenty babies, later treated for PDA, had significantly higher NTproBNP levels throughout. Areas under receiver operating characteristic (ROC) curves were 0.896, 0.897 and 0.931 on days 2, 3 and 7, respectively (p < 0.0001). A concentration > 2850 pmol/L had diagnostic sensitivity of 90% and specificity of 89% (95% CI: 68, 99; likelihood ratio 8.10). Ductal closure was associated with a fall in mean NTproBNP from 3003 to 839 pmol/L (p < 0.001). CONCLUSION: N-terminal pro B-type brain natriuretic peptide (NTproBNP) concentrations peaked and then declined in the first week but remained higher in preterm babies whose PDA required treatment. NTproBNP on day 3 predicted whether a neonatal physician blinded to results would treat a PDA. Fall in plasma NTproBNP indicated closure.

Young driver risk factors: successful and unsuccessful approaches for dealing with them and an agenda for the future.

The extent to which various interventions to deal with the young driver crash problem have worked are discussed, and promising interventions that should be tried are identified. Traditional forms of driver licensing and driver education have not worked. Graduated licensing reduces the problem and existing laws need to be strengthened. Programs involving parents and police have shown some potential to increase compliance with graduated licensing restrictions. Insurer discount programs also have potential. In other public health areas, comprehensive programs have worked better than those based on single components. There are continuing efforts to develop new driver education and training programs and methods of delivery that can combine with graduated licensing and contribute to reductions in the young driver problem. The most promising intervention strategy is likely to be a coordinated community based program in states with strong graduated licensing laws as a foundation, involving modern education and training techniques, insurance discount programs, and well publicized enforcement and education programs featuring parents and police in combination, with as much input and participation as possible from the target group of young drivers.

Neonatal hypoglycaemia: clinical and legal aspects.

Transiently low blood glucose levels are common in the neonatal period and may be considered a normal feature of adaptation to extrauterine life. There is no evidence that this causes brain injury in the absence of concurrent clinical manifestations. Conversely, persistent and severe hypoglycaemia may be associated with other underlying pathologies which themselves predispose to brain injury. Attribution of brain injury therefore requires demonstration of both 'significant' hypoglycaemia and a characteristic resulting pattern of brain injury. The prevention of hypoglycaemic brain injury requires early detection in infants considered 'at risk' and appropriate intervention. No single concentration of plasma glucose can be associated universally with either the appearance of clinical signs or causation of cerebral injury. For this reason we suggest that treatment be based upon 'operational thresholds' and guided by clinical assessment, not by the plasma glucose concentration alone. For example, the infant displaying neurological signs requires more urgent elevation of blood glucose concentration than the 'asymptomatic' one, regardless of the absolute plasma glucose value.

Temporal factors in motor vehicle crash deaths.

OBJECTIVE: To summarize fatal motor vehicle crash deaths in the United States by time of day, day of week, month, and season, and to determine why some days of the year tend to experience a relatively high number of deaths. METHOD: Crash deaths were identified and categorized using the Fatality Analysis Reporting System. Days of the year with relatively high crash deaths were compared to the two days that occurred exactly one week before and one week after. RESULTS: On average, motor vehicle crashes in the United States result in more than 100 deaths per day, but there is much day-to-day variability. During 1986-2002 the single day fatality count ranged from a low of 45 to a high of 252. Summer and fall months experience more crash deaths than winter and spring, largely due to increased vehicle travel. July 4 (Independence Day) has more crash deaths on average than any other day of the year, with a relatively high number of deaths involving alcohol. January 1 (New Year's Day) has more pedestrian crash deaths on average, plus it has the fifth largest number of deaths per day overall, also due to alcohol impairment. On other days the high numbers of deaths are likely due to increases in holiday or recreational travel. CONCLUSION: Every day of the year results in many crash deaths, but certain days stand out as particularly risky. The temporal and geographic spread of crash deaths, as well as the view of driving as a routine task, inures the public to this continuing problem. Innovative strategies are needed both to raise awareness and to work toward a solution.

Lymphoedema: an underestimated health problem.

BACKGROUND: Lymphoedema/chronic oedema is an important cause of morbidity in the population, but little is known of its epidemiology and impact on patients or health services. AIM: To determine the magnitude of the problem of chronic oedema in the community, and the likely impact of oedema on use of health resources, employment and patient's quality of life. DESIGN: Questionnaire-based survey. METHODS: Health professionals from dedicated lymphoedema services, specific out-patient clinics, hospital wards and community services (GP clinics and district nurses) were contacted to provide information on patients from within South West London Community Trust. A subset of the identified patients was interviewed. RESULTS: Within the catchment area, 823 patients had chronic oedema (crude prevalence 1.33/1000). Prevalence increased with age (5.4/1000 in those aged > 65 years), and was higher in women (2.15 vs. 0.47/1000). Only 529 (64%) were receiving treatment, despite two specialist lymphoedema clinics within the catchment area. Of 228 patients interviewed, 78% had oedema lasting > 1 year. Over the previous year, 64/218 (29%) had had an acute infection in the affected area, 17/64 (27%) being admitted for intravenous antibiotics. Mean length of stay for this condition was 12 days, estimated mean cost pound 2300. Oedema caused time off work in > 80%, and affected employment status in 9%. Quality of life was below normal, with 50% experiencing pain or discomfort from their oedema. DISCUSSION: Chronic oedema is a common problem in the community with at least 100 000 patients suffering in the UK alone, a problem poorly recognized by health professionals. Lymphoedema arising for reasons other than cancer treatment is much more prevalent than generally perceived, yet resources for treatment are mainly cancer-based, leading to inequalities of care.

Seatbelt use by high school students.

OBJECTIVE: To determine seatbelt use of teenage drivers arriving at high schools in the morning and at evening football games compared with belt use of adults driving teenage passengers to these events, and teenage passenger belt use depending on whether they were being driven by another teenager or an adult. METHODS: Unobtrusive observations of belt use were made at 12 high schools in Connecticut and Massachusetts. RESULTS: Among males, teenage drivers had lower belt use than adults; differences between female teenage and female adult drivers were slight. Teenage passengers had lower belt use in vehicles driven by other teenagers than in cars driven by adults, but more than 40% of teenage passengers in vehicles driven by adults, presumed in most cases to be the teenager's parent, were not belted. Teenage passenger belt use was lower than teenage driver use regardless of gender. These differences were found both at morning arrivals and at football games, but teenage belt use was not much different in these two settings. Teenage passengers were belted more often if drivers were belted, whether the driver was another teenager or an adult, but a third of male passengers and 25%-30% of female passengers were unbelted even when drivers were belted. CONCLUSION: Teenagers have high crash risk but low belt use, which adds to their injury problem. Avenues to address this include strong belt use laws and their enforcement, building belt use requirements into graduated licensing systems, keeping young beginners out of high risk driving situations, and finding ways to influence parents and other adults to ensure that their teenage passengers use seatbelts.

The need to monitor the usage of traditional herbal remedies

In the Caribbean, remedies made from Chenopodium ambrosioides are commonly used internally to treat many medical conditions such as: asthma, dysentry, fatigue and worms. The bioactive component found in the oil of this plant is ascaridole, which causes severe gastro-intestinal discomfort if used excessively. Other hazardous plants include Datura stramonium and Abrus precatorius. It is, therefore, imperative for awareness programs to be set up to educate the population about the use of herbal remedies. Assistance from the Chemistry, Food and Drugs Division of the Ministry of Health in Trinidad and Tobago is needed to formulate guidelines for the proper use of of herbal remedies by patients. A database of tropical poisonous herbs should be made available to hospitals and other health facilities around the country. It is imperative for physicians to ask about their use of herbal supplements and remedies as they are ideally situated to give good counseling and to even help in integrating herbal modalities into conventional care

A randomized controlled crossover study of manual lymphatic drainage therapy in women with breast cancer-related lymphoedema.

This paper describes a randomized controlled crossover study examining the effects of manual lymphatic drainage (MLD) in 31 women with breast cancer-related lymphoedema. MLD is a type of massage used in combination with skin care, support/compression therapy and exercise in the management of lymphoedema. A modified version of MLD, referred to as simple lymphatic drainage (SLD), is commonly taught as a self-help measure. There has been limited research into the efficacy of MLD and SLD. The study reported here explores the effects of MLD and SLD on a range of outcome measures. The findings demonstrate that MLD significantly reduces excess limb volume (difference, d=71, 95% CI=16-126, P=0.013) and reduced dermal thickness in the upper arm (d=0.15, 95% CI=0.12-0.29, P =0.03). Quality of life, in terms of emotional function (d=7.2, 95% CI=2.3-12.1, P=0.006), dyspnoea (d=-4.6, 95% CI=-9.1 to -0.15, P=0.04) and sleep disturbance (d =-9.2, 95% CI=-17.4 to -1.0, P=0.03), and a number of altered sensations, such as pain and heaviness, were also significantly improved by MLD. The study provides evidence to support the use of MLD in women with breast cancer-related lymphoedema. The limitations of the study are outlined and future areas for study are highlighted.

Effectiveness of Ford's belt reminder system in increasing seat belt use.

OBJECTIVES: The study investigated the effectiveness in increasing seat belt use of Ford's belt reminder system, a supplementary system that provides intermittent flashing lights and chimes for five minutes if drivers are not belted. METHODS: Seat belt use of drivers in relatively new cars with and without the reminder system was unobtrusively observed as vehicles were brought to dealerships for service. RESULTS: Overall use rates were estimated at 71% for drivers in vehicles without the reminder system and 76% for drivers in vehicles with belt reminders (p<0.01). CONCLUSIONS: Seat belt use is relatively low in the United States. The present study showed that vehicle based reminder systems can be at least modestly effective in increasing belt use, which may encourage further development of such systems.

Rationale for graduated licensing and the risks it should address.

The increased crash risk of young, beginning drivers has long been cause for concern. Graduated licensing systems, which seek to phase in driving experience gradually over time, have recently been adopted by many states in an effort to reduce these risks. In an attempt to define the basic rationale for graduated licensing, relevant research evidence that describes the conditions under which risk is known to be increased for young drivers was reviewed. Potential changes in licensing laws that best address these known risk factors are described. It was found that certain situations contribute to even greater crash risk, most notably nighttime driving and driving with passengers in the peer group. The underlying premise for graduated licensing is that while crash risk of young drivers is heightened under all situations, some situations are more or less risky than others. If experience can be gained initially under lower risk conditions, both in the learning stage and when first licensed, crash risk will be reduced.

Drinking histories of fatally injured drivers.

CONTEXT: About 30% of drivers killed in crashes have high blood alcohol concentrations (BACs) of 0.10+ g/dl. There is a question about whether these drivers primarily are problem drinkers who chronically drink and drive-the so-called hard core drinking drivers. OBJECTIVE: To investigate drinking histories of fatally injured drivers in relation to their BACs. DESIGN AND PARTICIPANTS: Retrospective cohort study of 818 fatally injured drivers who were included in the 1993 National Mortality Followback Survey (a national sample of US deaths in which next of kin were interviewed) and whose BACs were recorded by the Fatality Analysis Reporting System, a census of US traffic deaths. MAIN OUTCOME MEASURE: Problem drinking indicators. RESULTS: At least one indicator of potential problem drinking, primarily heavy drinking, was reported for 68% of drivers with very high BACs (0.15+ g/dl), 41% with BACs of 0.10-0.14 g/dl, 32% with BACs of 0.01-0.09 g/dl, and 7% with zero BACs. Spouses provided more credible responses than other relatives: they were more likely to report at least occasional drinking and driving among deceased drivers with high BACs. For the most direct signs of problem drinking (described as a problem drinker during the last month of life or frequently driving after having five or more drinks), spousal reports suggested the prevalence of problem drinking among drivers with very high BACs was 22% (having both indicators), 32% (frequently driving after having five or more drinks), 44% (described as problem drinker), or 57% (having either indicator). CONCLUSIONS: Drivers with BACs of 0.10+ g/dl were far more likely than sober drivers to be described as having markers of problem drinking. However, many did not have indicators suggestive of problem drinking. In addition to programs focused on repeat offenders or problem drinkers, countermeasures such as sobriety checkpoints that target a broader spectrum of drinking drivers are appropriate.

Older driver involvements in police reported crashes and fatal crashes: trends and projections.

OBJECTIVES: Older drivers have become a larger part of the driving population and will continue to do so as the baby boomers reach retirement age. The purpose of this study was to identify the potential effects of this population increase on highway safety. METHODS: Driver involvement rates for all police reported crashes were calculated per capita, per licensed driver, and per vehicle-mile of travel for 1990 and 1995. Also, driver involvement rates for fatal crashes were calculated for 1983, 1990, and 1995. Based on current crash rates per licensed driver and estimates of the future number of licensed drivers, projections of crashes involving drivers aged 65 and older were made for years 2010, 2020, and 2030. RESULTS: Driver crash involvement rates per capita decreased with age, but fatal involvement rates per capita increased starting at age 70. The same pattern existed for involvement rates per licensed driver. For both all crashes and fatal crashes, involvement rates per mile driven increased appreciably at age 70. Using projections of population growth, it was estimated that for all ages there will be a 34% increase in the number of drivers involved in police reported crashes and a 39% increase in the number involved in fatal crashes between 1999 and 2030. In contrast, among older drivers, police reported crash involvements are expected to increase by 178% and fatal involvements may increase by 155% by 2030. Drivers aged 65 and older will account for more than half of the total increase in fatal crashes and about 40% of the expected increase in all crash involvements; they are expected to account for as much as 25% of total driver fatalities in 2030, compared with 14% presently. CONCLUSIONS: By most measures, older drivers are at less risk of being involved in police reported crashes but at higher risk of being in fatal crashes. Although any projections of future crash counts have inherent uncertainty, there is strong evidence that older drivers will make up a substantially larger proportion of drivers involved in fatal crashes by 2030 because of future increases in the proportion of the population aged 65 and older, and trends toward increased licensure rates and higher annual mileage among older persons. Countermeasures to reduce the anticipated death toll among older drivers should address the increased susceptibility to injury of older vehicle occupants in crashes.

Plasma brain natriuretic peptide as a predictor of haemodynamically significant patent ductus arteriosus in preterm infants.

Patent ductus arteriosus (PDA) is an important cause of morbidity in extremely preterm infants. As increased plasma brain natriuretic peptide (BNP) is a common feature of adult cardiac disease, we investigated the value of plasma BNP concentration as a predictor of haemodynamically significant PDA in very preterm infants. We studied 18 preterm infants (12 male) of median gestational age 30 weeks (range 24-34), median birth weight 1.46 kg (0.54-2.13) and 11 healthy term controls. Plasma BNP levels were measured by double-antibody radioimmunoassay on days 3, 5 and 7 of life, and an echocardiogram was performed on day 7. Six infants of median gestation 26 weeks (26-30), median birth weight 0.92 kg (0.54-1.04) had PDA proven by echocardiography on day 7. BNP concentrations (pg/ml) on day 3 were significantly higher in these infants than in the remaining twelve [median 2012 (786-2759) versus 42 (7-704), P<0.001]. In four infants PDA was treated successfully (one surgically, three with non-steroidal anti-inflammatory drugs). Two had haemodynamically insignificant closing ducts. In these infants with therapeutic or spontaneous resolution of a PDA, plasma BNP fell to normal values [median after treatment 9 pg/ml (8-27)]. Early measurement of plasma BNP in the first few days of life is a useful method for predicting those preterm infants who may require intervention for PDA.