Stratified Simple Random Sampling Versus Volunteer Community-Wide Sampling for Estimates of COVID-19 Prevalence.

Objectives. To evaluate community-wide prevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection using stratified simple random sampling. Methods. We obtained data for the prevalence of SARS-CoV-2 in Jefferson County, Kentucky, from adult random (n = 7296) and volunteer (n = 7919) sampling over 8 waves from June 2020 through August 2021. We compared results with administratively reported rates of COVID-19. Results. Randomized and volunteer samples produced equivalent prevalence estimates (P < .001), which exceeded the administratively reported rates of prevalence. Differences between them decreased as time passed, likely because of seroprevalence temporal detection limitations. Conclusions. Structured targeted sampling for seropositivity against SARS-CoV-2, randomized or voluntary, provided better estimates of prevalence than administrative estimates based on incident disease. A low response rate to stratified simple random sampling may produce quantified disease prevalence estimates similar to a volunteer sample. Public Health Implications. Randomized targeted and invited sampling approaches provided better estimates of disease prevalence than administratively reported data. Cost and time permitting, targeted sampling is a superior modality for estimating community-wide prevalence of infectious disease, especially among Black individuals and those living in disadvantaged neighborhoods. (Am J Public Health. 2023;113(7):768-777. https://doi.org/10.2105/AJPH.2023.307303).

Dynamic SARS-CoV-2 surveillance model combining seroprevalence and wastewater concentrations for post-vaccine disease burden estimates.

BACKGROUND: Despite wide scale assessments, it remains unclear how large-scale severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination affected the wastewater concentration of the virus or the overall disease burden as measured by hospitalization rates. METHODS: We used weekly SARS-CoV-2 wastewater concentration with a stratified random sampling of seroprevalence, and linked vaccination and hospitalization data, from April 2021-August 2021 in Jefferson County, Kentucky (USA). Our susceptible ( S ), vaccinated ( V ), variant-specific infected ( I 1 and I 2 ), recovered ( R ), and seropositive ( T ) model ( S V I 2 R T ) tracked prevalence longitudinally. This was related to wastewater concentration. RESULTS: Here we show the 64% county vaccination rate translate into about a 61% decrease in SARS-CoV-2 incidence. The estimated effect of SARS-CoV-2 Delta variant emergence is a 24-fold increase of infection counts, which correspond to an over 9-fold increase in wastewater concentration. Hospitalization burden and wastewater concentration have the strongest correlation (r = 0.95) at 1 week lag. CONCLUSIONS: Our study underscores the importance of continuing environmental surveillance post-vaccine and provides a proof-of-concept for environmental epidemiology monitoring of infectious disease for future pandemic preparedness.

It is unclear how large-scale COVID-19 vaccination impacts wastewater concentration or overall disease burden. Here, we developed a mathematical surveillance model that allows estimation of overall vaccine impact based on the amount of SARS-CoV-2 in wastewater, seroprevalence and the number of cases admitted to hospitals between April 2021­August 2021 in Jefferson County, Kentucky USA. We found that a 64% vaccination coverage correlated to a 61% decrease in COVID-19 cases. The emergence of the SARS-CoV-2 Delta variant during the time of the surveillance directly correlated with a sharp increase in infection incidence as well as viral counts in wastewater. The hospitalization burden was closely reflected by the viral count found in the wastewater, indicating that post-vaccine environmental surveillance can be an effective method of estimating changing disease prevalence in future pandemics.

Effects of Address Coverage Enhancement on Estimates from Address-Based Sampling Studies.

For over a decade, address-based sampling (ABS) frames have often been used to draw samples for multistage area sample surveys in lieu of traditionally listed (or enumerated) address frames. However, it is well known that the use of ABS frames for face-to-face surveys suffer from undercoverage due to, for example, households that receive mail via a PO Box rather than being delivered to the household's street address. Undercoverage of ABS frames has typically been more prominent in rural areas but can also occur in urban areas where recent construction of households has taken place. Procedures have been developed to supplement ABS frames to address this undercoverage. In this article, we investigate a procedure called Address Coverage Enhancement (ACE) that supplements the ABS frame with addresses not found on the frame, and the resulting effects the addresses added to the sample through ACE have on estimates. Weighted estimates from two studies, the Population Assessment of Tobacco and Health Study and the 2017 US Program for the International Assessment of Adult Competencies, are calculated with and without supplemental addresses. Estimates are then calculated to assess if poststratifying analysis weights to control for urbanicity at the person level brings estimates closer to estimates from the supplemented frame. Our findings show that the noncoverage bias was likely minimal across both studies for a range of estimates. The main reason is because the Computerized Delivery Sequence file coverage rate is high, and when the coverage rate is high, only very large differences between the covered and not covered will result in meaningful bias.

Wastewater and seroprevalence for pandemic preparedness: variant analysis, vaccination effect, and hospitalization forecasting for SARS-CoV-2, in Jefferson County, Kentucky.

Despite wide scale assessments, it remains unclear how large-scale SARS-CoV-2 vaccination affected the wastewater concentration of the virus or the overall disease burden as measured by hospitalization rates. We used weekly SARS-CoV-2 wastewater concentration with a stratified random sampling of seroprevalence, and linked vaccination and hospitalization data, from April 2021-August 2021 in Jefferson County, Kentucky (USA). Our susceptible (S), vaccinated (V), variant-specific infected I1 and I2, recovered (R), and seropositive (T) model SVI2RT tracked prevalence longitudinally. This was related to wastewater concentration. The 64% county vaccination rate translated into about 61% decrease in SARS-CoV-2 incidence. The estimated effect of SARS-CoV-2 Delta variant emergence was a 24-fold increase of infection counts, which corresponded to an over 9-fold increase in wastewater concentration. Hospitalization burden and wastewater concentration had the strongest correlation (r = 0.95) at 1 week lag. Our study underscores the importance of continued environmental surveillance post-vaccine and provides a proof-of-concept for environmental epidemiology monitoring of infectious disease for future pandemic preparedness.

Public Awareness of and Support for the Use of Wastewater for SARS-CoV-2 Monitoring: A Community Survey in Louisville, Kentucky.

The majority of sewer systems in the United States and other countries are operated by public utilities. In the absence of any regulation, the public perception of wastewater monitoring for population health biomarkers is an important consideration for a public utility commission when allocating resources for this purpose. We conducted a survey in August 2021 as part of an ongoing COVID-19 community prevalence study in Louisville/Jefferson County, KY, US. The survey comprised seven questions about wastewater awareness and privacy concerns and was sent to approximately 35 000 households randomly distributed within the county. A total of 1220 adults were involved in the probability sample, and data from 981 respondents were used in the analysis. A total of 2444 adults additionally responded to the convenience sample, and data from 1751 respondents were used in the analysis. The samples were weighted to obtain estimates representative of all adults in the county. Public awareness of tracking the virus that causes COVID-19 in sewers was low. Opinions strongly support the public disclosure of monitoring results. Responses showed that people more strongly supported measurements in the largest areas (>50 000 households), typically representing population levels found in a large community wastewater treatment plant. Those with a history of COVID-19 infection were more likely to support highly localized monitoring. Understanding wastewater surveillance strategies and privacy concern thresholds requires an in-depth and comprehensive analysis of public opinion for continued success and effective public health monitoring.

Quantifying the relationship between sub-population wastewater samples and community-wide SARS-CoV-2 seroprevalence.

Robust epidemiological models relating wastewater to community disease prevalence are lacking. Assessments of SARS-CoV-2 infection rates have relied primarily on convenience sampling, which does not provide reliable estimates of community disease prevalence due to inherent biases. This study conducted serial stratified randomized samplings to estimate the prevalence of SARS-CoV-2 antibodies in 3717 participants, and obtained weekly samples of community wastewater for SARS-CoV-2 concentrations in Jefferson County, KY (USA) from August 2020 to February 2021. Using an expanded Susceptible-Infected-Recovered model, the longitudinal estimates of the disease prevalence were obtained and compared with the wastewater concentrations using regression analysis. The model analysis revealed significant temporal differences in epidemic peaks. The results showed that in some areas, the average incidence rate, based on serological sampling, was 50 % higher than the health department rate, which was based on convenience sampling. The model-estimated average prevalence rates correlated well with the wastewater (correlation = 0.63, CI (0.31,0.83)). In the regression analysis, a one copy per ml-unit increase in weekly average wastewater concentration of SARS-CoV-2 corresponded to an average increase of 1-1.3 cases of SARS-CoV-2 infection per 100,000 residents. The analysis indicates that wastewater may provide robust estimates of community spread of infection, in line with the modeled prevalence estimates obtained from stratified randomized sampling, and is therefore superior to publicly available health data.

Statistical and practical issues in the design of a national probability sample of births for the Vanguard Study of the National Children's Study.

The National Children's Study is a national household probability sample designed to identify 100,000 children at birth and follow the sampled children for 21 years. Data from the study will support examining numerous hypotheses concerning genetic and environmental effects on the health and development of children. The goals of the study present substantial challenges. For example, the need for preconception, prenatal, and postnatal data requires identifying women in the early stages of pregnancy, the collection of many types of data, and the retention of the children over time. In this paper, we give an overview of the sample design used in a pilot study called the Vanguard Study, and highlight the approaches used to address these challenges. We will also describe the rationale for the sampling choices made at each stage, the unique organizational structure of the NCS and issues we expect to face during implementation.

Exploring nonresponse bias in a health survey using neighborhood characteristics.

OBJECTIVES: We examined potential nonresponse bias in a large-scale, population-based, random-digit-dialed telephone survey in California and its association with the response rate. METHODS: We used California Health Interview Survey (CHIS) data and US Census data and linked the two data sets at the census tract level. We compared a broad range of neighborhood characteristics of respondents and nonrespondents to CHIS. We projected individual-level nonresponse bias using the neighborhood characteristics. RESULTS: We found little to no substantial difference in neighborhood characteristics between respondents and nonrespondents. The response propensity of the CHIS sample was similarly distributed across these characteristics. The projected nonresponse bias appeared very small. CONCLUSIONS: The response rate in CHIS did not result in significant nonresponse bias and did not substantially affect the level of data representativeness, and it is not valid to focus on response rates alone in determining the quality of survey data.

Muscle involvement in the scleroderma syndromes.

Muscle involvement was identified in 14 patients with scleroderma or a connective tissue disease overlap syndrome with predominant features of scleroderma. Patients presented with symmetrical proximal weakness indistinguishable from other inflammatory myopathies. Creatine kinase and electromyography were useful to demonstrate muscle involvement. Muscle histopathology demonstrated primarily the vasculopathy of scleroderma or polymyositis in similar numbers of patients. Scleroderma vasculopathy and polymyositis generally occur without specificity to diffuse scleroderma, the calcinosis, Raynaud's phenomenon, esophageal dysmotility, sclerodactyly, telangiectasia syndrome, or an overlap syndrome with arthritis. Polymyositis also occurs when the vasculopathy of scleroderma involves other organ systems.

Alterations of long-chain free fatty acid and magnesium concentrations in acute myocardial infarction.

Sixteen patients with acute myocardial infarction were subjects of a study of the changes in plasma magnesium and long-chain free fatty acid (FFA) levels. In each patient, there was a sharp fall of magnesium levels and a sharp rise of FFA levels shortly after onset of pain. Magnesium and FFA values returned to normal within three days. An absolute fall in total magnesium level and a probable fall in magnesium ion concentration could be important factors in arrhythmias during the first two days. The simultaneous rise in FFA and fall in magnesium levels in a variety of pathologic and physiologic conditions affords an explanation for divergent changes in FFA and magnesium concentrations in acute myocardial infarction. The FFA rise appears to be the fall in magnesium levels, which has been previously unexplained.

Vanishing cerebrovascular disease of pregnancy.

A woman developed TIAs in the last days of her pregnancy. Angiography revealed partial obstruction of the left middle cerebral artery. Following delivery and anticoagulation her symptoms abated. Angiography 11 weeks later revealed resolution of the obstruction. We propose that this intrinsic vascular lesion was secondary to reversible intimal hyperplasia brought on by reproductive steroids.

Perspective on carbamazepine-induced water intoxication: reversal by demeclocycline.

Carbamazepine (CBZ)-induced water intoxication occasionally limits its usefulness in refractory seizures and trigeminal neuralgia. Fluid restriction, CBZ dose reduction, or concomitant phenytoin therapy may be impractical or ineffective. Demeclocycline (7-chloro-6 demethyl tetracycline) (DMC) corrected the CBZ-induced water intoxication in a 51-year-old man with refractory complex partial seizures and a normal antidiuretic hormone (ADH) level. DMC inhibits ADH-sensitive adenylate cyclase activity in the renal collecting duct and may be useful in correcting the ADH-like or renal antidiuretic effect of CBZ.

Timber rattlesnake venom-induced myokymia: evidence for peripheral nerve origin.

Facial and limb myokymia occurred in four consecutive cases of timber rattlesnake envenomation and represents the "fasciculations" frequently reported in this entity. The facial myokymia disappears within hours of antivenin therapy and the limb myokymia by increasing serum ionized calcium. These observations suggest that the action of the venom is a biochemical one, increasing peripheral nerve excitability.

Calcium and myokymia of brainstem origin.

In five patients with Guillain-Barré syndrome, clinical myokymia increased and myokymic burst amplification occurred when ionized Ca++ was lowered by hyperventilation. Myokymia decreased when ionized Ca++ was increased after IV infusion of CaCl2. These responses were absent or diminished in the four patients with myokymia due to brainstem lesions, suggesting that the blood-brain barrier impedes the effects of altered serum ionized Ca++ on axonal excitability. Altering serum Ca++ can distinguish peripheral and central myokymia.

Exercise-induced membrane failure in paramyotonia congenita.

A marked decrease in the amplitude of the evoked thenar compound muscle action potential followed brief exercise at room temperature in two patients with paramyotonia congenita. This decline was more rapid and pronounced in our patient with coexistent thyrotoxicosis. The prolonged recovery period in paramyotonia congenita differs from the brief exercise-induced decreased compound muscle action potential seen in myotonia congenita and myotonic dystrophy. These findings suggest that exercise, like cold exposure, decreases membrane excitability in paramyotonia congenita.

Calcium effect on generation and amplification of myokymic discharges.

Maneuvers designed to manipulate ionized calcium (Ca++) were carried out in two patients with inflammatory polyradiculoneuropathy and myokymia. Increased clinical myokymia and myokymic burst amplification occurred when ionized Ca++ was lowered by plasma exchange or hyperventilation. Increasing ionized Ca++ (by intravenous infusion of CaCl2) decreased the myokymia. These findings indicate that myokymic discharges are altered by changes in serum ionized Ca++ and effects on axonal excitability.

Reversible coma with prolonged absence of pupillary and brainstem reflexes: an unusual response to a hypoxic-ischemic event in MS.

A quadriparetic man with multiple sclerosis became comatose with absent pupillary and brainstem reflexes for 48 hours following a respiratory arrest. A periodic electroencephalographic pattern was recorded 12 hours after arrest suggesting a poor prognosis. Despite the poor prognostic signs, clinical recovery to baseline occurred within 2 weeks. Reversible coma with absent pupillary and brainstem reflexes may occur in MS patients for prolonged periods and lead to potential errors in prognosis if not recognized.

Reflex epilepsy and nonketotic hyperglycemia in the elderly: a specific neuroendocrine syndrome.

We present five elderly patients with focal reflex or posture-induced seizures and nonketotic hyperglycemia (NKH). Each patient exhibited interictal focal findings, such as hemiparesis or hemisensory or aphasic deficits. With control of the hyperglycemia, the seizures stopped, and the neurologic deficits resolved. The syndrome of focal reflex epilepsy and neurologic deficits in the elderly is transient and almost invariably related to NKH, thus representing a specific neuroendocrine syndrome.

Evaluating the complaint of fatigue in primary care: diagnoses and outcomes.

PURPOSE: This case series describes associated diagnoses and prognoses of persistent fatigue in a community-based, primary care population. PATIENTS AND METHODS: All patients presenting to a private practice internist with a chief complaint of fatigue of more than 1 month's duration were prospectively evaluated with clinically directed examination and diagnostic testing. Patients were excluded if they had a previously diagnosed illness associated with fatigue. Fatigue was attributed to newly established diagnoses or medication use based on explicit criteria. Change in the state of each patient's fatigue was measured 6 months after entry. RESULTS: Fifty-two consecutive patients entered the study. The diagnoses associated with fatigue were a medical disorder in 25 patients, depression in 10 patients, and no definitive diagnosis in 18 patients. The mean cost of diagnostic testing was $131. At 6 months, 37 of 52 patients (72%) reported improvement in or resolution of their fatigue. CONCLUSION: In a primary care setting, many patients presenting with persistent fatigue have an associated, treatable disease that can be determined using a cost-effective, clinically directed approach. Most will experience an improvement in their fatigue.

Herpes zoster in patients with rheumatoid arthritis treated with weekly, low-dose methotrexate.

PURPOSE: Herpes zoster occurred in nine patients with methotrexate-treated rheumatoid arthritis. We compared these patients to a large group of methotrexate-treated rheumatoid arthritis patients in order to uncover potential factors explaining the occurrence of herpes zoster. PATIENTS AND METHODS: Data from 187 patients taking methotrexate were reviewed and compared with data from another nine patients who developed herpes zoster while taking the drug for rheumatoid arthritis, all from the same university-based arthritis clinic. Literature pertinent to infection in rheumatoid arthritis patients treated with methotrexate is reviewed. RESULTS: Herpes zoster occurred in 14.5 cases per 1,000 patient-years in our methotrexate-treated rheumatoid arthritis patients, as compared with the general population incidence of 1.3 to 4.8 cases per 1,000 patient-years. The infection was unrelated to duration of methotrexate usage, prednisone treatment, or the co-existence of diabetes mellitus, but appeared to occur in patients with high titers of rheumatoid factor and an overall longer duration of rheumatoid arthritis. There were no cases of systemic dissemination or recurrence of herpes zoster despite 27.4 years cumulative follow-up on continued methotrexate therapy. CONCLUSIONS: Herpes zoster may occur more frequently in patients with rheumatoid arthritis treated with low-dose methotrexate than in the general population. Herpes zoster in rheumatoid arthritis patients treated with methotrexate appears to be self-limited, benign, and statistically related to methotrexate use in the presence of longer-term rheumatoid disease.