Recombinant factor IX Fc fusion protein was effective, both as prophylaxis and in the treatment of bleeding episodes in previously untreated boys (< 18 years of age) with hemophilia B, according to Beatrice Nolan, MD, of Children’s Health Ireland at Crumlin, Dublin, and colleagues.

PUPs B-LONG is an open-label, single-arm, multicenter, phase 3 trial (Clinicaltrials.gov: NCT02234310) of rFIXFc in 33 previously untreated patients (PUPs) with hemophilia B; 79% of the patients were younger than 1 year of age at study entry. The primary endpoint was occurrence of inhibitor development, with a secondary endpoint of annualized bleed rate, according to the results of the study, published online in Blood Advances.

At the onset of the study, 22 patients (67%) received on-demand treatment and 11 (33%) started with a prophylactic regimen. Seventeen (77%) of 22 patients who initially received on-demand treatment subsequently switched to prophylaxis, for a total of 28 patients receiving prophylaxis during the study, according to the researchers. Twenty-seven patients (82%) completed the study, and six (18%) discontinued early.
 

Promising results

The median patient annualized bleeding rate was 1.24 for patients receiving prophylaxis. Most (85%) bleeding episodes required only one infusion for bleed resolution, according to the researchers.

One patient developed a low-titer inhibitor after 11 exposure days to rFIXFc; no high-titer inhibitors were detected. However, 23 patients (70%) had 58 treatment-emergent serious adverse events, of which 2 were assessed as related to treatment (FIX inhibition and hypersensitivity in 1 patient, resulting in withdrawal).

“rFIXFc was generally well tolerated. The incidence of inhibitor development was consistent with other FIX products, with 1 low-titer inhibitor and no high-titer inhibitors detected. In addition, rFIXFc was effective, both as prophylaxis and in the treatment of bleeding episodes,” the researchers concluded.

The PUPs B-LONG study was sponsored by Sanofi and Sobi. Dr. Nolan reported personal fees from Sobi and sponsorship from Sanofi and several other pharmaceutical companies. The other authors reported financial support from a variety of pharmaceutical companies.

[email protected]

Recombinant factor IX Fc fusion protein was effective, both as prophylaxis and in the treatment of bleeding episodes in previously untreated boys (< 18 years of age) with hemophilia B, according to Beatrice Nolan, MD, of Children’s Health Ireland at Crumlin, Dublin, and colleagues.

PUPs B-LONG is an open-label, single-arm, multicenter, phase 3 trial (Clinicaltrials.gov: NCT02234310) of rFIXFc in 33 previously untreated patients (PUPs) with hemophilia B; 79% of the patients were younger than 1 year of age at study entry. The primary endpoint was occurrence of inhibitor development, with a secondary endpoint of annualized bleed rate, according to the results of the study, published online in Blood Advances.

At the onset of the study, 22 patients (67%) received on-demand treatment and 11 (33%) started with a prophylactic regimen. Seventeen (77%) of 22 patients who initially received on-demand treatment subsequently switched to prophylaxis, for a total of 28 patients receiving prophylaxis during the study, according to the researchers. Twenty-seven patients (82%) completed the study, and six (18%) discontinued early.
 

Promising results

The median patient annualized bleeding rate was 1.24 for patients receiving prophylaxis. Most (85%) bleeding episodes required only one infusion for bleed resolution, according to the researchers.

One patient developed a low-titer inhibitor after 11 exposure days to rFIXFc; no high-titer inhibitors were detected. However, 23 patients (70%) had 58 treatment-emergent serious adverse events, of which 2 were assessed as related to treatment (FIX inhibition and hypersensitivity in 1 patient, resulting in withdrawal).

“rFIXFc was generally well tolerated. The incidence of inhibitor development was consistent with other FIX products, with 1 low-titer inhibitor and no high-titer inhibitors detected. In addition, rFIXFc was effective, both as prophylaxis and in the treatment of bleeding episodes,” the researchers concluded.

The PUPs B-LONG study was sponsored by Sanofi and Sobi. Dr. Nolan reported personal fees from Sobi and sponsorship from Sanofi and several other pharmaceutical companies. The other authors reported financial support from a variety of pharmaceutical companies.

[email protected]

Recombinant factor IX Fc fusion protein was effective, both as prophylaxis and in the treatment of bleeding episodes in previously untreated boys (< 18 years of age) with hemophilia B, according to Beatrice Nolan, MD, of Children’s Health Ireland at Crumlin, Dublin, and colleagues.

PUPs B-LONG is an open-label, single-arm, multicenter, phase 3 trial (Clinicaltrials.gov: NCT02234310) of rFIXFc in 33 previously untreated patients (PUPs) with hemophilia B; 79% of the patients were younger than 1 year of age at study entry. The primary endpoint was occurrence of inhibitor development, with a secondary endpoint of annualized bleed rate, according to the results of the study, published online in Blood Advances.

At the onset of the study, 22 patients (67%) received on-demand treatment and 11 (33%) started with a prophylactic regimen. Seventeen (77%) of 22 patients who initially received on-demand treatment subsequently switched to prophylaxis, for a total of 28 patients receiving prophylaxis during the study, according to the researchers. Twenty-seven patients (82%) completed the study, and six (18%) discontinued early.
 

Promising results

The median patient annualized bleeding rate was 1.24 for patients receiving prophylaxis. Most (85%) bleeding episodes required only one infusion for bleed resolution, according to the researchers.

One patient developed a low-titer inhibitor after 11 exposure days to rFIXFc; no high-titer inhibitors were detected. However, 23 patients (70%) had 58 treatment-emergent serious adverse events, of which 2 were assessed as related to treatment (FIX inhibition and hypersensitivity in 1 patient, resulting in withdrawal).

“rFIXFc was generally well tolerated. The incidence of inhibitor development was consistent with other FIX products, with 1 low-titer inhibitor and no high-titer inhibitors detected. In addition, rFIXFc was effective, both as prophylaxis and in the treatment of bleeding episodes,” the researchers concluded.

The PUPs B-LONG study was sponsored by Sanofi and Sobi. Dr. Nolan reported personal fees from Sobi and sponsorship from Sanofi and several other pharmaceutical companies. The other authors reported financial support from a variety of pharmaceutical companies.

[email protected]

The Diagnosis: Tinea Pseudoimbricata

Tinea pseudoimbricata and tinea indecisiva are synonyms describing cases of tinea corporis that manifest in scaly plaques in concentric rings evocative of those present in tinea imbricata. However, in contrast to tinea imbricata, cases of tinea pseudoimbricata are caused by dermatophytes other than Trichophyton concentricum. ¹ Tinea pseudoimbricata usually presents in association with immunosuppression, either systemic or local, and can be produced by application of topical medications such as corticosteroids.² Mask-Bull et al³ reported the case of a 21-year-old man in the United States with no history of immunosuppressive conditions who presented with scaly erythematous annular plaques on the lateral neck that resolved with 2 pulsed doses of terbinafine. Potassium hydroxide preparation and fungal culture were both consistent with Trichophyton tonsurans.³

Trichophyton concentricum is an anthropophilic species of dermatophyte endemic to areas within the South Pacific, Southeast Asia, and Central and South America. Infection with T concentricum produces tinea imbricata, which presents with concentric, scaly, annular rings. Cutaneous lesions of tinea imbricata caused by T concentricum have a more generalized distribution and more densely grouped, concentric circles than the cutaneous findings seen in patients with tinea pseudoimbricata.⁴ Affected patients typically demonstrate negative delayed-type hypersensitivity to T concentricum cytoplasmic antigen and T-lymphocyte hyporeactivity, which may contribute to the development of sequential waves of scaling observed in tinea imbricata.⁵

Trichophyton rubrum, the most common cause of tinea corporis, has been reported to cause some cases of tinea pseudoimbricata (indecisiva).^1,2 It utilizes keratinases such as subtilisins (Sub3 and Sub4), leucine aminopeptidases (Lap1 and Lap2), and dipeptidyl peptidases (DppIV and DppV) to invade the skin. Once inside, mannans, glycoprotein constituents of the cell wall, are released and bind to the cell surface of mononuclear phagocytes, subsequently moving into the cell by phagocytosis, thereafter interfering with RNA synthesis that is necessary for presentation of antigens to appropriate T cells and allowing for initiation of chronic infection.^6,7 The cytotoxic response to superficial dermatophyte infection is triggered by major histocompatibility complex class I molecule activation of CD8⁺ cells.^6,8

Our case is of interest given the localization of the superficial dermatophyte infection to only vitiliginous skin. This distribution and appearance while undergoing narrowband UVB (NB-UVB) treatment is rare. We postulate that our patient likely represents a case of locus minoris resistentiae, a phenomenon in which an area of skin exhibits a compromised immune microenvironment that predisposes it to disease.⁹

In vitiligo, NB-UVB modulates the immune response by increasing IL-10, thereby promoting regulatory T-cell differentiation with suppression of autoreactive T cells and induction of direct T-lymphocyte apoptosis.^10,11 Although the mechanism accounting for our patient’s presentation is unknown, we suspect NB-UVB–induced immunosuppression enabled persistence of the dermatophyte infection. The localization of the infection to the vitiliginous patches may result from the greater penetration of the UV light relative to the surrounding, normally pigmented skin. This relative difference in UV penetration would be expected to result in increased immunosuppression in the vitiliginous lesions and enhanced susceptibility to the fungal organisms.

Erythema annulare centrifugum is characterized by annular lesions with a trailing scale instead of the concentric rings seen in tinea pseudoimbricata. Erythema marginatum is seen in acute rheumatic fever and presents with a transient nonpruritic rash, usually on the trunk or extremities. Erythema migrans presents with fewer lesions that are less circinate in shape, and the patient often has a history of a tick bite. Tinea imbricata is caused by T concentricum, while tinea pseudoimbricata is caused by T tonsurans and other dermatophytes.

With the increasing use of immunosuppressant drugs, the prevalence of tinea pseudoimbricata is hypothesized to increase.¹ The presence of tinea pseudoimbricata should alert dermatologists to the possible overuse of topical corticosteroids, and other forms of immunosuppression also should be considered.

The Diagnosis: Tinea Pseudoimbricata

Tinea pseudoimbricata and tinea indecisiva are synonyms describing cases of tinea corporis that manifest in scaly plaques in concentric rings evocative of those present in tinea imbricata. However, in contrast to tinea imbricata, cases of tinea pseudoimbricata are caused by dermatophytes other than Trichophyton concentricum. ¹ Tinea pseudoimbricata usually presents in association with immunosuppression, either systemic or local, and can be produced by application of topical medications such as corticosteroids.² Mask-Bull et al³ reported the case of a 21-year-old man in the United States with no history of immunosuppressive conditions who presented with scaly erythematous annular plaques on the lateral neck that resolved with 2 pulsed doses of terbinafine. Potassium hydroxide preparation and fungal culture were both consistent with Trichophyton tonsurans.³

Trichophyton concentricum is an anthropophilic species of dermatophyte endemic to areas within the South Pacific, Southeast Asia, and Central and South America. Infection with T concentricum produces tinea imbricata, which presents with concentric, scaly, annular rings. Cutaneous lesions of tinea imbricata caused by T concentricum have a more generalized distribution and more densely grouped, concentric circles than the cutaneous findings seen in patients with tinea pseudoimbricata.⁴ Affected patients typically demonstrate negative delayed-type hypersensitivity to T concentricum cytoplasmic antigen and T-lymphocyte hyporeactivity, which may contribute to the development of sequential waves of scaling observed in tinea imbricata.⁵

Trichophyton rubrum, the most common cause of tinea corporis, has been reported to cause some cases of tinea pseudoimbricata (indecisiva).^1,2 It utilizes keratinases such as subtilisins (Sub3 and Sub4), leucine aminopeptidases (Lap1 and Lap2), and dipeptidyl peptidases (DppIV and DppV) to invade the skin. Once inside, mannans, glycoprotein constituents of the cell wall, are released and bind to the cell surface of mononuclear phagocytes, subsequently moving into the cell by phagocytosis, thereafter interfering with RNA synthesis that is necessary for presentation of antigens to appropriate T cells and allowing for initiation of chronic infection.^6,7 The cytotoxic response to superficial dermatophyte infection is triggered by major histocompatibility complex class I molecule activation of CD8⁺ cells.^6,8

Our case is of interest given the localization of the superficial dermatophyte infection to only vitiliginous skin. This distribution and appearance while undergoing narrowband UVB (NB-UVB) treatment is rare. We postulate that our patient likely represents a case of locus minoris resistentiae, a phenomenon in which an area of skin exhibits a compromised immune microenvironment that predisposes it to disease.⁹

In vitiligo, NB-UVB modulates the immune response by increasing IL-10, thereby promoting regulatory T-cell differentiation with suppression of autoreactive T cells and induction of direct T-lymphocyte apoptosis.^10,11 Although the mechanism accounting for our patient’s presentation is unknown, we suspect NB-UVB–induced immunosuppression enabled persistence of the dermatophyte infection. The localization of the infection to the vitiliginous patches may result from the greater penetration of the UV light relative to the surrounding, normally pigmented skin. This relative difference in UV penetration would be expected to result in increased immunosuppression in the vitiliginous lesions and enhanced susceptibility to the fungal organisms.

Erythema annulare centrifugum is characterized by annular lesions with a trailing scale instead of the concentric rings seen in tinea pseudoimbricata. Erythema marginatum is seen in acute rheumatic fever and presents with a transient nonpruritic rash, usually on the trunk or extremities. Erythema migrans presents with fewer lesions that are less circinate in shape, and the patient often has a history of a tick bite. Tinea imbricata is caused by T concentricum, while tinea pseudoimbricata is caused by T tonsurans and other dermatophytes.

With the increasing use of immunosuppressant drugs, the prevalence of tinea pseudoimbricata is hypothesized to increase.¹ The presence of tinea pseudoimbricata should alert dermatologists to the possible overuse of topical corticosteroids, and other forms of immunosuppression also should be considered.

The Diagnosis: Tinea Pseudoimbricata

Tinea pseudoimbricata and tinea indecisiva are synonyms describing cases of tinea corporis that manifest in scaly plaques in concentric rings evocative of those present in tinea imbricata. However, in contrast to tinea imbricata, cases of tinea pseudoimbricata are caused by dermatophytes other than Trichophyton concentricum. ¹ Tinea pseudoimbricata usually presents in association with immunosuppression, either systemic or local, and can be produced by application of topical medications such as corticosteroids.² Mask-Bull et al³ reported the case of a 21-year-old man in the United States with no history of immunosuppressive conditions who presented with scaly erythematous annular plaques on the lateral neck that resolved with 2 pulsed doses of terbinafine. Potassium hydroxide preparation and fungal culture were both consistent with Trichophyton tonsurans.³

Trichophyton concentricum is an anthropophilic species of dermatophyte endemic to areas within the South Pacific, Southeast Asia, and Central and South America. Infection with T concentricum produces tinea imbricata, which presents with concentric, scaly, annular rings. Cutaneous lesions of tinea imbricata caused by T concentricum have a more generalized distribution and more densely grouped, concentric circles than the cutaneous findings seen in patients with tinea pseudoimbricata.⁴ Affected patients typically demonstrate negative delayed-type hypersensitivity to T concentricum cytoplasmic antigen and T-lymphocyte hyporeactivity, which may contribute to the development of sequential waves of scaling observed in tinea imbricata.⁵

Trichophyton rubrum, the most common cause of tinea corporis, has been reported to cause some cases of tinea pseudoimbricata (indecisiva).^1,2 It utilizes keratinases such as subtilisins (Sub3 and Sub4), leucine aminopeptidases (Lap1 and Lap2), and dipeptidyl peptidases (DppIV and DppV) to invade the skin. Once inside, mannans, glycoprotein constituents of the cell wall, are released and bind to the cell surface of mononuclear phagocytes, subsequently moving into the cell by phagocytosis, thereafter interfering with RNA synthesis that is necessary for presentation of antigens to appropriate T cells and allowing for initiation of chronic infection.^6,7 The cytotoxic response to superficial dermatophyte infection is triggered by major histocompatibility complex class I molecule activation of CD8⁺ cells.^6,8

Our case is of interest given the localization of the superficial dermatophyte infection to only vitiliginous skin. This distribution and appearance while undergoing narrowband UVB (NB-UVB) treatment is rare. We postulate that our patient likely represents a case of locus minoris resistentiae, a phenomenon in which an area of skin exhibits a compromised immune microenvironment that predisposes it to disease.⁹

In vitiligo, NB-UVB modulates the immune response by increasing IL-10, thereby promoting regulatory T-cell differentiation with suppression of autoreactive T cells and induction of direct T-lymphocyte apoptosis.^10,11 Although the mechanism accounting for our patient’s presentation is unknown, we suspect NB-UVB–induced immunosuppression enabled persistence of the dermatophyte infection. The localization of the infection to the vitiliginous patches may result from the greater penetration of the UV light relative to the surrounding, normally pigmented skin. This relative difference in UV penetration would be expected to result in increased immunosuppression in the vitiliginous lesions and enhanced susceptibility to the fungal organisms.

Erythema annulare centrifugum is characterized by annular lesions with a trailing scale instead of the concentric rings seen in tinea pseudoimbricata. Erythema marginatum is seen in acute rheumatic fever and presents with a transient nonpruritic rash, usually on the trunk or extremities. Erythema migrans presents with fewer lesions that are less circinate in shape, and the patient often has a history of a tick bite. Tinea imbricata is caused by T concentricum, while tinea pseudoimbricata is caused by T tonsurans and other dermatophytes.

With the increasing use of immunosuppressant drugs, the prevalence of tinea pseudoimbricata is hypothesized to increase.¹ The presence of tinea pseudoimbricata should alert dermatologists to the possible overuse of topical corticosteroids, and other forms of immunosuppression also should be considered.

The Food and Drug Administration has approved the neoadjuvant use of pembrolizumab (Keytruda) in combination with chemotherapy for patients with high-risk early-stage triple-negative breast cancer (TNBC) and as single-agent adjuvant treatment to be continued after surgery.

This approval is based on findings from the randomized, phase 3 KEYNOTE-522 trial, which showed significantly prolonged event-free survival with the pembrolizumab regimen versus neoadjuvant chemotherapy alone for previously untreated stage II-III TNBC.

This is the 30th indication for pembrolizumab in the United States.

The immunotherapy received accelerated approval in November 2020 for adjuvant use in locally recurrent unresectable or metastatic TNBC for patients whose tumors express programmed death–ligand-1, as determined by an FDA-approved test. That accelerated approval was based on results from the phase 3 KEYNOTE-355 trial. The approval has now been converted to a full approval on the basis of confirmatory data from the KEYNOTE-522, notes a statement from the manufacturer, Merck.

“Triple-negative is a difficult-to-treat type of breast cancer that unfortunately is more common in the U.S. in younger women and in Black women,” commented Vicki Goodman, MD, vice president of clinical research, Merck Research Laboratories. “We are proud to offer a new treatment option for patients faced with this challenging cancer. This neoadjuvant and adjuvant combination with pembrolizumab is the first immunotherapy regimen to be approved in high-risk early-stage TNBC, marking a meaningful milestone for the breast cancer community.”

In KEYNOTE-522, participants were randomly assigned to receive either placebo or pembrolizumab plus chemotherapy with carboplatin and paclitaxel, followed by doxorubicin or epirubicin and cyclophosphamide before surgery, as well as placebo or pembrolizumab as single-agent therapy after surgery.

The results from this trial, first reported in 2019 at the annual meeting of the European Society of Medical Oncology, showed that, for patients in the pembrolizumab arm of the trial, the pathological complete response rate was nearly 65% versus 51% among the patients who received placebo. The benefit was seen both in those whose tumors were positive and those whose tumors were negative for PD-L1 expression.

Among patients in the pembrolizumab arm, there was a 37% reduction in the risk for disease progression that precluded definitive surgery, a local/distant recurrence, a second primary cancer, or death from any cause (hazard ratio, 0.63).

Pembrolizumab can be associated with immune-mediated adverse reactions that may be severe or fatal, Merck noted.

These events “can occur in any organ system or tissue and can affect more than one body system simultaneously. Immune-mediated adverse reactions can occur at any time during or after treatment,” Merck warned. The company states: “Early identification and management of immune-mediated adverse reactions are essential.”

Treatment may need to be withheld or permanently discontinued, and corticosteroids may be needed, depending on the severity of the adverse reaction, according to the statement.

Infusion-related reactions can also occur. Because of its mechanism of action, pembrolizumab can cause fetal harm when administered to women during pregnancy.

A version of this article first appeared on Medscape.com.

The Food and Drug Administration has approved the neoadjuvant use of pembrolizumab (Keytruda) in combination with chemotherapy for patients with high-risk early-stage triple-negative breast cancer (TNBC) and as single-agent adjuvant treatment to be continued after surgery.

This approval is based on findings from the randomized, phase 3 KEYNOTE-522 trial, which showed significantly prolonged event-free survival with the pembrolizumab regimen versus neoadjuvant chemotherapy alone for previously untreated stage II-III TNBC.

This is the 30th indication for pembrolizumab in the United States.

The immunotherapy received accelerated approval in November 2020 for adjuvant use in locally recurrent unresectable or metastatic TNBC for patients whose tumors express programmed death–ligand-1, as determined by an FDA-approved test. That accelerated approval was based on results from the phase 3 KEYNOTE-355 trial. The approval has now been converted to a full approval on the basis of confirmatory data from the KEYNOTE-522, notes a statement from the manufacturer, Merck.

“Triple-negative is a difficult-to-treat type of breast cancer that unfortunately is more common in the U.S. in younger women and in Black women,” commented Vicki Goodman, MD, vice president of clinical research, Merck Research Laboratories. “We are proud to offer a new treatment option for patients faced with this challenging cancer. This neoadjuvant and adjuvant combination with pembrolizumab is the first immunotherapy regimen to be approved in high-risk early-stage TNBC, marking a meaningful milestone for the breast cancer community.”

In KEYNOTE-522, participants were randomly assigned to receive either placebo or pembrolizumab plus chemotherapy with carboplatin and paclitaxel, followed by doxorubicin or epirubicin and cyclophosphamide before surgery, as well as placebo or pembrolizumab as single-agent therapy after surgery.

The results from this trial, first reported in 2019 at the annual meeting of the European Society of Medical Oncology, showed that, for patients in the pembrolizumab arm of the trial, the pathological complete response rate was nearly 65% versus 51% among the patients who received placebo. The benefit was seen both in those whose tumors were positive and those whose tumors were negative for PD-L1 expression.

Among patients in the pembrolizumab arm, there was a 37% reduction in the risk for disease progression that precluded definitive surgery, a local/distant recurrence, a second primary cancer, or death from any cause (hazard ratio, 0.63).

Pembrolizumab can be associated with immune-mediated adverse reactions that may be severe or fatal, Merck noted.

These events “can occur in any organ system or tissue and can affect more than one body system simultaneously. Immune-mediated adverse reactions can occur at any time during or after treatment,” Merck warned. The company states: “Early identification and management of immune-mediated adverse reactions are essential.”

Treatment may need to be withheld or permanently discontinued, and corticosteroids may be needed, depending on the severity of the adverse reaction, according to the statement.

Infusion-related reactions can also occur. Because of its mechanism of action, pembrolizumab can cause fetal harm when administered to women during pregnancy.

A version of this article first appeared on Medscape.com.

The Food and Drug Administration has approved the neoadjuvant use of pembrolizumab (Keytruda) in combination with chemotherapy for patients with high-risk early-stage triple-negative breast cancer (TNBC) and as single-agent adjuvant treatment to be continued after surgery.

This approval is based on findings from the randomized, phase 3 KEYNOTE-522 trial, which showed significantly prolonged event-free survival with the pembrolizumab regimen versus neoadjuvant chemotherapy alone for previously untreated stage II-III TNBC.

This is the 30th indication for pembrolizumab in the United States.

The immunotherapy received accelerated approval in November 2020 for adjuvant use in locally recurrent unresectable or metastatic TNBC for patients whose tumors express programmed death–ligand-1, as determined by an FDA-approved test. That accelerated approval was based on results from the phase 3 KEYNOTE-355 trial. The approval has now been converted to a full approval on the basis of confirmatory data from the KEYNOTE-522, notes a statement from the manufacturer, Merck.

“Triple-negative is a difficult-to-treat type of breast cancer that unfortunately is more common in the U.S. in younger women and in Black women,” commented Vicki Goodman, MD, vice president of clinical research, Merck Research Laboratories. “We are proud to offer a new treatment option for patients faced with this challenging cancer. This neoadjuvant and adjuvant combination with pembrolizumab is the first immunotherapy regimen to be approved in high-risk early-stage TNBC, marking a meaningful milestone for the breast cancer community.”

In KEYNOTE-522, participants were randomly assigned to receive either placebo or pembrolizumab plus chemotherapy with carboplatin and paclitaxel, followed by doxorubicin or epirubicin and cyclophosphamide before surgery, as well as placebo or pembrolizumab as single-agent therapy after surgery.

The results from this trial, first reported in 2019 at the annual meeting of the European Society of Medical Oncology, showed that, for patients in the pembrolizumab arm of the trial, the pathological complete response rate was nearly 65% versus 51% among the patients who received placebo. The benefit was seen both in those whose tumors were positive and those whose tumors were negative for PD-L1 expression.

Among patients in the pembrolizumab arm, there was a 37% reduction in the risk for disease progression that precluded definitive surgery, a local/distant recurrence, a second primary cancer, or death from any cause (hazard ratio, 0.63).

Pembrolizumab can be associated with immune-mediated adverse reactions that may be severe or fatal, Merck noted.

These events “can occur in any organ system or tissue and can affect more than one body system simultaneously. Immune-mediated adverse reactions can occur at any time during or after treatment,” Merck warned. The company states: “Early identification and management of immune-mediated adverse reactions are essential.”

Treatment may need to be withheld or permanently discontinued, and corticosteroids may be needed, depending on the severity of the adverse reaction, according to the statement.

Infusion-related reactions can also occur. Because of its mechanism of action, pembrolizumab can cause fetal harm when administered to women during pregnancy.

A version of this article first appeared on Medscape.com.

The CDC has reported two clusters of Candida auris infections resistant to all antifungal medications in long-term care facilities in 2021. Because these panresistant infections occurred without any exposure to antifungal drugs, the cases are even more worrisome. These clusters are the first time such nosocomial transmission has been detected.

In the District of Columbia, three panresistant isolates were discovered through screening for skin colonization with resistant organisms at a long-term acute care facility (LTAC) that cares for patients who are seriously ill, often on mechanical ventilation.

In Texas, the resistant organisms were found both by screening and in specimens from ill patients at an LTAC and a short-term acute care hospital that share patients. Two were panresistant, and five others were resistant to fluconazole and echinocandins.

These clusters occurred simultaneously and independently of each other; there were no links between the two institutions.

Colonization of skin with C. auris can lead to invasive infections in 5%-10% of affected patients. Routine skin surveillance cultures are not commonly done for Candida, although perirectal cultures for vancomycin-resistant enterococci and nasal swabs for MRSA have been done for years. Some areas, like Los Angeles, have recommended screening for C. auris in high-risk patients – defined as those who were on a ventilator or had a tracheostomy admitted from an LTAC or skilled nursing facility in Los Angeles County, New York, New Jersey, or Illinois.

In the past, about 85% of C. auris isolates in the United States have been resistant to azoles (for example, fluconazole), 33% to amphotericin B, and 1% to echinocandins. Because of generally strong susceptibility, an echinocandin such as micafungin or caspofungin has been the drug of choice for an invasive Candida infection.

C. auris is particularly difficult to deal with for several reasons. First, it can continue to live in the environment, on both dry or moist surfaces, for up to 2 weeks. Outbreaks have occurred both from hand (person-to-person) transmission or via inanimate surfaces that have become contaminated. Equally troublesome is that people become colonized with the yeast indefinitely.

Meghan Lyman, MD, of the fungal diseases branch of the CDC’s National Center for Emerging and Zoonotic Infectious Diseases, said in an interview that facilities might be slow in recognizing the problem and in identifying the organism. “We encounter problems in noninvasive specimens, especially urine,” Dr. Lyman added.

“Sometimes ... they consider Candida [to represent] colonization so they will often not speciate it.” She emphasized the need for facilities that care for ventilated patients to consider screening. “Higher priority ... are places in areas where there’s a lot of C. auris transmission or in nearby areas that are likely to get introductions.” Even those that do speciate may have difficulty identifying C. auris.

Further, Dr. Lyman stressed “the importance of antifungal susceptibility testing and testing for resistance. Because that’s also something that’s not widely available at all hospitals and clinical labs ... you can send it to the [CDC’s] antimicrobial resistance lab network” for testing.

COVID-19 has brought particular challenges. Rodney E. Rohde, PhD, MS, professor and chair, clinical lab science program, Texas State University, San Marcos, said in an interview that he is worried about all the steroids and broad-spectrum antibiotics patients receive.

They’re “being given medical interventions, whether it’s ventilators or [extracorporeal membrane oxygenation] or IVs or central lines or catheters for UTIs and you’re creating highways, right for something that may be right there,” said Dr. Rohde, who was not involved in the CDC study. “It’s a perfect storm, not just for C. auris, but I worry about bacterial resistance agents, too, like MRSA and so forth, having kind of a spike in those types of infections with COVID. So, it’s kind of a doubly dangerous time, I think.”

Multiresistant bacteria are a major health problem, causing illnesses in 2.8 million people annually in the United States, and causing about 35,000 deaths.

Dr. Rohde raised another, rarely mentioned concern. “We’re in crisis mode. People are leaving our field more than they ever had before. The medical laboratory is being decimated because people have burned out after these past 14 months. And so I worry just about competent medical laboratory professionals that are on board to deal with these types of other crises that are popping up within hospitals and long-term care facilities. It kind of keeps me awake.”

Dr. Rohde and Dr. Lyman shared their concern that COVID caused a decrease in screening for other infections and drug-resistant organisms. Bare-bones staffing and shortages of personal protective equipment have likely fueled the spread of these infections as well.

In an outbreak of C. auris in a Florida hospital’s COVID unit in 2020, 35 of 67 patients became colonized, and 6 became ill. The epidemiologists investigating thought that contaminated gowns or gloves, computers, and other equipment were likely sources of transmission.

Low pay, especially in nursing homes, is another problem Dr. Rohde mentioned. It’s an additional problem in both acute and long-term care that “some of the lowest-paid people are the environmental services people, and so the turnover is crazy.” Yet, we rely on them to keep everyone safe. He added that, in addition to pay, he “tries to give them the appreciation and the recognition that they really deserve.”

There are a few specific measures that can be taken to protect patients. Dr. Lyman concluded. “The best way is identifying cases and really ensuring good infection control to prevent the spread.” It’s back to basics – limiting broad-spectrum antibiotics and invasive medical devices, and especially good handwashing and thorough cleaning.

Dr. Lyman and Dr. Rohde have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

The CDC has reported two clusters of Candida auris infections resistant to all antifungal medications in long-term care facilities in 2021. Because these panresistant infections occurred without any exposure to antifungal drugs, the cases are even more worrisome. These clusters are the first time such nosocomial transmission has been detected.

In the District of Columbia, three panresistant isolates were discovered through screening for skin colonization with resistant organisms at a long-term acute care facility (LTAC) that cares for patients who are seriously ill, often on mechanical ventilation.

In Texas, the resistant organisms were found both by screening and in specimens from ill patients at an LTAC and a short-term acute care hospital that share patients. Two were panresistant, and five others were resistant to fluconazole and echinocandins.

These clusters occurred simultaneously and independently of each other; there were no links between the two institutions.

Colonization of skin with C. auris can lead to invasive infections in 5%-10% of affected patients. Routine skin surveillance cultures are not commonly done for Candida, although perirectal cultures for vancomycin-resistant enterococci and nasal swabs for MRSA have been done for years. Some areas, like Los Angeles, have recommended screening for C. auris in high-risk patients – defined as those who were on a ventilator or had a tracheostomy admitted from an LTAC or skilled nursing facility in Los Angeles County, New York, New Jersey, or Illinois.

In the past, about 85% of C. auris isolates in the United States have been resistant to azoles (for example, fluconazole), 33% to amphotericin B, and 1% to echinocandins. Because of generally strong susceptibility, an echinocandin such as micafungin or caspofungin has been the drug of choice for an invasive Candida infection.

C. auris is particularly difficult to deal with for several reasons. First, it can continue to live in the environment, on both dry or moist surfaces, for up to 2 weeks. Outbreaks have occurred both from hand (person-to-person) transmission or via inanimate surfaces that have become contaminated. Equally troublesome is that people become colonized with the yeast indefinitely.

Meghan Lyman, MD, of the fungal diseases branch of the CDC’s National Center for Emerging and Zoonotic Infectious Diseases, said in an interview that facilities might be slow in recognizing the problem and in identifying the organism. “We encounter problems in noninvasive specimens, especially urine,” Dr. Lyman added.

“Sometimes ... they consider Candida [to represent] colonization so they will often not speciate it.” She emphasized the need for facilities that care for ventilated patients to consider screening. “Higher priority ... are places in areas where there’s a lot of C. auris transmission or in nearby areas that are likely to get introductions.” Even those that do speciate may have difficulty identifying C. auris.

Further, Dr. Lyman stressed “the importance of antifungal susceptibility testing and testing for resistance. Because that’s also something that’s not widely available at all hospitals and clinical labs ... you can send it to the [CDC’s] antimicrobial resistance lab network” for testing.

COVID-19 has brought particular challenges. Rodney E. Rohde, PhD, MS, professor and chair, clinical lab science program, Texas State University, San Marcos, said in an interview that he is worried about all the steroids and broad-spectrum antibiotics patients receive.

They’re “being given medical interventions, whether it’s ventilators or [extracorporeal membrane oxygenation] or IVs or central lines or catheters for UTIs and you’re creating highways, right for something that may be right there,” said Dr. Rohde, who was not involved in the CDC study. “It’s a perfect storm, not just for C. auris, but I worry about bacterial resistance agents, too, like MRSA and so forth, having kind of a spike in those types of infections with COVID. So, it’s kind of a doubly dangerous time, I think.”

Multiresistant bacteria are a major health problem, causing illnesses in 2.8 million people annually in the United States, and causing about 35,000 deaths.

Dr. Rohde raised another, rarely mentioned concern. “We’re in crisis mode. People are leaving our field more than they ever had before. The medical laboratory is being decimated because people have burned out after these past 14 months. And so I worry just about competent medical laboratory professionals that are on board to deal with these types of other crises that are popping up within hospitals and long-term care facilities. It kind of keeps me awake.”

Dr. Rohde and Dr. Lyman shared their concern that COVID caused a decrease in screening for other infections and drug-resistant organisms. Bare-bones staffing and shortages of personal protective equipment have likely fueled the spread of these infections as well.

In an outbreak of C. auris in a Florida hospital’s COVID unit in 2020, 35 of 67 patients became colonized, and 6 became ill. The epidemiologists investigating thought that contaminated gowns or gloves, computers, and other equipment were likely sources of transmission.

Low pay, especially in nursing homes, is another problem Dr. Rohde mentioned. It’s an additional problem in both acute and long-term care that “some of the lowest-paid people are the environmental services people, and so the turnover is crazy.” Yet, we rely on them to keep everyone safe. He added that, in addition to pay, he “tries to give them the appreciation and the recognition that they really deserve.”

There are a few specific measures that can be taken to protect patients. Dr. Lyman concluded. “The best way is identifying cases and really ensuring good infection control to prevent the spread.” It’s back to basics – limiting broad-spectrum antibiotics and invasive medical devices, and especially good handwashing and thorough cleaning.

Dr. Lyman and Dr. Rohde have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

The CDC has reported two clusters of Candida auris infections resistant to all antifungal medications in long-term care facilities in 2021. Because these panresistant infections occurred without any exposure to antifungal drugs, the cases are even more worrisome. These clusters are the first time such nosocomial transmission has been detected.

In the District of Columbia, three panresistant isolates were discovered through screening for skin colonization with resistant organisms at a long-term acute care facility (LTAC) that cares for patients who are seriously ill, often on mechanical ventilation.

In Texas, the resistant organisms were found both by screening and in specimens from ill patients at an LTAC and a short-term acute care hospital that share patients. Two were panresistant, and five others were resistant to fluconazole and echinocandins.

These clusters occurred simultaneously and independently of each other; there were no links between the two institutions.

Colonization of skin with C. auris can lead to invasive infections in 5%-10% of affected patients. Routine skin surveillance cultures are not commonly done for Candida, although perirectal cultures for vancomycin-resistant enterococci and nasal swabs for MRSA have been done for years. Some areas, like Los Angeles, have recommended screening for C. auris in high-risk patients – defined as those who were on a ventilator or had a tracheostomy admitted from an LTAC or skilled nursing facility in Los Angeles County, New York, New Jersey, or Illinois.

In the past, about 85% of C. auris isolates in the United States have been resistant to azoles (for example, fluconazole), 33% to amphotericin B, and 1% to echinocandins. Because of generally strong susceptibility, an echinocandin such as micafungin or caspofungin has been the drug of choice for an invasive Candida infection.

C. auris is particularly difficult to deal with for several reasons. First, it can continue to live in the environment, on both dry or moist surfaces, for up to 2 weeks. Outbreaks have occurred both from hand (person-to-person) transmission or via inanimate surfaces that have become contaminated. Equally troublesome is that people become colonized with the yeast indefinitely.

Meghan Lyman, MD, of the fungal diseases branch of the CDC’s National Center for Emerging and Zoonotic Infectious Diseases, said in an interview that facilities might be slow in recognizing the problem and in identifying the organism. “We encounter problems in noninvasive specimens, especially urine,” Dr. Lyman added.

“Sometimes ... they consider Candida [to represent] colonization so they will often not speciate it.” She emphasized the need for facilities that care for ventilated patients to consider screening. “Higher priority ... are places in areas where there’s a lot of C. auris transmission or in nearby areas that are likely to get introductions.” Even those that do speciate may have difficulty identifying C. auris.

Further, Dr. Lyman stressed “the importance of antifungal susceptibility testing and testing for resistance. Because that’s also something that’s not widely available at all hospitals and clinical labs ... you can send it to the [CDC’s] antimicrobial resistance lab network” for testing.

COVID-19 has brought particular challenges. Rodney E. Rohde, PhD, MS, professor and chair, clinical lab science program, Texas State University, San Marcos, said in an interview that he is worried about all the steroids and broad-spectrum antibiotics patients receive.

They’re “being given medical interventions, whether it’s ventilators or [extracorporeal membrane oxygenation] or IVs or central lines or catheters for UTIs and you’re creating highways, right for something that may be right there,” said Dr. Rohde, who was not involved in the CDC study. “It’s a perfect storm, not just for C. auris, but I worry about bacterial resistance agents, too, like MRSA and so forth, having kind of a spike in those types of infections with COVID. So, it’s kind of a doubly dangerous time, I think.”

Multiresistant bacteria are a major health problem, causing illnesses in 2.8 million people annually in the United States, and causing about 35,000 deaths.

Dr. Rohde raised another, rarely mentioned concern. “We’re in crisis mode. People are leaving our field more than they ever had before. The medical laboratory is being decimated because people have burned out after these past 14 months. And so I worry just about competent medical laboratory professionals that are on board to deal with these types of other crises that are popping up within hospitals and long-term care facilities. It kind of keeps me awake.”

Dr. Rohde and Dr. Lyman shared their concern that COVID caused a decrease in screening for other infections and drug-resistant organisms. Bare-bones staffing and shortages of personal protective equipment have likely fueled the spread of these infections as well.

In an outbreak of C. auris in a Florida hospital’s COVID unit in 2020, 35 of 67 patients became colonized, and 6 became ill. The epidemiologists investigating thought that contaminated gowns or gloves, computers, and other equipment were likely sources of transmission.

Low pay, especially in nursing homes, is another problem Dr. Rohde mentioned. It’s an additional problem in both acute and long-term care that “some of the lowest-paid people are the environmental services people, and so the turnover is crazy.” Yet, we rely on them to keep everyone safe. He added that, in addition to pay, he “tries to give them the appreciation and the recognition that they really deserve.”

There are a few specific measures that can be taken to protect patients. Dr. Lyman concluded. “The best way is identifying cases and really ensuring good infection control to prevent the spread.” It’s back to basics – limiting broad-spectrum antibiotics and invasive medical devices, and especially good handwashing and thorough cleaning.

Dr. Lyman and Dr. Rohde have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Taking midodrine can reduce vasovagal syncope in younger healthy patients, according to a new study.

Vasovagal syncope is the most common cause of fainting and is often triggered by dehydration and upright posture, according to Johns Hopkins Medicine. But it can also be caused by stimuli like the sight of blood or sudden emotional distress. The stimulus causes the heart rate and blood pressure to drop rapidly, according to the Mayo Clinic.

The randomized, placebo-controlled, double-blind trial included 133 patients with recurrent vasovagal syncope and was published in Annals of Internal Medicine. Those that received midodrine were less likely to have one syncope episode (28 of 66 [42%]), compared with those that took the placebo (41 of 67 [61%]). The absolute risk reduction for vasovagal syncope was 19 percentage points (95% confidence interval, 2-36 percentage points).

The study included patients from 25 university hospitals in Canada, the United States, Mexico, and the United Kingdom, who were followed for 12 months. The trial participants were highly symptomatic for vasovagal syncope, having experienced a median of 23 episodes in their lifetime and 5 syncope episodes in the last year, and they had no comorbid conditions.

“We don’t have many arrows in our quiver,” said Robert Sheldon, MD, PhD, a cardiologist at University of Calgary (Alta.) and lead author of the study, referring to the lack of evidence-based treatments for syncope.

For 20 years Dr. Sheldon’s lab has been testing drugs that showed some potential. While a previous study of fludrocortisone (Florinef ) showed some benefit, “[midodrine] was the first to be unequivocally, slam-dunk positive,” he said in an interview.

Earlier trials of midodrine

Other studies have shown midodrine to prevent syncope on tilt tests. There have been two randomized trials where midodrine significantly reduced vasovagal syncope, but one of these was short and in children, and the other one was open label with no placebo control.

“Risk reduction was very high in previous studies,” Dr. Sheldon said in an interview. But, because they were open label, there was a huge placebo effect, he noted.

“There were no adequately done, adequately powered [studies] that have been positive,” Dr. Sheldon added.

New study methods and outcomes

The study published in Annals of Internal Medicine this week included patients over 18 years of age with a Calgary Syncope Symptom Score of at least 2. All were educated on lifestyle measures that can prevent syncopes before beginning to take 5 mg of study drug or placebo three times daily, 4 hours apart.

In these cases, the study authors wrote, “taking medication three times a day seems worth the effort.” But in patients with a lower frequency of episodes, midodrine might not have an adequate payoff.

These results are “impressive,” said Roopinder K. Sandhu, MD, MPH, clinical electrophysiologist at Cedar-Sinai in Los Angeles. “This study demonstrated that midodrine is the first medical therapy, in addition to education and lifestyle measures, to unequivocally pass the scrutiny of an international, placebo-controlled, RCT to show a significant reduction in syncope recurrence in a younger population with frequent syncope events.”

“[Taking midodrine] doesn’t carry the long-term consequence of pacemakers,” she added.

Study limitations

Limitations of the new study include its small size and short observation period, the authors wrote. Additionally, a large proportion of patients enrolled were also from a single center in Calgary that specializes in syncope care. Twenty-seven patients in the trial stopped taking their assigned medication during the year observation period, but the authors concluded these participants “likely would bias the results against midodrine.”

For doctors considering midodrine for their patients, it’s critical to confirm the diagnosis and to try patient education first, Dr. Sheldon advised.

Lifestyle factors like hydration, adequate sodium intake, and squatting or lying down when the syncope is coming on can sufficiently suppress syncopes in two-thirds of patients, he noted.

This is a treatment for young people, Dr. Sandhu said. The median age in the trial was 35, so patients taking midodrine should be younger than 50. Midodrine is also not effective in patients with high blood pressure or heart failure, she said.

“[Midodrine] is easy to use but kind of a pain at first,” Dr. Sheldon noted. Every patient should start out taking 5 mg doses, three times a day – during waking hours. But then you have to adjust the dosage, “and it’s tricky,” he said.

If a patient experiences goosebumps or the sensation of worms crawling in the hair, the dose might be too much, Dr. Sheldon noted.

If the patient is still fainting, first consider when they are fainting, he said. If it’s around the time they should take another dose, it might be trough effect.

Dr. Sandhu was not involved in the study, but Cedar Sinai was a participating center, and she considers Dr. Sheldon to be a mentor. Dr. Sandhu also noted that she has published papers with Dr. Sheldon, who reported no conflicts.

Taking midodrine can reduce vasovagal syncope in younger healthy patients, according to a new study.

Vasovagal syncope is the most common cause of fainting and is often triggered by dehydration and upright posture, according to Johns Hopkins Medicine. But it can also be caused by stimuli like the sight of blood or sudden emotional distress. The stimulus causes the heart rate and blood pressure to drop rapidly, according to the Mayo Clinic.

The randomized, placebo-controlled, double-blind trial included 133 patients with recurrent vasovagal syncope and was published in Annals of Internal Medicine. Those that received midodrine were less likely to have one syncope episode (28 of 66 [42%]), compared with those that took the placebo (41 of 67 [61%]). The absolute risk reduction for vasovagal syncope was 19 percentage points (95% confidence interval, 2-36 percentage points).

The study included patients from 25 university hospitals in Canada, the United States, Mexico, and the United Kingdom, who were followed for 12 months. The trial participants were highly symptomatic for vasovagal syncope, having experienced a median of 23 episodes in their lifetime and 5 syncope episodes in the last year, and they had no comorbid conditions.

“We don’t have many arrows in our quiver,” said Robert Sheldon, MD, PhD, a cardiologist at University of Calgary (Alta.) and lead author of the study, referring to the lack of evidence-based treatments for syncope.

For 20 years Dr. Sheldon’s lab has been testing drugs that showed some potential. While a previous study of fludrocortisone (Florinef ) showed some benefit, “[midodrine] was the first to be unequivocally, slam-dunk positive,” he said in an interview.

Earlier trials of midodrine

Other studies have shown midodrine to prevent syncope on tilt tests. There have been two randomized trials where midodrine significantly reduced vasovagal syncope, but one of these was short and in children, and the other one was open label with no placebo control.

“Risk reduction was very high in previous studies,” Dr. Sheldon said in an interview. But, because they were open label, there was a huge placebo effect, he noted.

“There were no adequately done, adequately powered [studies] that have been positive,” Dr. Sheldon added.

New study methods and outcomes

The study published in Annals of Internal Medicine this week included patients over 18 years of age with a Calgary Syncope Symptom Score of at least 2. All were educated on lifestyle measures that can prevent syncopes before beginning to take 5 mg of study drug or placebo three times daily, 4 hours apart.

In these cases, the study authors wrote, “taking medication three times a day seems worth the effort.” But in patients with a lower frequency of episodes, midodrine might not have an adequate payoff.

These results are “impressive,” said Roopinder K. Sandhu, MD, MPH, clinical electrophysiologist at Cedar-Sinai in Los Angeles. “This study demonstrated that midodrine is the first medical therapy, in addition to education and lifestyle measures, to unequivocally pass the scrutiny of an international, placebo-controlled, RCT to show a significant reduction in syncope recurrence in a younger population with frequent syncope events.”

“[Taking midodrine] doesn’t carry the long-term consequence of pacemakers,” she added.

Study limitations

Limitations of the new study include its small size and short observation period, the authors wrote. Additionally, a large proportion of patients enrolled were also from a single center in Calgary that specializes in syncope care. Twenty-seven patients in the trial stopped taking their assigned medication during the year observation period, but the authors concluded these participants “likely would bias the results against midodrine.”

For doctors considering midodrine for their patients, it’s critical to confirm the diagnosis and to try patient education first, Dr. Sheldon advised.

Lifestyle factors like hydration, adequate sodium intake, and squatting or lying down when the syncope is coming on can sufficiently suppress syncopes in two-thirds of patients, he noted.

This is a treatment for young people, Dr. Sandhu said. The median age in the trial was 35, so patients taking midodrine should be younger than 50. Midodrine is also not effective in patients with high blood pressure or heart failure, she said.

“[Midodrine] is easy to use but kind of a pain at first,” Dr. Sheldon noted. Every patient should start out taking 5 mg doses, three times a day – during waking hours. But then you have to adjust the dosage, “and it’s tricky,” he said.

If a patient experiences goosebumps or the sensation of worms crawling in the hair, the dose might be too much, Dr. Sheldon noted.

If the patient is still fainting, first consider when they are fainting, he said. If it’s around the time they should take another dose, it might be trough effect.

Dr. Sandhu was not involved in the study, but Cedar Sinai was a participating center, and she considers Dr. Sheldon to be a mentor. Dr. Sandhu also noted that she has published papers with Dr. Sheldon, who reported no conflicts.

Taking midodrine can reduce vasovagal syncope in younger healthy patients, according to a new study.

Vasovagal syncope is the most common cause of fainting and is often triggered by dehydration and upright posture, according to Johns Hopkins Medicine. But it can also be caused by stimuli like the sight of blood or sudden emotional distress. The stimulus causes the heart rate and blood pressure to drop rapidly, according to the Mayo Clinic.

The randomized, placebo-controlled, double-blind trial included 133 patients with recurrent vasovagal syncope and was published in Annals of Internal Medicine. Those that received midodrine were less likely to have one syncope episode (28 of 66 [42%]), compared with those that took the placebo (41 of 67 [61%]). The absolute risk reduction for vasovagal syncope was 19 percentage points (95% confidence interval, 2-36 percentage points).

The study included patients from 25 university hospitals in Canada, the United States, Mexico, and the United Kingdom, who were followed for 12 months. The trial participants were highly symptomatic for vasovagal syncope, having experienced a median of 23 episodes in their lifetime and 5 syncope episodes in the last year, and they had no comorbid conditions.

“We don’t have many arrows in our quiver,” said Robert Sheldon, MD, PhD, a cardiologist at University of Calgary (Alta.) and lead author of the study, referring to the lack of evidence-based treatments for syncope.

For 20 years Dr. Sheldon’s lab has been testing drugs that showed some potential. While a previous study of fludrocortisone (Florinef ) showed some benefit, “[midodrine] was the first to be unequivocally, slam-dunk positive,” he said in an interview.

Earlier trials of midodrine

Other studies have shown midodrine to prevent syncope on tilt tests. There have been two randomized trials where midodrine significantly reduced vasovagal syncope, but one of these was short and in children, and the other one was open label with no placebo control.

“Risk reduction was very high in previous studies,” Dr. Sheldon said in an interview. But, because they were open label, there was a huge placebo effect, he noted.

“There were no adequately done, adequately powered [studies] that have been positive,” Dr. Sheldon added.

New study methods and outcomes

The study published in Annals of Internal Medicine this week included patients over 18 years of age with a Calgary Syncope Symptom Score of at least 2. All were educated on lifestyle measures that can prevent syncopes before beginning to take 5 mg of study drug or placebo three times daily, 4 hours apart.

In these cases, the study authors wrote, “taking medication three times a day seems worth the effort.” But in patients with a lower frequency of episodes, midodrine might not have an adequate payoff.

These results are “impressive,” said Roopinder K. Sandhu, MD, MPH, clinical electrophysiologist at Cedar-Sinai in Los Angeles. “This study demonstrated that midodrine is the first medical therapy, in addition to education and lifestyle measures, to unequivocally pass the scrutiny of an international, placebo-controlled, RCT to show a significant reduction in syncope recurrence in a younger population with frequent syncope events.”

“[Taking midodrine] doesn’t carry the long-term consequence of pacemakers,” she added.

Study limitations

Limitations of the new study include its small size and short observation period, the authors wrote. Additionally, a large proportion of patients enrolled were also from a single center in Calgary that specializes in syncope care. Twenty-seven patients in the trial stopped taking their assigned medication during the year observation period, but the authors concluded these participants “likely would bias the results against midodrine.”

For doctors considering midodrine for their patients, it’s critical to confirm the diagnosis and to try patient education first, Dr. Sheldon advised.

Lifestyle factors like hydration, adequate sodium intake, and squatting or lying down when the syncope is coming on can sufficiently suppress syncopes in two-thirds of patients, he noted.

This is a treatment for young people, Dr. Sandhu said. The median age in the trial was 35, so patients taking midodrine should be younger than 50. Midodrine is also not effective in patients with high blood pressure or heart failure, she said.

“[Midodrine] is easy to use but kind of a pain at first,” Dr. Sheldon noted. Every patient should start out taking 5 mg doses, three times a day – during waking hours. But then you have to adjust the dosage, “and it’s tricky,” he said.

If a patient experiences goosebumps or the sensation of worms crawling in the hair, the dose might be too much, Dr. Sheldon noted.

If the patient is still fainting, first consider when they are fainting, he said. If it’s around the time they should take another dose, it might be trough effect.

Dr. Sandhu was not involved in the study, but Cedar Sinai was a participating center, and she considers Dr. Sheldon to be a mentor. Dr. Sandhu also noted that she has published papers with Dr. Sheldon, who reported no conflicts.

New COVID-19 cases in children soared by almost 86% over the course of just 1 week, while the number of 12- to 17-year-old children who have received at least one dose of vaccine rose by 5.4%, according to two separate sources.

There were 71,726 new cases reported during the week of July 23-29, compared with 38,654 the previous week, an increase of 85.6%. Meanwhile, the increase over the past 2 weeks – from 23,551 new cases for July 16-22 to almost 72,000 – works out to almost 205%, according to a report from the American Academy of Pediatrics and the Children’s Hospital Association.

Children represented 19.0% of the cases reported during the week of July 23-29, and they have made up 14.3% of all cases since the pandemic began, with the total number of cases in children now approaching 4.2 million, the AAP and CHA said in their weekly COVID report. About 22% of the U.S. population is under the age of 18 years.

As of Aug. 2, just over 9.8 million children aged 12-17 years had received at least one dose of the COVID vaccine, which was up by about 500,000, or 5.4%, from a week earlier, based on data from the Centers for Disease Control and Prevention.

Children aged 16-17 have reached a notable milestone on the journey that started with vaccine approval in December: 50.2% have gotten at least one dose and 40.3% are fully vaccinated. Among children aged 12-15 years, the proportion with at least one dose of vaccine is up to 39.5%, compared with 37.1% the previous week, while 29.0% are fully vaccinated (27.8% the week before), the CDC said on its COVID Data Tracker.

The national rates for child vaccination, however, tend to hide the disparities between states. There is a gap between Mississippi (lowest), where just 17% of children aged 12-17 years have gotten at least one dose, and Vermont (highest), which is up to 69%. Vermont also has the highest rate of vaccine completion (60%), while Alabama and Mississippi have the lowest (10%), according to a solo report from the AAP.

[email protected]

New COVID-19 cases in children soared by almost 86% over the course of just 1 week, while the number of 12- to 17-year-old children who have received at least one dose of vaccine rose by 5.4%, according to two separate sources.

There were 71,726 new cases reported during the week of July 23-29, compared with 38,654 the previous week, an increase of 85.6%. Meanwhile, the increase over the past 2 weeks – from 23,551 new cases for July 16-22 to almost 72,000 – works out to almost 205%, according to a report from the American Academy of Pediatrics and the Children’s Hospital Association.

Children represented 19.0% of the cases reported during the week of July 23-29, and they have made up 14.3% of all cases since the pandemic began, with the total number of cases in children now approaching 4.2 million, the AAP and CHA said in their weekly COVID report. About 22% of the U.S. population is under the age of 18 years.

As of Aug. 2, just over 9.8 million children aged 12-17 years had received at least one dose of the COVID vaccine, which was up by about 500,000, or 5.4%, from a week earlier, based on data from the Centers for Disease Control and Prevention.

Children aged 16-17 have reached a notable milestone on the journey that started with vaccine approval in December: 50.2% have gotten at least one dose and 40.3% are fully vaccinated. Among children aged 12-15 years, the proportion with at least one dose of vaccine is up to 39.5%, compared with 37.1% the previous week, while 29.0% are fully vaccinated (27.8% the week before), the CDC said on its COVID Data Tracker.

The national rates for child vaccination, however, tend to hide the disparities between states. There is a gap between Mississippi (lowest), where just 17% of children aged 12-17 years have gotten at least one dose, and Vermont (highest), which is up to 69%. Vermont also has the highest rate of vaccine completion (60%), while Alabama and Mississippi have the lowest (10%), according to a solo report from the AAP.

[email protected]

New COVID-19 cases in children soared by almost 86% over the course of just 1 week, while the number of 12- to 17-year-old children who have received at least one dose of vaccine rose by 5.4%, according to two separate sources.

There were 71,726 new cases reported during the week of July 23-29, compared with 38,654 the previous week, an increase of 85.6%. Meanwhile, the increase over the past 2 weeks – from 23,551 new cases for July 16-22 to almost 72,000 – works out to almost 205%, according to a report from the American Academy of Pediatrics and the Children’s Hospital Association.

Children represented 19.0% of the cases reported during the week of July 23-29, and they have made up 14.3% of all cases since the pandemic began, with the total number of cases in children now approaching 4.2 million, the AAP and CHA said in their weekly COVID report. About 22% of the U.S. population is under the age of 18 years.

As of Aug. 2, just over 9.8 million children aged 12-17 years had received at least one dose of the COVID vaccine, which was up by about 500,000, or 5.4%, from a week earlier, based on data from the Centers for Disease Control and Prevention.

Children aged 16-17 have reached a notable milestone on the journey that started with vaccine approval in December: 50.2% have gotten at least one dose and 40.3% are fully vaccinated. Among children aged 12-15 years, the proportion with at least one dose of vaccine is up to 39.5%, compared with 37.1% the previous week, while 29.0% are fully vaccinated (27.8% the week before), the CDC said on its COVID Data Tracker.

The national rates for child vaccination, however, tend to hide the disparities between states. There is a gap between Mississippi (lowest), where just 17% of children aged 12-17 years have gotten at least one dose, and Vermont (highest), which is up to 69%. Vermont also has the highest rate of vaccine completion (60%), while Alabama and Mississippi have the lowest (10%), according to a solo report from the AAP.

[email protected]

The American Gastroenterological Association published a clinical practice update expert review for managing malignant alimentary tract obstructions (MATOs) that includes 14 best practice advice statements, ranging from general principles to specific clinical choices.

“There are many options available for the management of MATOs, with the addition of new modalities as interventional endoscopy continues to evolve,” Osman Ahmed, MD, of the University of Toronto and colleagues wrote in Clinical Gastroenterology and Hepatology. “The important concept to understand for any physician managing MATOs is that there is no longer a ‘one-size-fits-all’ approach that can be applied to all patients.”

First, the investigators called for an individualized, multidisciplinary approach that includes oncologists, surgeons, and endoscopists. They advised physicians to “take into account the characteristics of the obstruction, patient’s expectations, prognosis, expected subsequent therapies, and functional status.”

The remaining advice statements are organized by site of obstruction, with various management approaches based on candidacy for resection and other patient factors.
 

Esophageal obstruction

For patients with esophageal obstruction who are candidates for resection or chemoradiation, Dr. Ahmed and colleagues advised against routine use of self-expanding metal stents (SEMS) due to “high rates of stent migration, higher morbidity and mortality, and potentially lower R0 (microscopically negative margins) resection rates.”

If such patients are at risk of malnutrition, an enteral feeding tube may be considered, although patients should be counseled about associated procedural risks, such as abdominal wall tumor seeding.

Among patients with esophageal obstruction who are not candidates for resection, SEMS insertion or brachytherapy may be used separately or in combination, according to the investigators.

“Clinicians should not consider the use of laser therapy or photodynamic therapy because of the lack of evidence of better outcomes and superior alternatives,” the investigators noted.

If SEMS placement is elected, Dr. Ahmed and colleagues noted there remains ongoing debate. For this expert review, the authors advised using a fully covered stent, based on potentially higher risk for tumor ingrowth and reinterventions with uncovered SEMS.
 

Gastric outlet obstruction

According to the update, patients with gastric outlet obstruction who have good functional status and a life expectancy greater than 2 months should undergo surgical gastrojejunostomy, ideally via a laparoscopic approach instead of an open approach because of shorter hospital stays and less blood loss. If a sufficiently experienced endoscopist is available, an endoscopic ultrasound-guided gastrojejunostomy may be performed, although Dr. Ahmed and colleagues noted that no devices have been approved by the Food and Drug Administration for this technique.

For patients who are not candidates for gastrojejunostomy, enteral stent insertion should be considered; however, they should not be used in patients with severely impaired gastric motility or multiple luminal obstructions “because of limited benefit in these scenarios.” Instead, a venting gastrostomy may be elected.
 

Colonic obstruction

For patients with malignant colonic obstruction, SEMS may be considered as a “bridge to surgery,” wrote Dr. Ahmed and colleagues, and in the case of proximal or right-sided malignant obstruction, as a bridge to surgery or a palliative measure, keeping in mind “the technical challenges of SEMS insertion in those areas.”

Extracolonic obstruction

Finally, the expert panel suggested that SEMS may be appropriate for selective extracolonic malignancy if patients are not surgical candidates, noting that SEMS placement in this scenario “is more technically challenging, clinical success rates are more variable, and complications (including stent migration) are more frequent.”

The investigators concluded by advising clinicians to remain within the realm of their abilities when managing MATOs, and to refer when needed.

“[I]t is important for physicians to understand their limits and expertise and recognize when cases are best managed at experienced high-volume centers,” they wrote.

The clinical practice update expert review was commissioned and approved by the AGA Institute Clinical Practice Updates Committee and the AGA Governing Board. Dr. Lee disclosed a relationship with Boston Scientific.

The American Gastroenterological Association published a clinical practice update expert review for managing malignant alimentary tract obstructions (MATOs) that includes 14 best practice advice statements, ranging from general principles to specific clinical choices.

“There are many options available for the management of MATOs, with the addition of new modalities as interventional endoscopy continues to evolve,” Osman Ahmed, MD, of the University of Toronto and colleagues wrote in Clinical Gastroenterology and Hepatology. “The important concept to understand for any physician managing MATOs is that there is no longer a ‘one-size-fits-all’ approach that can be applied to all patients.”

First, the investigators called for an individualized, multidisciplinary approach that includes oncologists, surgeons, and endoscopists. They advised physicians to “take into account the characteristics of the obstruction, patient’s expectations, prognosis, expected subsequent therapies, and functional status.”

The remaining advice statements are organized by site of obstruction, with various management approaches based on candidacy for resection and other patient factors.
 

Esophageal obstruction

For patients with esophageal obstruction who are candidates for resection or chemoradiation, Dr. Ahmed and colleagues advised against routine use of self-expanding metal stents (SEMS) due to “high rates of stent migration, higher morbidity and mortality, and potentially lower R0 (microscopically negative margins) resection rates.”

If such patients are at risk of malnutrition, an enteral feeding tube may be considered, although patients should be counseled about associated procedural risks, such as abdominal wall tumor seeding.

Among patients with esophageal obstruction who are not candidates for resection, SEMS insertion or brachytherapy may be used separately or in combination, according to the investigators.

“Clinicians should not consider the use of laser therapy or photodynamic therapy because of the lack of evidence of better outcomes and superior alternatives,” the investigators noted.

If SEMS placement is elected, Dr. Ahmed and colleagues noted there remains ongoing debate. For this expert review, the authors advised using a fully covered stent, based on potentially higher risk for tumor ingrowth and reinterventions with uncovered SEMS.
 

Gastric outlet obstruction

According to the update, patients with gastric outlet obstruction who have good functional status and a life expectancy greater than 2 months should undergo surgical gastrojejunostomy, ideally via a laparoscopic approach instead of an open approach because of shorter hospital stays and less blood loss. If a sufficiently experienced endoscopist is available, an endoscopic ultrasound-guided gastrojejunostomy may be performed, although Dr. Ahmed and colleagues noted that no devices have been approved by the Food and Drug Administration for this technique.

For patients who are not candidates for gastrojejunostomy, enteral stent insertion should be considered; however, they should not be used in patients with severely impaired gastric motility or multiple luminal obstructions “because of limited benefit in these scenarios.” Instead, a venting gastrostomy may be elected.
 

Colonic obstruction

For patients with malignant colonic obstruction, SEMS may be considered as a “bridge to surgery,” wrote Dr. Ahmed and colleagues, and in the case of proximal or right-sided malignant obstruction, as a bridge to surgery or a palliative measure, keeping in mind “the technical challenges of SEMS insertion in those areas.”

Extracolonic obstruction

Finally, the expert panel suggested that SEMS may be appropriate for selective extracolonic malignancy if patients are not surgical candidates, noting that SEMS placement in this scenario “is more technically challenging, clinical success rates are more variable, and complications (including stent migration) are more frequent.”

The investigators concluded by advising clinicians to remain within the realm of their abilities when managing MATOs, and to refer when needed.

“[I]t is important for physicians to understand their limits and expertise and recognize when cases are best managed at experienced high-volume centers,” they wrote.

The clinical practice update expert review was commissioned and approved by the AGA Institute Clinical Practice Updates Committee and the AGA Governing Board. Dr. Lee disclosed a relationship with Boston Scientific.

The American Gastroenterological Association published a clinical practice update expert review for managing malignant alimentary tract obstructions (MATOs) that includes 14 best practice advice statements, ranging from general principles to specific clinical choices.

“There are many options available for the management of MATOs, with the addition of new modalities as interventional endoscopy continues to evolve,” Osman Ahmed, MD, of the University of Toronto and colleagues wrote in Clinical Gastroenterology and Hepatology. “The important concept to understand for any physician managing MATOs is that there is no longer a ‘one-size-fits-all’ approach that can be applied to all patients.”

First, the investigators called for an individualized, multidisciplinary approach that includes oncologists, surgeons, and endoscopists. They advised physicians to “take into account the characteristics of the obstruction, patient’s expectations, prognosis, expected subsequent therapies, and functional status.”

The remaining advice statements are organized by site of obstruction, with various management approaches based on candidacy for resection and other patient factors.
 

Esophageal obstruction

For patients with esophageal obstruction who are candidates for resection or chemoradiation, Dr. Ahmed and colleagues advised against routine use of self-expanding metal stents (SEMS) due to “high rates of stent migration, higher morbidity and mortality, and potentially lower R0 (microscopically negative margins) resection rates.”

If such patients are at risk of malnutrition, an enteral feeding tube may be considered, although patients should be counseled about associated procedural risks, such as abdominal wall tumor seeding.

Among patients with esophageal obstruction who are not candidates for resection, SEMS insertion or brachytherapy may be used separately or in combination, according to the investigators.

“Clinicians should not consider the use of laser therapy or photodynamic therapy because of the lack of evidence of better outcomes and superior alternatives,” the investigators noted.

If SEMS placement is elected, Dr. Ahmed and colleagues noted there remains ongoing debate. For this expert review, the authors advised using a fully covered stent, based on potentially higher risk for tumor ingrowth and reinterventions with uncovered SEMS.
 

Gastric outlet obstruction

According to the update, patients with gastric outlet obstruction who have good functional status and a life expectancy greater than 2 months should undergo surgical gastrojejunostomy, ideally via a laparoscopic approach instead of an open approach because of shorter hospital stays and less blood loss. If a sufficiently experienced endoscopist is available, an endoscopic ultrasound-guided gastrojejunostomy may be performed, although Dr. Ahmed and colleagues noted that no devices have been approved by the Food and Drug Administration for this technique.

For patients who are not candidates for gastrojejunostomy, enteral stent insertion should be considered; however, they should not be used in patients with severely impaired gastric motility or multiple luminal obstructions “because of limited benefit in these scenarios.” Instead, a venting gastrostomy may be elected.
 

Colonic obstruction

For patients with malignant colonic obstruction, SEMS may be considered as a “bridge to surgery,” wrote Dr. Ahmed and colleagues, and in the case of proximal or right-sided malignant obstruction, as a bridge to surgery or a palliative measure, keeping in mind “the technical challenges of SEMS insertion in those areas.”

Extracolonic obstruction

Finally, the expert panel suggested that SEMS may be appropriate for selective extracolonic malignancy if patients are not surgical candidates, noting that SEMS placement in this scenario “is more technically challenging, clinical success rates are more variable, and complications (including stent migration) are more frequent.”

The investigators concluded by advising clinicians to remain within the realm of their abilities when managing MATOs, and to refer when needed.

“[I]t is important for physicians to understand their limits and expertise and recognize when cases are best managed at experienced high-volume centers,” they wrote.

The clinical practice update expert review was commissioned and approved by the AGA Institute Clinical Practice Updates Committee and the AGA Governing Board. Dr. Lee disclosed a relationship with Boston Scientific.

Low dose acetylsalicylic acid (LDASA) may have some protective benefit against cognitive decline, but only if started well before symptoms begin, according to a retrospective analysis of two large cohorts. The association with all-cause dementia was weak, but much more pronounced in subjects with coronary heart disease.

The results underscore that individuals with cardiovascular disease risk factors should be prescribed LDASA, and they should be encouraged to be compliant. The study differed from previous observational and randomized, controlled trials, which yielded mixed results. Many looked at individuals older than age 65. The pathological changes associated with dementia may occur up to 2 decades before symptom onset, and it appears that LDASA cannot counter cognitive decline after a diagnosis is made. “The use of LDASA at this age may be already too late,” said Thi Ngoc Mai Nguyen, a PhD student at Network Aging Research, Heidelberg University, Germany. She presented the results at the 2021 Alzheimer’s Association International Conference.

Previous studies also included individuals using LDASA to prevent cardiovascular disease, and they didn’t always adjust for these risk factors. The current work used two large databases, UK Biobank and ESTHER, with a follow-up time of over 10 years for both. “We were able to balance out the distribution of measured baseline covariates (to be) similar between LDASA users and nonusers, and thus, we were able to adjust for confounders more comprehensively,” said Ms. Nguyen.
 

Not yet a definitive answer

Although the findings are promising, Ms. Nguyen noted that the study is not the final word. “Residual confounding is possible, and causation cannot be tested. The only way to answer this is to have clinical trials with at least 10 years of follow-up,” said Ms. Nguyen. She plans to conduct similar studies in non-White populations, and also to examine whether LDASA can help preserve cognitive function in middle-age adults.

The study is interesting, said Claire Sexton, DPhil, who was asked to comment, but she suggested that it is not practice changing. “There is not evidence from the dementia science perspective that should go against whatever the recommendations are for cardiovascular risk,” said Dr. Sexton, director of scientific programs and outreach at the Alzheimer’s Association. “I don’t think this study alone can provide a definitive answer on low-dose aspirin and its association with dementia and Alzheimer’s disease, but it’s an important addition to the literature,” she added.
 

Meta-analysis data

The researchers examined two prospective cohort studies, and combined them into a meta-analysis. It included the ESTHER cohort from Saarland, Germany, with 5,258 individuals and 14.3 years of follow-up, and the UK Biobank cohort, with 305,394 individuals and 11.6 years of follow-up. Subjects selected for analysis were 55 years old or older.

The meta-analysis showed no significant association between LDASA use and reduced risk of Alzheimer’s disease, but there was an association between LDASA use and all-cause dementia (hazard ratio [HR], 0.96; 95% confidence interval [CI], 0.93-0.99).

There were no sex differences with respect to Alzheimer’s dementia, but in males, LDASA was associated with lower risk of vascular dementia (HR, 0.85; 95% CI, 0.79-0.93) and all-cause dementia (HR, 0.87; 95% CI, 0.83-0.92). However, in females, LDASA was tied to greater risk of both vascular dementia (HR, 1.13; 95% CI, 1.02-1.24) and all-cause dementia (HR, 1.07; 95% CI, 1.02-1.13).

The strongest association between LDASA and reduced dementia risk was found in subjects with coronary heart disease (HR, 0.69; 95% CI, 0.59-0.80).

The researchers also used UK Biobank primary care data to analyze associations between longer use of LDASA and reduced dementia risk. Those who used LDASA for 0-5 years were at a higher than average risk of all-cause dementia (HR, 2.80; 95% CI, 2.48-3.16), Alzheimer’s disease (HR, 2.26; 95% CI, 1.84-2.77), and vascular dementia (HR, 3.79; 95% CI, 3.17-4.53). Long-term LDASA users, defined as 10 years or longer, had a lower risk of all-cause dementia (HR, 0.51; 95% CI, 0.47-0.56), Alzheimer’s disease (HR, 0.58; 95% CI, 0.51-0.68), and vascular dementia (HR, 0.48; 95% CI, 0.42-0.56).

Dr. Nguyen and Dr. Sexton have no relevant financial disclosures.

Low dose acetylsalicylic acid (LDASA) may have some protective benefit against cognitive decline, but only if started well before symptoms begin, according to a retrospective analysis of two large cohorts. The association with all-cause dementia was weak, but much more pronounced in subjects with coronary heart disease.

The results underscore that individuals with cardiovascular disease risk factors should be prescribed LDASA, and they should be encouraged to be compliant. The study differed from previous observational and randomized, controlled trials, which yielded mixed results. Many looked at individuals older than age 65. The pathological changes associated with dementia may occur up to 2 decades before symptom onset, and it appears that LDASA cannot counter cognitive decline after a diagnosis is made. “The use of LDASA at this age may be already too late,” said Thi Ngoc Mai Nguyen, a PhD student at Network Aging Research, Heidelberg University, Germany. She presented the results at the 2021 Alzheimer’s Association International Conference.

Previous studies also included individuals using LDASA to prevent cardiovascular disease, and they didn’t always adjust for these risk factors. The current work used two large databases, UK Biobank and ESTHER, with a follow-up time of over 10 years for both. “We were able to balance out the distribution of measured baseline covariates (to be) similar between LDASA users and nonusers, and thus, we were able to adjust for confounders more comprehensively,” said Ms. Nguyen.
 

Not yet a definitive answer

Although the findings are promising, Ms. Nguyen noted that the study is not the final word. “Residual confounding is possible, and causation cannot be tested. The only way to answer this is to have clinical trials with at least 10 years of follow-up,” said Ms. Nguyen. She plans to conduct similar studies in non-White populations, and also to examine whether LDASA can help preserve cognitive function in middle-age adults.

The study is interesting, said Claire Sexton, DPhil, who was asked to comment, but she suggested that it is not practice changing. “There is not evidence from the dementia science perspective that should go against whatever the recommendations are for cardiovascular risk,” said Dr. Sexton, director of scientific programs and outreach at the Alzheimer’s Association. “I don’t think this study alone can provide a definitive answer on low-dose aspirin and its association with dementia and Alzheimer’s disease, but it’s an important addition to the literature,” she added.
 

Meta-analysis data

The researchers examined two prospective cohort studies, and combined them into a meta-analysis. It included the ESTHER cohort from Saarland, Germany, with 5,258 individuals and 14.3 years of follow-up, and the UK Biobank cohort, with 305,394 individuals and 11.6 years of follow-up. Subjects selected for analysis were 55 years old or older.

The meta-analysis showed no significant association between LDASA use and reduced risk of Alzheimer’s disease, but there was an association between LDASA use and all-cause dementia (hazard ratio [HR], 0.96; 95% confidence interval [CI], 0.93-0.99).

There were no sex differences with respect to Alzheimer’s dementia, but in males, LDASA was associated with lower risk of vascular dementia (HR, 0.85; 95% CI, 0.79-0.93) and all-cause dementia (HR, 0.87; 95% CI, 0.83-0.92). However, in females, LDASA was tied to greater risk of both vascular dementia (HR, 1.13; 95% CI, 1.02-1.24) and all-cause dementia (HR, 1.07; 95% CI, 1.02-1.13).

The strongest association between LDASA and reduced dementia risk was found in subjects with coronary heart disease (HR, 0.69; 95% CI, 0.59-0.80).

The researchers also used UK Biobank primary care data to analyze associations between longer use of LDASA and reduced dementia risk. Those who used LDASA for 0-5 years were at a higher than average risk of all-cause dementia (HR, 2.80; 95% CI, 2.48-3.16), Alzheimer’s disease (HR, 2.26; 95% CI, 1.84-2.77), and vascular dementia (HR, 3.79; 95% CI, 3.17-4.53). Long-term LDASA users, defined as 10 years or longer, had a lower risk of all-cause dementia (HR, 0.51; 95% CI, 0.47-0.56), Alzheimer’s disease (HR, 0.58; 95% CI, 0.51-0.68), and vascular dementia (HR, 0.48; 95% CI, 0.42-0.56).

Dr. Nguyen and Dr. Sexton have no relevant financial disclosures.

Low dose acetylsalicylic acid (LDASA) may have some protective benefit against cognitive decline, but only if started well before symptoms begin, according to a retrospective analysis of two large cohorts. The association with all-cause dementia was weak, but much more pronounced in subjects with coronary heart disease.

The results underscore that individuals with cardiovascular disease risk factors should be prescribed LDASA, and they should be encouraged to be compliant. The study differed from previous observational and randomized, controlled trials, which yielded mixed results. Many looked at individuals older than age 65. The pathological changes associated with dementia may occur up to 2 decades before symptom onset, and it appears that LDASA cannot counter cognitive decline after a diagnosis is made. “The use of LDASA at this age may be already too late,” said Thi Ngoc Mai Nguyen, a PhD student at Network Aging Research, Heidelberg University, Germany. She presented the results at the 2021 Alzheimer’s Association International Conference.

Previous studies also included individuals using LDASA to prevent cardiovascular disease, and they didn’t always adjust for these risk factors. The current work used two large databases, UK Biobank and ESTHER, with a follow-up time of over 10 years for both. “We were able to balance out the distribution of measured baseline covariates (to be) similar between LDASA users and nonusers, and thus, we were able to adjust for confounders more comprehensively,” said Ms. Nguyen.
 

Not yet a definitive answer

Although the findings are promising, Ms. Nguyen noted that the study is not the final word. “Residual confounding is possible, and causation cannot be tested. The only way to answer this is to have clinical trials with at least 10 years of follow-up,” said Ms. Nguyen. She plans to conduct similar studies in non-White populations, and also to examine whether LDASA can help preserve cognitive function in middle-age adults.

The study is interesting, said Claire Sexton, DPhil, who was asked to comment, but she suggested that it is not practice changing. “There is not evidence from the dementia science perspective that should go against whatever the recommendations are for cardiovascular risk,” said Dr. Sexton, director of scientific programs and outreach at the Alzheimer’s Association. “I don’t think this study alone can provide a definitive answer on low-dose aspirin and its association with dementia and Alzheimer’s disease, but it’s an important addition to the literature,” she added.
 

Meta-analysis data

The researchers examined two prospective cohort studies, and combined them into a meta-analysis. It included the ESTHER cohort from Saarland, Germany, with 5,258 individuals and 14.3 years of follow-up, and the UK Biobank cohort, with 305,394 individuals and 11.6 years of follow-up. Subjects selected for analysis were 55 years old or older.

The meta-analysis showed no significant association between LDASA use and reduced risk of Alzheimer’s disease, but there was an association between LDASA use and all-cause dementia (hazard ratio [HR], 0.96; 95% confidence interval [CI], 0.93-0.99).

There were no sex differences with respect to Alzheimer’s dementia, but in males, LDASA was associated with lower risk of vascular dementia (HR, 0.85; 95% CI, 0.79-0.93) and all-cause dementia (HR, 0.87; 95% CI, 0.83-0.92). However, in females, LDASA was tied to greater risk of both vascular dementia (HR, 1.13; 95% CI, 1.02-1.24) and all-cause dementia (HR, 1.07; 95% CI, 1.02-1.13).

The strongest association between LDASA and reduced dementia risk was found in subjects with coronary heart disease (HR, 0.69; 95% CI, 0.59-0.80).

The researchers also used UK Biobank primary care data to analyze associations between longer use of LDASA and reduced dementia risk. Those who used LDASA for 0-5 years were at a higher than average risk of all-cause dementia (HR, 2.80; 95% CI, 2.48-3.16), Alzheimer’s disease (HR, 2.26; 95% CI, 1.84-2.77), and vascular dementia (HR, 3.79; 95% CI, 3.17-4.53). Long-term LDASA users, defined as 10 years or longer, had a lower risk of all-cause dementia (HR, 0.51; 95% CI, 0.47-0.56), Alzheimer’s disease (HR, 0.58; 95% CI, 0.51-0.68), and vascular dementia (HR, 0.48; 95% CI, 0.42-0.56).

Dr. Nguyen and Dr. Sexton have no relevant financial disclosures.

Based on a large registry, there appears to be no adverse consequences for same-day discharge following an elective percutaneous cardiovascular intervention (PCI), according to an analysis of a nationwide registry.

“Our data suggest there has been no negative impact on patient outcomes as a result of increasing use of same-day discharge,” lead investigator Steven M. Bradley, MD, said in an interview.

The analysis was based on data on 819,091 patients who underwent an elective PCI procedure during July 2009–December 2017 in the National CathPCI Registry. During this period, the proportion of elective PCIs performed with same-day discharge rose from 4.5% to 28.6%, a fivefold gain, according to Dr. Bradley, an associate cardiologist at the Minneapolis Heart Institute, and colleagues.

Within this study, outcomes in 212,369 patients were analyzed through a link to Centers for Medicare & Medicaid Services data. Despite the growth in same-day discharge PCIs over the study period, there was no change in 30-day mortality rates while the rate of 30-day rehospitalization fell after risk adjustment.

These data are considered to have a message for routine practice, particularly for those hospitals that have been slow to move to same-day discharge for elective PCI when lack of complications makes this appropriate.

However, “this does not mean same-day discharge is safe for all patients,” Dr. Bradley cautioned, but these data suggest “there is a clear opportunity at sites with low rates” to look for strategies that allow patients to recover at home, which is preferred by many patients and lowers costs.

In 2009, the first year in which the data were analyzed, there was relatively little variation in the rate of same day discharge for elective PCI among the 1,716 hospitals that contributed patients to the registry. At that point, almost all hospitals had rates below 10%, according to the report published in JACC: Cardiovascular Interventions on Aug 2, 2021 .

From 2011 onward, there were progressive gains at most hospitals, with an even steeper rise beginning in 2014. By 2017, even though some hospitals were still performing almost no same-day discharge PCIs, many were discharging up to 40%, and the outliers were discharging nearly all.

Expressed in interquartiles at the hospital level, the range climbed from 0.0% to 4.7% in 2009 and reached 4.5% to 41.0% by 2017. For 2017, relative to 2009, this produced an odds ratio for same-day discharge that was more than fourfold greater, after adjustment for year and access site.

Access site was an important variable. For those undergoing PCI with radial access, the median same-day discharge rates climbed from 21.8% in 2009 to 58.3% in 2017. Same-day discharge rates for elective PCI performed by femoral access, already lower in 2009, have consistently lagged. By 2017, the median rate of same-day discharge for those undergoing PCI by the femoral route was less than half of that associated with radial access.

Despite the faster rise in same-day discharge and radial access over the course of the study, these were not directly correlated. In 2017, 25% of sites performing PCI by radial access were still discharging fewer than 10% of patients on the same day as their elective PCI.

Several previous studies have also found that same-day discharge can be offered selectively after elective PCI without adversely affecting outcomes, according to multiple citations provided by the authors. The advantage of early discharge includes both convenience for the patient and lower costs, with some of the studies attempting to quantify savings. In one, it was estimated that per-case savings from performing radial-access elective PCI with same-day discharge was nearly $3,700 when compared with transfemoral access and an overnight stay.

Radial access key to same-day success

An accompanying editorial by Deepak Bhatt, MD, and Jonathan G. Sung, MBChB, who are both interventional cardiologists at Brigham and Women’s Hospital, Boston, generally agreed with the premise that these data support judicious use of same-day discharge for elective PCI.

They pointed out limitations in the study, including its retrospective design and the inability to look at important outcomes other than mortality and 30-day rehospitalization, such as bleeding, that are relevant to the safety of early discharge, but concluded that same-day discharge, as well as radial access procedures, are underused.

“For uncomplicated elective PCI, we should aim for same-day discharge,” Dr. Bhatt said in an interview. He linked this to radial access.

“Radial access certainly facilitates same-day discharge, though even beyond that aspect, it should be the default route of vascular access whenever possible,” Dr. Bhatt said. Yet he was careful to say that neither same-day discharge nor radial access can be recommended in all patients. While the operator needs “to be comfortable” with a radial access approach, there are multiple factors that might preclude early discharge.

“Of course, if a long procedure, high contrast use, bleeding, a long travel distance to get home, etc. [are considered], then an overnight stay may be warranted,” he said.

Dr. Bradley advised centers planning to increase their same-day discharge rates for elective PCI to use a systematic approach.

“Sites should identify areas for opportunity in the use of same-day discharge and then track the implications on patient outcomes to ensure that the approach being used maintains high-quality care,” he said.

Dr. Bradley reported no potential conflicts of interest. Dr. Bhatt has received research funding from a large number of pharmaceutical and device manufacturers, including those that make products relevant to PCI.

Based on a large registry, there appears to be no adverse consequences for same-day discharge following an elective percutaneous cardiovascular intervention (PCI), according to an analysis of a nationwide registry.

“Our data suggest there has been no negative impact on patient outcomes as a result of increasing use of same-day discharge,” lead investigator Steven M. Bradley, MD, said in an interview.

The analysis was based on data on 819,091 patients who underwent an elective PCI procedure during July 2009–December 2017 in the National CathPCI Registry. During this period, the proportion of elective PCIs performed with same-day discharge rose from 4.5% to 28.6%, a fivefold gain, according to Dr. Bradley, an associate cardiologist at the Minneapolis Heart Institute, and colleagues.

Within this study, outcomes in 212,369 patients were analyzed through a link to Centers for Medicare & Medicaid Services data. Despite the growth in same-day discharge PCIs over the study period, there was no change in 30-day mortality rates while the rate of 30-day rehospitalization fell after risk adjustment.

These data are considered to have a message for routine practice, particularly for those hospitals that have been slow to move to same-day discharge for elective PCI when lack of complications makes this appropriate.

However, “this does not mean same-day discharge is safe for all patients,” Dr. Bradley cautioned, but these data suggest “there is a clear opportunity at sites with low rates” to look for strategies that allow patients to recover at home, which is preferred by many patients and lowers costs.

In 2009, the first year in which the data were analyzed, there was relatively little variation in the rate of same day discharge for elective PCI among the 1,716 hospitals that contributed patients to the registry. At that point, almost all hospitals had rates below 10%, according to the report published in JACC: Cardiovascular Interventions on Aug 2, 2021 .

From 2011 onward, there were progressive gains at most hospitals, with an even steeper rise beginning in 2014. By 2017, even though some hospitals were still performing almost no same-day discharge PCIs, many were discharging up to 40%, and the outliers were discharging nearly all.

Expressed in interquartiles at the hospital level, the range climbed from 0.0% to 4.7% in 2009 and reached 4.5% to 41.0% by 2017. For 2017, relative to 2009, this produced an odds ratio for same-day discharge that was more than fourfold greater, after adjustment for year and access site.

Access site was an important variable. For those undergoing PCI with radial access, the median same-day discharge rates climbed from 21.8% in 2009 to 58.3% in 2017. Same-day discharge rates for elective PCI performed by femoral access, already lower in 2009, have consistently lagged. By 2017, the median rate of same-day discharge for those undergoing PCI by the femoral route was less than half of that associated with radial access.

Despite the faster rise in same-day discharge and radial access over the course of the study, these were not directly correlated. In 2017, 25% of sites performing PCI by radial access were still discharging fewer than 10% of patients on the same day as their elective PCI.

Several previous studies have also found that same-day discharge can be offered selectively after elective PCI without adversely affecting outcomes, according to multiple citations provided by the authors. The advantage of early discharge includes both convenience for the patient and lower costs, with some of the studies attempting to quantify savings. In one, it was estimated that per-case savings from performing radial-access elective PCI with same-day discharge was nearly $3,700 when compared with transfemoral access and an overnight stay.

Radial access key to same-day success

An accompanying editorial by Deepak Bhatt, MD, and Jonathan G. Sung, MBChB, who are both interventional cardiologists at Brigham and Women’s Hospital, Boston, generally agreed with the premise that these data support judicious use of same-day discharge for elective PCI.

They pointed out limitations in the study, including its retrospective design and the inability to look at important outcomes other than mortality and 30-day rehospitalization, such as bleeding, that are relevant to the safety of early discharge, but concluded that same-day discharge, as well as radial access procedures, are underused.

“For uncomplicated elective PCI, we should aim for same-day discharge,” Dr. Bhatt said in an interview. He linked this to radial access.

“Radial access certainly facilitates same-day discharge, though even beyond that aspect, it should be the default route of vascular access whenever possible,” Dr. Bhatt said. Yet he was careful to say that neither same-day discharge nor radial access can be recommended in all patients. While the operator needs “to be comfortable” with a radial access approach, there are multiple factors that might preclude early discharge.

“Of course, if a long procedure, high contrast use, bleeding, a long travel distance to get home, etc. [are considered], then an overnight stay may be warranted,” he said.

Dr. Bradley advised centers planning to increase their same-day discharge rates for elective PCI to use a systematic approach.

“Sites should identify areas for opportunity in the use of same-day discharge and then track the implications on patient outcomes to ensure that the approach being used maintains high-quality care,” he said.

Dr. Bradley reported no potential conflicts of interest. Dr. Bhatt has received research funding from a large number of pharmaceutical and device manufacturers, including those that make products relevant to PCI.

Based on a large registry, there appears to be no adverse consequences for same-day discharge following an elective percutaneous cardiovascular intervention (PCI), according to an analysis of a nationwide registry.

“Our data suggest there has been no negative impact on patient outcomes as a result of increasing use of same-day discharge,” lead investigator Steven M. Bradley, MD, said in an interview.

The analysis was based on data on 819,091 patients who underwent an elective PCI procedure during July 2009–December 2017 in the National CathPCI Registry. During this period, the proportion of elective PCIs performed with same-day discharge rose from 4.5% to 28.6%, a fivefold gain, according to Dr. Bradley, an associate cardiologist at the Minneapolis Heart Institute, and colleagues.

Within this study, outcomes in 212,369 patients were analyzed through a link to Centers for Medicare & Medicaid Services data. Despite the growth in same-day discharge PCIs over the study period, there was no change in 30-day mortality rates while the rate of 30-day rehospitalization fell after risk adjustment.

These data are considered to have a message for routine practice, particularly for those hospitals that have been slow to move to same-day discharge for elective PCI when lack of complications makes this appropriate.

However, “this does not mean same-day discharge is safe for all patients,” Dr. Bradley cautioned, but these data suggest “there is a clear opportunity at sites with low rates” to look for strategies that allow patients to recover at home, which is preferred by many patients and lowers costs.

In 2009, the first year in which the data were analyzed, there was relatively little variation in the rate of same day discharge for elective PCI among the 1,716 hospitals that contributed patients to the registry. At that point, almost all hospitals had rates below 10%, according to the report published in JACC: Cardiovascular Interventions on Aug 2, 2021 .

From 2011 onward, there were progressive gains at most hospitals, with an even steeper rise beginning in 2014. By 2017, even though some hospitals were still performing almost no same-day discharge PCIs, many were discharging up to 40%, and the outliers were discharging nearly all.

Expressed in interquartiles at the hospital level, the range climbed from 0.0% to 4.7% in 2009 and reached 4.5% to 41.0% by 2017. For 2017, relative to 2009, this produced an odds ratio for same-day discharge that was more than fourfold greater, after adjustment for year and access site.

Access site was an important variable. For those undergoing PCI with radial access, the median same-day discharge rates climbed from 21.8% in 2009 to 58.3% in 2017. Same-day discharge rates for elective PCI performed by femoral access, already lower in 2009, have consistently lagged. By 2017, the median rate of same-day discharge for those undergoing PCI by the femoral route was less than half of that associated with radial access.

Despite the faster rise in same-day discharge and radial access over the course of the study, these were not directly correlated. In 2017, 25% of sites performing PCI by radial access were still discharging fewer than 10% of patients on the same day as their elective PCI.

Several previous studies have also found that same-day discharge can be offered selectively after elective PCI without adversely affecting outcomes, according to multiple citations provided by the authors. The advantage of early discharge includes both convenience for the patient and lower costs, with some of the studies attempting to quantify savings. In one, it was estimated that per-case savings from performing radial-access elective PCI with same-day discharge was nearly $3,700 when compared with transfemoral access and an overnight stay.

Radial access key to same-day success

An accompanying editorial by Deepak Bhatt, MD, and Jonathan G. Sung, MBChB, who are both interventional cardiologists at Brigham and Women’s Hospital, Boston, generally agreed with the premise that these data support judicious use of same-day discharge for elective PCI.

They pointed out limitations in the study, including its retrospective design and the inability to look at important outcomes other than mortality and 30-day rehospitalization, such as bleeding, that are relevant to the safety of early discharge, but concluded that same-day discharge, as well as radial access procedures, are underused.

“For uncomplicated elective PCI, we should aim for same-day discharge,” Dr. Bhatt said in an interview. He linked this to radial access.

“Radial access certainly facilitates same-day discharge, though even beyond that aspect, it should be the default route of vascular access whenever possible,” Dr. Bhatt said. Yet he was careful to say that neither same-day discharge nor radial access can be recommended in all patients. While the operator needs “to be comfortable” with a radial access approach, there are multiple factors that might preclude early discharge.

“Of course, if a long procedure, high contrast use, bleeding, a long travel distance to get home, etc. [are considered], then an overnight stay may be warranted,” he said.

Dr. Bradley advised centers planning to increase their same-day discharge rates for elective PCI to use a systematic approach.

“Sites should identify areas for opportunity in the use of same-day discharge and then track the implications on patient outcomes to ensure that the approach being used maintains high-quality care,” he said.

Dr. Bradley reported no potential conflicts of interest. Dr. Bhatt has received research funding from a large number of pharmaceutical and device manufacturers, including those that make products relevant to PCI.

I have been a proud hospitalist for more than 20 years, and yet I have never been prouder to be a hospitalist than now. The pandemic has been brutal, killing more than 600,000 Americans as of this writing. It has stretched the health care system, its doctors, nurses, and other providers to the limit. Yet we will get through it, we are getting through it, and hospitalists deserve a huge portion of the credit.

According to the CDC, there have been over 2.3 million COVID-19 hospitalizations. In my home state of Maryland, between two-thirds and three-quarters of hospitalized COVID patients are cared for on general medical floors, the domain of hospitalists. When hospitals needed COVID units, hospitalists stepped up to design and staff them. When our ICU colleagues needed support, especially in those early dark days, hospitalists stepped in. When our outpatient colleagues were called into the hospital, hospitalists were there to help them on board. When the House of Medicine was in chaos due to COVID-19, hospitalists ran towards that fire. Our previous 20+ years of collective experience made us the ideal specialty to manage the inpatient challenges over the last 18 months.

Need a new clinical schedule by Sunday? Check.

Need help with new clinical protocols? Check.

Need to help other colleagues? Check.

Need to reprogram the EMR? Check.

Need a new way to teach residents and students on the wards? Check.

Need a whole new unit – no, wait – a new hospital wing? No, scratch that – a whole new COVID hospital in a few weeks? Check. (I personally did that last one at the Baltimore Convention Center!)

For me and many hospitalists like me, it is as if the last 20 years were prep work for the pandemic.

Here at SHM, we know the pandemic is hard work – exhausting, even. SHM has been actively focused on supporting hospitalists during this crisis so that hospitalists can focus on patients. Early in the pandemic, SHM quickly pivoted to supply hospitalists with COVID-19 resources in their fight against the coronavirus. Numerous COVID-19 webinars, a COVID addendum to the State of Hospital Medicine Report, and a dedicated COVID issue of the Journal of Hospital Medicine were early and successful information dissemination strategies.

As the world – and hospitalists – dug in for a multi-year pandemic, SHM continued to advance the care of patients by opening our library of educational content for free to anyone. Our Public Policy Committee was active around both COVID-19- and hospitalist-related topics: immigration, telehealth, wellbeing, and financial impacts, to name a few.

As the pandemic slogged on, our Wellbeing Task Force came up with innovative support measures, including a check-in guide for hospitalists and fellow health care workers and dedicated wellness sessions complete with a licensed therapist for members. All the while, despite the restrictions and hurdles the pandemic has thrown our way, SHM members keep meeting and collaborating through virtual chapter events, committee work, special interest groups, and our annual conference, SHM Converge. Thank you to the countless members who donated their time to SHM, so that SHM could support hospitalists and their patients.

Now, we are transitioning into a new phase of the pandemic. The medical miracles that are the COVID-19 vaccines have made that possible. Fully vaccinated, I no longer worry that every time someone sneezes, or when I care for patients with a fever, that I am playing a high stakes poker game with my life. Don’t get me wrong; as I write, the Delta variant has a hold on the nation, and I know it’s not over yet. But it does appear as if the medical war on COVID is shifting from national to regional (or even local) responses.

During this new phase, we must rebuild our personal and professional lives. If you haven’t read Retired Lieutenant General Mark Hertling’s perspective piece in the August issue of the Journal of Hospital Medicine, I strongly encourage you to do so. He shares profound lessons on transitioning from active combat that are directly applicable to hospitalists who have been “deployed” battling COVID-19.

SHM will continue to pivot to meet our members’ needs too. We are already gearing up for more in-person education and networking. Chapters are starting to meet in person, and SHM is happy to provide visiting faculty. I will visit members from Florida to Maine and places in between starting this fall! Our Board of Directors and other SHM leaders are also starting to meet with members in person. Our own Leadership Academy will take place at Amelia Island in Florida in October, where we can learn, network, and even decompress. We also can’t wait for SHM Converge 2022 in Nashville, where we hope to reunite with many of you after 2 years of virtual conferences.

Our response to the pandemic, a once in a century crisis where our own safety was at risk, where doing the right thing might mean death or harming loved ones, our response of running into the fire to save lives is truly inspiring. The power of care – for our patients, for our family and friends, and for our hospital medicine community and the community at large – is evident more now than ever.

There have always been good reasons to be proud of being a hospitalist: taking care of the acutely ill, helping hospitals improve, teaching young doctors, and watching my specialty grow by leaps and bounds, to name just a few. But I’ve never been prouder than I am now.

Dr. Howell is the CEO of the Society of Hospital Medicine.

I have been a proud hospitalist for more than 20 years, and yet I have never been prouder to be a hospitalist than now. The pandemic has been brutal, killing more than 600,000 Americans as of this writing. It has stretched the health care system, its doctors, nurses, and other providers to the limit. Yet we will get through it, we are getting through it, and hospitalists deserve a huge portion of the credit.

According to the CDC, there have been over 2.3 million COVID-19 hospitalizations. In my home state of Maryland, between two-thirds and three-quarters of hospitalized COVID patients are cared for on general medical floors, the domain of hospitalists. When hospitals needed COVID units, hospitalists stepped up to design and staff them. When our ICU colleagues needed support, especially in those early dark days, hospitalists stepped in. When our outpatient colleagues were called into the hospital, hospitalists were there to help them on board. When the House of Medicine was in chaos due to COVID-19, hospitalists ran towards that fire. Our previous 20+ years of collective experience made us the ideal specialty to manage the inpatient challenges over the last 18 months.

Need a new clinical schedule by Sunday? Check.

Need help with new clinical protocols? Check.

Need to help other colleagues? Check.

Need to reprogram the EMR? Check.

Need a new way to teach residents and students on the wards? Check.

Need a whole new unit – no, wait – a new hospital wing? No, scratch that – a whole new COVID hospital in a few weeks? Check. (I personally did that last one at the Baltimore Convention Center!)

For me and many hospitalists like me, it is as if the last 20 years were prep work for the pandemic.

Here at SHM, we know the pandemic is hard work – exhausting, even. SHM has been actively focused on supporting hospitalists during this crisis so that hospitalists can focus on patients. Early in the pandemic, SHM quickly pivoted to supply hospitalists with COVID-19 resources in their fight against the coronavirus. Numerous COVID-19 webinars, a COVID addendum to the State of Hospital Medicine Report, and a dedicated COVID issue of the Journal of Hospital Medicine were early and successful information dissemination strategies.

As the world – and hospitalists – dug in for a multi-year pandemic, SHM continued to advance the care of patients by opening our library of educational content for free to anyone. Our Public Policy Committee was active around both COVID-19- and hospitalist-related topics: immigration, telehealth, wellbeing, and financial impacts, to name a few.

As the pandemic slogged on, our Wellbeing Task Force came up with innovative support measures, including a check-in guide for hospitalists and fellow health care workers and dedicated wellness sessions complete with a licensed therapist for members. All the while, despite the restrictions and hurdles the pandemic has thrown our way, SHM members keep meeting and collaborating through virtual chapter events, committee work, special interest groups, and our annual conference, SHM Converge. Thank you to the countless members who donated their time to SHM, so that SHM could support hospitalists and their patients.

Now, we are transitioning into a new phase of the pandemic. The medical miracles that are the COVID-19 vaccines have made that possible. Fully vaccinated, I no longer worry that every time someone sneezes, or when I care for patients with a fever, that I am playing a high stakes poker game with my life. Don’t get me wrong; as I write, the Delta variant has a hold on the nation, and I know it’s not over yet. But it does appear as if the medical war on COVID is shifting from national to regional (or even local) responses.

During this new phase, we must rebuild our personal and professional lives. If you haven’t read Retired Lieutenant General Mark Hertling’s perspective piece in the August issue of the Journal of Hospital Medicine, I strongly encourage you to do so. He shares profound lessons on transitioning from active combat that are directly applicable to hospitalists who have been “deployed” battling COVID-19.

SHM will continue to pivot to meet our members’ needs too. We are already gearing up for more in-person education and networking. Chapters are starting to meet in person, and SHM is happy to provide visiting faculty. I will visit members from Florida to Maine and places in between starting this fall! Our Board of Directors and other SHM leaders are also starting to meet with members in person. Our own Leadership Academy will take place at Amelia Island in Florida in October, where we can learn, network, and even decompress. We also can’t wait for SHM Converge 2022 in Nashville, where we hope to reunite with many of you after 2 years of virtual conferences.

Our response to the pandemic, a once in a century crisis where our own safety was at risk, where doing the right thing might mean death or harming loved ones, our response of running into the fire to save lives is truly inspiring. The power of care – for our patients, for our family and friends, and for our hospital medicine community and the community at large – is evident more now than ever.

There have always been good reasons to be proud of being a hospitalist: taking care of the acutely ill, helping hospitals improve, teaching young doctors, and watching my specialty grow by leaps and bounds, to name just a few. But I’ve never been prouder than I am now.

Dr. Howell is the CEO of the Society of Hospital Medicine.

I have been a proud hospitalist for more than 20 years, and yet I have never been prouder to be a hospitalist than now. The pandemic has been brutal, killing more than 600,000 Americans as of this writing. It has stretched the health care system, its doctors, nurses, and other providers to the limit. Yet we will get through it, we are getting through it, and hospitalists deserve a huge portion of the credit.

According to the CDC, there have been over 2.3 million COVID-19 hospitalizations. In my home state of Maryland, between two-thirds and three-quarters of hospitalized COVID patients are cared for on general medical floors, the domain of hospitalists. When hospitals needed COVID units, hospitalists stepped up to design and staff them. When our ICU colleagues needed support, especially in those early dark days, hospitalists stepped in. When our outpatient colleagues were called into the hospital, hospitalists were there to help them on board. When the House of Medicine was in chaos due to COVID-19, hospitalists ran towards that fire. Our previous 20+ years of collective experience made us the ideal specialty to manage the inpatient challenges over the last 18 months.

Need a new clinical schedule by Sunday? Check.

Need help with new clinical protocols? Check.

Need to help other colleagues? Check.

Need to reprogram the EMR? Check.

Need a new way to teach residents and students on the wards? Check.

Need a whole new unit – no, wait – a new hospital wing? No, scratch that – a whole new COVID hospital in a few weeks? Check. (I personally did that last one at the Baltimore Convention Center!)

For me and many hospitalists like me, it is as if the last 20 years were prep work for the pandemic.

Here at SHM, we know the pandemic is hard work – exhausting, even. SHM has been actively focused on supporting hospitalists during this crisis so that hospitalists can focus on patients. Early in the pandemic, SHM quickly pivoted to supply hospitalists with COVID-19 resources in their fight against the coronavirus. Numerous COVID-19 webinars, a COVID addendum to the State of Hospital Medicine Report, and a dedicated COVID issue of the Journal of Hospital Medicine were early and successful information dissemination strategies.

As the world – and hospitalists – dug in for a multi-year pandemic, SHM continued to advance the care of patients by opening our library of educational content for free to anyone. Our Public Policy Committee was active around both COVID-19- and hospitalist-related topics: immigration, telehealth, wellbeing, and financial impacts, to name a few.

As the pandemic slogged on, our Wellbeing Task Force came up with innovative support measures, including a check-in guide for hospitalists and fellow health care workers and dedicated wellness sessions complete with a licensed therapist for members. All the while, despite the restrictions and hurdles the pandemic has thrown our way, SHM members keep meeting and collaborating through virtual chapter events, committee work, special interest groups, and our annual conference, SHM Converge. Thank you to the countless members who donated their time to SHM, so that SHM could support hospitalists and their patients.

Now, we are transitioning into a new phase of the pandemic. The medical miracles that are the COVID-19 vaccines have made that possible. Fully vaccinated, I no longer worry that every time someone sneezes, or when I care for patients with a fever, that I am playing a high stakes poker game with my life. Don’t get me wrong; as I write, the Delta variant has a hold on the nation, and I know it’s not over yet. But it does appear as if the medical war on COVID is shifting from national to regional (or even local) responses.

During this new phase, we must rebuild our personal and professional lives. If you haven’t read Retired Lieutenant General Mark Hertling’s perspective piece in the August issue of the Journal of Hospital Medicine, I strongly encourage you to do so. He shares profound lessons on transitioning from active combat that are directly applicable to hospitalists who have been “deployed” battling COVID-19.

SHM will continue to pivot to meet our members’ needs too. We are already gearing up for more in-person education and networking. Chapters are starting to meet in person, and SHM is happy to provide visiting faculty. I will visit members from Florida to Maine and places in between starting this fall! Our Board of Directors and other SHM leaders are also starting to meet with members in person. Our own Leadership Academy will take place at Amelia Island in Florida in October, where we can learn, network, and even decompress. We also can’t wait for SHM Converge 2022 in Nashville, where we hope to reunite with many of you after 2 years of virtual conferences.

Our response to the pandemic, a once in a century crisis where our own safety was at risk, where doing the right thing might mean death or harming loved ones, our response of running into the fire to save lives is truly inspiring. The power of care – for our patients, for our family and friends, and for our hospital medicine community and the community at large – is evident more now than ever.

There have always been good reasons to be proud of being a hospitalist: taking care of the acutely ill, helping hospitals improve, teaching young doctors, and watching my specialty grow by leaps and bounds, to name just a few. But I’ve never been prouder than I am now.

Dr. Howell is the CEO of the Society of Hospital Medicine.