Sjogren syndrome (SS) is a chronic inflammatory autoimmune disorder characterized by lymphocytic infiltration of lacrimal and salivary glands causing sicca syndrome.¹ The disease can extend beyond the exocrine glands, and systemic manifestations, including vasculitis, lung, renal or neurologic involvement, can occur.² Lung disease associated with SS is more commonly seen in women aged ≥ 60 years. The most common symptoms include dry cough, chest pain, and dyspnea on exertion. Sjogren syndrome also may produce several respiratory complications, including bronchial hyperresponsiveness, bronchiolitis, bronchiectasis, pulmonary infections, pulmonary amyloidosis, pulmonary embolism, pulmonary hypertension, lymphomas, and interstitial lung diseases (ILD).² Although ILD typically occurs 5 to 10 years after the onset of SS, lung disease can precede SS.

Pulmonary involvement is associated with systemic manifestations, hypergammaglobulinemia, and anti-SSA and anti-SSB antibodies.² Laboratory tests that confirm a diagnosis of SS include antinuclear antibody (ANA), anti-Ro/SSA, and anti-La/SSB antibodies.² Pulmonary function test (PFT) results appear to reflect impairment of either the lung (restrictive syndrome) or airways (obstructive syndrome).² Imaging abnormalities may include ground-glass attenuation, subpleural small nodules, nonseptal linear opacities, interlobular septal thickening, bronchiectasis, and cysts.³ Therefore, many ILD cases show similar imaging and pathologic findings; nevertheless, they have identifiable etiology that are not idiopathic.

Case Presentation

A 67-year-old man with a medical history of hypertension, peripheral vascular disease, and keratoconjunctivitis sicca (treated with eye drops) developed progressive shortness of breath, dyspnea on exertion, and weight loss (40 pounds) over the course of 6 months. A pulmonary function test showed a restrictive abnormality with decreased diffusing capacity of the lungs for carbon monoxide (eFigure available online at www.fedprac.com). A chest computed tomography (CT) scan showed the presence of significant thickening of the interlobular septi that was more pronounced in the subpleural regions of the lungs and lower lobes, which was consistent with usual interstitial pneumonia. A chest X-ray conducted 4 months prior showed no significant acute cardiopulmonary abnormalities (Figure 1). An open lung wedge biopsy revealed chronic organizing pneumonia with mild interstitial chronic inflammation, smooth muscle hypertrophy, and honeycomb changes consistent with usual interstitial pneumonia.

The patient had been diagnosed with idiopathic pulmonary fibrosis (IPF) by a private physician and started pirfenidone and oxygen therapy. Three months later the patient presented to the VA Caribbean Healthcare System in San Juan Puerto Rico when he developed an exacerbation of IPF. The patient reported having fever, chills, dry cough, night sweats, and marked shortness of breath. He was found hypoxemic (partial pressure of O₂ was 50 mm Hg) and required a venturi mask set to 50% fractioned of inspired O₂ to maintain a peripheral oxygen saturation around 90%. A chest X-ray showed decreased lung volume with bilateral interstitial and alveolar disease (Figure 2). Leukocytosis was present at 17×10^-3/µl. The chest CT scan showed interval worsening of diffuse ground-glass airspace opacities and worsening of interstitial opacities; there

After careful clinical assessment (+ dry eyes) and radiographic pattern evaluation (diffuse bilateral interstitial and ground-glass opacities), the clinical diagnosis of IPF was queried after the patient’s rheumatologic workup came back positive for ANA and anti-Ro/SSA tests. Since the etiology of ILD was secondary to SS, pirfenidone was discontinued, and the patient was started on steroid therapy with subsequent marked clinical improvement. Parotid biopsy revealed the presence of inflammatory cells supporting the diagnosis of ILD associated to SS. The patient was discharged home on a tapering dose of steroids. Four months after therapy with steroids, a follow-up chest CT scan without contrast showed a chronic ILD with improved ground-glass opacities (Figure 4). The patient currently is in good health without oxygen supplementation.

Discussion

Diagnosis of SS is challenging, since it may mimic other conditions such as IPF. The most common type of SS-associated ILD is nonspecific interstitial pneumonia (NSIP), although usual interstitial pneumonia (UIP) can be visualized, as in this case study. Usual interstitial pneumonia

Diagnosing IPF cannot be solely based on a lung biopsy consistent with UIP. Appropriate diagnosis should consider the clinical presentation; PFT, laboratory findings (including rheumatologic workup), imaging (especially radiographic patterns), and biopsies. Moreover, the pathologic characteristic of IPF, which is UIP, can be found with other diseases, such as SS. Thus, it is important to make an accurate diagnosis to provide the appropriate treatment available. Patients with ILD associated with SS who have worsening symptoms, PFT, and radiographic abnormalities may be treated with oral prednisone (daily dose: 1 mg/kg).

Conclusion

This case highlights the importance of making an adequate diagnosis of ILD considering that available treatments differ for all possible etiologies other than IPF. This is a true clinical concern taking into account that many patients might be receiving inappropriate therapy for IPF diagnosis, as illustrated in the case study.

Sjogren syndrome (SS) is a chronic inflammatory autoimmune disorder characterized by lymphocytic infiltration of lacrimal and salivary glands causing sicca syndrome.¹ The disease can extend beyond the exocrine glands, and systemic manifestations, including vasculitis, lung, renal or neurologic involvement, can occur.² Lung disease associated with SS is more commonly seen in women aged ≥ 60 years. The most common symptoms include dry cough, chest pain, and dyspnea on exertion. Sjogren syndrome also may produce several respiratory complications, including bronchial hyperresponsiveness, bronchiolitis, bronchiectasis, pulmonary infections, pulmonary amyloidosis, pulmonary embolism, pulmonary hypertension, lymphomas, and interstitial lung diseases (ILD).² Although ILD typically occurs 5 to 10 years after the onset of SS, lung disease can precede SS.

Pulmonary involvement is associated with systemic manifestations, hypergammaglobulinemia, and anti-SSA and anti-SSB antibodies.² Laboratory tests that confirm a diagnosis of SS include antinuclear antibody (ANA), anti-Ro/SSA, and anti-La/SSB antibodies.² Pulmonary function test (PFT) results appear to reflect impairment of either the lung (restrictive syndrome) or airways (obstructive syndrome).² Imaging abnormalities may include ground-glass attenuation, subpleural small nodules, nonseptal linear opacities, interlobular septal thickening, bronchiectasis, and cysts.³ Therefore, many ILD cases show similar imaging and pathologic findings; nevertheless, they have identifiable etiology that are not idiopathic.

Case Presentation

A 67-year-old man with a medical history of hypertension, peripheral vascular disease, and keratoconjunctivitis sicca (treated with eye drops) developed progressive shortness of breath, dyspnea on exertion, and weight loss (40 pounds) over the course of 6 months. A pulmonary function test showed a restrictive abnormality with decreased diffusing capacity of the lungs for carbon monoxide (eFigure available online at www.fedprac.com). A chest computed tomography (CT) scan showed the presence of significant thickening of the interlobular septi that was more pronounced in the subpleural regions of the lungs and lower lobes, which was consistent with usual interstitial pneumonia. A chest X-ray conducted 4 months prior showed no significant acute cardiopulmonary abnormalities (Figure 1). An open lung wedge biopsy revealed chronic organizing pneumonia with mild interstitial chronic inflammation, smooth muscle hypertrophy, and honeycomb changes consistent with usual interstitial pneumonia.

The patient had been diagnosed with idiopathic pulmonary fibrosis (IPF) by a private physician and started pirfenidone and oxygen therapy. Three months later the patient presented to the VA Caribbean Healthcare System in San Juan Puerto Rico when he developed an exacerbation of IPF. The patient reported having fever, chills, dry cough, night sweats, and marked shortness of breath. He was found hypoxemic (partial pressure of O₂ was 50 mm Hg) and required a venturi mask set to 50% fractioned of inspired O₂ to maintain a peripheral oxygen saturation around 90%. A chest X-ray showed decreased lung volume with bilateral interstitial and alveolar disease (Figure 2). Leukocytosis was present at 17×10^-3/µl. The chest CT scan showed interval worsening of diffuse ground-glass airspace opacities and worsening of interstitial opacities; there

After careful clinical assessment (+ dry eyes) and radiographic pattern evaluation (diffuse bilateral interstitial and ground-glass opacities), the clinical diagnosis of IPF was queried after the patient’s rheumatologic workup came back positive for ANA and anti-Ro/SSA tests. Since the etiology of ILD was secondary to SS, pirfenidone was discontinued, and the patient was started on steroid therapy with subsequent marked clinical improvement. Parotid biopsy revealed the presence of inflammatory cells supporting the diagnosis of ILD associated to SS. The patient was discharged home on a tapering dose of steroids. Four months after therapy with steroids, a follow-up chest CT scan without contrast showed a chronic ILD with improved ground-glass opacities (Figure 4). The patient currently is in good health without oxygen supplementation.

Discussion

Diagnosis of SS is challenging, since it may mimic other conditions such as IPF. The most common type of SS-associated ILD is nonspecific interstitial pneumonia (NSIP), although usual interstitial pneumonia (UIP) can be visualized, as in this case study. Usual interstitial pneumonia

Diagnosing IPF cannot be solely based on a lung biopsy consistent with UIP. Appropriate diagnosis should consider the clinical presentation; PFT, laboratory findings (including rheumatologic workup), imaging (especially radiographic patterns), and biopsies. Moreover, the pathologic characteristic of IPF, which is UIP, can be found with other diseases, such as SS. Thus, it is important to make an accurate diagnosis to provide the appropriate treatment available. Patients with ILD associated with SS who have worsening symptoms, PFT, and radiographic abnormalities may be treated with oral prednisone (daily dose: 1 mg/kg).

Conclusion

This case highlights the importance of making an adequate diagnosis of ILD considering that available treatments differ for all possible etiologies other than IPF. This is a true clinical concern taking into account that many patients might be receiving inappropriate therapy for IPF diagnosis, as illustrated in the case study.

Sjogren syndrome (SS) is a chronic inflammatory autoimmune disorder characterized by lymphocytic infiltration of lacrimal and salivary glands causing sicca syndrome.¹ The disease can extend beyond the exocrine glands, and systemic manifestations, including vasculitis, lung, renal or neurologic involvement, can occur.² Lung disease associated with SS is more commonly seen in women aged ≥ 60 years. The most common symptoms include dry cough, chest pain, and dyspnea on exertion. Sjogren syndrome also may produce several respiratory complications, including bronchial hyperresponsiveness, bronchiolitis, bronchiectasis, pulmonary infections, pulmonary amyloidosis, pulmonary embolism, pulmonary hypertension, lymphomas, and interstitial lung diseases (ILD).² Although ILD typically occurs 5 to 10 years after the onset of SS, lung disease can precede SS.

Pulmonary involvement is associated with systemic manifestations, hypergammaglobulinemia, and anti-SSA and anti-SSB antibodies.² Laboratory tests that confirm a diagnosis of SS include antinuclear antibody (ANA), anti-Ro/SSA, and anti-La/SSB antibodies.² Pulmonary function test (PFT) results appear to reflect impairment of either the lung (restrictive syndrome) or airways (obstructive syndrome).² Imaging abnormalities may include ground-glass attenuation, subpleural small nodules, nonseptal linear opacities, interlobular septal thickening, bronchiectasis, and cysts.³ Therefore, many ILD cases show similar imaging and pathologic findings; nevertheless, they have identifiable etiology that are not idiopathic.

Case Presentation

A 67-year-old man with a medical history of hypertension, peripheral vascular disease, and keratoconjunctivitis sicca (treated with eye drops) developed progressive shortness of breath, dyspnea on exertion, and weight loss (40 pounds) over the course of 6 months. A pulmonary function test showed a restrictive abnormality with decreased diffusing capacity of the lungs for carbon monoxide (eFigure available online at www.fedprac.com). A chest computed tomography (CT) scan showed the presence of significant thickening of the interlobular septi that was more pronounced in the subpleural regions of the lungs and lower lobes, which was consistent with usual interstitial pneumonia. A chest X-ray conducted 4 months prior showed no significant acute cardiopulmonary abnormalities (Figure 1). An open lung wedge biopsy revealed chronic organizing pneumonia with mild interstitial chronic inflammation, smooth muscle hypertrophy, and honeycomb changes consistent with usual interstitial pneumonia.

The patient had been diagnosed with idiopathic pulmonary fibrosis (IPF) by a private physician and started pirfenidone and oxygen therapy. Three months later the patient presented to the VA Caribbean Healthcare System in San Juan Puerto Rico when he developed an exacerbation of IPF. The patient reported having fever, chills, dry cough, night sweats, and marked shortness of breath. He was found hypoxemic (partial pressure of O₂ was 50 mm Hg) and required a venturi mask set to 50% fractioned of inspired O₂ to maintain a peripheral oxygen saturation around 90%. A chest X-ray showed decreased lung volume with bilateral interstitial and alveolar disease (Figure 2). Leukocytosis was present at 17×10^-3/µl. The chest CT scan showed interval worsening of diffuse ground-glass airspace opacities and worsening of interstitial opacities; there

After careful clinical assessment (+ dry eyes) and radiographic pattern evaluation (diffuse bilateral interstitial and ground-glass opacities), the clinical diagnosis of IPF was queried after the patient’s rheumatologic workup came back positive for ANA and anti-Ro/SSA tests. Since the etiology of ILD was secondary to SS, pirfenidone was discontinued, and the patient was started on steroid therapy with subsequent marked clinical improvement. Parotid biopsy revealed the presence of inflammatory cells supporting the diagnosis of ILD associated to SS. The patient was discharged home on a tapering dose of steroids. Four months after therapy with steroids, a follow-up chest CT scan without contrast showed a chronic ILD with improved ground-glass opacities (Figure 4). The patient currently is in good health without oxygen supplementation.

Discussion

Diagnosis of SS is challenging, since it may mimic other conditions such as IPF. The most common type of SS-associated ILD is nonspecific interstitial pneumonia (NSIP), although usual interstitial pneumonia (UIP) can be visualized, as in this case study. Usual interstitial pneumonia

Diagnosing IPF cannot be solely based on a lung biopsy consistent with UIP. Appropriate diagnosis should consider the clinical presentation; PFT, laboratory findings (including rheumatologic workup), imaging (especially radiographic patterns), and biopsies. Moreover, the pathologic characteristic of IPF, which is UIP, can be found with other diseases, such as SS. Thus, it is important to make an accurate diagnosis to provide the appropriate treatment available. Patients with ILD associated with SS who have worsening symptoms, PFT, and radiographic abnormalities may be treated with oral prednisone (daily dose: 1 mg/kg).

Conclusion

This case highlights the importance of making an adequate diagnosis of ILD considering that available treatments differ for all possible etiologies other than IPF. This is a true clinical concern taking into account that many patients might be receiving inappropriate therapy for IPF diagnosis, as illustrated in the case study.

Is there a prodrome for multiple sclerosis? Betamethasone saves babies and dollars, patients want answers on religious hospitals’ care restrictions, and is faster always better in large-vessel stroke?

Listen to the MDedge Daily News podcast for all the details on today’s top news.

Is there a prodrome for multiple sclerosis? Betamethasone saves babies and dollars, patients want answers on religious hospitals’ care restrictions, and is faster always better in large-vessel stroke?

Listen to the MDedge Daily News podcast for all the details on today’s top news.

Is there a prodrome for multiple sclerosis? Betamethasone saves babies and dollars, patients want answers on religious hospitals’ care restrictions, and is faster always better in large-vessel stroke?

Listen to the MDedge Daily News podcast for all the details on today’s top news.

Photo by Larry Young

LA JOLLA, CA—The dual PI3K δ/γ inhibitor tenalisib has demonstrated activity in a phase 1 trial of patients with relapsed/refractory T-cell lymphomas.

Tenalisib produced “encouraging” response rates of 44% in patients with cutaneous T-cell lymphoma (CTCL) and 50% in patients with peripheral T-cell lymphoma (PTCL), according to study investigator Bradley M. Haverkos, MD, of the University of Colorado School of Medicine in Aurora.

Dr Haverkos also said tenalisib had an acceptable safety profile.

The most common treatment-related adverse event (AE) in both patient groups was transaminitis.

Dr Haverkos and his colleagues presented these results in a pair of posters and an oral presentation at the 10th Annual T-cell Lymphoma Forum.

The trial was sponsored by Rhizen Pharmaceuticals, the company developing tenalisib (formerly RP6530).

The researchers have enrolled 55 patients in this trial—28 with CTCL and 27 with PTCL.

The study has a standard 3+3 design, starting with a 200 mg daily fasting dose of tenalisib and escalating to an 800 mg daily fasting dose, followed by an 800 mg daily fed cohort.

There were 3 dose-limiting toxicities in the 800 mg fed cohort—transaminitis, rash, and neutropenia. Therefore, the 800 mg fasting dose was considered the maximum-tolerated dose.

Patients in the PTCL and CTCL expansion cohorts received the maximum-tolerated dose.

Patients were scheduled to receive 8 cycles (28 days each) of tenalisib, but treatment could be extended to 24 months.

The data cutoff was January 10, 2018.

Efficacy in PTCL

Most PTCL patients (n=24) had PTCL not otherwise specified (NOS), 2 had angioimmunoblastic T-cell lymphoma (AITL), and 1 had subcutaneous panniculitis-like T-cell lymphoma (SPTCL).

The patients’ median age at baseline was 63 (range, 40-89), and 63% are male. Sixty-three percent of patients had relapsed disease at baseline, 37% were refractory, and 93% had stage 3 or 4 disease. Patients had received a median of 3 prior therapies (range, 1-7).

The median duration of treatment with tenalisib was 1.9 months.

Fourteen patients were evaluable for efficacy. Eleven patients had progressed prior to the first protocol-defined assessment, and 2 patients had not reached their first efficacy assessment at the data cutoff.

Seven of the 14 evaluable patients responded (50%). Three patients (21%) had a complete response (CR), 4 (29%) had a partial response (PR), 3 (21%) had stable disease, and 4 (29%) progressed.

“There were several patients with lengthy responses,” Dr Haverkos noted. “One patient had an ongoing response at 16 months, another at 11 months, and a number of patients had ongoing responses at 7 months.”

All 3 patients with a CR had PTCL NOS and received the 800 mg fasting dose of tenalisib.

Two patients with a PR had PTCL NOS, 1 had AITL, and 1 had SPTCL. The SPTCL patient received the 200 mg dose.

The AITL patient and 1 of the PTCL NOS patients received the 800 mg fasting dose. The other PTCL NOS patient received the 400 mg dose.

Efficacy in CTCL

Most CTCL patients (n=23) had mycosis fungoides, but 5 had Sézary syndrome. The patients’ median age at baseline was 68 (range, 39-84), and 57% are female.

Forty-three percent of patients had relapsed disease at baseline, 57% were refractory, and 46% had stage 3 or 4 disease. Patients had received a median of 6 prior therapies (range, 2-15).

The median duration of treatment with tenalisib was 3.4 months.

Eighteen patients were evaluable for efficacy. Eight patients had progressed prior to the first protocol-defined assessment, and 2 patients had not yet reached their first efficacy assessment.

Eight of the 18 evaluable patients responded (44%), all with PRs. Seven patients (39%) had stable disease, and 3 (17%) progressed.

Four patients were still in response beyond 8 months of follow-up, and 1 patient was still in PR beyond 11 months.

Five patients with a PR had received the 800 mg fasting dose of tenalisib. Two received the 800 mg fed dose, and 1 patient received the drug at 400 mg.

Overall safety

Treatment-related AEs included transaminitis (25%, 14/55), diarrhea (11%, n=6), fatigue (6%, n=11), headache (9%, n=5), rash (9%, n=5), nausea (5%, n=3), vomiting (5%, n=3), pyrexia (5%, n=3), and dizziness (5%, n=3). Dizziness was only observed in CTCL patients.

Treatment-related grade 3 or higher AEs included transaminitis (20%, n=11), rash (5%, n=3), neutropenia (2%, n=1), hypophosphatemia (2%, n=1), international normalized ratio increase (2%, n=1), sepsis (2%, n=1), pyrexia (2%, n=1), and diplopia secondary to neuropathy (2%, n=1).

Seventy-six percent (n=42) of patients discontinued treatment. Sixty-eight percent (n=29) stopped due to progression, 5% (n=2) stopped at investigators’ discretion, 9% (n=4) withdrew consent, 12% (n=5) had a treatment-related AE, and 5% (n=2) had an unrelated AE.

Seventeen PTCL patients stopped treatment due to progression, as did 12 CTCL patients. One patient in each group stopped treatment at investigators’ discretion, and all 4 patients who withdrew consent had CTCL.

Four CTCL patients stopped treatment due to a related AE—transaminitis, sepsis, diarrhea, and diplopia secondary to neuropathy. One PTCL patient stopped treatment due to a related AE, which was transaminitis.

“Tenalisib at the 800 mg fasting dose has demonstrated acceptable safety and tolerability,” Dr Haverkos concluded. “We’ve observed encouraging response rates thus far, which support further evaluation of tenalisib in these patients.”

Photo by Larry Young

LA JOLLA, CA—The dual PI3K δ/γ inhibitor tenalisib has demonstrated activity in a phase 1 trial of patients with relapsed/refractory T-cell lymphomas.

Tenalisib produced “encouraging” response rates of 44% in patients with cutaneous T-cell lymphoma (CTCL) and 50% in patients with peripheral T-cell lymphoma (PTCL), according to study investigator Bradley M. Haverkos, MD, of the University of Colorado School of Medicine in Aurora.

Dr Haverkos also said tenalisib had an acceptable safety profile.

The most common treatment-related adverse event (AE) in both patient groups was transaminitis.

Dr Haverkos and his colleagues presented these results in a pair of posters and an oral presentation at the 10th Annual T-cell Lymphoma Forum.

The trial was sponsored by Rhizen Pharmaceuticals, the company developing tenalisib (formerly RP6530).

The researchers have enrolled 55 patients in this trial—28 with CTCL and 27 with PTCL.

The study has a standard 3+3 design, starting with a 200 mg daily fasting dose of tenalisib and escalating to an 800 mg daily fasting dose, followed by an 800 mg daily fed cohort.

There were 3 dose-limiting toxicities in the 800 mg fed cohort—transaminitis, rash, and neutropenia. Therefore, the 800 mg fasting dose was considered the maximum-tolerated dose.

Patients in the PTCL and CTCL expansion cohorts received the maximum-tolerated dose.

Patients were scheduled to receive 8 cycles (28 days each) of tenalisib, but treatment could be extended to 24 months.

The data cutoff was January 10, 2018.

Efficacy in PTCL

Most PTCL patients (n=24) had PTCL not otherwise specified (NOS), 2 had angioimmunoblastic T-cell lymphoma (AITL), and 1 had subcutaneous panniculitis-like T-cell lymphoma (SPTCL).

The patients’ median age at baseline was 63 (range, 40-89), and 63% are male. Sixty-three percent of patients had relapsed disease at baseline, 37% were refractory, and 93% had stage 3 or 4 disease. Patients had received a median of 3 prior therapies (range, 1-7).

The median duration of treatment with tenalisib was 1.9 months.

Fourteen patients were evaluable for efficacy. Eleven patients had progressed prior to the first protocol-defined assessment, and 2 patients had not reached their first efficacy assessment at the data cutoff.

Seven of the 14 evaluable patients responded (50%). Three patients (21%) had a complete response (CR), 4 (29%) had a partial response (PR), 3 (21%) had stable disease, and 4 (29%) progressed.

“There were several patients with lengthy responses,” Dr Haverkos noted. “One patient had an ongoing response at 16 months, another at 11 months, and a number of patients had ongoing responses at 7 months.”

All 3 patients with a CR had PTCL NOS and received the 800 mg fasting dose of tenalisib.

Two patients with a PR had PTCL NOS, 1 had AITL, and 1 had SPTCL. The SPTCL patient received the 200 mg dose.

The AITL patient and 1 of the PTCL NOS patients received the 800 mg fasting dose. The other PTCL NOS patient received the 400 mg dose.

Efficacy in CTCL

Most CTCL patients (n=23) had mycosis fungoides, but 5 had Sézary syndrome. The patients’ median age at baseline was 68 (range, 39-84), and 57% are female.

Forty-three percent of patients had relapsed disease at baseline, 57% were refractory, and 46% had stage 3 or 4 disease. Patients had received a median of 6 prior therapies (range, 2-15).

The median duration of treatment with tenalisib was 3.4 months.

Eighteen patients were evaluable for efficacy. Eight patients had progressed prior to the first protocol-defined assessment, and 2 patients had not yet reached their first efficacy assessment.

Eight of the 18 evaluable patients responded (44%), all with PRs. Seven patients (39%) had stable disease, and 3 (17%) progressed.

Four patients were still in response beyond 8 months of follow-up, and 1 patient was still in PR beyond 11 months.

Five patients with a PR had received the 800 mg fasting dose of tenalisib. Two received the 800 mg fed dose, and 1 patient received the drug at 400 mg.

Overall safety

Treatment-related AEs included transaminitis (25%, 14/55), diarrhea (11%, n=6), fatigue (6%, n=11), headache (9%, n=5), rash (9%, n=5), nausea (5%, n=3), vomiting (5%, n=3), pyrexia (5%, n=3), and dizziness (5%, n=3). Dizziness was only observed in CTCL patients.

Treatment-related grade 3 or higher AEs included transaminitis (20%, n=11), rash (5%, n=3), neutropenia (2%, n=1), hypophosphatemia (2%, n=1), international normalized ratio increase (2%, n=1), sepsis (2%, n=1), pyrexia (2%, n=1), and diplopia secondary to neuropathy (2%, n=1).

Seventy-six percent (n=42) of patients discontinued treatment. Sixty-eight percent (n=29) stopped due to progression, 5% (n=2) stopped at investigators’ discretion, 9% (n=4) withdrew consent, 12% (n=5) had a treatment-related AE, and 5% (n=2) had an unrelated AE.

Seventeen PTCL patients stopped treatment due to progression, as did 12 CTCL patients. One patient in each group stopped treatment at investigators’ discretion, and all 4 patients who withdrew consent had CTCL.

Four CTCL patients stopped treatment due to a related AE—transaminitis, sepsis, diarrhea, and diplopia secondary to neuropathy. One PTCL patient stopped treatment due to a related AE, which was transaminitis.

“Tenalisib at the 800 mg fasting dose has demonstrated acceptable safety and tolerability,” Dr Haverkos concluded. “We’ve observed encouraging response rates thus far, which support further evaluation of tenalisib in these patients.”

Photo by Larry Young

LA JOLLA, CA—The dual PI3K δ/γ inhibitor tenalisib has demonstrated activity in a phase 1 trial of patients with relapsed/refractory T-cell lymphomas.

Tenalisib produced “encouraging” response rates of 44% in patients with cutaneous T-cell lymphoma (CTCL) and 50% in patients with peripheral T-cell lymphoma (PTCL), according to study investigator Bradley M. Haverkos, MD, of the University of Colorado School of Medicine in Aurora.

Dr Haverkos also said tenalisib had an acceptable safety profile.

The most common treatment-related adverse event (AE) in both patient groups was transaminitis.

Dr Haverkos and his colleagues presented these results in a pair of posters and an oral presentation at the 10th Annual T-cell Lymphoma Forum.

The trial was sponsored by Rhizen Pharmaceuticals, the company developing tenalisib (formerly RP6530).

The researchers have enrolled 55 patients in this trial—28 with CTCL and 27 with PTCL.

The study has a standard 3+3 design, starting with a 200 mg daily fasting dose of tenalisib and escalating to an 800 mg daily fasting dose, followed by an 800 mg daily fed cohort.

There were 3 dose-limiting toxicities in the 800 mg fed cohort—transaminitis, rash, and neutropenia. Therefore, the 800 mg fasting dose was considered the maximum-tolerated dose.

Patients in the PTCL and CTCL expansion cohorts received the maximum-tolerated dose.

Patients were scheduled to receive 8 cycles (28 days each) of tenalisib, but treatment could be extended to 24 months.

The data cutoff was January 10, 2018.

Efficacy in PTCL

Most PTCL patients (n=24) had PTCL not otherwise specified (NOS), 2 had angioimmunoblastic T-cell lymphoma (AITL), and 1 had subcutaneous panniculitis-like T-cell lymphoma (SPTCL).

The patients’ median age at baseline was 63 (range, 40-89), and 63% are male. Sixty-three percent of patients had relapsed disease at baseline, 37% were refractory, and 93% had stage 3 or 4 disease. Patients had received a median of 3 prior therapies (range, 1-7).

The median duration of treatment with tenalisib was 1.9 months.

Fourteen patients were evaluable for efficacy. Eleven patients had progressed prior to the first protocol-defined assessment, and 2 patients had not reached their first efficacy assessment at the data cutoff.

Seven of the 14 evaluable patients responded (50%). Three patients (21%) had a complete response (CR), 4 (29%) had a partial response (PR), 3 (21%) had stable disease, and 4 (29%) progressed.

“There were several patients with lengthy responses,” Dr Haverkos noted. “One patient had an ongoing response at 16 months, another at 11 months, and a number of patients had ongoing responses at 7 months.”

All 3 patients with a CR had PTCL NOS and received the 800 mg fasting dose of tenalisib.

Two patients with a PR had PTCL NOS, 1 had AITL, and 1 had SPTCL. The SPTCL patient received the 200 mg dose.

The AITL patient and 1 of the PTCL NOS patients received the 800 mg fasting dose. The other PTCL NOS patient received the 400 mg dose.

Efficacy in CTCL

Most CTCL patients (n=23) had mycosis fungoides, but 5 had Sézary syndrome. The patients’ median age at baseline was 68 (range, 39-84), and 57% are female.

Forty-three percent of patients had relapsed disease at baseline, 57% were refractory, and 46% had stage 3 or 4 disease. Patients had received a median of 6 prior therapies (range, 2-15).

The median duration of treatment with tenalisib was 3.4 months.

Eighteen patients were evaluable for efficacy. Eight patients had progressed prior to the first protocol-defined assessment, and 2 patients had not yet reached their first efficacy assessment.

Eight of the 18 evaluable patients responded (44%), all with PRs. Seven patients (39%) had stable disease, and 3 (17%) progressed.

Four patients were still in response beyond 8 months of follow-up, and 1 patient was still in PR beyond 11 months.

Five patients with a PR had received the 800 mg fasting dose of tenalisib. Two received the 800 mg fed dose, and 1 patient received the drug at 400 mg.

Overall safety

Treatment-related AEs included transaminitis (25%, 14/55), diarrhea (11%, n=6), fatigue (6%, n=11), headache (9%, n=5), rash (9%, n=5), nausea (5%, n=3), vomiting (5%, n=3), pyrexia (5%, n=3), and dizziness (5%, n=3). Dizziness was only observed in CTCL patients.

Treatment-related grade 3 or higher AEs included transaminitis (20%, n=11), rash (5%, n=3), neutropenia (2%, n=1), hypophosphatemia (2%, n=1), international normalized ratio increase (2%, n=1), sepsis (2%, n=1), pyrexia (2%, n=1), and diplopia secondary to neuropathy (2%, n=1).

Seventy-six percent (n=42) of patients discontinued treatment. Sixty-eight percent (n=29) stopped due to progression, 5% (n=2) stopped at investigators’ discretion, 9% (n=4) withdrew consent, 12% (n=5) had a treatment-related AE, and 5% (n=2) had an unrelated AE.

Seventeen PTCL patients stopped treatment due to progression, as did 12 CTCL patients. One patient in each group stopped treatment at investigators’ discretion, and all 4 patients who withdrew consent had CTCL.

Four CTCL patients stopped treatment due to a related AE—transaminitis, sepsis, diarrhea, and diplopia secondary to neuropathy. One PTCL patient stopped treatment due to a related AE, which was transaminitis.

“Tenalisib at the 800 mg fasting dose has demonstrated acceptable safety and tolerability,” Dr Haverkos concluded. “We’ve observed encouraging response rates thus far, which support further evaluation of tenalisib in these patients.”

Catalyst Biosciences

MADRID—The recombinant factor IX (FIX) product CB 2679d/ISU304 can increase FIX levels in patients with severe hemophilia B, according to a phase 1/2 trial.

Results showed a continuous linear increase in FIX activity levels following daily subcutaneous (SQ) dosing of CB 2679d for 6 days.

Adverse events were mild to moderate, and none of the patients have developed inhibitors to CB 2679d or FIX.

Howard Levy, MB ChB, PhD, chief medical officer of Catalyst Biosciences, Inc., presented these results at the 11th Annual Congress of The European Association for Haemophilia and Allied Disorders (EAHAD).

The research was sponsored by Catalyst Biosciences, Inc.

This phase 1/2 trial was divided into 5 cohorts.

In cohort 1, researchers compared single doses of intravenous (IV) CB 2679d and IV BeneFIX (recombinant FIX). CB 2679d proved 22 times more potent than BeneFIX. The products’ half-lives were 27.0 hours and 21.0 hours, respectively.

In cohorts 2 and 3, researchers compared single, ascending doses of IV CB 2679d to SQ CB 2679d. The bioavailability of SQ CB 2679d was 18.5%, and the half-life was 98.7 hours.

Cohort 4 was dropped, as it was another comparison of IV and SQ CB 2679d, which was considered unnecessary.

Cohort 5 included 5 patients who received daily doses of SQ CB 2679d. For 6 days, patients received CB 2679d at a dose of 140 IU/kg SQ.

The patients’ FIX activity levels increased from a median of <1% at baseline to a median of 15.7% (interquartile range, 14.9% to 16.6%) after all 6 doses.

The increase in FIX activity levels after the daily dosing was linear, indicating that continued SQ dosing may increase FIX activity further.

The median half-life was 63.2 hours (interquartile range, 60.2 to 64 hours), with the result that activity levels were still at 4% to 6.4% five days after the last dose.

No inhibitors to CB 2679d or FIX were observed in any of the cohorts in this trial.

In cohort 5, adverse events included pain, erythema, redness, and bruising after injections. Bruising occurred only with initial injections, and the severity of pain, erythema, and redness decreased over time (from moderate to mild).

“Existing IV therapies have FIX trough levels that can drop as low as 1% to 3% before repeat dosing,” Dr Levey said. “Daily subcutaneous dosing of CB 2679d has the potential to minimize the variability in FIX activity levels observed between IV doses and maintain individuals in the mild or even normal hemophilia range. This study demonstrates that, even after just 6 days of treatment, CB 2679d compares favorably to currently approved therapies for hemophilia B, all of which are infused IV.”

Catalyst Biosciences

MADRID—The recombinant factor IX (FIX) product CB 2679d/ISU304 can increase FIX levels in patients with severe hemophilia B, according to a phase 1/2 trial.

Results showed a continuous linear increase in FIX activity levels following daily subcutaneous (SQ) dosing of CB 2679d for 6 days.

Adverse events were mild to moderate, and none of the patients have developed inhibitors to CB 2679d or FIX.

Howard Levy, MB ChB, PhD, chief medical officer of Catalyst Biosciences, Inc., presented these results at the 11th Annual Congress of The European Association for Haemophilia and Allied Disorders (EAHAD).

The research was sponsored by Catalyst Biosciences, Inc.

This phase 1/2 trial was divided into 5 cohorts.

In cohort 1, researchers compared single doses of intravenous (IV) CB 2679d and IV BeneFIX (recombinant FIX). CB 2679d proved 22 times more potent than BeneFIX. The products’ half-lives were 27.0 hours and 21.0 hours, respectively.

In cohorts 2 and 3, researchers compared single, ascending doses of IV CB 2679d to SQ CB 2679d. The bioavailability of SQ CB 2679d was 18.5%, and the half-life was 98.7 hours.

Cohort 4 was dropped, as it was another comparison of IV and SQ CB 2679d, which was considered unnecessary.

Cohort 5 included 5 patients who received daily doses of SQ CB 2679d. For 6 days, patients received CB 2679d at a dose of 140 IU/kg SQ.

The patients’ FIX activity levels increased from a median of <1% at baseline to a median of 15.7% (interquartile range, 14.9% to 16.6%) after all 6 doses.

The increase in FIX activity levels after the daily dosing was linear, indicating that continued SQ dosing may increase FIX activity further.

The median half-life was 63.2 hours (interquartile range, 60.2 to 64 hours), with the result that activity levels were still at 4% to 6.4% five days after the last dose.

No inhibitors to CB 2679d or FIX were observed in any of the cohorts in this trial.

In cohort 5, adverse events included pain, erythema, redness, and bruising after injections. Bruising occurred only with initial injections, and the severity of pain, erythema, and redness decreased over time (from moderate to mild).

“Existing IV therapies have FIX trough levels that can drop as low as 1% to 3% before repeat dosing,” Dr Levey said. “Daily subcutaneous dosing of CB 2679d has the potential to minimize the variability in FIX activity levels observed between IV doses and maintain individuals in the mild or even normal hemophilia range. This study demonstrates that, even after just 6 days of treatment, CB 2679d compares favorably to currently approved therapies for hemophilia B, all of which are infused IV.”

Catalyst Biosciences

MADRID—The recombinant factor IX (FIX) product CB 2679d/ISU304 can increase FIX levels in patients with severe hemophilia B, according to a phase 1/2 trial.

Results showed a continuous linear increase in FIX activity levels following daily subcutaneous (SQ) dosing of CB 2679d for 6 days.

Adverse events were mild to moderate, and none of the patients have developed inhibitors to CB 2679d or FIX.

Howard Levy, MB ChB, PhD, chief medical officer of Catalyst Biosciences, Inc., presented these results at the 11th Annual Congress of The European Association for Haemophilia and Allied Disorders (EAHAD).

The research was sponsored by Catalyst Biosciences, Inc.

This phase 1/2 trial was divided into 5 cohorts.

In cohort 1, researchers compared single doses of intravenous (IV) CB 2679d and IV BeneFIX (recombinant FIX). CB 2679d proved 22 times more potent than BeneFIX. The products’ half-lives were 27.0 hours and 21.0 hours, respectively.

In cohorts 2 and 3, researchers compared single, ascending doses of IV CB 2679d to SQ CB 2679d. The bioavailability of SQ CB 2679d was 18.5%, and the half-life was 98.7 hours.

Cohort 4 was dropped, as it was another comparison of IV and SQ CB 2679d, which was considered unnecessary.

Cohort 5 included 5 patients who received daily doses of SQ CB 2679d. For 6 days, patients received CB 2679d at a dose of 140 IU/kg SQ.

The patients’ FIX activity levels increased from a median of <1% at baseline to a median of 15.7% (interquartile range, 14.9% to 16.6%) after all 6 doses.

The increase in FIX activity levels after the daily dosing was linear, indicating that continued SQ dosing may increase FIX activity further.

The median half-life was 63.2 hours (interquartile range, 60.2 to 64 hours), with the result that activity levels were still at 4% to 6.4% five days after the last dose.

No inhibitors to CB 2679d or FIX were observed in any of the cohorts in this trial.

In cohort 5, adverse events included pain, erythema, redness, and bruising after injections. Bruising occurred only with initial injections, and the severity of pain, erythema, and redness decreased over time (from moderate to mild).

“Existing IV therapies have FIX trough levels that can drop as low as 1% to 3% before repeat dosing,” Dr Levey said. “Daily subcutaneous dosing of CB 2679d has the potential to minimize the variability in FIX activity levels observed between IV doses and maintain individuals in the mild or even normal hemophilia range. This study demonstrates that, even after just 6 days of treatment, CB 2679d compares favorably to currently approved therapies for hemophilia B, all of which are infused IV.”

Photo by Chad McNeeley

Results of a case-control study suggest a cytoprotective agent can reduce treatment-related gastrointestinal (GI) toxicity in patients with multiple myeloma (MM).

Use of this agent, amifostine, was associated with significantly lower rates of grade 2 or higher oral mucositis, nausea, vomiting, and diarrhea.

Additionally, amifostine did not appear to compromise the anti-myeloma activity of treatment, which consisted of high-dose melphalan (HDM) and autologous hematopoietic stem cell transplant (auto-HSCT).

Ehsan Malek, MD, of Case Western Reserve University in Cleveland, Ohio, and his colleagues reported these findings in Leukemia & Lymphoma.

The researchers compared HDM plus auto-HSCT, with or without pre-treatment amifostine, in previously treated MM patients.

There were 107 patients who received amifostine and 114 who did not. The 107 patients received amifostine at 740 mg/m², given as a bolus infusion at 24 hours and 15 minutes before HDM.

Baseline characteristics were largely similar in the amifostine and control groups. However, more patients in the amifostine group received a tandem HSCT (17 vs 0), and more patients in the control group had an ECOG performance status of 0 (64.3% vs 43%).

Patients in the amifostine group had a longer median time from diagnosis to first HSCT—10 months (range, 4-39) vs 7 months (range, 1-95).

A majority of patients in both groups were in partial response or better at baseline. However, more patients in the control group had stable disease (6.2% vs 1%) or progressive disease (8% vs 0%).

Results

For all-grade GI toxicities, there was largely no significant difference between the amifostine and control groups. However, patients in the amifostine group had significantly lower rates of grade 2 or higher GI toxicities.

Rates of all-grade GI toxicities in the amifostine and control groups, respectively, were:

• Oral mucositis—53.3% vs 64.0%, P=0.104
• Nausea—90.7% vs 95.6%, P=0.143
• Vomiting—65.4% vs 75.4%, P=0.102
• Diarrhea—93.5% vs 84.2%,P=0.030.

Rates of grade 2 or higher GI toxicities in the amifostine and control groups, respectively, were:

• Oral mucositis—27.1% vs 47.4%, P=0.002
• Nausea—31.8% vs 86.0%, P<0.0001
• Vomiting—18.7% vs 52.6%, P<0.0001
• Diarrhea—56.1% vs 73.7%, P=0.006.

The researchers said amifostine was well tolerated and produced no significant adverse effects.

They also said amifostine had “no discernable effect” on engraftment, progression-free survival, or overall survival.

The median time to neutrophil engraftment was 11 days (range, 9-16) in the control group and 10 days (range, 6-21) in the amifostine group (P=0.011). The median time to platelet engraftment was 18 days (range, 0-26) and 19 days (range, 8-71), respectively (P<0.21).

The median progression-free survival was 40 months in the amifostine group and 32 months in the control group (P=0.012). The median overall survival was 70 months and 67 months, respectively (P=0.84).

Photo by Chad McNeeley

Results of a case-control study suggest a cytoprotective agent can reduce treatment-related gastrointestinal (GI) toxicity in patients with multiple myeloma (MM).

Use of this agent, amifostine, was associated with significantly lower rates of grade 2 or higher oral mucositis, nausea, vomiting, and diarrhea.

Additionally, amifostine did not appear to compromise the anti-myeloma activity of treatment, which consisted of high-dose melphalan (HDM) and autologous hematopoietic stem cell transplant (auto-HSCT).

Ehsan Malek, MD, of Case Western Reserve University in Cleveland, Ohio, and his colleagues reported these findings in Leukemia & Lymphoma.

The researchers compared HDM plus auto-HSCT, with or without pre-treatment amifostine, in previously treated MM patients.

There were 107 patients who received amifostine and 114 who did not. The 107 patients received amifostine at 740 mg/m², given as a bolus infusion at 24 hours and 15 minutes before HDM.

Baseline characteristics were largely similar in the amifostine and control groups. However, more patients in the amifostine group received a tandem HSCT (17 vs 0), and more patients in the control group had an ECOG performance status of 0 (64.3% vs 43%).

Patients in the amifostine group had a longer median time from diagnosis to first HSCT—10 months (range, 4-39) vs 7 months (range, 1-95).

A majority of patients in both groups were in partial response or better at baseline. However, more patients in the control group had stable disease (6.2% vs 1%) or progressive disease (8% vs 0%).

Results

For all-grade GI toxicities, there was largely no significant difference between the amifostine and control groups. However, patients in the amifostine group had significantly lower rates of grade 2 or higher GI toxicities.

Rates of all-grade GI toxicities in the amifostine and control groups, respectively, were:

• Oral mucositis—53.3% vs 64.0%, P=0.104
• Nausea—90.7% vs 95.6%, P=0.143
• Vomiting—65.4% vs 75.4%, P=0.102
• Diarrhea—93.5% vs 84.2%,P=0.030.

Rates of grade 2 or higher GI toxicities in the amifostine and control groups, respectively, were:

• Oral mucositis—27.1% vs 47.4%, P=0.002
• Nausea—31.8% vs 86.0%, P<0.0001
• Vomiting—18.7% vs 52.6%, P<0.0001
• Diarrhea—56.1% vs 73.7%, P=0.006.

The researchers said amifostine was well tolerated and produced no significant adverse effects.

They also said amifostine had “no discernable effect” on engraftment, progression-free survival, or overall survival.

The median time to neutrophil engraftment was 11 days (range, 9-16) in the control group and 10 days (range, 6-21) in the amifostine group (P=0.011). The median time to platelet engraftment was 18 days (range, 0-26) and 19 days (range, 8-71), respectively (P<0.21).

The median progression-free survival was 40 months in the amifostine group and 32 months in the control group (P=0.012). The median overall survival was 70 months and 67 months, respectively (P=0.84).

Photo by Chad McNeeley

Results of a case-control study suggest a cytoprotective agent can reduce treatment-related gastrointestinal (GI) toxicity in patients with multiple myeloma (MM).

Use of this agent, amifostine, was associated with significantly lower rates of grade 2 or higher oral mucositis, nausea, vomiting, and diarrhea.

Additionally, amifostine did not appear to compromise the anti-myeloma activity of treatment, which consisted of high-dose melphalan (HDM) and autologous hematopoietic stem cell transplant (auto-HSCT).

Ehsan Malek, MD, of Case Western Reserve University in Cleveland, Ohio, and his colleagues reported these findings in Leukemia & Lymphoma.

The researchers compared HDM plus auto-HSCT, with or without pre-treatment amifostine, in previously treated MM patients.

There were 107 patients who received amifostine and 114 who did not. The 107 patients received amifostine at 740 mg/m², given as a bolus infusion at 24 hours and 15 minutes before HDM.

Baseline characteristics were largely similar in the amifostine and control groups. However, more patients in the amifostine group received a tandem HSCT (17 vs 0), and more patients in the control group had an ECOG performance status of 0 (64.3% vs 43%).

Patients in the amifostine group had a longer median time from diagnosis to first HSCT—10 months (range, 4-39) vs 7 months (range, 1-95).

A majority of patients in both groups were in partial response or better at baseline. However, more patients in the control group had stable disease (6.2% vs 1%) or progressive disease (8% vs 0%).

Results

For all-grade GI toxicities, there was largely no significant difference between the amifostine and control groups. However, patients in the amifostine group had significantly lower rates of grade 2 or higher GI toxicities.

Rates of all-grade GI toxicities in the amifostine and control groups, respectively, were:

• Oral mucositis—53.3% vs 64.0%, P=0.104
• Nausea—90.7% vs 95.6%, P=0.143
• Vomiting—65.4% vs 75.4%, P=0.102
• Diarrhea—93.5% vs 84.2%,P=0.030.

Rates of grade 2 or higher GI toxicities in the amifostine and control groups, respectively, were:

• Oral mucositis—27.1% vs 47.4%, P=0.002
• Nausea—31.8% vs 86.0%, P<0.0001
• Vomiting—18.7% vs 52.6%, P<0.0001
• Diarrhea—56.1% vs 73.7%, P=0.006.

The researchers said amifostine was well tolerated and produced no significant adverse effects.

They also said amifostine had “no discernable effect” on engraftment, progression-free survival, or overall survival.

The median time to neutrophil engraftment was 11 days (range, 9-16) in the control group and 10 days (range, 6-21) in the amifostine group (P=0.011). The median time to platelet engraftment was 18 days (range, 0-26) and 19 days (range, 8-71), respectively (P<0.21).

The median progression-free survival was 40 months in the amifostine group and 32 months in the control group (P=0.012). The median overall survival was 70 months and 67 months, respectively (P=0.84).

ANSWER

The radiograph demonstrates a compression fracture of T12 with moderate loss of height approaching 50% anteriorly. In addition, there is a vertically oriented fracture within the middle of the vertebral body, causing the back portion to be posteriorly displaced.

This type of burst fracture is potentially unstable and should be treated as such. The patient was placed on strict spine precautions and transferred to a facility where trauma and neurosurgical services were available.

ANSWER

The radiograph demonstrates a compression fracture of T12 with moderate loss of height approaching 50% anteriorly. In addition, there is a vertically oriented fracture within the middle of the vertebral body, causing the back portion to be posteriorly displaced.

This type of burst fracture is potentially unstable and should be treated as such. The patient was placed on strict spine precautions and transferred to a facility where trauma and neurosurgical services were available.

ANSWER

The radiograph demonstrates a compression fracture of T12 with moderate loss of height approaching 50% anteriorly. In addition, there is a vertically oriented fracture within the middle of the vertebral body, causing the back portion to be posteriorly displaced.

This type of burst fracture is potentially unstable and should be treated as such. The patient was placed on strict spine precautions and transferred to a facility where trauma and neurosurgical services were available.

Fluoroquinolone use tied to higher risk of aortic dissection and aneurysm

A meta-analysis of two observational studies found that current fluoroquinolone use was associated with modestly higher risk of aortic dissection (OR 2.79, 95% CI 2.31-3.37) and aortic aneurysm (OR 2.25, 95% CI 2.03-2.49).

Citation: Singh S, Nautiyal A. Aortic dissection and aortic aneurysms associated with fluoroquinolones: A systematic review and meta-analysis. Am J Med [online ahead of print, July 21, 2017].
 

Optimal lengths of postoperative opioid prescription range from 4 to 15 days

Citation: Scully RE, Schoenfeld AJ, Jiang W, et al. Defining optimal length of opioid pain medication prescription after common surgical procedures. JAMA Surg. Sept 2017.
 

Increased mortality in weekend and holiday hospital admissions

A meta-analysis of 97 studies showed a greater relative risk of mortality for patients admitted during the weekend or holidays compared to those admitted during the week. Subgroup analyses did not reveal significant effect modification by staffing level and other hospital factors. Further research to identify contributing factors and potential interventions is needed.

Citation: Pauls LA, Johnson-Paben R, McGready J, Murphy JD, Pronovost PJ, Wu CL. The weekend effect in hospitalized patients: a meta-analysis. J Hosp Med. 2017;12(9):760-6.
 

Kayexalate should not be taken at the same time as other medications

The Food and Drug Administration has released a drug safety communication on kayexalate (sodium polystyrene sulfonate). Given recent research showing that kayexalate may decrease the absorption and effectiveness of many oral medications, the FDA recommended that when prescribing kayexalate, it should be given at least 3 hours before or after administration of other oral medications. This time should be increased to 6 hours for those with conditions that result in delayed gastric emptying.

Citation: Food and Drug Administration. Kayexalate (sodium polystyrene sulfonate): Drug Safety Communication. 09/06/2017.
 

Most thrombophilia testing done in the hospital does not add value

A retrospective cohort study among emergency department and hospitalized patients at an academic medical center examined 163 patients and 1,451 thrombophilia tests; 63% of tests were of “minimal clinical utility.”

Citation: Cox N, Johnson SA, Vazquez S, et al. Patterns and appropriateness of thrombophilia testing in an academic medical center. J Hosp Med. 2017;12(9):705-709.

Fluoroquinolone use tied to higher risk of aortic dissection and aneurysm

A meta-analysis of two observational studies found that current fluoroquinolone use was associated with modestly higher risk of aortic dissection (OR 2.79, 95% CI 2.31-3.37) and aortic aneurysm (OR 2.25, 95% CI 2.03-2.49).

Citation: Singh S, Nautiyal A. Aortic dissection and aortic aneurysms associated with fluoroquinolones: A systematic review and meta-analysis. Am J Med [online ahead of print, July 21, 2017].
 

Optimal lengths of postoperative opioid prescription range from 4 to 15 days

Citation: Scully RE, Schoenfeld AJ, Jiang W, et al. Defining optimal length of opioid pain medication prescription after common surgical procedures. JAMA Surg. Sept 2017.
 

Increased mortality in weekend and holiday hospital admissions

A meta-analysis of 97 studies showed a greater relative risk of mortality for patients admitted during the weekend or holidays compared to those admitted during the week. Subgroup analyses did not reveal significant effect modification by staffing level and other hospital factors. Further research to identify contributing factors and potential interventions is needed.

Citation: Pauls LA, Johnson-Paben R, McGready J, Murphy JD, Pronovost PJ, Wu CL. The weekend effect in hospitalized patients: a meta-analysis. J Hosp Med. 2017;12(9):760-6.
 

Kayexalate should not be taken at the same time as other medications

The Food and Drug Administration has released a drug safety communication on kayexalate (sodium polystyrene sulfonate). Given recent research showing that kayexalate may decrease the absorption and effectiveness of many oral medications, the FDA recommended that when prescribing kayexalate, it should be given at least 3 hours before or after administration of other oral medications. This time should be increased to 6 hours for those with conditions that result in delayed gastric emptying.

Citation: Food and Drug Administration. Kayexalate (sodium polystyrene sulfonate): Drug Safety Communication. 09/06/2017.
 

Most thrombophilia testing done in the hospital does not add value

A retrospective cohort study among emergency department and hospitalized patients at an academic medical center examined 163 patients and 1,451 thrombophilia tests; 63% of tests were of “minimal clinical utility.”

Citation: Cox N, Johnson SA, Vazquez S, et al. Patterns and appropriateness of thrombophilia testing in an academic medical center. J Hosp Med. 2017;12(9):705-709.

Fluoroquinolone use tied to higher risk of aortic dissection and aneurysm

A meta-analysis of two observational studies found that current fluoroquinolone use was associated with modestly higher risk of aortic dissection (OR 2.79, 95% CI 2.31-3.37) and aortic aneurysm (OR 2.25, 95% CI 2.03-2.49).

Citation: Singh S, Nautiyal A. Aortic dissection and aortic aneurysms associated with fluoroquinolones: A systematic review and meta-analysis. Am J Med [online ahead of print, July 21, 2017].
 

Optimal lengths of postoperative opioid prescription range from 4 to 15 days

Citation: Scully RE, Schoenfeld AJ, Jiang W, et al. Defining optimal length of opioid pain medication prescription after common surgical procedures. JAMA Surg. Sept 2017.
 

Increased mortality in weekend and holiday hospital admissions

A meta-analysis of 97 studies showed a greater relative risk of mortality for patients admitted during the weekend or holidays compared to those admitted during the week. Subgroup analyses did not reveal significant effect modification by staffing level and other hospital factors. Further research to identify contributing factors and potential interventions is needed.

Citation: Pauls LA, Johnson-Paben R, McGready J, Murphy JD, Pronovost PJ, Wu CL. The weekend effect in hospitalized patients: a meta-analysis. J Hosp Med. 2017;12(9):760-6.
 

Kayexalate should not be taken at the same time as other medications

The Food and Drug Administration has released a drug safety communication on kayexalate (sodium polystyrene sulfonate). Given recent research showing that kayexalate may decrease the absorption and effectiveness of many oral medications, the FDA recommended that when prescribing kayexalate, it should be given at least 3 hours before or after administration of other oral medications. This time should be increased to 6 hours for those with conditions that result in delayed gastric emptying.

Citation: Food and Drug Administration. Kayexalate (sodium polystyrene sulfonate): Drug Safety Communication. 09/06/2017.
 

Most thrombophilia testing done in the hospital does not add value

A retrospective cohort study among emergency department and hospitalized patients at an academic medical center examined 163 patients and 1,451 thrombophilia tests; 63% of tests were of “minimal clinical utility.”

Citation: Cox N, Johnson SA, Vazquez S, et al. Patterns and appropriateness of thrombophilia testing in an academic medical center. J Hosp Med. 2017;12(9):705-709.

Large-vessel vasculitis (LVV) associated with HIV-infected patients occurs more frequently in men and is significantly more severe, compared with the disease in their noninfected counterparts, according to a retrospective analysis of medical records during 2000-2015.

The study was conducted at Pitié-Salpêtrière Hospital in Paris to investigate the occurrence, characteristics, and treatment outcomes of LVV of patients infected with HIV, reported in the Journal of Vascular Surgery. Yasmina Ferfar, MD, and her colleagues diagnosed LVV using available imaging (computed tomography, positron emission tomography, and magnetic resonance angiography), histology, and Ishikawa or American College of Rheumatology (ACR) criteria of Takayasu arteritis (TA). All 93 patients selected for the study had LVV.

Comstock/Thinkstock

SOURCE: Ferfar Y. et al. J Vasc Surg. 2018 Dec 11. doi. org/10.1016/j.jvs.2017.08.099.


 

Large-vessel vasculitis (LVV) associated with HIV-infected patients occurs more frequently in men and is significantly more severe, compared with the disease in their noninfected counterparts, according to a retrospective analysis of medical records during 2000-2015.

The study was conducted at Pitié-Salpêtrière Hospital in Paris to investigate the occurrence, characteristics, and treatment outcomes of LVV of patients infected with HIV, reported in the Journal of Vascular Surgery. Yasmina Ferfar, MD, and her colleagues diagnosed LVV using available imaging (computed tomography, positron emission tomography, and magnetic resonance angiography), histology, and Ishikawa or American College of Rheumatology (ACR) criteria of Takayasu arteritis (TA). All 93 patients selected for the study had LVV.

Comstock/Thinkstock

SOURCE: Ferfar Y. et al. J Vasc Surg. 2018 Dec 11. doi. org/10.1016/j.jvs.2017.08.099.


 

Large-vessel vasculitis (LVV) associated with HIV-infected patients occurs more frequently in men and is significantly more severe, compared with the disease in their noninfected counterparts, according to a retrospective analysis of medical records during 2000-2015.

The study was conducted at Pitié-Salpêtrière Hospital in Paris to investigate the occurrence, characteristics, and treatment outcomes of LVV of patients infected with HIV, reported in the Journal of Vascular Surgery. Yasmina Ferfar, MD, and her colleagues diagnosed LVV using available imaging (computed tomography, positron emission tomography, and magnetic resonance angiography), histology, and Ishikawa or American College of Rheumatology (ACR) criteria of Takayasu arteritis (TA). All 93 patients selected for the study had LVV.

Comstock/Thinkstock

SOURCE: Ferfar Y. et al. J Vasc Surg. 2018 Dec 11. doi. org/10.1016/j.jvs.2017.08.099.


 

Only one-third of lupus patients on Medicaid had a baseline retinal exam before initiating treatment with hydroxychloroquine in an analysis of a claims database, despite the exam being recommended as the standard in multiple clinical guidelines.

The analysis of 12,755 patients with systemic lupus erythematosus (SLE) on Medicaid from 29 of the most populated U.S. states between 2001 and 2010 found that 32.5% received a baseline dilated eye exam 30 days before, and up to 1 year after, starting treatment with the anchor drug hydroxychloroquine (HCQ). This figure rose to 40% when Humphrey visual field tests and other “optional” eye exams were included, Tzu-Chieh Lin, PhD, of Brigham and Women’s Hospital, Boston, and his colleagues reported in Arthritis Care & Research.

HCQ is known to cause retinal damage in some patients, binding to and accumulating in the retinal pigment epithelium melanin. If undetected, patients may gradually lose central vision. There is particular risk for HCQ-induced retinal damage in patients on higher doses (5 mg/kg or greater of actual weight), HCQ exposure over 5 years, or renal, hepatic, or retinal disease, the research team explained.

Baseline retinal examinations for first-time HCQ users were first recommended by American Academy of Ophthalmology guidelines in 2002, and in 2009 the American College of Rheumatology developed guidelines specifically for SLE that also recommended a funduscopic exam within 1 year of starting HCQ.

The proportion of patients beginning treatment with HCQ who received a retinal exam only slightly increased from 31% in 2001 to 34.4% in 2009 (P value for linear trend over time = .12).

Women were significantly more likely to have a baseline retinal exam (odds ratio, 1.30; 95% confidence interval, 1.08-1.55), and certain sociodemographic factors also predicted who received a baseline exam, likely reflecting problems with adherence and access to health care.

For example, the likelihood of having a baseline exam proved significantly lower for blacks and American Indian/Alaska natives (OR, 0.85; 95% CI, 0.77-0.93; and OR, 0.69; 95% CI, 0.47-1.02) than for whites, whereas Asian Americans had greater odds than whites (OR, 1.30; 95% CI, 1.06-1.60).

“We have previously observed that these sociodemographic factors have been associated with differences in both access to care and adherence in the SLE Medicaid population for indicated care, including infection prevention, adherence to indicated medications including HCQ, treatments for lupus nephritis, and choices in renal replacement therapies and use of erythropoietin-stimulating agents among SLE end-stage renal disease patients,” they wrote.

Patients who had received multiple SLE-related laboratory tests (OR, 1.33; 95% CI, 1.16-1.52) and liver function tests (OR, 1.16; 95% CI, 1.04-1.29) were also more likely to have an eye exam before commencing HCQ.

The researchers said both patient and physician factors likely played a role in adherence to preventive medical care.

“While adherence to daily dosing, by the latest recommendations less than 5 mg/kg actual weight, is a more important factor determining renal toxicity risk, baseline examinations are necessary to avoid treating patients with preexisting retinal disease and to allow early detection of changes from baseline,” the research team concluded.

The work was supported by grant awards from the Rheumatology Research Foundation and the National Institutes of Health. No disclosures were made.

rhnews@frontlinemedcom.com

SOURCE: Lin T et al. Arthritis Care Res. 2018 Feb 6. doi: 10.1002/acr.23530.

Only one-third of lupus patients on Medicaid had a baseline retinal exam before initiating treatment with hydroxychloroquine in an analysis of a claims database, despite the exam being recommended as the standard in multiple clinical guidelines.

The analysis of 12,755 patients with systemic lupus erythematosus (SLE) on Medicaid from 29 of the most populated U.S. states between 2001 and 2010 found that 32.5% received a baseline dilated eye exam 30 days before, and up to 1 year after, starting treatment with the anchor drug hydroxychloroquine (HCQ). This figure rose to 40% when Humphrey visual field tests and other “optional” eye exams were included, Tzu-Chieh Lin, PhD, of Brigham and Women’s Hospital, Boston, and his colleagues reported in Arthritis Care & Research.

HCQ is known to cause retinal damage in some patients, binding to and accumulating in the retinal pigment epithelium melanin. If undetected, patients may gradually lose central vision. There is particular risk for HCQ-induced retinal damage in patients on higher doses (5 mg/kg or greater of actual weight), HCQ exposure over 5 years, or renal, hepatic, or retinal disease, the research team explained.

Baseline retinal examinations for first-time HCQ users were first recommended by American Academy of Ophthalmology guidelines in 2002, and in 2009 the American College of Rheumatology developed guidelines specifically for SLE that also recommended a funduscopic exam within 1 year of starting HCQ.

The proportion of patients beginning treatment with HCQ who received a retinal exam only slightly increased from 31% in 2001 to 34.4% in 2009 (P value for linear trend over time = .12).

Women were significantly more likely to have a baseline retinal exam (odds ratio, 1.30; 95% confidence interval, 1.08-1.55), and certain sociodemographic factors also predicted who received a baseline exam, likely reflecting problems with adherence and access to health care.

For example, the likelihood of having a baseline exam proved significantly lower for blacks and American Indian/Alaska natives (OR, 0.85; 95% CI, 0.77-0.93; and OR, 0.69; 95% CI, 0.47-1.02) than for whites, whereas Asian Americans had greater odds than whites (OR, 1.30; 95% CI, 1.06-1.60).

“We have previously observed that these sociodemographic factors have been associated with differences in both access to care and adherence in the SLE Medicaid population for indicated care, including infection prevention, adherence to indicated medications including HCQ, treatments for lupus nephritis, and choices in renal replacement therapies and use of erythropoietin-stimulating agents among SLE end-stage renal disease patients,” they wrote.

Patients who had received multiple SLE-related laboratory tests (OR, 1.33; 95% CI, 1.16-1.52) and liver function tests (OR, 1.16; 95% CI, 1.04-1.29) were also more likely to have an eye exam before commencing HCQ.

The researchers said both patient and physician factors likely played a role in adherence to preventive medical care.

“While adherence to daily dosing, by the latest recommendations less than 5 mg/kg actual weight, is a more important factor determining renal toxicity risk, baseline examinations are necessary to avoid treating patients with preexisting retinal disease and to allow early detection of changes from baseline,” the research team concluded.

The work was supported by grant awards from the Rheumatology Research Foundation and the National Institutes of Health. No disclosures were made.

rhnews@frontlinemedcom.com

SOURCE: Lin T et al. Arthritis Care Res. 2018 Feb 6. doi: 10.1002/acr.23530.

Only one-third of lupus patients on Medicaid had a baseline retinal exam before initiating treatment with hydroxychloroquine in an analysis of a claims database, despite the exam being recommended as the standard in multiple clinical guidelines.

The analysis of 12,755 patients with systemic lupus erythematosus (SLE) on Medicaid from 29 of the most populated U.S. states between 2001 and 2010 found that 32.5% received a baseline dilated eye exam 30 days before, and up to 1 year after, starting treatment with the anchor drug hydroxychloroquine (HCQ). This figure rose to 40% when Humphrey visual field tests and other “optional” eye exams were included, Tzu-Chieh Lin, PhD, of Brigham and Women’s Hospital, Boston, and his colleagues reported in Arthritis Care & Research.

HCQ is known to cause retinal damage in some patients, binding to and accumulating in the retinal pigment epithelium melanin. If undetected, patients may gradually lose central vision. There is particular risk for HCQ-induced retinal damage in patients on higher doses (5 mg/kg or greater of actual weight), HCQ exposure over 5 years, or renal, hepatic, or retinal disease, the research team explained.

Baseline retinal examinations for first-time HCQ users were first recommended by American Academy of Ophthalmology guidelines in 2002, and in 2009 the American College of Rheumatology developed guidelines specifically for SLE that also recommended a funduscopic exam within 1 year of starting HCQ.

The proportion of patients beginning treatment with HCQ who received a retinal exam only slightly increased from 31% in 2001 to 34.4% in 2009 (P value for linear trend over time = .12).

Women were significantly more likely to have a baseline retinal exam (odds ratio, 1.30; 95% confidence interval, 1.08-1.55), and certain sociodemographic factors also predicted who received a baseline exam, likely reflecting problems with adherence and access to health care.

For example, the likelihood of having a baseline exam proved significantly lower for blacks and American Indian/Alaska natives (OR, 0.85; 95% CI, 0.77-0.93; and OR, 0.69; 95% CI, 0.47-1.02) than for whites, whereas Asian Americans had greater odds than whites (OR, 1.30; 95% CI, 1.06-1.60).

“We have previously observed that these sociodemographic factors have been associated with differences in both access to care and adherence in the SLE Medicaid population for indicated care, including infection prevention, adherence to indicated medications including HCQ, treatments for lupus nephritis, and choices in renal replacement therapies and use of erythropoietin-stimulating agents among SLE end-stage renal disease patients,” they wrote.

Patients who had received multiple SLE-related laboratory tests (OR, 1.33; 95% CI, 1.16-1.52) and liver function tests (OR, 1.16; 95% CI, 1.04-1.29) were also more likely to have an eye exam before commencing HCQ.

The researchers said both patient and physician factors likely played a role in adherence to preventive medical care.

“While adherence to daily dosing, by the latest recommendations less than 5 mg/kg actual weight, is a more important factor determining renal toxicity risk, baseline examinations are necessary to avoid treating patients with preexisting retinal disease and to allow early detection of changes from baseline,” the research team concluded.

The work was supported by grant awards from the Rheumatology Research Foundation and the National Institutes of Health. No disclosures were made.

rhnews@frontlinemedcom.com

SOURCE: Lin T et al. Arthritis Care Res. 2018 Feb 6. doi: 10.1002/acr.23530.

DALLAS – Monthly ultrasound scans in the last trimester pick up just as many fetal growth and amniotic fluid problems as do scans done every 2 weeks, Suneet P. Chauhan, MD, reported at the meeting sponsored by the Society for Maternal-Fetal Medicine.

“We found that about one in three of these high-risk pregnancies was complicated by an abnormality of fetal growth or amniotic fluid,” said Dr. Chauhan of the department of obstetrics, gynecology, and reproductive sciences at the University of Texas, Houston. “But more frequent scans did not increase the frequency of identifying these abnormalities. And since there are approximately 1.7 million such high-risk pregnancies each year, these findings have significant implications on personal, departmental, and societal levels.”

Michele G. Sullivan/Frontline Medical News

However, he added, the SUN trial, which randomized women to monthly or biweekly scans, wasn’t large enough to definitively determine the optimal timing of ultrasounds in this population. “We need larger trials to determine this.”

The trial results, published in the American Journal of Obstetrics & Gynecology, comprised 228 women with singleton pregnancies complicated by medical comorbidities, putting the fetus at risk of problems with growth or amniotic fluid volume. They were randomized to ultrasound scans every 2 weeks or every 4 weeks during the last trimester. The primary outcome was identification of four pregnancy complications: fetal growth restriction, large for gestational age, oligohydramnios, or polyhydramnios.

There were also secondary outcomes of composite maternal morbidity (chorioamnionitis, wound infection, transfusion, diabetic ketoacidosis, venous thromboembolism, ICU admission, and death) and neonatal morbidity (Apgar score of less than 5 at 5 minutes, umbilical artery pH less than 7, hyperbilirubinemia, intubation, high-grade intraventricular hemorrhage, necrotizing enterocolitis, and death).

Women were eligible for the study if they had autoimmune disease, a body mass index of 40 kg/m² or higher, a history of delivering a small for gestational age or macrosomic infant, hypertensive disease, substance abuse, or sickle cell disease.

About half had multiple risk factors, the three most common being high body mass index, diabetes (either gestational or insulin-dependent), and hypertensive disease. Their gestational age at randomization was a mean of 23 weeks. The first scan was conducted at a mean of 29 weeks.

There were 28% more scans in the 2-week group than in the 4-week group (492 vs. 382). There were also more exams for potentially concerning findings, including more scans looking at growth (359 vs. 278), biophysical profiles (99 vs. 79), and umbilical artery Dopplers (34 vs. 27). Despite the increased scans and investigations, the primary outcome was detected at similar points (31.7 vs. 32.2 weeks).

A primary outcome finding was detected in 38% of the 2-week group and 32% of the 4-week group – not significantly different. There were no significant differences in the proportion of outcomes detected in each group, including fetal growth restriction (19% vs. 16%), large for gestational age (14% each group), oligohydramnios (4% each group) and polyhydramnios (9% each group).

Infants in each group were born at about the same time – 13.5 weeks after randomization. The mean gestational age in both groups was 37 weeks, with about 28.5% less than 37 weeks at birth. There were no significant differences in the rate of cesarean deliveries, or small or large for gestational age births.

The composite maternal morbidity outcome was similar in the 2-week and 4-week groups (26% vs. 22%). There were no significant differences in any of the individual components of the outcome. No mother died.

The composite neonatal outcome was also similar between the groups (14% vs. 12%). There were no significant differences in any of the individual components. No infant died.

The study was sponsored by the University of Texas Health Science Center, Houston. Dr. Chauhan had no financial disclosures.

msullivan@frontlinemedcom.com

SOURCE: Roberts RP et al. Am J Obstet Gynecol. 2018;218:S3.

DALLAS – Monthly ultrasound scans in the last trimester pick up just as many fetal growth and amniotic fluid problems as do scans done every 2 weeks, Suneet P. Chauhan, MD, reported at the meeting sponsored by the Society for Maternal-Fetal Medicine.

“We found that about one in three of these high-risk pregnancies was complicated by an abnormality of fetal growth or amniotic fluid,” said Dr. Chauhan of the department of obstetrics, gynecology, and reproductive sciences at the University of Texas, Houston. “But more frequent scans did not increase the frequency of identifying these abnormalities. And since there are approximately 1.7 million such high-risk pregnancies each year, these findings have significant implications on personal, departmental, and societal levels.”

Michele G. Sullivan/Frontline Medical News

However, he added, the SUN trial, which randomized women to monthly or biweekly scans, wasn’t large enough to definitively determine the optimal timing of ultrasounds in this population. “We need larger trials to determine this.”

The trial results, published in the American Journal of Obstetrics & Gynecology, comprised 228 women with singleton pregnancies complicated by medical comorbidities, putting the fetus at risk of problems with growth or amniotic fluid volume. They were randomized to ultrasound scans every 2 weeks or every 4 weeks during the last trimester. The primary outcome was identification of four pregnancy complications: fetal growth restriction, large for gestational age, oligohydramnios, or polyhydramnios.

There were also secondary outcomes of composite maternal morbidity (chorioamnionitis, wound infection, transfusion, diabetic ketoacidosis, venous thromboembolism, ICU admission, and death) and neonatal morbidity (Apgar score of less than 5 at 5 minutes, umbilical artery pH less than 7, hyperbilirubinemia, intubation, high-grade intraventricular hemorrhage, necrotizing enterocolitis, and death).

Women were eligible for the study if they had autoimmune disease, a body mass index of 40 kg/m² or higher, a history of delivering a small for gestational age or macrosomic infant, hypertensive disease, substance abuse, or sickle cell disease.

About half had multiple risk factors, the three most common being high body mass index, diabetes (either gestational or insulin-dependent), and hypertensive disease. Their gestational age at randomization was a mean of 23 weeks. The first scan was conducted at a mean of 29 weeks.

There were 28% more scans in the 2-week group than in the 4-week group (492 vs. 382). There were also more exams for potentially concerning findings, including more scans looking at growth (359 vs. 278), biophysical profiles (99 vs. 79), and umbilical artery Dopplers (34 vs. 27). Despite the increased scans and investigations, the primary outcome was detected at similar points (31.7 vs. 32.2 weeks).

A primary outcome finding was detected in 38% of the 2-week group and 32% of the 4-week group – not significantly different. There were no significant differences in the proportion of outcomes detected in each group, including fetal growth restriction (19% vs. 16%), large for gestational age (14% each group), oligohydramnios (4% each group) and polyhydramnios (9% each group).

Infants in each group were born at about the same time – 13.5 weeks after randomization. The mean gestational age in both groups was 37 weeks, with about 28.5% less than 37 weeks at birth. There were no significant differences in the rate of cesarean deliveries, or small or large for gestational age births.

The composite maternal morbidity outcome was similar in the 2-week and 4-week groups (26% vs. 22%). There were no significant differences in any of the individual components of the outcome. No mother died.

The composite neonatal outcome was also similar between the groups (14% vs. 12%). There were no significant differences in any of the individual components. No infant died.

The study was sponsored by the University of Texas Health Science Center, Houston. Dr. Chauhan had no financial disclosures.

msullivan@frontlinemedcom.com

SOURCE: Roberts RP et al. Am J Obstet Gynecol. 2018;218:S3.

DALLAS – Monthly ultrasound scans in the last trimester pick up just as many fetal growth and amniotic fluid problems as do scans done every 2 weeks, Suneet P. Chauhan, MD, reported at the meeting sponsored by the Society for Maternal-Fetal Medicine.

“We found that about one in three of these high-risk pregnancies was complicated by an abnormality of fetal growth or amniotic fluid,” said Dr. Chauhan of the department of obstetrics, gynecology, and reproductive sciences at the University of Texas, Houston. “But more frequent scans did not increase the frequency of identifying these abnormalities. And since there are approximately 1.7 million such high-risk pregnancies each year, these findings have significant implications on personal, departmental, and societal levels.”

Michele G. Sullivan/Frontline Medical News

However, he added, the SUN trial, which randomized women to monthly or biweekly scans, wasn’t large enough to definitively determine the optimal timing of ultrasounds in this population. “We need larger trials to determine this.”

The trial results, published in the American Journal of Obstetrics & Gynecology, comprised 228 women with singleton pregnancies complicated by medical comorbidities, putting the fetus at risk of problems with growth or amniotic fluid volume. They were randomized to ultrasound scans every 2 weeks or every 4 weeks during the last trimester. The primary outcome was identification of four pregnancy complications: fetal growth restriction, large for gestational age, oligohydramnios, or polyhydramnios.

There were also secondary outcomes of composite maternal morbidity (chorioamnionitis, wound infection, transfusion, diabetic ketoacidosis, venous thromboembolism, ICU admission, and death) and neonatal morbidity (Apgar score of less than 5 at 5 minutes, umbilical artery pH less than 7, hyperbilirubinemia, intubation, high-grade intraventricular hemorrhage, necrotizing enterocolitis, and death).

Women were eligible for the study if they had autoimmune disease, a body mass index of 40 kg/m² or higher, a history of delivering a small for gestational age or macrosomic infant, hypertensive disease, substance abuse, or sickle cell disease.

About half had multiple risk factors, the three most common being high body mass index, diabetes (either gestational or insulin-dependent), and hypertensive disease. Their gestational age at randomization was a mean of 23 weeks. The first scan was conducted at a mean of 29 weeks.

There were 28% more scans in the 2-week group than in the 4-week group (492 vs. 382). There were also more exams for potentially concerning findings, including more scans looking at growth (359 vs. 278), biophysical profiles (99 vs. 79), and umbilical artery Dopplers (34 vs. 27). Despite the increased scans and investigations, the primary outcome was detected at similar points (31.7 vs. 32.2 weeks).

A primary outcome finding was detected in 38% of the 2-week group and 32% of the 4-week group – not significantly different. There were no significant differences in the proportion of outcomes detected in each group, including fetal growth restriction (19% vs. 16%), large for gestational age (14% each group), oligohydramnios (4% each group) and polyhydramnios (9% each group).

Infants in each group were born at about the same time – 13.5 weeks after randomization. The mean gestational age in both groups was 37 weeks, with about 28.5% less than 37 weeks at birth. There were no significant differences in the rate of cesarean deliveries, or small or large for gestational age births.

The composite maternal morbidity outcome was similar in the 2-week and 4-week groups (26% vs. 22%). There were no significant differences in any of the individual components of the outcome. No mother died.

The composite neonatal outcome was also similar between the groups (14% vs. 12%). There were no significant differences in any of the individual components. No infant died.

The study was sponsored by the University of Texas Health Science Center, Houston. Dr. Chauhan had no financial disclosures.

msullivan@frontlinemedcom.com

SOURCE: Roberts RP et al. Am J Obstet Gynecol. 2018;218:S3.